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1. ECG/echo indexes in the diagnostic approach to amyloid cardiomyopathy: A head-to-head comparison from the AC-TIVE study

Author: Pagura, L, Porcari, A, Cameli, M, Biagini, E, Canepa, M, Crotti, L, Imazio, M, Forleo, C, Pavasini, R, Limongelli, G, Perlini, S, Metra, M, Boriani, G, Emdin, M, Sinagra, G, Merlo, M, Longo, F, Rossi, M, Varrà, G, Saro, R, Dore, F, Girardi, F, Vergaro, G, Musumeci, B, Autore, C, Cappelli, F, Perfetto, F, Olivotto, I, Favale, S, Carella, M, Guaricci, A, Ciccone, M, Di Bella, G, Tomasoni, D, Rella, V, Branzi, G, Badano, L, Parati, G, Palmiero, G, Caiazza, M, Caponetti, A, Saturi, G, Labate, M, Andreis, A, Paneva, E, De Ferrari, G, Di Ienno, L, De Carli, G, Giacomin, E, Arzilli, C, Pagura L., Porcari A., Cameli M., Biagini E., Canepa M., Crotti L., Imazio M., Forleo C., Pavasini R., Limongelli G., Perlini S., Metra M., Boriani G., Emdin M., Sinagra G., Merlo M., Longo F., Rossi M., Varrà G. G., Saro R., Dore F., Girardi F., Vergaro G., Musumeci B., Autore C., Cappelli F., Perfetto F., Olivotto I., Favale S., Carella M. C., Guaricci A. I., Ciccone M. M., Di Bella G., Tomasoni D., Rella V., Branzi G., Badano L., Parati G., Palmiero G., Caiazza M., Caponetti A. G., Saturi G., Labate M. E., Andreis A., Paneva E., De Ferrari G. M., Di Ienno L., De Carli G., Giacomin E., Arzilli C., Pagura, L, Porcari, A, Cameli, M, Biagini, E, Canepa, M, Crotti, L, Imazio, M, Forleo, C, Pavasini, R, Limongelli, G, Perlini, S, Metra, M, Boriani, G, Emdin, M, Sinagra, G, Merlo, M, Longo, F, Rossi, M, Varrà, G, Saro, R, Dore, F, Girardi, F, Vergaro, G, Musumeci, B, Autore, C, Cappelli, F, Perfetto, F, Olivotto, I, Favale, S, Carella, M, Guaricci, A, Ciccone, M, Di Bella, G, Tomasoni, D, Rella, V, Branzi, G, Badano, L, Parati, G, Palmiero, G, Caiazza, M, Caponetti, A, Saturi, G, Labate, M, Andreis, A, Paneva, E, De Ferrari, G, Di Ienno, L, De Carli, G, Giacomin, E, Arzilli, C, Pagura L., Porcari A., Cameli M., Biagini E., Canepa M., Crotti L., Imazio M., Forleo C., Pavasini R., Limongelli G., Perlini S., Metra M., Boriani G., Emdin M., Sinagra G., Merlo M., Longo F., Rossi M., Varrà G. G., Saro R., Dore F., Girardi F., Vergaro G., Musumeci B., Autore C., Cappelli F., Perfetto F., Olivotto I., Favale S., Carella M. C., Guaricci A. I., Ciccone M. M., Di Bella G., Tomasoni D., Rella V., Branzi G., Badano L., Parati G., Palmiero G., Caiazza M., Caponetti A. G., Saturi G., Labate M. E., Andreis A., Paneva E., De Ferrari G. M., Di Ienno L., De Carli G., Giacomin E., and Arzilli C.
Abstract: Background and aims: The discordance between QRS voltages on electrocardiogram (ECG) and left ventricle (LV) wall thickness (LVWT) on echocardiogram (echo) is a recognized red flag (RF) of amyloid cardiomyopathy (AC) and can be measured by specific indexes. No head-to-head comparison of different ECG/echo indexes among subjects with echocardiographic suspicion of AC has yet been undertaken. The study aimed at evaluating the performance and the incremental diagnostic value of different ECG/echo indexes in this subset of patients. Methods: Electrocardiograms of subjects with LV hypertrophy, preserved ejection fraction and ≥ 1 echocardiographic RF of AC participating in the AC-TIVE study, an Italian prospective multicenter study, were independently analyzed by two cardiologists. Low QRS voltages and 8 different ECG/echo indexes were evaluated. Cohort specific cut-offs were computed. Results: Among 170 patients, 55 (32 %) were diagnosed with AC. Combination of low QRS voltages with interventricular septum ≥ 1,6 cm was the most specific (specificity 100 %, positive predictive value 100 %) ECG/echo index, while the ratio between the sum of all QRS voltages and LVWT <7,8 was the most sensitive and accurate (sensitivity 94 %, negative predictive value 97 %, accuracy 82 %). When the latter index was added to a model using easily-accessible clinical variables, the diagnostic accuracy for AC greatly increased (AUC from 0,84 to 0,95; p = 0,007). Conclusions: Among patients with non-dilated hypertrophic ventricles with normal ejection fraction and echocardiographic RF of AC, easily-measurable ECG/echo indexes, mainly when added to few clinical variables, can help the physician orient second level investigations. External validation of the results is warranted.
Published: 2024

2. Uncertainties in cardiovascular risk factors: sodium-glucose cotransporter 2 inhibitors for all diabetic patients with high cardiovascular risk and in all patients with renal insufficiency, regardless of albuminuria? Glucagon-like peptide-1 receptor agonists as a weapon against obesity? [Incertezze nei fattori di rischio cardiovascolare: inibitori del cotrasportatore sodio-glucosio di tipo 2 per tutti i pazienti diabetici ad elevato rischio cardiovascolare e per tutti i pazienti con insufficienza renale indipendentemente dall’albuminuria? Agonisti del recettore del glucagon-like peptide-1 come arma contro l’obesità?]

Author: Avogaro, A, Corsini, A, Sinagra, G, Borghi, C, Sciatti, E, Trevisan, R, Fioretto, P, Calabrò, P, Di Pasquale, G, Senni, M, Avogaro A., Corsini A., Sinagra G., Borghi C., Sciatti E., Trevisan R., Fioretto P., Calabrò P., Di Pasquale G., Senni M., Avogaro, A, Corsini, A, Sinagra, G, Borghi, C, Sciatti, E, Trevisan, R, Fioretto, P, Calabrò, P, Di Pasquale, G, Senni, M, Avogaro A., Corsini A., Sinagra G., Borghi C., Sciatti E., Trevisan R., Fioretto P., Calabrò P., Di Pasquale G., and Senni M.
Abstract: The clinical guidelines, while representing an objective reference to perform correct therapeutic choices, contain grey zones, where the recommendations are not supported by solid evidence. In the fifth National Congress Grey Zones held in Bergamo in June 2022, an attempt was made to highlight some of the main grey zones in Cardiology and, through a comparison between experts, to draw shared conclusions that can illuminate our clinical practice. This manuscript contains the statements of the symposium concerning the controversies regarding cardiovascular risk factors. The manuscript represents the organization of the meeting, with an initial revision of the present guidelines on this topic, followed by an expert presentation of pros (White) and cons (Black) related to the identified "gaps of evidence". For every issue is then reported the "response" derived from the votes of the experts and the public, the discussion and, finally, the highlights, which are intended as practical "take home messages" to be used in the everyday clinical practice. The first gap in evidence discussed is the indication for therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors for all diabetic patients at high cardiovascular risk. The second examines the possibility of using SGLT2 inhibitors in all patients with renal insufficiency, regardless of albuminuria. The last gap in evidence regards the possible use of glucagon-like peptide-1 receptor agonists as a weapon against obesity.
Published: 2023

3. Diagnostic pathways to wild-type transthyretin amyloid cardiomyopathy: a multicentre network study

Author: Tini, G, Milani, P, Zampieri, M, Caponetti, A, Fabris, F, Foli, A, Argiro, A, Mazzoni, C, Gagliardi, C, Longhi, S, Saturi, G, Vergaro, G, Aimo, A, Russo, D, Varra, G, Serenelli, M, Fabbri, G, De Michieli, L, Palmiero, G, Ciliberti, G, Carigi, S, Sessarego, E, Mandoli, G, Ricci Lucchi, G, Rella, V, Monti, E, Gardini, E, Bartolotti, M, Crotti, L, Merli, E, Mussinelli, R, Vianello, P, Cameli, M, Marzo, F, Guerra, F, Limongelli, G, Cipriani, A, Perlini, S, Obici, L, Perfetto, F, Autore, C, Porto, I, Rapezzi, C, Sinagra, G, Merlo, M, Musumeci, B, Emdin, M, Biagini, E, Cappelli, F, Palladini, G, Canepa, M, Tini G., Milani P., Zampieri M., Caponetti A. G., Fabris F., Foli A., Argiro A., Mazzoni C., Gagliardi C., Longhi S., Saturi G., Vergaro G., Aimo A., Russo D., Varra G. G., Serenelli M., Fabbri G., De Michieli L., Palmiero G., Ciliberti G., Carigi S., Sessarego E., Mandoli G. E., Ricci Lucchi G., Rella V., Monti E., Gardini E., Bartolotti M., Crotti L., Merli E., Mussinelli R., Vianello P. F., Cameli M., Marzo F., Guerra F., Limongelli G., Cipriani A., Perlini S., Obici L., Perfetto F., Autore C., Porto I., Rapezzi C., Sinagra G., Merlo M., Musumeci B., Emdin M., Biagini E., Cappelli F., Palladini G., Canepa M., Tini, G, Milani, P, Zampieri, M, Caponetti, A, Fabris, F, Foli, A, Argiro, A, Mazzoni, C, Gagliardi, C, Longhi, S, Saturi, G, Vergaro, G, Aimo, A, Russo, D, Varra, G, Serenelli, M, Fabbri, G, De Michieli, L, Palmiero, G, Ciliberti, G, Carigi, S, Sessarego, E, Mandoli, G, Ricci Lucchi, G, Rella, V, Monti, E, Gardini, E, Bartolotti, M, Crotti, L, Merli, E, Mussinelli, R, Vianello, P, Cameli, M, Marzo, F, Guerra, F, Limongelli, G, Cipriani, A, Perlini, S, Obici, L, Perfetto, F, Autore, C, Porto, I, Rapezzi, C, Sinagra, G, Merlo, M, Musumeci, B, Emdin, M, Biagini, E, Cappelli, F, Palladini, G, Canepa, M, Tini G., Milani P., Zampieri M., Caponetti A. G., Fabris F., Foli A., Argiro A., Mazzoni C., Gagliardi C., Longhi S., Saturi G., Vergaro G., Aimo A., Russo D., Varra G. G., Serenelli M., Fabbri G., De Michieli L., Palmiero G., Ciliberti G., Carigi S., Sessarego E., Mandoli G. E., Ricci Lucchi G., Rella V., Monti E., Gardini E., Bartolotti M., Crotti L., Merli E., Mussinelli R., Vianello P. F., Cameli M., Marzo F., Guerra F., Limongelli G., Cipriani A., Perlini S., Obici L., Perfetto F., Autore C., Porto I., Rapezzi C., Sinagra G., Merlo M., Musumeci B., Emdin M., Biagini E., Cappelli F., Palladini G., and Canepa M.
Abstract: Aim: Epidemiology of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) remains poorly defined. A better characterization of pathways leading to ATTRwt-CA diagnosis is of key importance, and potentially informative of disease course and prognosis. The aim of this study was to describe the characteristics of contemporary pathways leading to ATTRwt-CA diagnosis, and their potential association with survival. Methods and results: This was a retrospective study of patients diagnosed with ATTRwt-CA at 17 Italian referral centres for CA. Patients were categorized into different ‘pathways’ according to the medical reason that triggered the diagnosis of ATTRwt-CA (hypertrophic cardiomyopathy [HCM] pathway, heart failure [HF] pathway, incidental imaging or incidental clinical pathway). Prognosis was investigated with all-cause mortality as endpoint. Overall, 1281 ATTRwt-CA patients were included in the study. The diagnostic pathway leading to ATTRwt-CA diagnosis was HCM in 7% of patients, HF in 51%, incidental imaging in 23%, incidental clinical in 19%. Patients in the HF pathway, as compared to the others, were older and had a greater prevalence of New York Heart Association (NYHA) class III–IV and chronic kidney disease. Survival was significantly worse in the HF versus other pathways, but similar among the three others. In multivariate model, older age at diagnosis, NYHA class III–IV and some comorbidities but not the HF pathway were independently associated with worse survival. Conclusions: Half of contemporary ATTRwt-CA diagnoses occur in a HF setting. These patients had worse clinical profile and outcome than those diagnosed either due to suspected HCM or incidentally, although prognosis remained primarily related to age, NYHA functional class and comorbidities rather than the diagnostic pathway itself.
Published: 2023

4. Razionale e valore fondamentale della Rete Italiana integrata dell’Amiloidosi Cardiaca [Rationale and significance of the Italian Network for Cardiac Amyloidosis]

Author: Sinagra, G, Emdin, M, Merlo, M, Vergaro, G, Aimo, A, Biagini, E, Imazio, M, Porcari, A, Limongelli, G, Cipriani, A, Canepa, M, Musumeci, B, Cameli, M, Crotti, L, Di Bella, G, Di Lenarda, A, Cappelli, F, Chimenti, C, Obici, L, Iacoviello, M, Perlini, S, Pieroni, M, Metra, M, Oliva, F, Perrone Filardi, P, Colivicchi, F, Indolfi, C, Sinagra G., Emdin M., Merlo M., Vergaro G., Aimo A., Biagini E., Imazio M., Porcari A., Limongelli G., Cipriani A., Canepa M., Musumeci B., Cameli M., Crotti L., Di Bella G., Di Lenarda A., Cappelli F., Chimenti C., Obici L., Iacoviello M., Perlini S., Pieroni M., Metra M., Oliva F., Perrone Filardi P., Colivicchi F., Indolfi C., Sinagra, G, Emdin, M, Merlo, M, Vergaro, G, Aimo, A, Biagini, E, Imazio, M, Porcari, A, Limongelli, G, Cipriani, A, Canepa, M, Musumeci, B, Cameli, M, Crotti, L, Di Bella, G, Di Lenarda, A, Cappelli, F, Chimenti, C, Obici, L, Iacoviello, M, Perlini, S, Pieroni, M, Metra, M, Oliva, F, Perrone Filardi, P, Colivicchi, F, Indolfi, C, Sinagra G., Emdin M., Merlo M., Vergaro G., Aimo A., Biagini E., Imazio M., Porcari A., Limongelli G., Cipriani A., Canepa M., Musumeci B., Cameli M., Crotti L., Di Bella G., Di Lenarda A., Cappelli F., Chimenti C., Obici L., Iacoviello M., Perlini S., Pieroni M., Metra M., Oliva F., Perrone Filardi P., Colivicchi F., and Indolfi C.
Abstract: The perspective on amyloidosis has changed deeply over the last 10 years following major advances in diagnosis and treatment options, especially in cardiac amyloidosis. This intrinsically heterogeneous disease exposes to the risk of fragmentation of knowledge and requires the interaction among experts of different specialties and subspecialties. Suspicion of disease, timely recognition and confirmation of final diagnosis, prognostic stratification, clinical management and therapeutic strategies represent essential steps to be taken. Missing or delaying the diagnosis may have dramatic impact on patient outcome, as in the case of chemotherapy in unrecognized light-chain amyloidosis. Therefore, there is an urgent need for the foundation of an Italian Amyloidosis Network to deal with the challenges of this condition and orient clinical management at national and local levels. The present consensus document aims to provide the rationale and scopes of the Italian Amyloidosis Network, which has been conceived as an organizational framework for professionals managing patients with amyloidosis.
Published: 2023

5. Acute Myocarditis Associated With Desmosomal Gene Variants

Author: Ammirati, E, Raimondi, F, Piriou, N, Sardo Infirri, L, Mohiddin, S, Mazzanti, A, Shenoy, C, Cavallari, U, Imazio, M, Aquaro, G, Olivotto, I, Pedrotti, P, Sekhri, N, Van de Heyning, C, Broeckx, G, Peretto, G, Guttmann, O, Dellegrottaglie, S, Scatteia, A, Gentile, P, Merlo, M, Goldberg, R, Reyentovich, A, Sciamanna, C, Klaassen, S, Poller, W, Trankle, C, Abbate, A, Keren, A, Horowitz-Cederboim, S, Cadrin-Tourigny, J, Tadros, R, Annoni, G, Bonoldi, E, Toquet, C, Marteau, L, Probst, V, Trochu, J, Kissopoulou, A, Grosu, A, Kukavica, D, Trancuccio, A, Gil, C, Tini, G, Pedrazzini, M, Torchio, M, Sinagra, G, Gimeno, J, Bernasconi, D, Valsecchi, M, Klingel, K, Adler, E, Camici, P, Cooper, L, Ammirati E., Raimondi F., Piriou N., Sardo Infirri L., Mohiddin S. A., Mazzanti A., Shenoy C., Cavallari U. A., Imazio M., Aquaro G. D., Olivotto I., Pedrotti P., Sekhri N., Van de Heyning C. M., Broeckx G., Peretto G., Guttmann O., Dellegrottaglie S., Scatteia A., Gentile P., Merlo M., Goldberg R. I., Reyentovich A., Sciamanna C., Klaassen S., Poller W., Trankle C. R., Abbate A., Keren A., Horowitz-Cederboim S., Cadrin-Tourigny J., Tadros R., Annoni G. A., Bonoldi E., Toquet C., Marteau L., Probst V., Trochu J. N., Kissopoulou A., Grosu A., Kukavica D., Trancuccio A., Gil C., Tini G., Pedrazzini M., Torchio M., Sinagra G., Gimeno J. R., Bernasconi D., Valsecchi M. G., Klingel K., Adler E. D., Camici P. G., Cooper L. T., Ammirati, E, Raimondi, F, Piriou, N, Sardo Infirri, L, Mohiddin, S, Mazzanti, A, Shenoy, C, Cavallari, U, Imazio, M, Aquaro, G, Olivotto, I, Pedrotti, P, Sekhri, N, Van de Heyning, C, Broeckx, G, Peretto, G, Guttmann, O, Dellegrottaglie, S, Scatteia, A, Gentile, P, Merlo, M, Goldberg, R, Reyentovich, A, Sciamanna, C, Klaassen, S, Poller, W, Trankle, C, Abbate, A, Keren, A, Horowitz-Cederboim, S, Cadrin-Tourigny, J, Tadros, R, Annoni, G, Bonoldi, E, Toquet, C, Marteau, L, Probst, V, Trochu, J, Kissopoulou, A, Grosu, A, Kukavica, D, Trancuccio, A, Gil, C, Tini, G, Pedrazzini, M, Torchio, M, Sinagra, G, Gimeno, J, Bernasconi, D, Valsecchi, M, Klingel, K, Adler, E, Camici, P, Cooper, L, Ammirati E., Raimondi F., Piriou N., Sardo Infirri L., Mohiddin S. A., Mazzanti A., Shenoy C., Cavallari U. A., Imazio M., Aquaro G. D., Olivotto I., Pedrotti P., Sekhri N., Van de Heyning C. M., Broeckx G., Peretto G., Guttmann O., Dellegrottaglie S., Scatteia A., Gentile P., Merlo M., Goldberg R. I., Reyentovich A., Sciamanna C., Klaassen S., Poller W., Trankle C. R., Abbate A., Keren A., Horowitz-Cederboim S., Cadrin-Tourigny J., Tadros R., Annoni G. A., Bonoldi E., Toquet C., Marteau L., Probst V., Trochu J. N., Kissopoulou A., Grosu A., Kukavica D., Trancuccio A., Gil C., Tini G., Pedrazzini M., Torchio M., Sinagra G., Gimeno J. R., Bernasconi D., Valsecchi M. G., Klingel K., Adler E. D., Camici P. G., and Cooper L. T.
Abstract: Background: The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown. Objectives: The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV. Methods: In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[−]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up. Results: In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(−) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. Conclusions: Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk.
Published: 2022

6. Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from Phase 2 of the AC-TIVE study, an Italian nationwide survey

Author: Merlo, M, Pagura, L, Porcari, A, Cameli, M, Vergaro, G, Musumeci, B, Biagini, E, Canepa, M, Crotti, L, Imazio, M, Forleo, C, Cappelli, F, Perfetto, F, Favale, S, Di Bella, G, Dore, F, Girardi, F, Tomasoni, D, Pavasini, R, Rella, V, Palmiero, G, Caiazza, M, Carella, M, Igoren Guaricci, A, Branzi, G, Caponetti, A, Saturi, G, La Malfa, G, Merlo, A, Andreis, A, Bruno, F, Longo, F, Rossi, M, Varra, G, Saro, R, Di Ienno, L, De Carli, G, Giacomin, E, Arzilli, C, Limongelli, G, Autore, C, Olivotto, I, Badano, L, Parati, G, Perlini, S, Metra, M, Emdin, M, Rapezzi, C, Sinagra, G, Merlo M., Pagura L., Porcari A., Cameli M., Vergaro G., Musumeci B., Biagini E., Canepa M., Crotti L., Imazio M., Forleo C., Cappelli F., Perfetto F., Favale S., Di Bella G., Dore F., Girardi F., Tomasoni D., Pavasini R., Rella V., Palmiero G., Caiazza M., Carella M. C., Igoren Guaricci A., Branzi G., Caponetti A. G., Saturi G., La Malfa G., Merlo A. C., Andreis A., Bruno F., Longo F., Rossi M., Varra G. G., Saro R., Di Ienno L., De Carli G., Giacomin E., Arzilli C., Limongelli G., Autore C., Olivotto I., Badano L., Parati G., Perlini S., Metra M., Emdin M., Rapezzi C., Sinagra G., Merlo, M, Pagura, L, Porcari, A, Cameli, M, Vergaro, G, Musumeci, B, Biagini, E, Canepa, M, Crotti, L, Imazio, M, Forleo, C, Cappelli, F, Perfetto, F, Favale, S, Di Bella, G, Dore, F, Girardi, F, Tomasoni, D, Pavasini, R, Rella, V, Palmiero, G, Caiazza, M, Carella, M, Igoren Guaricci, A, Branzi, G, Caponetti, A, Saturi, G, La Malfa, G, Merlo, A, Andreis, A, Bruno, F, Longo, F, Rossi, M, Varra, G, Saro, R, Di Ienno, L, De Carli, G, Giacomin, E, Arzilli, C, Limongelli, G, Autore, C, Olivotto, I, Badano, L, Parati, G, Perlini, S, Metra, M, Emdin, M, Rapezzi, C, Sinagra, G, Merlo M., Pagura L., Porcari A., Cameli M., Vergaro G., Musumeci B., Biagini E., Canepa M., Crotti L., Imazio M., Forleo C., Cappelli F., Perfetto F., Favale S., Di Bella G., Dore F., Girardi F., Tomasoni D., Pavasini R., Rella V., Palmiero G., Caiazza M., Carella M. C., Igoren Guaricci A., Branzi G., Caponetti A. G., Saturi G., La Malfa G., Merlo A. C., Andreis A., Bruno F., Longo F., Rossi M., Varra G. G., Saro R., Di Ienno L., De Carli G., Giacomin E., Arzilli C., Limongelli G., Autore C., Olivotto I., Badano L., Parati G., Perlini S., Metra M., Emdin M., Rapezzi C., and Sinagra G.
Abstract: Aim: To investigate the prevalence of amyloid cardiomyopathy (AC) and the diagnostic accuracy of echocardiographic red flags of AC among consecutive adult patients undergoing transthoracic echocardiogram for reason other than AC in 13 Italian institutions. Methods and results: This is an Italian prospective multicentre study, involving a clinical and instrumental work-up to assess AC prevalence among patients ≥55 years old with an echocardiogram suggestive of AC (i.e. at least one echocardiographic red flag of AC in hypertrophic, non-dilated left ventricles with preserved ejection fraction). The study was registered at ClinicalTrials.gov (NCT04738266). Overall, 381 patients with an echocardiogram suggestive of AC were identified among a cohort of 5315 screened subjects, and 217 patients completed the investigations. A final diagnosis of AC was made in 62 patients with an estimated prevalence of 29% (95% confidence interval 23%–35%). Transthyretin-related AC (ATTR-AC) was diagnosed in 51 and light chain-related AC (AL-AC) in 11 patients. Either apical sparing or a combination of ≥2 other echocardiographic red flags, excluding interatrial septum thickness, provided a diagnostic accuracy >70%. Conclusion: In a cohort of consecutive adults with echocardiographic findings suggestive of AC and preserved left ventricular ejection fraction, the prevalence of AC (either ATTR or AL) was 29%. Easily available echocardiographic red flags, when combined together, demonstrated good diagnostic accuracy.
Published: 2022

7. Patient adherence to drug treatment in a community based-sample of patients with chronic heart failure

Author: Rea, F, Iorio, A, Barbati, G, Bessi, R, Castrichini, M, Nuzzi, V, Scagnetto, A, Senni, M, Corrao, G, Sinagra, G, Di Lenarda, A, Rea F., Iorio A., Barbati G., Bessi R., Castrichini M., Nuzzi V., Scagnetto A., Senni M., Corrao G., Sinagra G., Di Lenarda A., Rea, F, Iorio, A, Barbati, G, Bessi, R, Castrichini, M, Nuzzi, V, Scagnetto, A, Senni, M, Corrao, G, Sinagra, G, Di Lenarda, A, Rea F., Iorio A., Barbati G., Bessi R., Castrichini M., Nuzzi V., Scagnetto A., Senni M., Corrao G., Sinagra G., and Di Lenarda A.
Published: 2022

8. Combined Role of Troponin and Natriuretic Peptides Measurements in Patients With Covid-19 (from the Cardio-COVID-Italy Multicenter Study)

Author: Iorio, A, Lombardi, C, Specchia, C, Merlo, M, Nuzzi, V, Ferraro, I, Peveri, G, Oriecuia, C, Pozzi, A, Inciardi, R, Carubelli, V, Bellasi, A, Canale, C, Camporotondo, R, Catagnano, F, Dalla Vecchia, L, Giovinazzo, S, Maccagni, G, Mapelli, M, Margonato, D, Monzo, L, Provenzale, G, Sarullo, F, Tomasoni, D, Ameri, P, Gnecchi, M, Leonardi, S, Agostoni, P, Carugo, S, Danzi, G, Guazzi, M, La Rovere, M, Mortara, A, Piepoli, M, Porto, I, Volterrani, M, Sinagra, G, Senni, M, Metra, M, Iorio A., Lombardi C. M., Specchia C., Merlo M., Nuzzi V., Ferraro I., Peveri G., Oriecuia C., Pozzi A., Inciardi R. M., Carubelli V., Bellasi A., Canale C., Camporotondo R., Catagnano F., Dalla Vecchia L., Giovinazzo S., Maccagni G., Mapelli M., Margonato D., Monzo L., Provenzale G., Sarullo F., Tomasoni D., Ameri P., Gnecchi M., Leonardi S., Agostoni P., Carugo S., Danzi G. B., Guazzi M., La Rovere M. T., Mortara A., Piepoli M., Porto I., Volterrani M., Sinagra G., Senni M., Metra M., Iorio, A, Lombardi, C, Specchia, C, Merlo, M, Nuzzi, V, Ferraro, I, Peveri, G, Oriecuia, C, Pozzi, A, Inciardi, R, Carubelli, V, Bellasi, A, Canale, C, Camporotondo, R, Catagnano, F, Dalla Vecchia, L, Giovinazzo, S, Maccagni, G, Mapelli, M, Margonato, D, Monzo, L, Provenzale, G, Sarullo, F, Tomasoni, D, Ameri, P, Gnecchi, M, Leonardi, S, Agostoni, P, Carugo, S, Danzi, G, Guazzi, M, La Rovere, M, Mortara, A, Piepoli, M, Porto, I, Volterrani, M, Sinagra, G, Senni, M, Metra, M, Iorio A., Lombardi C. M., Specchia C., Merlo M., Nuzzi V., Ferraro I., Peveri G., Oriecuia C., Pozzi A., Inciardi R. M., Carubelli V., Bellasi A., Canale C., Camporotondo R., Catagnano F., Dalla Vecchia L., Giovinazzo S., Maccagni G., Mapelli M., Margonato D., Monzo L., Provenzale G., Sarullo F., Tomasoni D., Ameri P., Gnecchi M., Leonardi S., Agostoni P., Carugo S., Danzi G. B., Guazzi M., La Rovere M. T., Mortara A., Piepoli M., Porto I., Volterrani M., Sinagra G., Senni M., and Metra M.
Abstract: Data concerning the combined prognostic role of natriuretic peptide (NP) and troponin in patients with COVID-19 are lacking. The aim of the study is to evaluate the combined prognostic value of NPs and troponin in hospitalized COVID-19 patients. From March 1, 2020 to April 9, 2020, consecutive patients with COVID-19 and available data on cardiac biomarkers at admission were recruited. Patients admitted for acute coronary syndrome were excluded. Troponin levels were defined as elevated when greater than the 99th percentile of normal values. NPs were considered elevated if above the limit for ruling in acute heart failure (HF). A total of 341 patients were included in this study, mean age 68 ± 13 years, 72% were men. During a median follow-up period of 14 days, 81 patients (24%) died. In the Cox regression analysis, patients with elevated both NPs and troponin levels had higher risk of death compared with those with normal levels of both (hazard ratio 2.94; 95% confidence interval 1.31 to 6.64; p = 0.009), and this remained significant after adjustment for age, gender, oxygen saturation, HF history, and chronic kidney disease. Interestingly, NPs provided risk stratification also in patients with normal troponin values (hazard ratio 2.86; 95% confidence interval 1.21 to 6.72; p = 0.016 with high NPs levels). These data show the combined prognostic role of troponin and NPs in COVID-19 patients. NPs value may be helpful in identifying patients with a worse prognosis among those with normal troponin values. Further, NPs’ cut-point used for diagnosis of acute HF has a predictive role in patients with COVID-19.
Published: 2022

9. Position paper of the Italian Society of Cardiology: The renin-angiotensin-aldosterone system (RAAS) blockade in heart failure patients - Part I: From RAAS identification to clinical trials [Position paper della Società Italiana di Cardiologia: Il blocco del sistema renina-angiotensina-aldosterone (RAAS) nel paziente con scompenso cardiaco – Parte I: Dalla scoperta del RAAS ai trial clinici]

Author: Filardi, P, Paolillo, S, Indolfi, C, Agostoni, P, Basso, C, Barilla, F, Correale, M, Curcio, A, Mancone, M, Merlo, M, Metra, M, Muscoli, S, Nodari, S, Palazzuoli, A, Pedrinelli, R, Pontremoli, R, Senni, M, Volpe, M, Sinagra, G, Filardi P. P., Paolillo S., Indolfi C., Agostoni P., Basso C., Barilla F., Correale M., Curcio A., Mancone M., Merlo M., Metra M., Muscoli S., Nodari S., Palazzuoli A., Pedrinelli R., Pontremoli R., Senni M., Volpe M., Sinagra G., Filardi, P, Paolillo, S, Indolfi, C, Agostoni, P, Basso, C, Barilla, F, Correale, M, Curcio, A, Mancone, M, Merlo, M, Metra, M, Muscoli, S, Nodari, S, Palazzuoli, A, Pedrinelli, R, Pontremoli, R, Senni, M, Volpe, M, Sinagra, G, Filardi P. P., Paolillo S., Indolfi C., Agostoni P., Basso C., Barilla F., Correale M., Curcio A., Mancone M., Merlo M., Metra M., Muscoli S., Nodari S., Palazzuoli A., Pedrinelli R., Pontremoli R., Senni M., Volpe M., and Sinagra G.
Abstract: L’inibizione del sistema renina-angiotensina-aldosterone (RAAS) rappresenta un caposaldo del trattamento farmacologico dello scompenso cardiaco a ridotta frazione di eiezione ed è stato potenziato dall’arrivo degli inibitori del recettore dell’angiotensina e della neprilisina (ARNI) che combinano l’inibizione del RAAS con l’inibizione della neprilisina responsabile di un incremento delle attività favorevoli dei peptidi natriuretici. Sacubitril/valsartan ha dimostrato nello studio PARADIGM-HF un netto vantaggio rispetto ad enalapril in termini di riduzione di mortalità ed ospedalizzazioni per insufficienza cardiaca e numerosi altri trial randomizzati e studi clinici ne hanno testato l’efficacia in differenti contesti. Dai risultati di questi studi è derivata la raccomandazione di classe I per l’utilizzo del farmaco in pazienti con frazione di eiezione ridotta. La prima parte di questo position paper esplora la storia dell’inibizione del RAAS per passare poi ad una dettagliata analisi dei risultati ottenuti negli studi clinici con gli ARNI che ne supportano le raccomandazioni delle più recenti linee guida., Renin-angiotensin-aldosterone (RAAS) system inhibition is a mainstay of the pharmacological treatment of heart failure with reduced ejection fraction and has been implemented by the introduction of angiotensin receptor-neprilysin inhibitors (ARNI), that combine RAAS inhibition with the inhibition of neprilysin, enhancing the favorable effects of natriuretic peptides. The PARADIGM-HF trial demonstrated a favorable effect of sacubitril/valsartan over enalapril in terms of mortality and heart failure hospitalization rate reduction. Then several randomized clinical trials and observational studies confirmed the favorable role of ARNI in different clinical scenarios, supporting the guideline class I recommendation for the use of sacubitrilvalsartan in patients with reduced systolic function. The first part of this position paper summarizes the history of RAAS inhibition and reports the results of ARNI trials that support the recommendations of the most recent guidelines.
Published: 2022

10. Position paper of the Italian Society of Cardiology: The renin-angiotensin-aldosterone system blockade in heart failure patients - Part II: Mechanistic effects of sacubitril/valsartan, placement in current guidelines and use in clinical practice [Position paper della Società Italiana di Cardiologia: Il blocco del sistema renina-angiotensina-aldosterone nel paziente con scompenso cardiaco – Parte II: Effetti meccanicistici di sacubitril/valsartan, posizionamento nelle linee guida ed utilizzo nella pratica clinica]

Author: Filardi, P, Indolfi, C, Paolillo, S, Agostoni, P, Basso, C, Barilla, F, Correale, M, Curcio, A, Mancone, M, Merlo, M, Metra, M, Muscoli, S, Nodari, S, Palazzuoli, A, Pedrinelli, R, Pontremoli, R, Senni, M, Volpe, M, Sinagra, G, Filardi P. P., Indolfi C., Paolillo S., Agostoni P., Basso C., Barilla F., Correale M., Curcio A., Mancone M., Merlo M., Metra M., Muscoli S., Nodari S., Palazzuoli A., Pedrinelli R., Pontremoli R., Senni M., Volpe M., Sinagra G., Filardi, P, Indolfi, C, Paolillo, S, Agostoni, P, Basso, C, Barilla, F, Correale, M, Curcio, A, Mancone, M, Merlo, M, Metra, M, Muscoli, S, Nodari, S, Palazzuoli, A, Pedrinelli, R, Pontremoli, R, Senni, M, Volpe, M, Sinagra, G, Filardi P. P., Indolfi C., Paolillo S., Agostoni P., Basso C., Barilla F., Correale M., Curcio A., Mancone M., Merlo M., Metra M., Muscoli S., Nodari S., Palazzuoli A., Pedrinelli R., Pontremoli R., Senni M., Volpe M., and Sinagra G.
Abstract: Il trattamento con sacubitril/valsartan ha assunto un ruolo di primo piano nelle ultime linee guida sia europee che americane, ed è attualmente raccomandato in classe I per il trattamento dei pazienti con ridotta frazione di eiezione. Accanto ai ben noti effetti sulla mortalità, sacubitril/valsartan agisce positivamente sulla riduzione dei valori di NT-proBNP e su parametri di rimodellamento ventricolare sinistro, determinando un rimodellamento inverso riconosciuto come uno degli effetti meccanicistici del farmaco atto a spiegare in parte il suo effetto favorevole sulla prognosi. Un’attenta valutazione del profilo di ogni singolo paziente consente un utilizzo più mirato e meglio tollerato del farmaco, garantendo anche in ambito di insufficienza cardiaca la strada della medicina di precisione. La seconda parte di questo position paper esplora gli effetti meccanicistici degli inibitori del recettore dell’angiotensina e della neprilisina e il loro posizionamento nelle linee guida, proponendo in ultima analisi un uso di sacubitril/valsartan in specifici contesti clinici., The use of sacubitril/valsartan has been fully recognized in the most recent European and American guidelines that recommend in class I the prescription of this drug in heart failure patients with reduced systolic function. Besides the effects on cardiovascular mortality and heart failure hospitalization, sacubitril/valsartan significantly reduces NT-proBNP levels and improves cardiac remodeling, recognized as one of the mechanistic effects of the drug that is linked to favorable prognostic effects. A careful evaluation of the patients' clinical profile is needed to implement the use of sacubitril/valsartan into clinical practice and to make the treatment successful. This second part of the position paper focuses on the mechanistic effects of angiotensin receptor-neprilysin inhibitors and on its placement in current guidelines, also suggesting the use of sacubitril/valsartan in specific clinical settings.
Published: 2022

11. Renin-angiotensin-aldosterone system inhibition in patients affected by heart failure: efficacy, mechanistic effects and practical use of sacubitril/valsartan. Position Paper of the Italian Society of Cardiology

Author: Perrone-Filardi, P, Paolillo, S, Agostoni, P, Basile, C, Basso, C, Barilla, F, Correale, M, Curcio, A, Mancone, M, Merlo, M, Metra, M, Muscoli, S, Nodari, S, Palazzuoli, A, Pedrinelli, R, Pontremoli, R, Senni, M, Volpe, M, Indolfi, C, Sinagra, G, Perrone-Filardi P., Paolillo S., Agostoni P., Basile C., Basso C., Barilla F., Correale M., Curcio A., Mancone M., Merlo M., Metra M., Muscoli S., Nodari S., Palazzuoli A., Pedrinelli R., Pontremoli R., Senni M., Volpe M., Indolfi C., Sinagra G., Perrone-Filardi, P, Paolillo, S, Agostoni, P, Basile, C, Basso, C, Barilla, F, Correale, M, Curcio, A, Mancone, M, Merlo, M, Metra, M, Muscoli, S, Nodari, S, Palazzuoli, A, Pedrinelli, R, Pontremoli, R, Senni, M, Volpe, M, Indolfi, C, Sinagra, G, Perrone-Filardi P., Paolillo S., Agostoni P., Basile C., Basso C., Barilla F., Correale M., Curcio A., Mancone M., Merlo M., Metra M., Muscoli S., Nodari S., Palazzuoli A., Pedrinelli R., Pontremoli R., Senni M., Volpe M., Indolfi C., and Sinagra G.
Abstract: Renin-angiotensin-aldosterone system (RAAS) inhibition is a mainstay of the pharmacological treatment of heart failure with reduced ejection fraction (HFrEF). In the last years RAAS blockade has been improved by the introduction of the Angiotensin Receptor-Neprilysin Inhibitor (ARNI) sacubitril/valsartan, that combines RAAS inhibition with the block of neprilysin, boosting the positive effects of natriuretic peptides. The PARADIGM-HF trial demonstrated a significant advantage of sacubitril/valsartan over enalapril on the reduction of cardiovascular (CV) mortality and heart failure hospitalizations rates. Then, several randomized clinical trials and observational studies investigated its role in different clinical settings and its efficacy has been fully recognized in the most recent HFrEF European and USA guidelines. The effects of sacubitril/valsartan on major CV outcomes are associated with reduction of NT-proBNP levels and reverse cardiac remodeling and mitral regurgitation, recognized as one of the mechanistic effects of the drug explaining the favorable prognostic effects. A careful evaluation of patients’ clinical profile is relevant to implement the use of ARNI in the clinical practice and to obtain the maximal treatment efficacy. The present Position Paper reports the opinion of the Italian Society of Cardiology on the optimal blockade of the RAAS system in HF patients with the aim of fostering widespread implementation of scientific evidence and practice guidelines in the medical community.
Published: 2022

12. Sex-related differences in patients with coronavirus disease 2019: Results of the Cardio-COVID-Italy multicentre study

Author: Lombardi, C, Specchia, C, Conforti, F, Rovere, M, Carubelli, V, Agostoni, P, Carugo, S, Danzi, G, Guazzi, M, Mortara, A, Piepoli, M, Porto, I, Sinagra, G, Volterrani, M, Ameri, P, Gnecchi, M, Leonardi, S, Merlo, M, Iorio, A, Bellasi, A, Canale, C, Camporotondo, R, Catagnano, F, Dalla Vecchia, L, Di Pasquale, M, Giovinazzo, S, Maccagni, G, Mapelli, M, Margonato, D, Monzo, L, Nuzzi, V, Oriecuia, C, Pala, L, Peveri, G, Pozzi, A, Provenzale, G, Sarullo, F, Adamo, M, Tomasoni, D, Inciardi, R, Senni, M, Metra, M, Lombardi C. M., Specchia C., Conforti F., Rovere M. T. L., Carubelli V., Agostoni P., Carugo S., Danzi G. B., Guazzi M., Mortara A., Piepoli M., Porto I., Sinagra G., Volterrani M., Ameri P., Gnecchi M., Leonardi S., Merlo M., Iorio A., Bellasi A., Canale C., Camporotondo R., Catagnano F., Dalla Vecchia L. A., Di Pasquale M., Giovinazzo S., Maccagni G., Mapelli M., Margonato D., Monzo L., Nuzzi V., Oriecuia C., Pala L., Peveri G., Pozzi A., Provenzale G., Sarullo F., Adamo M., Tomasoni D., Inciardi R. M., Senni M., Metra M., Lombardi, C, Specchia, C, Conforti, F, Rovere, M, Carubelli, V, Agostoni, P, Carugo, S, Danzi, G, Guazzi, M, Mortara, A, Piepoli, M, Porto, I, Sinagra, G, Volterrani, M, Ameri, P, Gnecchi, M, Leonardi, S, Merlo, M, Iorio, A, Bellasi, A, Canale, C, Camporotondo, R, Catagnano, F, Dalla Vecchia, L, Di Pasquale, M, Giovinazzo, S, Maccagni, G, Mapelli, M, Margonato, D, Monzo, L, Nuzzi, V, Oriecuia, C, Pala, L, Peveri, G, Pozzi, A, Provenzale, G, Sarullo, F, Adamo, M, Tomasoni, D, Inciardi, R, Senni, M, Metra, M, Lombardi C. M., Specchia C., Conforti F., Rovere M. T. L., Carubelli V., Agostoni P., Carugo S., Danzi G. B., Guazzi M., Mortara A., Piepoli M., Porto I., Sinagra G., Volterrani M., Ameri P., Gnecchi M., Leonardi S., Merlo M., Iorio A., Bellasi A., Canale C., Camporotondo R., Catagnano F., Dalla Vecchia L. A., Di Pasquale M., Giovinazzo S., Maccagni G., Mapelli M., Margonato D., Monzo L., Nuzzi V., Oriecuia C., Pala L., Peveri G., Pozzi A., Provenzale G., Sarullo F., Adamo M., Tomasoni D., Inciardi R. M., Senni M., and Metra M.
Abstract: IntroductionThe role of sex compared to comorbidities and other prognostic variables in patients with coronavirus disease (COVID-19) is unclear.MethodsThis is a retrospective observational study on patients with COVID-19 infection, referred to 13 cardiology units. The primary objective was to assess the difference in risk of death between the sexes. The secondary objective was to explore sex-based heterogeneity in the association between demographic, clinical and laboratory variables, and patients' risk of death.ResultsSeven hundred and one patients were included: 214 (30.5%) women and 487 (69.5%) men. During a median follow-up of 15-days, deaths occurred in 39 (18.2%) women and 126 (25.9%) men. In a multivariable Cox regression model, men had a nonsignificantly higher risk of death vs. women (P = 0.07).The risk of death was more than double in men with a low lymphocytes count as compared with men with a high lymphocytes count [overall survival hazard ratio (OS-HR) 2.56, 95% confidence interval (CI) 1.72-3.81]. In contrast, lymphocytes count was not related to death in women (P=0.03).Platelets count was associated with better outcome in men (OS-HR for increase of 50-×-103units: 0.88 95% CI 0.78-1.00) but not in women. The strength of association between higher PaO2/FiO2ratio and lower risk of death was larger in women (OS-HR for increase of 50-mmHg/%: 0.72, 95% CI 0.59-0.89) vs. men (OS-HR: 0.88, 95% CI 0.80-0.98; P-=-0.05).ConclusionsPatients' sex is a relevant variable that should be taken into account when evaluating risk of death from COVID-19. There is a sex-based heterogeneity in the association between baseline variables and patients' risk of death.
Published: 2022

13. Genetic insights into resting heart rate and its role in cardiovascular disease.

Author: Vegte, Y.J. van de, Eppinga, R.N., Ende, M.Y. van der, Hagemeijer, Y.P., Mahendran, Y., Salfati, E., Smith, A.V., Tan, V.Y., Arking, D.E., Ntalla, I., Appel, E.V., Schurmann, C., Brody, J.A., Rueedi, R., Polasek, O., Sveinbjornsson, G., Lecoeur, C., Ladenvall, C., Zhao, J.H., Isaacs, A., Wang, L., Luan, Jian'an, Hwang, S.J., Mononen, N., Auro, K., Jackson, A.U., Bielak, L.F., Zeng, L., Shah, N., Nethander, M., Campbell, A., Rankinen, T., Pechlivanis, S., Qi, L., Zhao, Wei, Rizzi, F., Tanaka, T., Robino, A., Cocca, M., Lange, L., Müller-Nurasyid, M., Roselli, C., Zhang, W, Kleber, M.E., Guo, X., Lin, H.J., Pavani, F., Galesloot, T.E., Noordam, R., Milaneschi, Y., Schraut, K.E., Hoed, M. den, Degenhardt, F., Trompet, S., Berg, M.E. van den, Pistis, G., Tham, Y.C., Weiss, S., Sim, X.S., Li, H.L., Most, P.J. van der, Nolte, I.M., Lyytikäinen, L.P., Said, M.A., Witte, D.R., Iribarren, C., Launer, L., Ring, S.M., Vries, P.S. de, Sever, P., Linneberg, A., Bottinger, E.P., Padmanabhan, S., Psaty, B.M., Sotoodehnia, N., Kolcic, I., Arnar, D.O., Gudbjartsson, D.F., Holm, H., Balkau, B., Silva, C.T., Newton-Cheh, C.H., Nikus, K., Salo, P., Mohlke, K.L., Peyser, P.A., Schunkert, H., Lorentzon, M., Lahti, J., Rao, D.C., Cornelis, M.C., Faul, J.D., Smith, J.A., Stolarz-Skrzypek, K., Bandinelli, S., Concas, M.P., Sinagra, G., Meitinger, T., Waldenberger, M., Sinner, M.F., Strauch, K., Delgado, G.E., Taylor, K.D., Yao, J., Foco, L., Melander, O., Graaf, J. de, Mutsert, R. de, Geus, E.J.C. de, Johansson, Å., Joshi, P.K., Lind, L., Franke, A., Macfarlane, P.W., Tarasov, K.V., Tan, N., Felix, S.B., Tai, E.S., Quek, D.Q., Snieder, H., Ormel, J., Ingelsson, M., Lindgren, C., Morris, A.P., Raitakari, O.T., Hansen, T., Assimes, T., Gudnason, V., Timpson, N.J., Morrison, A.C., Munroe, P.B., Strachan, D.P., Grarup, N., Loos, R.J.F., Heckbert, S.R., Vollenweider, P., Hayward, C., Stefansson, K., Froguel, P., Groop, L., Wareham, N.J., Duijn, C.M. van, Feitosa, M.F., O'Donnell, C.J., Kähönen, M., Perola, M., Boehnke, M., Kardia, S.L.R., Erdmann, J., Palmer, C.N.A., Ohlsson, C., Porteous, D.J., Eriksson, J.G., Bouchard, C., Moebus, S., Kraft, P., Weir, D.R., Cusi, D., Ferrucci, L., Ulivi, S., Girotto, G., Correa, A., Kääb, S., Peters, A., Chambers, J.C., Kooner, J.S., März, W., Rotter, J.I., Hicks, A.A., Smith, J.G., Kiemeney, L.A.L.M., Mook-Kanamori, D.O., Penninx, B.W.J.H., Gyllensten, U., Wilson, J.F., Burgess, S., Sundström, J., Lieb, W., Jukema, J.W., Eijgelsheim, M., Lakatta, E.L.M., Cheng, C.Y., Dörr, M., Wong, T.Y., Sabanayagam, C., Oldehinkel, A.J., Riese, H., Lehtimäki, T., Verweij, N., Harst, P. van der, Vegte, Y.J. van de, Eppinga, R.N., Ende, M.Y. van der, Hagemeijer, Y.P., Mahendran, Y., Salfati, E., Smith, A.V., Tan, V.Y., Arking, D.E., Ntalla, I., Appel, E.V., Schurmann, C., Brody, J.A., Rueedi, R., Polasek, O., Sveinbjornsson, G., Lecoeur, C., Ladenvall, C., Zhao, J.H., Isaacs, A., Wang, L., Luan, Jian'an, Hwang, S.J., Mononen, N., Auro, K., Jackson, A.U., Bielak, L.F., Zeng, L., Shah, N., Nethander, M., Campbell, A., Rankinen, T., Pechlivanis, S., Qi, L., Zhao, Wei, Rizzi, F., Tanaka, T., Robino, A., Cocca, M., Lange, L., Müller-Nurasyid, M., Roselli, C., Zhang, W, Kleber, M.E., Guo, X., Lin, H.J., Pavani, F., Galesloot, T.E., Noordam, R., Milaneschi, Y., Schraut, K.E., Hoed, M. den, Degenhardt, F., Trompet, S., Berg, M.E. van den, Pistis, G., Tham, Y.C., Weiss, S., Sim, X.S., Li, H.L., Most, P.J. van der, Nolte, I.M., Lyytikäinen, L.P., Said, M.A., Witte, D.R., Iribarren, C., Launer, L., Ring, S.M., Vries, P.S. de, Sever, P., Linneberg, A., Bottinger, E.P., Padmanabhan, S., Psaty, B.M., Sotoodehnia, N., Kolcic, I., Arnar, D.O., Gudbjartsson, D.F., Holm, H., Balkau, B., Silva, C.T., Newton-Cheh, C.H., Nikus, K., Salo, P., Mohlke, K.L., Peyser, P.A., Schunkert, H., Lorentzon, M., Lahti, J., Rao, D.C., Cornelis, M.C., Faul, J.D., Smith, J.A., Stolarz-Skrzypek, K., Bandinelli, S., Concas, M.P., Sinagra, G., Meitinger, T., Waldenberger, M., Sinner, M.F., Strauch, K., Delgado, G.E., Taylor, K.D., Yao, J., Foco, L., Melander, O., Graaf, J. de, Mutsert, R. de, Geus, E.J.C. de, Johansson, Å., Joshi, P.K., Lind, L., Franke, A., Macfarlane, P.W., Tarasov, K.V., Tan, N., Felix, S.B., Tai, E.S., Quek, D.Q., Snieder, H., Ormel, J., Ingelsson, M., Lindgren, C., Morris, A.P., Raitakari, O.T., Hansen, T., Assimes, T., Gudnason, V., Timpson, N.J., Morrison, A.C., Munroe, P.B., Strachan, D.P., Grarup, N., Loos, R.J.F., Heckbert, S.R., Vollenweider, P., Hayward, C., Stefansson, K., Froguel, P., Groop, L., Wareham, N.J., Duijn, C.M. van, Feitosa, M.F., O'Donnell, C.J., Kähönen, M., Perola, M., Boehnke, M., Kardia, S.L.R., Erdmann, J., Palmer, C.N.A., Ohlsson, C., Porteous, D.J., Eriksson, J.G., Bouchard, C., Moebus, S., Kraft, P., Weir, D.R., Cusi, D., Ferrucci, L., Ulivi, S., Girotto, G., Correa, A., Kääb, S., Peters, A., Chambers, J.C., Kooner, J.S., März, W., Rotter, J.I., Hicks, A.A., Smith, J.G., Kiemeney, L.A.L.M., Mook-Kanamori, D.O., Penninx, B.W.J.H., Gyllensten, U., Wilson, J.F., Burgess, S., Sundström, J., Lieb, W., Jukema, J.W., Eijgelsheim, M., Lakatta, E.L.M., Cheng, C.Y., Dörr, M., Wong, T.Y., Sabanayagam, C., Oldehinkel, A.J., Riese, H., Lehtimäki, T., Verweij, N., and Harst, P. van der
Abstract: Contains fulltext : 296013.pdf (Publisher’s version ) (Open Access), Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
Published: 2023

14. Outcome and Morphofunctional Changes on Cardiac Magnetic Resonance in Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination

Author: Ammirati, E, Lupi, L, Palazzini, M, Ciabatti, M, Rossi, V, Gentile, P, Uribarri, A, Vecchio, C, Nassiacos, D, Cereda, A, Conca, C, Tumminello, G, Piriou, N, Lelarge, C, Pedrotti, P, Stucchi, M, Peretto, G, Galasso, M, Huang, F, Ianni, U, Procopio, A, Saponara, G, Cimaglia, P, Tomasoni, D, Moroni, F, Turco, A, Sala, S, Di Tano, G, Bollano, E, Moro, C, Abbate, A, Della Bona, R, Porto, I, Carugo, S, Campodonico, J, Pontone, G, Grosu, A, Bolognese, L, Salamanca, J, Diez-Villanueva, P, Ozieranski, K, Tyminska, A, Sardo Infirri, L, Bromage, D, Cannatà, A, Hong, K, Adamo, M, Quattrocchi, G, Foà, A, Potena, L, Garascia, A, Giannattasio, C, Adler, E, Sinagra, G, Ruschitzka, F, Camici, P, Metra, M, Pieroni, M, Ammirati, Enrico, Lupi, Laura, Palazzini, Matteo, Ciabatti, Michele, Rossi, Valentina A, Gentile, Piero, Uribarri, Aitor, Vecchio, Chiara R, Nassiacos, Daniele, Cereda, Alberto, Conca, Cristina, Tumminello, Gabriele, Piriou, Nicolas, Lelarge, Coline, Pedrotti, Patrizia, Stucchi, Miriam, Peretto, Giovanni, Galasso, Michele, Huang, Florent, Ianni, Umberto, Procopio, Antonio, Saponara, Gianluigi, Cimaglia, Paolo, Tomasoni, Daniela, Moroni, Francesco, Turco, Annalisa, Sala, Simone, Di Tano, Giuseppe, Bollano, Entela, Moro, Claudio, Abbate, Antonio, Della Bona, Roberta, Porto, Italo, Carugo, Stefano, Campodonico, Jeness, Pontone, Gianluca, Grosu, Aurelia, Bolognese, Leonardo, Salamanca, Jorge, Diez-Villanueva, Pablo, Ozieranski, Krzysztof, Tyminska, Agata, Sardo Infirri, Loren, Bromage, Daniel, Cannatà, Antonio, Hong, Kimberly N, Adamo, Marianna, Quattrocchi, Giuseppina, Foà, Alberto, Potena, Luciano, Garascia, Andrea, Giannattasio, Cristina, Adler, Eric D, Sinagra, Gianfranco, Ruschitzka, Frank, Camici, Paolo G, Metra, Marco, Pieroni, Maurizio, Ammirati, E, Lupi, L, Palazzini, M, Ciabatti, M, Rossi, V, Gentile, P, Uribarri, A, Vecchio, C, Nassiacos, D, Cereda, A, Conca, C, Tumminello, G, Piriou, N, Lelarge, C, Pedrotti, P, Stucchi, M, Peretto, G, Galasso, M, Huang, F, Ianni, U, Procopio, A, Saponara, G, Cimaglia, P, Tomasoni, D, Moroni, F, Turco, A, Sala, S, Di Tano, G, Bollano, E, Moro, C, Abbate, A, Della Bona, R, Porto, I, Carugo, S, Campodonico, J, Pontone, G, Grosu, A, Bolognese, L, Salamanca, J, Diez-Villanueva, P, Ozieranski, K, Tyminska, A, Sardo Infirri, L, Bromage, D, Cannatà, A, Hong, K, Adamo, M, Quattrocchi, G, Foà, A, Potena, L, Garascia, A, Giannattasio, C, Adler, E, Sinagra, G, Ruschitzka, F, Camici, P, Metra, M, Pieroni, M, Ammirati, Enrico, Lupi, Laura, Palazzini, Matteo, Ciabatti, Michele, Rossi, Valentina A, Gentile, Piero, Uribarri, Aitor, Vecchio, Chiara R, Nassiacos, Daniele, Cereda, Alberto, Conca, Cristina, Tumminello, Gabriele, Piriou, Nicolas, Lelarge, Coline, Pedrotti, Patrizia, Stucchi, Miriam, Peretto, Giovanni, Galasso, Michele, Huang, Florent, Ianni, Umberto, Procopio, Antonio, Saponara, Gianluigi, Cimaglia, Paolo, Tomasoni, Daniela, Moroni, Francesco, Turco, Annalisa, Sala, Simone, Di Tano, Giuseppe, Bollano, Entela, Moro, Claudio, Abbate, Antonio, Della Bona, Roberta, Porto, Italo, Carugo, Stefano, Campodonico, Jeness, Pontone, Gianluca, Grosu, Aurelia, Bolognese, Leonardo, Salamanca, Jorge, Diez-Villanueva, Pablo, Ozieranski, Krzysztof, Tyminska, Agata, Sardo Infirri, Loren, Bromage, Daniel, Cannatà, Antonio, Hong, Kimberly N, Adamo, Marianna, Quattrocchi, Giuseppina, Foà, Alberto, Potena, Luciano, Garascia, Andrea, Giannattasio, Cristina, Adler, Eric D, Sinagra, Gianfranco, Ruschitzka, Frank, Camici, Paolo G, Metra, Marco, and Pieroni, Maurizio
Published: 2023

15. Current patterns of beta-blocker prescription in cardiac amyloidosis: an Italian nationwide survey

Author: Tini, G, Cappelli, F, Biagini, E, Musumeci, B, Merlo, M, Crotti, L, Cameli, M, Di Bella, G, Cipriani, A, Marzo, F, Guerra, F, Forleo, C, Gagliardi, C, Zampieri, M, Carigi, S, Vianello, P, Mandoli, G, Ciliberti, G, Lichelli, L, Mariani, D, Porcari, A, Russo, D, Licordari, R, Ponziani, A, Porto, I, Perfetto, F, Autore, C, Rapezzi, C, Sinagra, G, Canepa, M, Tini G., Cappelli F., Biagini E., Musumeci B., Merlo M., Crotti L., Cameli M., Di Bella G., Cipriani A., Marzo F., Guerra F., Forleo C., Gagliardi C., Zampieri M., Carigi S., Vianello P. F., Mandoli G. E., Ciliberti G., Lichelli L., Mariani D., Porcari A., Russo D., Licordari R., Ponziani A., Porto I., Perfetto F., Autore C., Rapezzi C., Sinagra G., Canepa M., Tini, G, Cappelli, F, Biagini, E, Musumeci, B, Merlo, M, Crotti, L, Cameli, M, Di Bella, G, Cipriani, A, Marzo, F, Guerra, F, Forleo, C, Gagliardi, C, Zampieri, M, Carigi, S, Vianello, P, Mandoli, G, Ciliberti, G, Lichelli, L, Mariani, D, Porcari, A, Russo, D, Licordari, R, Ponziani, A, Porto, I, Perfetto, F, Autore, C, Rapezzi, C, Sinagra, G, Canepa, M, Tini G., Cappelli F., Biagini E., Musumeci B., Merlo M., Crotti L., Cameli M., Di Bella G., Cipriani A., Marzo F., Guerra F., Forleo C., Gagliardi C., Zampieri M., Carigi S., Vianello P. F., Mandoli G. E., Ciliberti G., Lichelli L., Mariani D., Porcari A., Russo D., Licordari R., Ponziani A., Porto I., Perfetto F., Autore C., Rapezzi C., Sinagra G., and Canepa M.
Abstract: Aims: The use of beta-blocker therapy in cardiac amyloidosis (CA) is debated. We aimed at describing patterns of beta-blocker prescription through a nationwide survey. Methods and results: From 11 referral centres, we retrospectively collected data of CA patients with a first evaluation after 2016 (n = 642). Clinical characteristics at first and last evaluation were collected, with a focus on medical therapy. For patients in whom beta-blocker therapy was started, stopped, or continued between first and last evaluation, the main reason for beta-blocker management was requested. Median age of study population was 77 years; 81% were men. Arterial hypertension was found in 58% of patients, atrial fibrillation (AF) in 57%, and coronary artery disease in 16%. Left ventricular ejection fraction was preserved in 62% of cases, and 74% of patients had advanced diastolic dysfunction. Out of the 250 CA patients on beta-blockers at last evaluation, 215 (33%) were already taking this therapy at first evaluation, while 35 (5%) were started it, in both cases primarily because of high-rate AF. One-hundred-nineteen patients (19%) who were on beta-blocker at first evaluation had this therapy withdrawn, mainly because of intolerance in the presence of heart failure with advanced diastolic dysfunction. The remaining 273 patients (43%) had never received beta-blocker therapy. Beta-blockers usage was similar between CA aetiologies. Patients taking vs. not taking beta-blockers differed only for a greater prevalence of arterial hypertension, coronary artery disease, AF, and non-restrictive filling pattern (P < 0.01 for all) in the former group. Conclusions: Beta-blockers prescription is not infrequent in CA. Such therapy may be tolerated in the presence of co-morbidities for which beta-blockers are routinely used and in the absence of advanced diastolic dysfunction.
Published: 2021

16. Implications of atrial fibrillation on the clinical course and outcomes of hospitalized COVID-19 patients: Results of the Cardio-COVID-Italy multicentre study

Author: Paris, S, Inciardi, R, Lombardi, C, Tomasoni, D, Ameri, P, Carubelli, V, Agostoni, P, Canale, C, Carugo, S, Danzi, G, Di Pasquale, M, Sarullo, F, La Rovere, M, Mortara, A, Piepoli, M, Porto, I, Sinagra, G, Volterrani, M, Gnecchi, M, Leonardi, S, Merlo, M, Iorio, A, Giovinazzo, S, Bellasi, A, Zaccone, G, Camporotondo, R, Catagnano, F, Dalla Vecchia, L, Maccagni, G, Mapelli, M, Margonato, D, Monzo, L, Nuzzi, V, Pozzi, A, Provenzale, G, Specchia, C, Tedino, C, Guazzi, M, Senni, M, Metra, M, Paris S, Inciardi RM, Lombardi CM, Tomasoni D, Ameri P, Carubelli V, Agostoni P, Canale C, Carugo S, Danzi G, Di Pasquale M, Sarullo F, La Rovere MT, Mortara A, Piepoli M, Porto I, Sinagra G, Volterrani M, Gnecchi M, Leonardi S, Merlo M, Iorio A, Giovinazzo S, Bellasi A, Zaccone G, Camporotondo R, Catagnano F, Dalla Vecchia L, Maccagni G, Mapelli M, Margonato D, Monzo L, Nuzzi V, Pozzi A, Provenzale G, Specchia C, Tedino C, Guazzi M, Senni M, Metra M, Paris, S, Inciardi, R, Lombardi, C, Tomasoni, D, Ameri, P, Carubelli, V, Agostoni, P, Canale, C, Carugo, S, Danzi, G, Di Pasquale, M, Sarullo, F, La Rovere, M, Mortara, A, Piepoli, M, Porto, I, Sinagra, G, Volterrani, M, Gnecchi, M, Leonardi, S, Merlo, M, Iorio, A, Giovinazzo, S, Bellasi, A, Zaccone, G, Camporotondo, R, Catagnano, F, Dalla Vecchia, L, Maccagni, G, Mapelli, M, Margonato, D, Monzo, L, Nuzzi, V, Pozzi, A, Provenzale, G, Specchia, C, Tedino, C, Guazzi, M, Senni, M, Metra, M, Paris S, Inciardi RM, Lombardi CM, Tomasoni D, Ameri P, Carubelli V, Agostoni P, Canale C, Carugo S, Danzi G, Di Pasquale M, Sarullo F, La Rovere MT, Mortara A, Piepoli M, Porto I, Sinagra G, Volterrani M, Gnecchi M, Leonardi S, Merlo M, Iorio A, Giovinazzo S, Bellasi A, Zaccone G, Camporotondo R, Catagnano F, Dalla Vecchia L, Maccagni G, Mapelli M, Margonato D, Monzo L, Nuzzi V, Pozzi A, Provenzale G, Specchia C, Tedino C, Guazzi M, Senni M, and Metra M
Abstract: Aims: To assess the clinical relevance of a history of atrial fibrillation (AF) in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods and results: We enrolled 696 consecutive patients (mean age 67.4 ± 13.2 years, 69.7% males) admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. One hundred and six patients (15%) had a history of AF and the median hospitalization length was 14 days (interquartile range 9-24). Patients with a history of AF were older and with a higher burden of cardiovascular risk factors. Compared to patients without AF, they showed a higher rate of in-hospital death (38.7% vs. 20.8%; P < 0.001). History of AF was associated with an increased risk of death after adjustment for clinical confounders related to COVID-19 severity and cardiovascular comorbidities, including history of heart failure (HF) and increased plasma troponin [adjusted hazard ratio (HR): 1.73; 95% confidence interval (CI) 1.06-2.84; P = 0.029]. Patients with a history of AF also had more in-hospital clinical events including new-onset AF (36.8% vs. 7.9%; P < 0.001), acute HF (25.3% vs. 6.3%; P < 0.001), and multiorgan failure (13.9% vs. 5.8%; P = 0.010). The association between AF and worse outcome was not modified by previous or concomitant use of anticoagulants or steroid therapy (P for interaction >0.05 for both) and was not related to stroke or bleeding events. Conclusion: Among hospitalized patients with COVID-19, a history of AF contributes to worse clinical course with a higher mortality and in-hospital events including new-onset AF, acute HF, and multiorgan failure. The mortality risk remains significant after adjustment for variables associated with COVID-19 severity and comorbidities.
Published: 2021

17. Determinants of the protective effect of glucocorticoids on mortality in hospitalized patients with COVID-19: Insights from the Cardio-COVID-Italy multicenter study

Author: Pagnesi, M, Inciardi, R, Lombardi, C, Agostoni, P, Ameri, P, Barbieri, L, Bellasi, A, Camporotondo, R, Canale, C, Carubelli, V, Carugo, S, Catagnano, F, Dalla Vecchia, L, Danzi, G, Di Pasquale, M, Gaudenzi, M, Giovinazzo, S, Gnecchi, M, Guazzi, M, Iorio, A, La Rovere, M, Leonardi, S, Maccagni, G, Mapelli, M, Margonato, D, Merlo, M, Monzo, L, Mortara, A, Nuzzi, V, Piepoli, M, Porto, I, Pozzi, A, Sarullo, F, Sinagra, G, Tedino, C, Tomasoni, D, Volterrani, M, Zaccone, G, Senni, M, Metra, M, Pagnesi M, Inciardi RM, Lombardi CM, Agostoni P, Ameri P, Barbieri L, Bellasi A, Camporotondo R, Canale C, Carubelli V, Carugo S, Catagnano F, Dalla Vecchia LA, Danzi GB, Di Pasquale M, Gaudenzi M, Giovinazzo S, Gnecchi M, Guazzi M, Iorio A, La Rovere MT, Leonardi S, Maccagni G, Mapelli M, Margonato D, Merlo M, Monzo L, Mortara A, Nuzzi V, Piepoli M, Porto I, Pozzi A, Sarullo F, Sinagra G, Tedino C, Tomasoni D, Volterrani M, Zaccone G, Senni M, Metra M, Pagnesi, M, Inciardi, R, Lombardi, C, Agostoni, P, Ameri, P, Barbieri, L, Bellasi, A, Camporotondo, R, Canale, C, Carubelli, V, Carugo, S, Catagnano, F, Dalla Vecchia, L, Danzi, G, Di Pasquale, M, Gaudenzi, M, Giovinazzo, S, Gnecchi, M, Guazzi, M, Iorio, A, La Rovere, M, Leonardi, S, Maccagni, G, Mapelli, M, Margonato, D, Merlo, M, Monzo, L, Mortara, A, Nuzzi, V, Piepoli, M, Porto, I, Pozzi, A, Sarullo, F, Sinagra, G, Tedino, C, Tomasoni, D, Volterrani, M, Zaccone, G, Senni, M, Metra, M, Pagnesi M, Inciardi RM, Lombardi CM, Agostoni P, Ameri P, Barbieri L, Bellasi A, Camporotondo R, Canale C, Carubelli V, Carugo S, Catagnano F, Dalla Vecchia LA, Danzi GB, Di Pasquale M, Gaudenzi M, Giovinazzo S, Gnecchi M, Guazzi M, Iorio A, La Rovere MT, Leonardi S, Maccagni G, Mapelli M, Margonato D, Merlo M, Monzo L, Mortara A, Nuzzi V, Piepoli M, Porto I, Pozzi A, Sarullo F, Sinagra G, Tedino C, Tomasoni D, Volterrani M, Zaccone G, Senni M, and Metra M
Abstract: Background: Glucocorticoid therapy has emerged as an effective therapeutic option in hospitalized patients with coronavirus disease 2019 (COVID-19). This study aimed to focus on the impact of relevant clinical and laboratory factors on the protective effect of glucocorticoids on mortality. Methods: A sub-analysis was performed of the multicenter Cardio-COVID-Italy registry, enrolling consecutive patients with COVID-19 admitted to 13 Italian cardiology units between 01 March 2020 and 09 April 2020. The primary endpoint was in-hospital mortality. Results: A total of 706 COVID-19 patients were included (349 treated with glucocorticoids, 357 not treated with glucocorticoids). After adjustment for relevant covariates, use of glucocorticoids was associated with a lower risk of in-hospital mortality (adjusted HR 0.44; 95% CI 0.26–0.72; p = 0.001). A significant interaction was observed between the protective effect of glucocorticoids on mortality and PaO2/FiO2 ratio on admission (p = 0.042), oxygen saturation on admission (p = 0.017), and peak CRP (0.023). Such protective effects of glucocorticoids were mainly observed in patients with lower PaO2/FiO2 ratio (<300), lower oxygen saturation ([removed]100 mg/L). Conclusions: The protective effects of glucocorticoids on mortality in COVID-19 were more evident among patients with worse respiratory parameters and higher systemic inflammation.
Published: 2021

18. The prognostic value of serial troponin measurements in patients admitted for COVID-19

Author: Nuzzi, V, Merlo, M, Specchia, C, Lombardi, C, Carubelli, V, Iorio, A, Inciardi, R, Bellasi, A, Canale, C, Camporotondo, R, Catagnano, F, Dalla Vecchia, L, Giovinazzo, S, Maccagni, G, Mapelli, M, Margonato, D, Monzo, L, Oriecuia, C, Peveri, G, Pozzi, A, Provenzale, G, Sarullo, F, Tomasoni, D, Ameri, P, Gnecchi, M, Leonardi, S, Agostoni, P, Carugo, S, Danzi, G, Guazzi, M, La Rovere, M, Mortara, A, Piepoli, M, Porto, I, Volterrani, M, Senni, M, Metra, M, Sinagra, G, Nuzzi V, Merlo M, Specchia C, Lombardi CM, Carubelli V, Iorio A, Inciardi RM, Bellasi A, Canale C, Camporotondo R, Catagnano F, Dalla Vecchia LA, Giovinazzo S, Maccagni G, Mapelli M, Margonato D, Monzo L, Oriecuia C, Peveri G, Pozzi A, Provenzale G, Sarullo F, Tomasoni D, Ameri P, Gnecchi M, Leonardi S, Agostoni P, Carugo S, Danzi GB, Guazzi M, La Rovere MT, Mortara A, Piepoli M, Porto I, Volterrani M, Senni M, Metra M, Sinagra G, Nuzzi, V, Merlo, M, Specchia, C, Lombardi, C, Carubelli, V, Iorio, A, Inciardi, R, Bellasi, A, Canale, C, Camporotondo, R, Catagnano, F, Dalla Vecchia, L, Giovinazzo, S, Maccagni, G, Mapelli, M, Margonato, D, Monzo, L, Oriecuia, C, Peveri, G, Pozzi, A, Provenzale, G, Sarullo, F, Tomasoni, D, Ameri, P, Gnecchi, M, Leonardi, S, Agostoni, P, Carugo, S, Danzi, G, Guazzi, M, La Rovere, M, Mortara, A, Piepoli, M, Porto, I, Volterrani, M, Senni, M, Metra, M, Sinagra, G, Nuzzi V, Merlo M, Specchia C, Lombardi CM, Carubelli V, Iorio A, Inciardi RM, Bellasi A, Canale C, Camporotondo R, Catagnano F, Dalla Vecchia LA, Giovinazzo S, Maccagni G, Mapelli M, Margonato D, Monzo L, Oriecuia C, Peveri G, Pozzi A, Provenzale G, Sarullo F, Tomasoni D, Ameri P, Gnecchi M, Leonardi S, Agostoni P, Carugo S, Danzi GB, Guazzi M, La Rovere MT, Mortara A, Piepoli M, Porto I, Volterrani M, Senni M, Metra M, and Sinagra G
Abstract: Aims: Myocardial injury (MI) in coronavirus disease-19 (COVID-19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in-hospital evolution of MI and its prognostic impact. Methods and results: We performed an analysis from an Italian multicentre study enrolling COVID-19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in-hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P < 0.001). At multivariable analysis, patients with normal troponin at admission and MI injury on Day 2 had the highest mortality risk (hazard ratio 3.78, 95% confidence interval 1.10–13.09, P = 0.035). Conclusions: In patients admitted for COVID-19, re-test MI on Day 2 provides a prognostic value. A non-negligible proportion of patients with incident MI on Day 2 is identified at high risk of death only by the second measurement.
Published: 2021

19. Cardiac contractility modulation in heart failure with reduced ejection fraction: critical review of evidence and application perspectives [Modulazione della contrattilità cardiaca nello scompenso cardiaco a frazione di eiezione ridotta: revisione critica delle evidenze ed aspetti decisionali pratici]

Author: Biffi, M, Aspromonte, N, Bongiorni, M, Clemenza, F, D'Onofrio, A, De Ferrari, G, Giallauria, F, Grimaldi, M, Oliva, F, Senni, M, Tondo, C, Zecchin, M, Cappannoli, L, Giannotti Santoro, M, Ziacchi, M, Porcari, A, Sinagra, G, Biffi M, Aspromonte N, Bongiorni MG, Clemenza F, D'Onofrio A, De Ferrari GM, Giallauria F, Grimaldi M, Oliva F, Senni M, Tondo C, Zecchin M, Cappannoli L, Giannotti Santoro M, Ziacchi M, Porcari A, Sinagra G, Biffi, M, Aspromonte, N, Bongiorni, M, Clemenza, F, D'Onofrio, A, De Ferrari, G, Giallauria, F, Grimaldi, M, Oliva, F, Senni, M, Tondo, C, Zecchin, M, Cappannoli, L, Giannotti Santoro, M, Ziacchi, M, Porcari, A, Sinagra, G, Biffi M, Aspromonte N, Bongiorni MG, Clemenza F, D'Onofrio A, De Ferrari GM, Giallauria F, Grimaldi M, Oliva F, Senni M, Tondo C, Zecchin M, Cappannoli L, Giannotti Santoro M, Ziacchi M, Porcari A, and Sinagra G
Abstract: This critical review illustrates the pathophysiological aspects and available scientific evidence about cardiac contractility modulation therapy. A useful algorithm dealing with the essential decisional knots to consider for device implantation in patients with heart failure in NYHA class >II and ejection fraction <= 45% is presented. The present review paves the way for the development of an Italian registry aiming at analyzing the characteristics of implanted patients based on a multiparametric approach, including cardiac bio markers, to identify clinical profiles and predictors of response to therapy. The "Answers and Questions" section provides useful insights into pathophysiology, technical specifications, clinically relevant scenarios and future perspectives.
Published: 2021

20. Pulmonary embolism in patients with COVID-19: characteristics and outcomes in the Cardio-COVID Italy multicenter study

Author: Ameri, P, Inciardi, R, Di Pasquale, M, Agostoni, P, Bellasi, A, Camporotondo, R, Canale, C, Carubelli, V, Carugo, S, Catagnano, F, Danzi, G, Dalla Vecchia, L, Giovinazzo, S, Gnecchi, M, Guazzi, M, Iorio, A, La Rovere, M, Leonardi, S, Maccagni, G, Mapelli, M, Margonato, D, Merlo, M, Monzo, L, Mortara, A, Nuzzi, V, Piepoli, M, Porto, I, Pozzi, A, Provenzale, G, Sarullo, F, Sinagra, G, Tedino, C, Tomasoni, D, Volterrani, M, Zaccone, G, Lombardi, C, Senni, M, Metra, M, Ameri P, Inciardi RM, Di Pasquale M, Agostoni P, Bellasi A, Camporotondo R, Canale C, Carubelli V, Carugo S, Catagnano F, Danzi G, Dalla Vecchia L, Giovinazzo S, Gnecchi M, Guazzi M, Iorio A, La Rovere MT, Leonardi S, Maccagni G, Mapelli M, Margonato D, Merlo M, Monzo L, Mortara A, Nuzzi V, Piepoli M, Porto I, Pozzi A, Provenzale G, Sarullo F, Sinagra G, Tedino C, Tomasoni D, Volterrani M, Zaccone G, Lombardi CM, Senni M, Metra M, Ameri, P, Inciardi, R, Di Pasquale, M, Agostoni, P, Bellasi, A, Camporotondo, R, Canale, C, Carubelli, V, Carugo, S, Catagnano, F, Danzi, G, Dalla Vecchia, L, Giovinazzo, S, Gnecchi, M, Guazzi, M, Iorio, A, La Rovere, M, Leonardi, S, Maccagni, G, Mapelli, M, Margonato, D, Merlo, M, Monzo, L, Mortara, A, Nuzzi, V, Piepoli, M, Porto, I, Pozzi, A, Provenzale, G, Sarullo, F, Sinagra, G, Tedino, C, Tomasoni, D, Volterrani, M, Zaccone, G, Lombardi, C, Senni, M, Metra, M, Ameri P, Inciardi RM, Di Pasquale M, Agostoni P, Bellasi A, Camporotondo R, Canale C, Carubelli V, Carugo S, Catagnano F, Danzi G, Dalla Vecchia L, Giovinazzo S, Gnecchi M, Guazzi M, Iorio A, La Rovere MT, Leonardi S, Maccagni G, Mapelli M, Margonato D, Merlo M, Monzo L, Mortara A, Nuzzi V, Piepoli M, Porto I, Pozzi A, Provenzale G, Sarullo F, Sinagra G, Tedino C, Tomasoni D, Volterrani M, Zaccone G, Lombardi CM, Senni M, and Metra M
Abstract: Background: Pulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited. Methods: Data were retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between d-dimer levels and PE incidence was evaluated using restricted cubic splines models. Results: The study included 689 patients (67.3 ± 13.2 year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9–24) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involvement, and higher admission d-dimer [4344 (1099–15,118) vs. 818.5 (417–1460) ng/mL, p < 0.001]. They also received more frequently darunavir/ritonavir, tocilizumab and ventilation support. Furthermore, they faced more bleeding episodes requiring transfusion (15.6% vs. 5.1%, p < 0.001) and non-significantly higher in-hospital mortality (34.6% vs. 22.9%, p = 0.06). In multivariate regression, only d-dimer was associated with PE (HR 1.72, 95% CI 1.13–2.62; p = 0.01). The relation between d-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline d-dimer < 500 ng/mL. Conclusions: PE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of d-dimer in this population need to be clarified. Graphic abstract: [Figure not available: see fulltext.].
Published: 2021

21. ANMCO/SICI-GISE/SIC/SIECVI/SIRM Consensus document: Appropriateness of multimodality imaging in cardiovascular disease [Documento di consenso ANMCO/SICI-GISE/SIC/SIECVI/SIRM: Appropriatezza dell’imaging multimodale nelle patologie cardiovascolari]

Author: Nardi, F, Pino, P, Gabrielli, D, Colivicchi, F, Abrignani, M, Amico, A, Aspromonte, N, Benedetto, F, Bertella, E, Boccardi, L, Bucciarelli Ducci, C, Caldarola, P, Campana, M, Caso, P, Citro, R, Costante, A, De Chiara, B, Di Cesare, E, Di Fusco, S, Domenicucci, S, Enea, I, Erba, P, Faganello, G, Favilli, S, Geraci, G, Giubbini, R, Giunta, N, Guido, V, Imazio, M, Khoury, G, La Canna, G, Mele, D, Moreo, A, Mercuro, G, Musumeci, G, Neglia, D, Parrini, I, Pinamonti, B, Pollarolo, L, Pontone, G, Privitera, C, Riccio, C, Sinagra, G, Urbinati, S, Varbella, F, Berisso, M, Zuin, G, Di Lenarda, A, Gulizia, M, Nardi F., Pino P. G., Gabrielli D., Colivicchi F., Abrignani M. G., Amico A. F., Aspromonte N., Benedetto F. A., Bertella E., Boccardi L. M., Bucciarelli Ducci C., Caldarola P., Campana M., Caso P., Citro R., Costante A. M., De Chiara B. C., Di Cesare E., Di Fusco S. A., Domenicucci S., Enea I., Erba P., Faganello G., Favilli S., Geraci G., Giubbini R., Giunta N., Guido V., Imazio M., Khoury G., La Canna G., Mele D., Moreo A. M., Mercuro G. G., Musumeci G., Neglia D., Parrini I., Pinamonti B., Pollarolo L., Pontone G., Privitera C., Riccio C., Sinagra G., Urbinati S., Varbella F., Berisso M. Z., Zuin G., Di Lenarda A., Gulizia M. M., Nardi, F, Pino, P, Gabrielli, D, Colivicchi, F, Abrignani, M, Amico, A, Aspromonte, N, Benedetto, F, Bertella, E, Boccardi, L, Bucciarelli Ducci, C, Caldarola, P, Campana, M, Caso, P, Citro, R, Costante, A, De Chiara, B, Di Cesare, E, Di Fusco, S, Domenicucci, S, Enea, I, Erba, P, Faganello, G, Favilli, S, Geraci, G, Giubbini, R, Giunta, N, Guido, V, Imazio, M, Khoury, G, La Canna, G, Mele, D, Moreo, A, Mercuro, G, Musumeci, G, Neglia, D, Parrini, I, Pinamonti, B, Pollarolo, L, Pontone, G, Privitera, C, Riccio, C, Sinagra, G, Urbinati, S, Varbella, F, Berisso, M, Zuin, G, Di Lenarda, A, Gulizia, M, Nardi F., Pino P. G., Gabrielli D., Colivicchi F., Abrignani M. G., Amico A. F., Aspromonte N., Benedetto F. A., Bertella E., Boccardi L. M., Bucciarelli Ducci C., Caldarola P., Campana M., Caso P., Citro R., Costante A. M., De Chiara B. C., Di Cesare E., Di Fusco S. A., Domenicucci S., Enea I., Erba P., Faganello G., Favilli S., Geraci G., Giubbini R., Giunta N., Guido V., Imazio M., Khoury G., La Canna G., Mele D., Moreo A. M., Mercuro G. G., Musumeci G., Neglia D., Parrini I., Pinamonti B., Pollarolo L., Pontone G., Privitera C., Riccio C., Sinagra G., Urbinati S., Varbella F., Berisso M. Z., Zuin G., Di Lenarda A., and Gulizia M. M.
Abstract: The complexity of cardiovascular diseases has led to an extensive use of technological instruments and the development of multimodality imaging. This extensive use of different cardiovascular imaging tests in the same patient has increased costs and waiting times.The concept of appropriateness has changed over time. Appropriateness criteria address the need for specific cardiovascular imaging tests in well-defined clinical scenarios, and define the kind of cardiovascular imaging that is appropriated for each clinical scenario in different stages of the disease. The concept of appropriateness criteria has replaced the old idea of appropriate use criteria and reflects the increasing effort of the international Scientific Societies to create and review in a critical way the management of diagnostic tests used by clinicians.The aim of this Italian consensus document is to address the use of multimodality imaging in the diagnosis and management of the major cardiovascular clinical scenarios, taking into consideration not only the international guidelines and scientific documents already published, but also the reality of Italian laws as well as the various professional profiles involved in patient management and availability of technological diagnostic instruments.
Published: 2020

22. Cardiovascular Death Risk in Recovered Mid-Range Ejection Fraction Heart Failure: Insights From Cardiopulmonary Exercise Test

Author: Magrì, D, Piepoli, M, Corrà, U, Gallo, G, Maruotti, A, Vignati, C, Salvioni, E, Mapelli, M, Paolillo, S, Perrone Filardi, P, Girola, D, Metra, M, Scardovi, A, Lagioia, R, Limongelli, G, Senni, M, Scrutinio, D, Emdin, M, Passino, C, Lombardi, C, Cattadori, G, Parati, G, Cicoira, M, Correale, M, Frigerio, M, Clemenza, F, Bussotti, M, Guazzi, M, Badagliacca, R, Sciomer, S, DI Lenarda, A, Maggioni, A, Sinagra, G, Volpe, M, Agostoni, P, MagrÌ D, Piepoli M, CorrÀ U, Gallo G, Maruotti A, Vignati C, Salvioni E, Mapelli M, Paolillo S, Perrone Filardi P, Girola D, Metra M, Scardovi AB, Lagioia R, Limongelli G, Senni M, Scrutinio D, Emdin M, Passino C, Lombardi C, Cattadori G, Parati G, Cicoira M, Correale M, Frigerio M, Clemenza F, Bussotti M, Guazzi M, Badagliacca R, Sciomer S, DI Lenarda A, Maggioni A, Sinagra G, Volpe M, Agostoni P, Magrì, D, Piepoli, M, Corrà, U, Gallo, G, Maruotti, A, Vignati, C, Salvioni, E, Mapelli, M, Paolillo, S, Perrone Filardi, P, Girola, D, Metra, M, Scardovi, A, Lagioia, R, Limongelli, G, Senni, M, Scrutinio, D, Emdin, M, Passino, C, Lombardi, C, Cattadori, G, Parati, G, Cicoira, M, Correale, M, Frigerio, M, Clemenza, F, Bussotti, M, Guazzi, M, Badagliacca, R, Sciomer, S, DI Lenarda, A, Maggioni, A, Sinagra, G, Volpe, M, Agostoni, P, MagrÌ D, Piepoli M, CorrÀ U, Gallo G, Maruotti A, Vignati C, Salvioni E, Mapelli M, Paolillo S, Perrone Filardi P, Girola D, Metra M, Scardovi AB, Lagioia R, Limongelli G, Senni M, Scrutinio D, Emdin M, Passino C, Lombardi C, Cattadori G, Parati G, Cicoira M, Correale M, Frigerio M, Clemenza F, Bussotti M, Guazzi M, Badagliacca R, Sciomer S, DI Lenarda A, Maggioni A, Sinagra G, Volpe M, and Agostoni P
Abstract: Background: Heart failure with midrange ejection fraction (HFmrEF) represents a heterogeneous category where phenotype, as well as prognostic assessment, remains debated. The present study explores a specific HFmrEF subset, namely those who recovered from a reduced EF (rec-HFmrEF) and, particularly, it focuses on the possible additive prognostic role of cardiopulmonary exercise testing. Methods and Results: We analyzed data from 4535 patients with HFrEF and 1176 patients with rec-HFmrEF from the Metabolic Exercise combined with Cardiac and Kidney Indexes database. The end point was cardiovascular death at 5 years. The median follow-up was 1343 days (25th–75th range 627–2403 days). Cardiovascular death occurred in 552 HFrEF and 61 rec-HFmrEF patients. The multivariate analysis confirmed an independent role of the MECKI score's variables in HFrEF (C-index = 0.744) whereas, in the rec-HFmrEF group, only age and peak oxygen uptake (pVO2) remained associated to the end point (C-index = 0.745). A peak oxygen uptake of ≤55% of predicted and a ventilatory efficiency of ≥31 resulted as the most accurate cut-off values in the outcome prediction. Conclusions: Present data support the cardiopulmonary exercise test and, particularly, the peak oxygen uptake, as a useful tool in the rec-HFmrEF prognostic assessment. A peak VO2 of ≤55% predicted and ventilatory efficiency of ≥31 might help to identify a high-risk rec-HFmrEF subgroup.
Published: 2020

23. Association of Troponin Levels with Mortality in Italian Patients Hospitalized with Coronavirus Disease 2019: Results of a Multicenter Study

Author: Lombardi, C, Carubelli, V, Iorio, A, Inciardi, R, Bellasi, A, Canale, C, Camporotondo, R, Catagnano, F, Dalla Vecchia, L, Giovinazzo, S, Maccagni, G, Mapelli, M, Margonato, D, Monzo, L, Nuzzi, V, Oriecuia, C, Peveri, G, Pozzi, A, Provenzale, G, Sarullo, F, Tomasoni, D, Ameri, P, Gnecchi, M, Leonardi, S, Merlo, M, Agostoni, P, Carugo, S, Danzi, G, Guazzi, M, La Rovere, M, Mortara, A, Piepoli, M, Porto, I, Sinagra, G, Volterrani, M, Specchia, C, Metra, M, Senni, M, Lombardi CM, Carubelli V, Iorio A, Inciardi RM, Bellasi A, Canale C, Camporotondo R, Catagnano F, Dalla Vecchia LA, Giovinazzo S, Maccagni G, Mapelli M, Margonato D, Monzo L, Nuzzi V, Oriecuia C, Peveri G, Pozzi A, Provenzale G, Sarullo F, Tomasoni D, Ameri P, Gnecchi M, Leonardi S, Merlo M, Agostoni P, Carugo S, Danzi GB, Guazzi M, La Rovere MT, Mortara A, Piepoli M, Porto I, Sinagra G, Volterrani M, Specchia C, Metra M, Senni M, Lombardi, C, Carubelli, V, Iorio, A, Inciardi, R, Bellasi, A, Canale, C, Camporotondo, R, Catagnano, F, Dalla Vecchia, L, Giovinazzo, S, Maccagni, G, Mapelli, M, Margonato, D, Monzo, L, Nuzzi, V, Oriecuia, C, Peveri, G, Pozzi, A, Provenzale, G, Sarullo, F, Tomasoni, D, Ameri, P, Gnecchi, M, Leonardi, S, Merlo, M, Agostoni, P, Carugo, S, Danzi, G, Guazzi, M, La Rovere, M, Mortara, A, Piepoli, M, Porto, I, Sinagra, G, Volterrani, M, Specchia, C, Metra, M, Senni, M, Lombardi CM, Carubelli V, Iorio A, Inciardi RM, Bellasi A, Canale C, Camporotondo R, Catagnano F, Dalla Vecchia LA, Giovinazzo S, Maccagni G, Mapelli M, Margonato D, Monzo L, Nuzzi V, Oriecuia C, Peveri G, Pozzi A, Provenzale G, Sarullo F, Tomasoni D, Ameri P, Gnecchi M, Leonardi S, Merlo M, Agostoni P, Carugo S, Danzi GB, Guazzi M, La Rovere MT, Mortara A, Piepoli M, Porto I, Sinagra G, Volterrani M, Specchia C, Metra M, and Senni M
Abstract: Importance: Myocardial injury, detected by elevated plasma troponin levels, has been associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19). However, the initial data were reported from single-center or 2-center studies in Chinese populations. Compared with these patients, European and US patients are older, with more comorbidities and higher mortality rates. Objective: To evaluate the prevalence and prognostic value of myocardial injury, detected by elevated plasma troponin levels, in a large population of White Italian patients with COVID-19. Design, Setting, and Participants: This is a multicenter, cross-sectional study enrolling consecutive patients with laboratory-confirmed COVID-19 who were hospitalized in 13 Italian cardiology units from March 1 to April 9, 2020. Patients admitted for acute coronary syndrome were excluded. Elevated troponin levels were defined as values greater than the 99th percentile of normal values. Main Outcomes and Measures: Clinical characteristics and outcomes stratified as elevated or normal cardiac troponin levels at admission, defined as troponin T or troponin I at a level greater than the 99th percentile of normal values. Results: A total of 614 patients with COVID-19 were included in this study (mean age [SD], 67 [13] years; 70.8% male), of whom 148 patients (24.1%) died during the hospitalization. Elevated troponin levels were found in 278 patients (45.3%). These patients were older (mean [SD] age, 64.0 [13.6] years vs 71.3 [12.0] years; P <.001) and had higher prevalence of hypertension (168 patients [50.5%] vs 182 patients [65.9%]; P <.001), heart failure (24 [7.2%]; 63 [22.8%]; P <.001), coronary artery disease (50 [15.0%] vs 87 [31.5%]; P <.001), and atrial fibrillation (33 [9.9%] vs 67 [24.3%]; P <.001). Elevated troponin levels were associated with an increased in-hospital mortality (37% vs 13%; HR, 1.71 [95% CI, 1.13-2.59]; P =.01 via multivariable Cox regression analysi
Published: 2020

24. Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era

Author: De Rosa, S, Spaccarotella, C, Basso, C, Calabro, M, Curcio, A, Filardi, P, Mancone, M, Mercuro, G, Muscoli, S, Nodari, S, Pedrinelli, R, Sinagra, G, Indolfi, C, Angelini, F, Barilla, F, Bartorelli, A, Benedetto, F, Bernabo, P, Bolognese, L, Briani, M, Cacciavillani, L, Calabrese, A, Calabro, P, Caliendo, L, Calo, L, Casella, G, Casu, G, Cavallini, C, Ciampi, Q, Ciccone, M, Comito, M, Corrada, E, Crea, F, D'Andrea, A, D'Urbano, M, De Caterina, R, De Ferrari, G, De Ponti, R, Della Mattia, A, DI Mario, C, Donnazzan, L, Esposito, G, Fedele, F, Ferraro, A, Galasso, G, Galie, N, Gnecchi, M, Golino, P, Golia, B, Guarini, P, Leonardi, S, Locuratolo, N, Luzza, F, Manganiello, V, Francesca Marchetti, M, Marenzi, G, Margonato, A, Meloni, L, Metra, M, Milo, M, Mongiardo, A, Monzo, L, Morisco, C, Novo, G, Pancaldi, S, Parollo, M, Paterno, G, Patti, G, Priori, S, Ravera, A, Giuseppe Rebuzzi, A, Rossi, M, Scherillo, M, Semprini, F, Senni, M, Sibilio, G, Siviglia, M, Tamburino, C, Tortorici, G, Versace, F, Villari, B, Volpe, M, De Rosa S., Spaccarotella C., Basso C., Calabro M. P., Curcio A., Filardi P. P., Mancone M., Mercuro G., Muscoli S., Nodari S., Pedrinelli R., Sinagra G., Indolfi C., Angelini F., Barilla F., Bartorelli A., Benedetto F., Bernabo P., Bolognese L., Briani M., Cacciavillani L., Calabrese A., Calabro P., Caliendo L., Calo L., Casella G., Casu G., Cavallini C., Ciampi Q., Ciccone M., Comito M., Corrada E., Crea F., D'Andrea A., D'Urbano M., De Caterina R., De Ferrari G., De Ponti R., Della Mattia A., DI Mario C., Donnazzan L., Esposito G., Fedele F., Ferraro A., Galasso G., Galie N., Gnecchi M., Golino P., Golia B., Guarini P., Leonardi S., Locuratolo N., Luzza F., Manganiello V., Francesca Marchetti M., Marenzi G., Margonato A., Meloni L., Metra M., Milo M., Mongiardo A., Monzo L., Morisco C., Novo G., Pancaldi S., Parollo M., Paterno G., Patti G., Priori S., Ravera A., Giuseppe Rebuzzi A., Rossi M., Scherillo M., Semprini F., Senni M., Sibilio G., Siviglia M., Tamburino C., Tortorici G., Versace F., Villari B., Volpe M., De Rosa, S, Spaccarotella, C, Basso, C, Calabro, M, Curcio, A, Filardi, P, Mancone, M, Mercuro, G, Muscoli, S, Nodari, S, Pedrinelli, R, Sinagra, G, Indolfi, C, Angelini, F, Barilla, F, Bartorelli, A, Benedetto, F, Bernabo, P, Bolognese, L, Briani, M, Cacciavillani, L, Calabrese, A, Calabro, P, Caliendo, L, Calo, L, Casella, G, Casu, G, Cavallini, C, Ciampi, Q, Ciccone, M, Comito, M, Corrada, E, Crea, F, D'Andrea, A, D'Urbano, M, De Caterina, R, De Ferrari, G, De Ponti, R, Della Mattia, A, DI Mario, C, Donnazzan, L, Esposito, G, Fedele, F, Ferraro, A, Galasso, G, Galie, N, Gnecchi, M, Golino, P, Golia, B, Guarini, P, Leonardi, S, Locuratolo, N, Luzza, F, Manganiello, V, Francesca Marchetti, M, Marenzi, G, Margonato, A, Meloni, L, Metra, M, Milo, M, Mongiardo, A, Monzo, L, Morisco, C, Novo, G, Pancaldi, S, Parollo, M, Paterno, G, Patti, G, Priori, S, Ravera, A, Giuseppe Rebuzzi, A, Rossi, M, Scherillo, M, Semprini, F, Senni, M, Sibilio, G, Siviglia, M, Tamburino, C, Tortorici, G, Versace, F, Villari, B, Volpe, M, De Rosa S., Spaccarotella C., Basso C., Calabro M. P., Curcio A., Filardi P. P., Mancone M., Mercuro G., Muscoli S., Nodari S., Pedrinelli R., Sinagra G., Indolfi C., Angelini F., Barilla F., Bartorelli A., Benedetto F., Bernabo P., Bolognese L., Briani M., Cacciavillani L., Calabrese A., Calabro P., Caliendo L., Calo L., Casella G., Casu G., Cavallini C., Ciampi Q., Ciccone M., Comito M., Corrada E., Crea F., D'Andrea A., D'Urbano M., De Caterina R., De Ferrari G., De Ponti R., Della Mattia A., DI Mario C., Donnazzan L., Esposito G., Fedele F., Ferraro A., Galasso G., Galie N., Gnecchi M., Golino P., Golia B., Guarini P., Leonardi S., Locuratolo N., Luzza F., Manganiello V., Francesca Marchetti M., Marenzi G., Margonato A., Meloni L., Metra M., Milo M., Mongiardo A., Monzo L., Morisco C., Novo G., Pancaldi S., Parollo M., Paterno G., Patti G., Priori S., Ravera A., Giuseppe Rebuzzi A., Rossi M., Scherillo M., Semprini F., Senni M., Sibilio G., Siviglia M., Tamburino C., Tortorici G., Versace F., Villari B., and Volpe M.
Abstract: Aims: To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results: We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7-32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3-70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7-6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1-2.8; P = 0.009). Conclusion: Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.
Published: 2020

25. Impact of heart failure on the clinical course and outcomes of patients hospitalized for COVID-19. Results of the Cardio-COVID-Italy multicentre study

Author: Tomasoni, D, Inciardi, R, Lombardi, C, Tedino, C, Agostoni, P, Ameri, P, Barbieri, L, Bellasi, A, Camporotondo, R, Canale, C, Carubelli, V, Carugo, S, Catagnano, F, Dalla Vecchia, L, Danzi, G, Di Pasquale, M, Gaudenzi, M, Giovinazzo, S, Gnecchi, M, Iorio, A, La Rovere, M, Leonardi, S, Maccagni, G, Mapelli, M, Margonato, D, Merlo, M, Monzo, L, Mortara, A, Nuzzi, V, Piepoli, M, Porto, I, Pozzi, A, Sarullo, F, Sinagra, G, Volterrani, M, Zaccone, G, Guazzi, M, Senni, M, Metra, M, Tomasoni D, Inciardi RM, Lombardi CM, Tedino C, Agostoni P, Ameri P, Barbieri L, Bellasi A, Camporotondo R, Canale C, Carubelli V, Carugo S, Catagnano F, Dalla Vecchia LA, Danzi GB, Di Pasquale M, Gaudenzi M, Giovinazzo S, Gnecchi M, Iorio A, La Rovere MT, Leonardi S, Maccagni G, Mapelli M, Margonato D, Merlo M, Monzo L, Mortara A, Nuzzi V, Piepoli M, Porto I, Pozzi A, Sarullo F, Sinagra G, Volterrani M, Zaccone G, Guazzi M, Senni M, Metra M, Tomasoni, D, Inciardi, R, Lombardi, C, Tedino, C, Agostoni, P, Ameri, P, Barbieri, L, Bellasi, A, Camporotondo, R, Canale, C, Carubelli, V, Carugo, S, Catagnano, F, Dalla Vecchia, L, Danzi, G, Di Pasquale, M, Gaudenzi, M, Giovinazzo, S, Gnecchi, M, Iorio, A, La Rovere, M, Leonardi, S, Maccagni, G, Mapelli, M, Margonato, D, Merlo, M, Monzo, L, Mortara, A, Nuzzi, V, Piepoli, M, Porto, I, Pozzi, A, Sarullo, F, Sinagra, G, Volterrani, M, Zaccone, G, Guazzi, M, Senni, M, Metra, M, Tomasoni D, Inciardi RM, Lombardi CM, Tedino C, Agostoni P, Ameri P, Barbieri L, Bellasi A, Camporotondo R, Canale C, Carubelli V, Carugo S, Catagnano F, Dalla Vecchia LA, Danzi GB, Di Pasquale M, Gaudenzi M, Giovinazzo S, Gnecchi M, Iorio A, La Rovere MT, Leonardi S, Maccagni G, Mapelli M, Margonato D, Merlo M, Monzo L, Mortara A, Nuzzi V, Piepoli M, Porto I, Pozzi A, Sarullo F, Sinagra G, Volterrani M, Zaccone G, Guazzi M, Senni M, and Metra M
Abstract: Aims: To assess the prognostic value of a history of heart failure (HF) in patients with coronavirus disease 2019 (COVID-19). Methods and results: We enrolled 692 consecutive patients admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. Mean age was 67.4 ± 13.2 years, 69.5% of patients were males, 90 (13.0%) had a history of HF, median hospitalization length was 14 days (interquartile range 9–24). In-hospital death occurred in 37 of 90 patients (41.1%) with HF history vs. 126 of those with no HF history (20.9%). The increased risk of death associated with HF history remained significant after adjustment for clinical variables related to COVID-19 and HF severity, including comorbidities, oxygen saturation, lymphocyte count and plasma troponin [adjusted hazard ratio (HR) for death: 2.25; 95% confidence interval (CI) 1.26–4.02; P = 0.006 at multivariable Cox regression model including 404 patients]. Patients with a history of HF also had more in-hospital complications including. acute HF (33.3% vs. 5.1%, P < 0.001), acute renal failure (28.1% vs. 12.9%, P < 0.001), multiorgan failure (15.9% vs. 5.8%, P = 0.004) and sepsis (18.4% vs. 8.9%, P = 0.006). Other independent predictors of outcome were age, sex, oxygen saturation and oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen ratio (PaO2/FiO2). In-hospital treatment with corticosteroids and heparin had beneficial effects (adjusted HR for death: 0.46; 95% CI 0.29–0.74; P = 0.001; n = 404 for corticosteroids, and adjusted HR 0.41; 95% CI 0.25–0.67; P < 0.001; n = 364 for heparin). Conclusions: Hospitalized patients with COVID-19 and a history of HF have an extremely poor outcome with higher mortality and in-hospital complications. HF history is an independent predictor of increased in-hospital mortality.
Published: 2020

26. Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy.

Author: Norrish, G, Cleary, A, Field, E, Cervi, E, Boleti, O, Ziółkowska, L, Olivotto, I, Khraiche, D, Limongelli, G, Anastasakis, A, Weintraub, R, Biagini, E, Ragni, L, Prendiville, T, Duignan, S, McLeod, K, Ilina, M, Fernandez, A, Marrone, C, Bökenkamp, R, Baban, A, Kubus, P, Daubeney, PEF, Sarquella-Brugada, G, Cesar, S, Klaassen, S, Ojala, TH, Bhole, V, Medrano, C, Uzun, O, Brown, E, Gran, F, Sinagra, G, Castro, FJ, Stuart, G, Yamazawa, H, Barriales-Villa, R, Garcia-Guereta, L, Adwani, S, Linter, K, Bharucha, T, Gonzales-Lopez, E, Siles, A, Rasmussen, TB, Calcagnino, M, Jones, CB, De Wilde, H, Kubo, T, Felice, T, Popoiu, A, Mogensen, J, Mathur, S, Centeno, F, Reinhardt, Z, Schouvey, S, Elliott, PM, Kaski, JP, Norrish, G, Cleary, A, Field, E, Cervi, E, Boleti, O, Ziółkowska, L, Olivotto, I, Khraiche, D, Limongelli, G, Anastasakis, A, Weintraub, R, Biagini, E, Ragni, L, Prendiville, T, Duignan, S, McLeod, K, Ilina, M, Fernandez, A, Marrone, C, Bökenkamp, R, Baban, A, Kubus, P, Daubeney, PEF, Sarquella-Brugada, G, Cesar, S, Klaassen, S, Ojala, TH, Bhole, V, Medrano, C, Uzun, O, Brown, E, Gran, F, Sinagra, G, Castro, FJ, Stuart, G, Yamazawa, H, Barriales-Villa, R, Garcia-Guereta, L, Adwani, S, Linter, K, Bharucha, T, Gonzales-Lopez, E, Siles, A, Rasmussen, TB, Calcagnino, M, Jones, CB, De Wilde, H, Kubo, T, Felice, T, Popoiu, A, Mogensen, J, Mathur, S, Centeno, F, Reinhardt, Z, Schouvey, S, Elliott, PM, and Kaski, JP
Abstract: BACKGROUND: Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. OBJECTIVES: The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. METHODS: Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. RESULTS: At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. CONCLUSIONS: Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.
Published: 2022

27. Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy

Author: Escobar-Lopez, L., Ochoa, J.P., Royuela, A., Verdonschot, J.A.J., Ferro, M., Espinosa, M.A., Sabater-Molina, M., Gallego-Delgado, M., Larrañaga-Moreira, J.M., Garcia-Pinilla, J.M., Basurte-Elorz, M.T., Rodríguez-Palomares, J.F., Climent, V., Bermudez-Jimenez, F.J., Mogollón-Jiménez, M.V., Lopez, J., Peña-Peña, M.L., Garcia-Alvarez, A., López-Abel, B., Ripoll-Vera, T., Palomino-Doza, J., Bayes-Genis, A., Brugada, R., Idiazabal, U., Mirelis, J.G., Dominguez, F., Henkens, M., Krapels, I.P.C., Brunner, H.G., Paldino, A., Zaffalon, D., Mestroni, L., Sinagra, G., Heymans, S.R.B., Merlo, M., Garcia-Pavia, P., Escobar-Lopez, L., Ochoa, J.P., Royuela, A., Verdonschot, J.A.J., Ferro, M., Espinosa, M.A., Sabater-Molina, M., Gallego-Delgado, M., Larrañaga-Moreira, J.M., Garcia-Pinilla, J.M., Basurte-Elorz, M.T., Rodríguez-Palomares, J.F., Climent, V., Bermudez-Jimenez, F.J., Mogollón-Jiménez, M.V., Lopez, J., Peña-Peña, M.L., Garcia-Alvarez, A., López-Abel, B., Ripoll-Vera, T., Palomino-Doza, J., Bayes-Genis, A., Brugada, R., Idiazabal, U., Mirelis, J.G., Dominguez, F., Henkens, M., Krapels, I.P.C., Brunner, H.G., Paldino, A., Zaffalon, D., Mestroni, L., Sinagra, G., Heymans, S.R.B., Merlo, M., and Garcia-Pavia, P.
Abstract: Contains fulltext : 284808.pdf (Publisher’s version ) (Open Access), BACKGROUND: Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption. OBJECTIVES: This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD. METHODS: Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD. Multivariable logistic regression analysis was used to identify variables independently predicting G+, which were summed to create the Madrid Genotype Score. The external validation sample comprised 1,097 genotyped patients from the Maastricht and Trieste registries. RESULTS: A G+ result was found in 377 (37%) and 289 (26%) patients from the derivation and validation cohorts, respectively. Independent predictors of a G+ result in the derivation cohort were: family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P < 0.001), low electrocardiogram voltage in peripheral leads (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001), skeletal myopathy (OR: 3.42; 95% CI: 1.60-7.31; P = 0.001), absence of hypertension (OR: 2.28; 95% CI: 1.67-3.13; P < 0.001), and absence of left bundle branch block (OR: 3.58; 95% CI: 2.57-5.01; P < 0.001). A score containing these factors predicted a G+ result, ranging from 3% when all predictors were absent to 79% when ≥4 predictors were present. Internal validation provided a C-statistic of 0.74 (95% CI: 0.71-0.77) and a calibration slope of 0.94 (95% CI: 0.80-1.10). The C-statistic in the external validation cohort was 0.74 (95% CI: 0.71-0.78). CONCLUSIONS: The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD.
Published: 2022

28. Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy

Author: Escobar-Lopez, L., Ochoa, J.P., Royuela, A., Verdonschot, J.A.J., Ferro, M., Espinosa, M.A., Sabater-Molina, M., Gallego-Delgado, M., Larrañaga-Moreira, J.M., Garcia-Pinilla, J.M., Basurte-Elorz, M.T., Rodríguez-Palomares, J.F., Climent, V., Bermudez-Jimenez, F.J., Mogollón-Jiménez, M.V., Lopez, J., Peña-Peña, M.L., Garcia-Alvarez, A., López-Abel, B., Ripoll-Vera, T., Palomino-Doza, J., Bayes-Genis, A., Brugada, R., Idiazabal, U., Mirelis, J.G., Dominguez, F., Henkens, M., Krapels, I.P.C., Brunner, H.G., Paldino, A., Zaffalon, D., Mestroni, L., Sinagra, G., Heymans, S.R.B., Merlo, M., Garcia-Pavia, P., Escobar-Lopez, L., Ochoa, J.P., Royuela, A., Verdonschot, J.A.J., Ferro, M., Espinosa, M.A., Sabater-Molina, M., Gallego-Delgado, M., Larrañaga-Moreira, J.M., Garcia-Pinilla, J.M., Basurte-Elorz, M.T., Rodríguez-Palomares, J.F., Climent, V., Bermudez-Jimenez, F.J., Mogollón-Jiménez, M.V., Lopez, J., Peña-Peña, M.L., Garcia-Alvarez, A., López-Abel, B., Ripoll-Vera, T., Palomino-Doza, J., Bayes-Genis, A., Brugada, R., Idiazabal, U., Mirelis, J.G., Dominguez, F., Henkens, M., Krapels, I.P.C., Brunner, H.G., Paldino, A., Zaffalon, D., Mestroni, L., Sinagra, G., Heymans, S.R.B., Merlo, M., and Garcia-Pavia, P.
Abstract: Contains fulltext : 284808.pdf (Publisher’s version ) (Open Access), BACKGROUND: Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption. OBJECTIVES: This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD. METHODS: Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD. Multivariable logistic regression analysis was used to identify variables independently predicting G+, which were summed to create the Madrid Genotype Score. The external validation sample comprised 1,097 genotyped patients from the Maastricht and Trieste registries. RESULTS: A G+ result was found in 377 (37%) and 289 (26%) patients from the derivation and validation cohorts, respectively. Independent predictors of a G+ result in the derivation cohort were: family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P < 0.001), low electrocardiogram voltage in peripheral leads (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001), skeletal myopathy (OR: 3.42; 95% CI: 1.60-7.31; P = 0.001), absence of hypertension (OR: 2.28; 95% CI: 1.67-3.13; P < 0.001), and absence of left bundle branch block (OR: 3.58; 95% CI: 2.57-5.01; P < 0.001). A score containing these factors predicted a G+ result, ranging from 3% when all predictors were absent to 79% when ≥4 predictors were present. Internal validation provided a C-statistic of 0.74 (95% CI: 0.71-0.77) and a calibration slope of 0.94 (95% CI: 0.80-1.10). The C-statistic in the external validation cohort was 0.74 (95% CI: 0.71-0.78). CONCLUSIONS: The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD.
Published: 2022

29. Relationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic Cardiomyopathy.

Author: Norrish, G, Ding, T, Field, E, Cervi, E, Ziółkowska, L, Olivotto, I, Khraiche, D, Limongelli, G, Anastasakis, A, Weintraub, R, Biagini, E, Ragni, L, Prendiville, T, Duignan, S, McLeod, K, Ilina, M, Fernández, A, Marrone, C, Bökenkamp, R, Baban, A, Kubus, P, Daubeney, PEF, Sarquella-Brugada, G, Cesar, S, Klaassen, S, Ojala, TH, Bhole, V, Medrano, C, Uzun, O, Brown, E, Gran, F, Sinagra, G, Castro, FJ, Stuart, G, Vignati, G, Yamazawa, H, Barriales-Villa, R, Garcia-Guereta, L, Adwani, S, Linter, K, Bharucha, T, Garcia-Pavia, P, Siles, A, Rasmussen, TB, Calcagnino, M, Jones, CB, De Wilde, H, Kubo, T, Felice, T, Popoiu, A, Mogensen, J, Mathur, S, Centeno, F, Reinhardt, Z, Schouvey, S, O'Mahony, C, Omar, RZ, Elliott, PM, Kaski, JP, Norrish, G, Ding, T, Field, E, Cervi, E, Ziółkowska, L, Olivotto, I, Khraiche, D, Limongelli, G, Anastasakis, A, Weintraub, R, Biagini, E, Ragni, L, Prendiville, T, Duignan, S, McLeod, K, Ilina, M, Fernández, A, Marrone, C, Bökenkamp, R, Baban, A, Kubus, P, Daubeney, PEF, Sarquella-Brugada, G, Cesar, S, Klaassen, S, Ojala, TH, Bhole, V, Medrano, C, Uzun, O, Brown, E, Gran, F, Sinagra, G, Castro, FJ, Stuart, G, Vignati, G, Yamazawa, H, Barriales-Villa, R, Garcia-Guereta, L, Adwani, S, Linter, K, Bharucha, T, Garcia-Pavia, P, Siles, A, Rasmussen, TB, Calcagnino, M, Jones, CB, De Wilde, H, Kubo, T, Felice, T, Popoiu, A, Mogensen, J, Mathur, S, Centeno, F, Reinhardt, Z, Schouvey, S, O'Mahony, C, Omar, RZ, Elliott, PM, and Kaski, JP
Abstract: BACKGROUND: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. METHODS: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). RESULTS: MLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. CONCLUSIONS: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter def
Published: 2022

30. A national survey on prevalence of possible echocardiographic red flags of amyloid cardiomyopathy in consecutive patients undergoing routine echocardiography: study design and patients characterization-the first insight from the AC-TIVE Study

Author: Merlo, M, Porcari, A, Pagura, L, Cameli, M, Vergaro, G, Musumeci, B, Biagini, E, Canepa, M, Crotti, L, Imazio, M, Forleo, C, Cappelli, F, Favale, S, Di Bella, G, Dore, F, Lombardi, C, Pavasini, R, Rella, V, Palmiero, G, Caiazza, M, Albanese, M, Guaricci, A, Branzi, G, Caponetti, A, Saturi, G, La Malfa, G, Merlo, A, Andreis, A, Bruno, F, Longo, F, Sfriso, E, Di Ienno, L, De Carli, G, Giacomin, E, Spini, V, Milidoni, A, Limongelli, G, Autore, C, Olivotto, I, Badano, L, Parati, G, Perlini, S, Metra, M, Emdin, M, Rapezzi, C, Sinagra, G, Merlo, Marco, Porcari, Aldostefano, Pagura, Linda, Cameli, Matteo, Vergaro, Giuseppe, Musumeci, Beatrice, Biagini, Elena, Canepa, Marco, Crotti, Lia, Imazio, Massimo, Forleo, Cinzia, Cappelli, Francesco, Favale, Stefano, Di Bella, Gianluca, Dore, Franca, Lombardi, Carlo Mario, Pavasini, Rita, Rella, Valeria, Palmiero, Giuseppe, Caiazza, Martina, Albanese, Miriam, Guaricci, Andrea Igoren, Branzi, Giovanna, Caponetti, Angelo Giuseppe, Saturi, Giulia, La Malfa, Giovanni, Merlo, Andrea Carlo, Andreis, Alessandro, Bruno, Francesco, Longo, Francesca, Sfriso, Enrico, Di Ienno, Luca, De Carli, Giuseppe, Giacomin, Elisa, Spini, Valentina, Milidoni, Antonino, Limongelli, Giuseppe, Autore, Camillo, Olivotto, Iacopo, Badano, Luigi, Parati, Gianfranco, Perlini, Stefano, Metra, Marco, Emdin, Michele, Rapezzi, Claudio, Sinagra, Gianfranco, Merlo, M, Porcari, A, Pagura, L, Cameli, M, Vergaro, G, Musumeci, B, Biagini, E, Canepa, M, Crotti, L, Imazio, M, Forleo, C, Cappelli, F, Favale, S, Di Bella, G, Dore, F, Lombardi, C, Pavasini, R, Rella, V, Palmiero, G, Caiazza, M, Albanese, M, Guaricci, A, Branzi, G, Caponetti, A, Saturi, G, La Malfa, G, Merlo, A, Andreis, A, Bruno, F, Longo, F, Sfriso, E, Di Ienno, L, De Carli, G, Giacomin, E, Spini, V, Milidoni, A, Limongelli, G, Autore, C, Olivotto, I, Badano, L, Parati, G, Perlini, S, Metra, M, Emdin, M, Rapezzi, C, Sinagra, G, Merlo, Marco, Porcari, Aldostefano, Pagura, Linda, Cameli, Matteo, Vergaro, Giuseppe, Musumeci, Beatrice, Biagini, Elena, Canepa, Marco, Crotti, Lia, Imazio, Massimo, Forleo, Cinzia, Cappelli, Francesco, Favale, Stefano, Di Bella, Gianluca, Dore, Franca, Lombardi, Carlo Mario, Pavasini, Rita, Rella, Valeria, Palmiero, Giuseppe, Caiazza, Martina, Albanese, Miriam, Guaricci, Andrea Igoren, Branzi, Giovanna, Caponetti, Angelo Giuseppe, Saturi, Giulia, La Malfa, Giovanni, Merlo, Andrea Carlo, Andreis, Alessandro, Bruno, Francesco, Longo, Francesca, Sfriso, Enrico, Di Ienno, Luca, De Carli, Giuseppe, Giacomin, Elisa, Spini, Valentina, Milidoni, Antonino, Limongelli, Giuseppe, Autore, Camillo, Olivotto, Iacopo, Badano, Luigi, Parati, Gianfranco, Perlini, Stefano, Metra, Marco, Emdin, Michele, Rapezzi, Claudio, and Sinagra, Gianfranco
Published: 2022

31. Exercise oscillatory ventilation and prognosis in heart failure patients with reduced and mid-range ejection fraction

Author: Rovai, S, Corra, U, Piepoli, M, Vignati, C, Salvioni, E, Bonomi, A, Mattavelli, I, Arcari, L, Scardovi, A, Perrone Filardi, P, Lagioia, R, Paolillo, S, Magri, D, Limongelli, G, Metra, M, Senni, M, Scrutinio, D, Raimondo, R, Emdin, M, Lombardi, C, Cattadori, G, Parati, G, Re, F, Cicoira, M, Villani, G, Mina, C, Correale, M, Frigerio, M, Perna, E, Mapelli, M, Magini, A, Clemenza, F, Bussotti, M, Battaia, E, Guazzi, M, Bandera, F, Badagliacca, R, Di Lenarda, A, Pacileo, G, Maggioni, A, Passino, C, Sciomer, S, Sinagra, G, Agostoni, P, Rovai S., Corra U., Piepoli M., Vignati C., Salvioni E., Bonomi A., Mattavelli I., Arcari L., Scardovi A. B., Perrone Filardi P., Lagioia R., Paolillo S., Magri D., Limongelli G., Metra M., Senni M., Scrutinio D., Raimondo R., Emdin M., Lombardi C., Cattadori G., Parati G., Re F., Cicoira M., Villani G. Q., Mina C., Correale M., Frigerio M., Perna E., Mapelli M., Magini A., Clemenza F., Bussotti M., Battaia E., Guazzi M., Bandera F., Badagliacca R., Di Lenarda A., Pacileo G., Maggioni A., Passino C., Sciomer S., Sinagra G., Agostoni P., Rovai, S, Corra, U, Piepoli, M, Vignati, C, Salvioni, E, Bonomi, A, Mattavelli, I, Arcari, L, Scardovi, A, Perrone Filardi, P, Lagioia, R, Paolillo, S, Magri, D, Limongelli, G, Metra, M, Senni, M, Scrutinio, D, Raimondo, R, Emdin, M, Lombardi, C, Cattadori, G, Parati, G, Re, F, Cicoira, M, Villani, G, Mina, C, Correale, M, Frigerio, M, Perna, E, Mapelli, M, Magini, A, Clemenza, F, Bussotti, M, Battaia, E, Guazzi, M, Bandera, F, Badagliacca, R, Di Lenarda, A, Pacileo, G, Maggioni, A, Passino, C, Sciomer, S, Sinagra, G, Agostoni, P, Rovai S., Corra U., Piepoli M., Vignati C., Salvioni E., Bonomi A., Mattavelli I., Arcari L., Scardovi A. B., Perrone Filardi P., Lagioia R., Paolillo S., Magri D., Limongelli G., Metra M., Senni M., Scrutinio D., Raimondo R., Emdin M., Lombardi C., Cattadori G., Parati G., Re F., Cicoira M., Villani G. Q., Mina C., Correale M., Frigerio M., Perna E., Mapelli M., Magini A., Clemenza F., Bussotti M., Battaia E., Guazzi M., Bandera F., Badagliacca R., Di Lenarda A., Pacileo G., Maggioni A., Passino C., Sciomer S., Sinagra G., and Agostoni P.
Abstract: Aims: Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction (<40%, HFrEF) and with HF with preserved ejection fraction (>50%, HFpEF), but no data are available for patients with HF with mid-range ejection fraction (40–49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients. Methods and results: We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2-year follow-up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF,. respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV− patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV− patients. Kaplan–Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV− of the same ejection fraction groups. EOV-associated survival differences in HFmrEF patients started after 18 months of follow-up. Conclusion: Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow-up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV− patients diverged only after 18 months.
Published: 2019

32. Persistent left ventricular dysfunction after acute lymphocytic myocarditis: Frequency and predictors

Author: Merlo, M, Ammirati, E, Gentile, P, Artico, J, Cannata, A, Finocchiaro, G, Barbati, G, Sormani, P, Varrenti, M, Perkan, A, Fabris, E, Aleksova, A, Bussani, R, Petrella, D, Cipriani, M, Raineri, C, Frigerio, M, Sinagra, G, Merlo M., Ammirati E., Gentile P., Artico J., CANNATA, ADALGISA, Finocchiaro G., Barbati G., Sormani P., Varrenti M., Perkan A., Fabris E., Aleksova A., Bussani R., Petrella D., Cipriani M., Raineri C., Frigerio M., Sinagra G., Merlo, M, Ammirati, E, Gentile, P, Artico, J, Cannata, A, Finocchiaro, G, Barbati, G, Sormani, P, Varrenti, M, Perkan, A, Fabris, E, Aleksova, A, Bussani, R, Petrella, D, Cipriani, M, Raineri, C, Frigerio, M, Sinagra, G, Merlo M., Ammirati E., Gentile P., Artico J., CANNATA, ADALGISA, Finocchiaro G., Barbati G., Sormani P., Varrenti M., Perkan A., Fabris E., Aleksova A., Bussani R., Petrella D., Cipriani M., Raineri C., Frigerio M., and Sinagra G.
Abstract: Background Persistent left ventricular (LV) systolic dysfunction in patients with acute lymphocytic myocarditis (LM) is widely unexplored. Objectives To assess the frequency and predictors of persistent LV dysfunction in patients with LM and reduced LVEF at admission. Methods and results We retrospectively evaluated 89 consecutive patients with histologically-proven acute myocarditis enrolled at three Italian referral hospitals. A subgroup of 48 patients with LM, baseline systolic impairment and an available echocardiographic assessment at 12 months (6–18) from discharge constituted the study population. The primary study end-point was persistent LV dysfunction, defined as LVEF <50% at 1-year, and was observed in 27/48 patients (56.3%). Higher LV end-diastolic diameter at admission (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.04–1.43, p = 0.002), non-fulminant presentation (OR 8.46, 95% CI 1.28–55.75, p = 0.013) and presence of a poor lymphocytic infiltrate (OR 12.40, 95% CI 1.23–124.97, p = 0.010) emerged as independent predictors of persistent LV dysfunction at multivariate analysis (area under the curve 0.91, 95% CI 0.82–0.99). Pre-discharge LVEF was lower in patients with persistent LV dysfunction compared to the others (32%±8 vs. 53%±8, p <0.001), and this single variable showed the best accuracy in predicting the study end-point (area under the curve 0.95, 95% CI 0.89–1.00). Conclusions More than half of patients presenting with acute LM and LVEF <50% who survive the acute phase show persistent LV dysfunction after 1-year from hospital discharge. Features of sub-acute inflammatory process and of established myocardial damage at initial hospitalization emerged as predictors of this end-point
Published: 2019

33. Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction

Author: Ammirati, E, Veronese, G, Brambatti, M, Merlo, M, Cipriani, M, Potena, L, Sormani, P, Aoki, T, Sugimura, K, Sawamura, A, Okumura, T, Pinney, S, Hong, K, Shah, P, Braun, O, Van de Heyning, C, Montero, S, Petrella, D, Huang, F, Schmidt, M, Raineri, C, Lala, A, Varrenti, M, Foa, A, Leone, O, Gentile, P, Artico, J, Agostini, V, Patel, R, Garascia, A, Van Craenenbroeck, E, Hirose, K, Isotani, A, Murohara, T, Arita, Y, Sionis, A, Fabris, E, Hashem, S, Garcia-Hernando, V, Oliva, F, Greenberg, B, Shimokawa, H, Sinagra, G, Adler, E, Frigerio, M, Camici, P, Ammirati E., Veronese G., Brambatti M., Merlo M., Cipriani M., Potena L., Sormani P., Aoki T., Sugimura K., Sawamura A., Okumura T., Pinney S., Hong K., Shah P., Braun O., Van de Heyning C. M., Montero S., Petrella D., Huang F., Schmidt M., Raineri C., Lala A., Varrenti M., Foa A., Leone O., Gentile P., Artico J., Agostini V., Patel R., Garascia A., Van Craenenbroeck E. M., Hirose K., Isotani A., Murohara T., Arita Y., Sionis A., Fabris E., Hashem S., Garcia-Hernando V., Oliva F., Greenberg B., Shimokawa H., Sinagra G., Adler E. D., Frigerio M., Camici P. G., Ammirati, E, Veronese, G, Brambatti, M, Merlo, M, Cipriani, M, Potena, L, Sormani, P, Aoki, T, Sugimura, K, Sawamura, A, Okumura, T, Pinney, S, Hong, K, Shah, P, Braun, O, Van de Heyning, C, Montero, S, Petrella, D, Huang, F, Schmidt, M, Raineri, C, Lala, A, Varrenti, M, Foa, A, Leone, O, Gentile, P, Artico, J, Agostini, V, Patel, R, Garascia, A, Van Craenenbroeck, E, Hirose, K, Isotani, A, Murohara, T, Arita, Y, Sionis, A, Fabris, E, Hashem, S, Garcia-Hernando, V, Oliva, F, Greenberg, B, Shimokawa, H, Sinagra, G, Adler, E, Frigerio, M, Camici, P, Ammirati E., Veronese G., Brambatti M., Merlo M., Cipriani M., Potena L., Sormani P., Aoki T., Sugimura K., Sawamura A., Okumura T., Pinney S., Hong K., Shah P., Braun O., Van de Heyning C. M., Montero S., Petrella D., Huang F., Schmidt M., Raineri C., Lala A., Varrenti M., Foa A., Leone O., Gentile P., Artico J., Agostini V., Patel R., Garascia A., Van Craenenbroeck E. M., Hirose K., Isotani A., Murohara T., Arita Y., Sionis A., Fabris E., Hashem S., Garcia-Hernando V., Oliva F., Greenberg B., Shimokawa H., Sinagra G., Adler E. D., Frigerio M., and Camici P. G.
Abstract: Background: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. Objectives: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. Methods: A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. Results: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). Conclusions: This international registry confirms that patients with FM have higher rates of cardiac death and heart
Published: 2019

34. Towards standardization of echocardiography for the evaluation of left ventricular function in adult rodents: a position paper of the ESC Working Group on Myocardial Function

Author: Zacchigna, S, Paldino, A, Falcao-Pires, I, Daskalopoulos, EP, Dal Ferro, M, Vodret, S, Lesizza, P, Cannata, A, Miranda-Silva, D, Lourenco, A P, Pinamonti, B, Sinagra, G, Weinberger, F, Eschenhagen, T, Carrier, L, Kehat, I, Tocchetti, CG, Russo, M, Ghigo, A, Cimino, J, Hirsch, E, Dawson, D, Ciccarelli, M, Oliveti, M, Linke, WA, Cuijpers, I, Heymans, S, Hamdani, N, Boer, Monique, Duncker, Dirk-jan, Kuster, D, Velden, J, Beauloye, C, Bertrand, L, Mayr, M, Giacca, M, Leuschner, F, Backs, J, Thum, T, Zacchigna, S, Paldino, A, Falcao-Pires, I, Daskalopoulos, EP, Dal Ferro, M, Vodret, S, Lesizza, P, Cannata, A, Miranda-Silva, D, Lourenco, A P, Pinamonti, B, Sinagra, G, Weinberger, F, Eschenhagen, T, Carrier, L, Kehat, I, Tocchetti, CG, Russo, M, Ghigo, A, Cimino, J, Hirsch, E, Dawson, D, Ciccarelli, M, Oliveti, M, Linke, WA, Cuijpers, I, Heymans, S, Hamdani, N, Boer, Monique, Duncker, Dirk-jan, Kuster, D, Velden, J, Beauloye, C, Bertrand, L, Mayr, M, Giacca, M, Leuschner, F, Backs, J, and Thum, T
Abstract: Echocardiography is a reliable and reproducible method to assess non-invasively cardiac function in clinical and experimental research. Significant progress in the development of echocardiographic equipment and transducers has led to the successful translation of this methodology from humans to rodents, allowing for the scoring of disease severity and progression, testing of new drugs, and monitoring cardiac function in genetically modified or pharmacologically treated animals. However, as yet, there is no standardization in the procedure to acquire echocardiographic measurements in small animals. This position paper focuses on the appropriate acquisition and analysis of echocardiographic parameters in adult mice and rats, and provides reference values, representative images, and videos for the accurate and reproducible quantification of left ventricular function in healthy and pathological conditions.
Published: 2021

35. Heart failure in COVID-19: the multicentre, multinational PCHF-COVICAV registry

Author: Sokolski, M., Trenson, S., Sokolska, J. M., D'Amario, D., Meyer, P., Poku, N. K., Biering-Sorensen, T., Hojbjerg Lassen, M. C., Skaarup, K. G., Barge-Caballero, E., Pouleur, A. -C., Stolfo, D., Sinagra, G., Ablasser, K., Muster, V., Rainer, P. P., Wallner, M., Chiodini, A., Heiniger, P. S., Mikulicic, F., Schwaiger, J., Winnik, S., Cakmak, H. A., Gaudenzi, M., Mapelli, M., Mattavelli, I., Paul, M., Cabac-Pogorevici, I., Bouleti, C., Lilliu, M., Minoia, C., Dauw, J., Costa, J., Celik, A., Mewton, N., Montenegro, C. E. L., Matsue, Y., Loncar, G., Marchel, M., Bechlioulis, A., Michalis, L., Dorr, M., Prihadi, E., Schoenrath, F., Messroghli, D. R., Mullens, W., Lund, L. H., Rosano, G. M. C., Ponikowski, P., Ruschitzka, F., Flammer, A. J., D'Amario D., Sokolski, M., Trenson, S., Sokolska, J. M., D'Amario, D., Meyer, P., Poku, N. K., Biering-Sorensen, T., Hojbjerg Lassen, M. C., Skaarup, K. G., Barge-Caballero, E., Pouleur, A. -C., Stolfo, D., Sinagra, G., Ablasser, K., Muster, V., Rainer, P. P., Wallner, M., Chiodini, A., Heiniger, P. S., Mikulicic, F., Schwaiger, J., Winnik, S., Cakmak, H. A., Gaudenzi, M., Mapelli, M., Mattavelli, I., Paul, M., Cabac-Pogorevici, I., Bouleti, C., Lilliu, M., Minoia, C., Dauw, J., Costa, J., Celik, A., Mewton, N., Montenegro, C. E. L., Matsue, Y., Loncar, G., Marchel, M., Bechlioulis, A., Michalis, L., Dorr, M., Prihadi, E., Schoenrath, F., Messroghli, D. R., Mullens, W., Lund, L. H., Rosano, G. M. C., Ponikowski, P., Ruschitzka, F., Flammer, A. J., and D'Amario D.
Abstract: Aims: We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. Methods and results: International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62–81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44–2.59], P < 0.001). After adjusting, HF remained associated with in-hospital mortality (OR 1.45 [95% confidence interval: 1.01–2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in-hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24–4.29], P < 0.001). Conclusions: Hospitalized COVID-19 patients with HF are at increased risk for in-hospital death. In-hospital worsening of HF or acute HF de novo are common and associated with a further increase in in-hospital mortality.
Published: 2021

36. Cardiovascular risk management in type 2 diabetes mellitus: a joint position paper of the Italian Cardiology (SIC) and Italian Diabetes (SID) Societies

Author: Avogaro, A, Barillà, F, Cavalot, F, Consoli, A, Federici, M, Mancone, M, Paolillo, S, Pedrinelli, R, Perseghin, G, Filardi, P, Scicali, R, Sinagra, G, Spaccarotella, C, Indolfi, C, Purrello, F, Avogaro, Angelo, Barillà, Francesco, Cavalot, Franco, Consoli, Agostino, Federici, Massimo, Mancone, Massimo, Paolillo, Stefania, Pedrinelli, Roberto, Perseghin, Gianluca, Filardi, Pasquale Perrone, Scicali, Roberto, Sinagra, Gianfranco, Spaccarotella, Carmen, Indolfi, Ciro, Purrello, Francesco, Avogaro, A, Barillà, F, Cavalot, F, Consoli, A, Federici, M, Mancone, M, Paolillo, S, Pedrinelli, R, Perseghin, G, Filardi, P, Scicali, R, Sinagra, G, Spaccarotella, C, Indolfi, C, Purrello, F, Avogaro, Angelo, Barillà, Francesco, Cavalot, Franco, Consoli, Agostino, Federici, Massimo, Mancone, Massimo, Paolillo, Stefania, Pedrinelli, Roberto, Perseghin, Gianluca, Filardi, Pasquale Perrone, Scicali, Roberto, Sinagra, Gianfranco, Spaccarotella, Carmen, Indolfi, Ciro, and Purrello, Francesco
Abstract: Aim: This review represents a joint effort of the Italian Societies of Cardiology (SIC) and Diabetes (SID) to define the state of the art in a field of great clinical and scientific interest which is experiencing a moment of major cultural advancements, the cardiovascular risk management in type 2 diabetes mellitus. Data synthesis: Consists of six chapters that examine various aspects of pathophysiology, diagnosis and therapy which in recent months have seen numerous scientific innovations and several clinical studies that require extensive sharing. Conclusions: The continuous evolution of our knowledge in this field confirms the great cultural vitality of these two cultural spheres, which requires, under the leadership of the scientific Societies, an ever greater and effective collaboration.
Published: 2021

37. Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial

Author: Cardinale, D, Ciceri, F, Latini, R, Franzosi, M, Sandri, M, Civelli, M, Cucchi, G, Menatti, E, Mangiavacchi, M, Cavina, R, Barbieri, E, Gori, S, Colombo, A, Curigliano, G, Salvatici, M, Rizzo, A, Ghisoni, F, Bianchi, A, Falci, C, Aquilina, M, Rocca, A, Monopoli, A, Milandri, C, Rossetti, G, Bregni, M, Malossi, A, Nassiacos, D, Verusio, C, Giordano, M, Staszewsky, L, Barlera, S, Nicolis, E, Magnoli, M, Masson, S, Cipolla, C, Curigliano, Sicuro, M, Rossetti, Maggioni, A, Labianca, R, Tettamanti, M, Senni, M, Finzi, A, Grosso, F, Vago, T, Gramenzi, S, Balconi, G, Bernasconi, R, Buratti, M, Ojeda-Fernandez, M, Vasami, A, Thiebat, B, Bare, C, Corzani, A, Coccolo, F, Colecchia, S, Pellegrini, C, Appio, L, Caico, I, Mesenzani, O, Campana, C, Gilardoni, M, Scognamiglio, G, Corrado, G, Battagin, D, De Rosa, F, Carpino, C, Palazzo, S, Giannessi, P, Zipoli, G, Pastori, P, Callegari, S, Sesenna, C, Fodor, C, Guiducci, D, Mazza, R, Turazza, F, Vallerio, P, Marbello, L, Sala, E, Fragasso, G, Trinca, S, Farolfi, A, Andreis, D, Lanzoni, L, Marchetti, F, Mioranza, E, Banzato, A, Re, F, Gaibazzi, N, Gullo, M, Turina, M, Gervasi, E, Giaroli, F, Barco, B, Bertolini, A, Sinagra, G, Aleksova, A, Guglielmi, A, Pinotti, G, Gueli, R, Mongiardi, C, Vallini, I, Cardinale D., Ciceri F., Latini R., Franzosi M. G., Sandri M. T., Civelli M., Cucchi G., Menatti E., Mangiavacchi M., Cavina R., Barbieri E., Gori S., Colombo A., Curigliano G., Salvatici M., Rizzo A., Ghisoni F., Bianchi A., Falci C., Aquilina M., Rocca A., Monopoli A., Milandri C., Rossetti G., Bregni M., Malossi A., Nassiacos D., Verusio C., Giordano M., Staszewsky L., Barlera S., Nicolis E. B., Magnoli M., Masson S., Cipolla C. M., Sicuro M., Maggioni A. P., Labianca R., Tettamanti M., Senni M., Finzi A., Grosso F., Vago T., Gramenzi S., Balconi G., Bernasconi R., Nicolis E., Buratti M. G., Ojeda-Fernandez M. L., Vasami A., Thiebat B., Bare C., Corzani A., Coccolo F., Colecchia S., Pellegrini C., Appio L., Caico I., Mesenzani O., Campana C., Gilardoni M., Scognamiglio G., Corrado G., Battagin D., De Rosa F., Carpino C., Palazzo S., Giannessi P. G., Zipoli G., Pastori P., Callegari S., Sesenna C., Fodor C., Guiducci D., Mazza R., Turazza F. M., Vallerio P., Marbello L., Sala E., Fragasso G., Trinca S., Farolfi A., Andreis D., Lanzoni L., Marchetti F., Mioranza E., Banzato A., Re F., Gaibazzi N., Gullo M., Turina M. C., Gervasi E., Giaroli F., Barco B., Bertolini A., Sinagra G., Aleksova A., Guglielmi A., Pinotti G., Gueli R., Mongiardi C., Vallini I., Cardinale, D, Ciceri, F, Latini, R, Franzosi, M, Sandri, M, Civelli, M, Cucchi, G, Menatti, E, Mangiavacchi, M, Cavina, R, Barbieri, E, Gori, S, Colombo, A, Curigliano, G, Salvatici, M, Rizzo, A, Ghisoni, F, Bianchi, A, Falci, C, Aquilina, M, Rocca, A, Monopoli, A, Milandri, C, Rossetti, G, Bregni, M, Malossi, A, Nassiacos, D, Verusio, C, Giordano, M, Staszewsky, L, Barlera, S, Nicolis, E, Magnoli, M, Masson, S, Cipolla, C, Curigliano, Sicuro, M, Rossetti, Maggioni, A, Labianca, R, Tettamanti, M, Senni, M, Finzi, A, Grosso, F, Vago, T, Gramenzi, S, Balconi, G, Bernasconi, R, Buratti, M, Ojeda-Fernandez, M, Vasami, A, Thiebat, B, Bare, C, Corzani, A, Coccolo, F, Colecchia, S, Pellegrini, C, Appio, L, Caico, I, Mesenzani, O, Campana, C, Gilardoni, M, Scognamiglio, G, Corrado, G, Battagin, D, De Rosa, F, Carpino, C, Palazzo, S, Giannessi, P, Zipoli, G, Pastori, P, Callegari, S, Sesenna, C, Fodor, C, Guiducci, D, Mazza, R, Turazza, F, Vallerio, P, Marbello, L, Sala, E, Fragasso, G, Trinca, S, Farolfi, A, Andreis, D, Lanzoni, L, Marchetti, F, Mioranza, E, Banzato, A, Re, F, Gaibazzi, N, Gullo, M, Turina, M, Gervasi, E, Giaroli, F, Barco, B, Bertolini, A, Sinagra, G, Aleksova, A, Guglielmi, A, Pinotti, G, Gueli, R, Mongiardi, C, Vallini, I, Cardinale D., Ciceri F., Latini R., Franzosi M. G., Sandri M. T., Civelli M., Cucchi G., Menatti E., Mangiavacchi M., Cavina R., Barbieri E., Gori S., Colombo A., Curigliano G., Salvatici M., Rizzo A., Ghisoni F., Bianchi A., Falci C., Aquilina M., Rocca A., Monopoli A., Milandri C., Rossetti G., Bregni M., Malossi A., Nassiacos D., Verusio C., Giordano M., Staszewsky L., Barlera S., Nicolis E. B., Magnoli M., Masson S., Cipolla C. M., Sicuro M., Maggioni A. P., Labianca R., Tettamanti M., Senni M., Finzi A., Grosso F., Vago T., Gramenzi S., Balconi G., Bernasconi R., Nicolis E., Buratti M. G., Ojeda-Fernandez M. L., Vasami A., Thiebat B., Bare C., Corzani A., Coccolo F., Colecchia S., Pellegrini C., Appio L., Caico I., Mesenzani O., Campana C., Gilardoni M., Scognamiglio G., Corrado G., Battagin D., De Rosa F., Carpino C., Palazzo S., Giannessi P. G., Zipoli G., Pastori P., Callegari S., Sesenna C., Fodor C., Guiducci D., Mazza R., Turazza F. M., Vallerio P., Marbello L., Sala E., Fragasso G., Trinca S., Farolfi A., Andreis D., Lanzoni L., Marchetti F., Mioranza E., Banzato A., Re F., Gaibazzi N., Gullo M., Turina M. C., Gervasi E., Giaroli F., Barco B., Bertolini A., Sinagra G., Aleksova A., Guglielmi A., Pinotti G., Gueli R., Mongiardi C., and Vallini I.
Abstract: Background: Troponin changes over time have been suggested to allow for an early diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with troponin elevation may benefit of therapy with enalapril. It is unknown whether a preventive treatment with enalapril may further increase the benefit. Methods: The International CardioOncology Society-one trial (ICOS-ONE) was a controlled, open-label trial conducted in 21 Italian hospitals. Patients were randomly assigned to two strategies: enalapril in all patients started before chemotherapy (CT; ‘prevention’ arm), and enalapril started only in patients with an increase in troponin during or after CT (‘troponin-triggered’ arm). Troponin was assayed locally in 2596 blood samples, before and after each anthracycline-containing CT cycle and at each study visit; electrocardiogram and echocardiogram were done at baseline, and at 1, 3, 6 and 12-month follow-up. Primary outcome was the incidence of troponin elevation above the threshold. Findings: Of the 273 patients, 88% were women, mean age 51 ± 12 years. The majority (76%) had breast cancer, 3% had a history of hypertension and 4% were diabetic. Epirubicin and doxorubicin were most commonly prescribed, with median cumulative doses of 360 [270–360] and 240 [240–240] mg/m2, respectively. The incidence of troponin elevation was 23% in the prevention and 26% in the troponin-triggered group (p = 0.50). Three patients (1.1%) -two in the prevention, one in the troponin-triggered group-developed cardiotoxicity, defined as 10% point reduction of LV ejection fraction, with values lower than 50%. Interpretation: Low cumulative doses of anthracyclines in adult patients with low cardiovascular risk can raise troponins, without differences between the two strategies of giving enalapril. Considering a benefit of enalapril in the prevention of LV dysfunction, a troponin-triggered strategy may be more convenient.
Published: 2018

38. Prevalence and prognostic impact of non-cardiac co-morbidities in heart failure outpatients with preserved and reduced ejection fraction: a community-based study

Author: Iorio, A, Senni, M, Barbati, G, Greene, S, Poli, S, Zambon, E, Di Nora, C, Cioffi, G, Tarantini, L, Gavazzi, A, Sinagra, G, Di Lenarda, A, Iorio A, Senni M, Barbati G, Greene SJ, Poli S, Zambon E, Di Nora C, Cioffi G, Tarantini L, Gavazzi A, Sinagra G, Di Lenarda A, Iorio, A, Senni, M, Barbati, G, Greene, S, Poli, S, Zambon, E, Di Nora, C, Cioffi, G, Tarantini, L, Gavazzi, A, Sinagra, G, Di Lenarda, A, Iorio A, Senni M, Barbati G, Greene SJ, Poli S, Zambon E, Di Nora C, Cioffi G, Tarantini L, Gavazzi A, Sinagra G, and Di Lenarda A
Abstract: Aim: To assess adverse outcomes attributable to non-cardiac co-morbidities and to compare their effects by left ventricular ejection fraction (LVEF) group [LVEF <50% (heart failure with reduced ejection fraction, HFrEF), LVEF ≥50% (heart failure with preserved ejection fraction, HFpEF)] in a contemporary, unselected chronic heart failure population. Methods and results: This community-based cohort enrolled patients from October 2009 to December 2013. Adjusted hazard ratio (HR) and the population attributable fraction (PAF) were used to compare the contribution of 15 non-cardiac co-morbidities to adverse outcome. Overall, 2314 patients (mean age 77 ±10 years, 57% men) were recruited [n = 941 (41%) HFrEF, n = 1373 (59%) HFpEF]. Non-cardiac co-morbidity rates were similarly high, except for obesity and hypertension which were more prevalent in HFpEF. At a median follow-up of 31 (interquartile range 16–41) months, 472 (20%) patients died. Adjusted mortality rates were not significantly different between the HFrEF and HFpEF groups. After adjustment, an increasing number of non-cardiac co-morbidities was associated with a higher risk for all-cause mortality [HR 1.25; 95% confidence interval (CI) 1.10–1.26; P < 0.001], all-cause hospitalization (HR 1.17; 95% CI 1.12–1.23; P < 0.001), heart failure hospitalization (HR 1.28; 95% CI 1.19–1.38; P < 0.001), non-cardiovascular hospitalization (HR 1.16; 95% CI 1.11–1.22; P < 0.001). The co-morbidities contributing to high PAF were: anaemia, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus, and peripheral artery disease. These findings were similar for HFrEF and HFpEF. Interaction analysis yielded similar results. Conclusions: In a contemporary community population with chronic heart failure, non-cardiac co-morbidities confer a similar contribution to outcomes in HFrEF and HFpEF. These observations suggest that quality improvement initiatives aimed at optimizing co-morbidities may be
Published: 2018

39. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, I. (Ioanna), Weng, L.-C., Cartwright, J.H. (James H.), Hall, A.W. (Amelia Weber), Sveinbjornsson, G. (Gardar), Tucker, N.R. (Nathan R.), Choi, S.H. (Seung Hoan), Chaffin, M.D. (Mark D.), Roselli, C. (Carolina), Barnes, M.J. (Michael), Mifsud, B. (Borbala), Warren, H.R. (Helen R.), Hayward, C. (Caroline), Marten, J. (Jonathan), Cranley, J.J. (James J.), Concas, M.P. (Maria Pina), Gasparini, P. (Paolo), Boutin, T. (Thibaud), Kolcic, I. (Ivana), Polasek, O. (Ozren), Rudan, I. (Igor), Araujo, N.M. (Nathalia M.), Lima-Costa, M.F. (Maria Fernanda), Ribeiro, A.L. (Antonio), Souza, R.P. (Renan P.), Tarazona-Santos, E. (Eduardo), Giedraitis, V. (Vilmantas), Ingelsson, E. (Erik), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Del Greco M, F. (Fabiola), Foco, L. (Luisa), Gögele, M. (Martin), Hicks, A.A. (Andrew A.), Cook, J.P. (James P.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Sundström, J. (Johan), Nelson, C.P. (Christopher P.), Riaz, M.B. (Muhammad B.), Samani, N.J. (Nilesh), Sinagra, G. (Gianfranco), Ulivi, S. (Shelia), Kähönen, M. (Mika), Mishra, P.P. (Pashupati P.), Mononen, N. (Nina), Nikus, K. (Kjell), Caulfield, M. (Mark), Dominiczak, A. (Anna), Padmanabhan, S. (Sandosh), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Ryan, K. (Kathleen), Shuldiner, A.R. (Alan R.), Aeschbacher, S. (Stefanie), Conen, D. (David), Risch, L. (Lorenz), Thériault, S. (Sébastien), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Lyytikäinen, L.-P. (Leo-Pekka), Raitakari, O. (Olli), Barnes, C.L.K. (Catriona L. K.), Campbell, H. (Harry), Joshi, P.K. (Peter), Wilson, J.F. (James), Isaacs, A.J. (Aaron), Kors, J.A. (Jan), Duijn, C.M. (Cornelia) van, Huang, P.L. (Paul L.), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara B.), Launer, L.J. (Lenore), Smith, A.V. (Albert), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Nadkarni, G. (Girish), Preuss, M. (Michael), Correa, D.D., Mei, H. (Hao), Meitinger, T. (Thomas), Müller-Nurasyid, M. (Martina), Peters, A. (Annette), Waldenberger, M. (Melanie), Mangino, M. (Massimo), Spector, T.D. (Timothy), Rienstra, S.A., van de Vegte, Y.J. (Yordi J.), Harst, P. (Pim) van der, Verweij, N. (Niek), Kääb, S. (Stefan), Schramm, K. (Katharina), Sinner, M.F. (Moritz), Strauch, K. (Konstantin), Cutler, M.J. (Michael J.), Fatkin, D. (Diane), London, B. (Barry), Olesen, M.S. (Morten S.), Roden, D.M. (Dan M.), Benjamin Shoemaker, M. (M.), Gustav Smith, J. (J.), Biggs, M.L. (M.), Bis, J.C. (Joshua), Brody, J.A. (Jennifer A.), Psaty, B.M. (Bruce), Rice, K.M. (Kenneth), Sotoodehnia, N. (Nona), Grandi, A. (Alessandro) de, Fuchsberger, C. (Christian), Penninx, B.W.J.H., Pramstaller, P.P. (Peter Paul), Ford, I. (Ian), Jukema, J.W. (Jan Wouter), Macfarlane, P.W. (Peter W.), Trompet, S. (Stella), Dörr, M. (Marcus), Felix, S.B. (Stephan B.), Völker, U. (Uwe), Weiss, S. (Stefan), Havulinna, A.S. (Aki), Jula, A. (Antti), Sääksjärvi, K. (K.), Salomaa, V. (Veikko), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Lin, H.J. (Henry J.), Rotter, J.I. (Jerome I.), Taylor, K.D. (Kent), Yao, J. (Jie), Mutsert, R. (Reneé) de, Maan, A.C. (Arie C.), Mook-Kanamori, D.O. (Dennis O.), Noordam, R. (Raymond), Cucca, F. (Francesco), Ding, J. (Jun), Lakatta, E. (Edward), Qian, Y. (Yong), Tarasov, K.V. (Kirill V.), Levy, D. (Daniel), Lin, H. (Honghuang), Newton-Cheh, C. (Christopher), Lunetta, K.L. (Kathryn), Murray, A.D. (Alison D.), Porteous, D.J. (David J.), Smith, B.H. (Blair), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Berg, M.E. (Marten) van den, Haessler, J. (Jeff), Jackson, R.D. (Rebecca), Kooperberg, C. (Charles), Peters, U. (Ulrike), Reiner, A.P. (Alexander P.), Whitsel, E.A. (Eric), Alonso, A. (Alvaro), Arking, D.E. (Dan E.), Boerwinkle, E.A. (Eric), Ehret, G.B. (Georg B.), Soliman, E.Z. (Elsayed Z.), Avery, C.L., Gogarten, S.M., Kerr, K.F. (Kathleen), Laurie, C.C. (Cathy C.), Seyerle, A.A. (Amanda A.), Stilp, A. (Adrienne), Assa, S. (Solmaz), Abdullah Said, M. (M.), Yldau van der Ende, M. (M.), Lambiase, P.D. (Pier), Orini, M. (Michele), Ramirez, J. (Julia), Van Duijvenboden, S. (Stefan), Arnar, D.O. (David O.), Gudbjartsson, D.F. (Daniel), Holm, H. (Hilma), Sulem, P. (Patrick), Thorleifsson, G. (Gudmar), Thorolfsdottir, R.B. (Rosa B.), Thorsteinsdottir, U. (Unnur), Benjamin, E.J. (Emelia J.), Tinker, A. (Andrew), Zwart, J-A. (John-Anker), Ellinor, P.T. (Patrick), Jamshidi, Y. (Yalda), Lubitz, S.A. (Steven), Munroe, P. (Patricia), Ntalla, I. (Ioanna), Weng, L.-C., Cartwright, J.H. (James H.), Hall, A.W. (Amelia Weber), Sveinbjornsson, G. (Gardar), Tucker, N.R. (Nathan R.), Choi, S.H. (Seung Hoan), Chaffin, M.D. (Mark D.), Roselli, C. (Carolina), Barnes, M.J. (Michael), Mifsud, B. (Borbala), Warren, H.R. (Helen R.), Hayward, C. (Caroline), Marten, J. (Jonathan), Cranley, J.J. (James J.), Concas, M.P. (Maria Pina), Gasparini, P. (Paolo), Boutin, T. (Thibaud), Kolcic, I. (Ivana), Polasek, O. (Ozren), Rudan, I. (Igor), Araujo, N.M. (Nathalia M.), Lima-Costa, M.F. (Maria Fernanda), Ribeiro, A.L. (Antonio), Souza, R.P. (Renan P.), Tarazona-Santos, E. (Eduardo), Giedraitis, V. (Vilmantas), Ingelsson, E. (Erik), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Del Greco M, F. (Fabiola), Foco, L. (Luisa), Gögele, M. (Martin), Hicks, A.A. (Andrew A.), Cook, J.P. (James P.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Sundström, J. (Johan), Nelson, C.P. (Christopher P.), Riaz, M.B. (Muhammad B.), Samani, N.J. (Nilesh), Sinagra, G. (Gianfranco), Ulivi, S. (Shelia), Kähönen, M. (Mika), Mishra, P.P. (Pashupati P.), Mononen, N. (Nina), Nikus, K. (Kjell), Caulfield, M. (Mark), Dominiczak, A. (Anna), Padmanabhan, S. (Sandosh), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Ryan, K. (Kathleen), Shuldiner, A.R. (Alan R.), Aeschbacher, S. (Stefanie), Conen, D. (David), Risch, L. (Lorenz), Thériault, S. (Sébastien), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Lyytikäinen, L.-P. (Leo-Pekka), Raitakari, O. (Olli), Barnes, C.L.K. (Catriona L. K.), Campbell, H. (Harry), Joshi, P.K. (Peter), Wilson, J.F. (James), Isaacs, A.J. (Aaron), Kors, J.A. (Jan), Duijn, C.M. (Cornelia) van, Huang, P.L. (Paul L.), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara B.), Launer, L.J. (Lenore), Smith, A.V. (Albert), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Nadkarni, G. (Girish), Preuss, M. (Michael), Correa, D.D., Mei, H. (Hao), Meitinger, T. (Thomas), Müller-Nurasyid, M. (Martina), Peters, A. (Annette), Waldenberger, M. (Melanie), Mangino, M. (Massimo), Spector, T.D. (Timothy), Rienstra, S.A., van de Vegte, Y.J. (Yordi J.), Harst, P. (Pim) van der, Verweij, N. (Niek), Kääb, S. (Stefan), Schramm, K. (Katharina), Sinner, M.F. (Moritz), Strauch, K. (Konstantin), Cutler, M.J. (Michael J.), Fatkin, D. (Diane), London, B. (Barry), Olesen, M.S. (Morten S.), Roden, D.M. (Dan M.), Benjamin Shoemaker, M. (M.), Gustav Smith, J. (J.), Biggs, M.L. (M.), Bis, J.C. (Joshua), Brody, J.A. (Jennifer A.), Psaty, B.M. (Bruce), Rice, K.M. (Kenneth), Sotoodehnia, N. (Nona), Grandi, A. (Alessandro) de, Fuchsberger, C. (Christian), Penninx, B.W.J.H., Pramstaller, P.P. (Peter Paul), Ford, I. (Ian), Jukema, J.W. (Jan Wouter), Macfarlane, P.W. (Peter W.), Trompet, S. (Stella), Dörr, M. (Marcus), Felix, S.B. (Stephan B.), Völker, U. (Uwe), Weiss, S. (Stefan), Havulinna, A.S. (Aki), Jula, A. (Antti), Sääksjärvi, K. (K.), Salomaa, V. (Veikko), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Lin, H.J. (Henry J.), Rotter, J.I. (Jerome I.), Taylor, K.D. (Kent), Yao, J. (Jie), Mutsert, R. (Reneé) de, Maan, A.C. (Arie C.), Mook-Kanamori, D.O. (Dennis O.), Noordam, R. (Raymond), Cucca, F. (Francesco), Ding, J. (Jun), Lakatta, E. (Edward), Qian, Y. (Yong), Tarasov, K.V. (Kirill V.), Levy, D. (Daniel), Lin, H. (Honghuang), Newton-Cheh, C. (Christopher), Lunetta, K.L. (Kathryn), Murray, A.D. (Alison D.), Porteous, D.J. (David J.), Smith, B.H. (Blair), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Berg, M.E. (Marten) van den, Haessler, J. (Jeff), Jackson, R.D. (Rebecca), Kooperberg, C. (Charles), Peters, U. (Ulrike), Reiner, A.P. (Alexander P.), Whitsel, E.A. (Eric), Alonso, A. (Alvaro), Arking, D.E. (Dan E.), Boerwinkle, E.A. (Eric), Ehret, G.B. (Georg B.), Soliman, E.Z. (Elsayed Z.), Avery, C.L., Gogarten, S.M., Kerr, K.F. (Kathleen), Laurie, C.C. (Cathy C.), Seyerle, A.A. (Amanda A.), Stilp, A. (Adrienne), Assa, S. (Solmaz), Abdullah Said, M. (M.), Yldau van der Ende, M. (M.), Lambiase, P.D. (Pier), Orini, M. (Michele), Ramirez, J. (Julia), Van Duijvenboden, S. (Stefan), Arnar, D.O. (David O.), Gudbjartsson, D.F. (Daniel), Holm, H. (Hilma), Sulem, P. (Patrick), Thorleifsson, G. (Gudmar), Thorolfsdottir, R.B. (Rosa B.), Thorsteinsdottir, U. (Unnur), Benjamin, E.J. (Emelia J.), Tinker, A. (Andrew), Zwart, J-A. (John-Anker), Ellinor, P.T. (Patrick), Jamshidi, Y. (Yalda), Lubitz, S.A. (Steven), and Munroe, P. (Patricia)
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduc
Published: 2020
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40. Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era

Author: De Rosa, Miriam Stefania, Spaccarotella, C., Basso, C., Calabro, M. P., Curcio, A., Filardi, P. P., Mancone, M., Mercuro, G., Muscoli, S., Nodari, S., Pedrinelli, R., Sinagra, G., Indolfi, C., Angelini, F., Barilla, F., Bartorelli, A., Benedetto, F., Bernabo, P., Bolognese, L., Briani, M., Cacciavillani, L., Calabrese, Anna Chiara, Calabro, P., Caliendo, L., Calo, L., Casella, Gioietta, Casu, G., Cavallini, C., Ciampi, Q., Ciccone, M., Comito, M., Corrada, E., Crea, Filippo, D'Andrea, A., D'Urbano, M., De Caterina, R., De Ferrari, G., De Ponti, R., Della Mattia, A., Di Mario, Clara, Donnazzan, L., Esposito, Gianfranco, Fedele, F., Ferraro, A., Galasso, G., Galie, N., Gnecchi, M., Golino, P., Golia, B., Guarini, P., Leonardi, S., Locuratolo, N., Luzza, F., Manganiello, V., Francesca Marchetti, M., Marenzi, Giancarlo, Margonato, A., Meloni, L., Metra, M., Milo, Anna Maria, Mongiardo, A., Monzo, L., Morisco, C., Novo, G., Pancaldi, S., Parollo, M., Paterno, G., Patti, G., Priori, S., Ravera, A., Giuseppe Rebuzzi, A., Rossi, M., Scherillo, M., Semprini, F., Senni, M., Sibilio, G., Siviglia, M., Tamburino, C., Tortorici, G., Versace, F., Villari, B., Volpe, M., De Rosa S. (ORCID:0000-0002-8869-155X), Calabrese A., Casella G., Crea F. (ORCID:0000-0001-9404-8846), DI Mario C., Esposito G., Marenzi G., Milo M., De Rosa, Miriam Stefania, Spaccarotella, C., Basso, C., Calabro, M. P., Curcio, A., Filardi, P. P., Mancone, M., Mercuro, G., Muscoli, S., Nodari, S., Pedrinelli, R., Sinagra, G., Indolfi, C., Angelini, F., Barilla, F., Bartorelli, A., Benedetto, F., Bernabo, P., Bolognese, L., Briani, M., Cacciavillani, L., Calabrese, Anna Chiara, Calabro, P., Caliendo, L., Calo, L., Casella, Gioietta, Casu, G., Cavallini, C., Ciampi, Q., Ciccone, M., Comito, M., Corrada, E., Crea, Filippo, D'Andrea, A., D'Urbano, M., De Caterina, R., De Ferrari, G., De Ponti, R., Della Mattia, A., Di Mario, Clara, Donnazzan, L., Esposito, Gianfranco, Fedele, F., Ferraro, A., Galasso, G., Galie, N., Gnecchi, M., Golino, P., Golia, B., Guarini, P., Leonardi, S., Locuratolo, N., Luzza, F., Manganiello, V., Francesca Marchetti, M., Marenzi, Giancarlo, Margonato, A., Meloni, L., Metra, M., Milo, Anna Maria, Mongiardo, A., Monzo, L., Morisco, C., Novo, G., Pancaldi, S., Parollo, M., Paterno, G., Patti, G., Priori, S., Ravera, A., Giuseppe Rebuzzi, A., Rossi, M., Scherillo, M., Semprini, F., Senni, M., Sibilio, G., Siviglia, M., Tamburino, C., Tortorici, G., Versace, F., Villari, B., Volpe, M., De Rosa S. (ORCID:0000-0002-8869-155X), Calabrese A., Casella G., Crea F. (ORCID:0000-0001-9404-8846), DI Mario C., Esposito G., Marenzi G., and Milo M.
Abstract: Aims: To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results: We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7-32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3-70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7-6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1-2.8; P = 0.009). Conclusion: Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.
Published: 2020

41. Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies, myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC)

Author: Pelliccia, A., Solberg, E.E., Papadakis, M., Adami, P.E., Biffi, A., Caselli, S., Gerche, A. La, Niebauer, J., Pressler, A., Schmied, C.M., Serratosa, L., Halle, M., Buuren, F. van, Borjesson, M., Carre, F., Panhuyzen-Goedkoop, N.M., Heidbuchel, H., Olivotto, I., Corrado, D., Sinagra, G., Sharma, S, Pelliccia, A., Solberg, E.E., Papadakis, M., Adami, P.E., Biffi, A., Caselli, S., Gerche, A. La, Niebauer, J., Pressler, A., Schmied, C.M., Serratosa, L., Halle, M., Buuren, F. van, Borjesson, M., Carre, F., Panhuyzen-Goedkoop, N.M., Heidbuchel, H., Olivotto, I., Corrado, D., Sinagra, G., and Sharma, S
Abstract: Contains fulltext : 209356.pdf (publisher's version ) (Closed access), Myocardial diseases are associated with an increased risk of potentially fatal cardiac arrhythmias and sudden cardiac death/cardiac arrest during exercise, including hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular non-compaction, arrhythmogenic cardiomyopathy, and myo-pericarditis. Practicing cardiologists and sport physicians are required to identify high-risk individuals harbouring these cardiac diseases in a timely fashion in the setting of preparticipation screening or medical consultation and provide appropriate advice regarding the participation in competitive sport activities and/or regular exercise programmes. Many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to participate in leisure-time and amateur sport activities to take advantage of the multiple benefits of a physically active lifestyle. In 2005, The European Society of Cardiology (ESC) published recommendations for participation in competitive sport in athletes with cardiomyopathies and myo-pericarditis. One decade on, these recommendations are partly obsolete given the evolving knowledge of the diagnosis, management and treatment of cardiomyopathies and myo-pericarditis. The present document, therefore, aims to offer a comprehensive overview of the most updated recommendations for practicing cardiologists and sport physicians managing athletes with cardiomyopathies and myo-pericarditis and provides pragmatic advice for safe participation in competitive sport at professional and amateur level, as well as in a variety of recreational physical activities.
Published: 2019

42. Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies, myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC)

Author: Pelliccia, A., Solberg, E.E., Papadakis, M., Adami, P.E., Biffi, A., Caselli, S., Gerche, A. La, Niebauer, J., Pressler, A., Schmied, C.M., Serratosa, L., Halle, M., Buuren, F. van, Borjesson, M., Carre, F., Panhuyzen-Goedkoop, N.M., Heidbuchel, H., Olivotto, I., Corrado, D., Sinagra, G., Sharma, S, Pelliccia, A., Solberg, E.E., Papadakis, M., Adami, P.E., Biffi, A., Caselli, S., Gerche, A. La, Niebauer, J., Pressler, A., Schmied, C.M., Serratosa, L., Halle, M., Buuren, F. van, Borjesson, M., Carre, F., Panhuyzen-Goedkoop, N.M., Heidbuchel, H., Olivotto, I., Corrado, D., Sinagra, G., and Sharma, S
Abstract: Contains fulltext : 209356.pdf (publisher's version ) (Closed access), Myocardial diseases are associated with an increased risk of potentially fatal cardiac arrhythmias and sudden cardiac death/cardiac arrest during exercise, including hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular non-compaction, arrhythmogenic cardiomyopathy, and myo-pericarditis. Practicing cardiologists and sport physicians are required to identify high-risk individuals harbouring these cardiac diseases in a timely fashion in the setting of preparticipation screening or medical consultation and provide appropriate advice regarding the participation in competitive sport activities and/or regular exercise programmes. Many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to participate in leisure-time and amateur sport activities to take advantage of the multiple benefits of a physically active lifestyle. In 2005, The European Society of Cardiology (ESC) published recommendations for participation in competitive sport in athletes with cardiomyopathies and myo-pericarditis. One decade on, these recommendations are partly obsolete given the evolving knowledge of the diagnosis, management and treatment of cardiomyopathies and myo-pericarditis. The present document, therefore, aims to offer a comprehensive overview of the most updated recommendations for practicing cardiologists and sport physicians managing athletes with cardiomyopathies and myo-pericarditis and provides pragmatic advice for safe participation in competitive sport at professional and amateur level, as well as in a variety of recreational physical activities.
Published: 2019

43. Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies, myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC)

Author: Pelliccia, A., Solberg, E.E., Papadakis, M., Adami, P.E., Biffi, A., Caselli, S., Gerche, A. La, Niebauer, J., Pressler, A., Schmied, C.M., Serratosa, L., Halle, M., Buuren, F. van, Borjesson, M., Carre, F., Panhuyzen-Goedkoop, N.M., Heidbuchel, H., Olivotto, I., Corrado, D., Sinagra, G., Sharma, S, Pelliccia, A., Solberg, E.E., Papadakis, M., Adami, P.E., Biffi, A., Caselli, S., Gerche, A. La, Niebauer, J., Pressler, A., Schmied, C.M., Serratosa, L., Halle, M., Buuren, F. van, Borjesson, M., Carre, F., Panhuyzen-Goedkoop, N.M., Heidbuchel, H., Olivotto, I., Corrado, D., Sinagra, G., and Sharma, S
Abstract: Contains fulltext : 209356.pdf (publisher's version ) (Closed access), Myocardial diseases are associated with an increased risk of potentially fatal cardiac arrhythmias and sudden cardiac death/cardiac arrest during exercise, including hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular non-compaction, arrhythmogenic cardiomyopathy, and myo-pericarditis. Practicing cardiologists and sport physicians are required to identify high-risk individuals harbouring these cardiac diseases in a timely fashion in the setting of preparticipation screening or medical consultation and provide appropriate advice regarding the participation in competitive sport activities and/or regular exercise programmes. Many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to participate in leisure-time and amateur sport activities to take advantage of the multiple benefits of a physically active lifestyle. In 2005, The European Society of Cardiology (ESC) published recommendations for participation in competitive sport in athletes with cardiomyopathies and myo-pericarditis. One decade on, these recommendations are partly obsolete given the evolving knowledge of the diagnosis, management and treatment of cardiomyopathies and myo-pericarditis. The present document, therefore, aims to offer a comprehensive overview of the most updated recommendations for practicing cardiologists and sport physicians managing athletes with cardiomyopathies and myo-pericarditis and provides pragmatic advice for safe participation in competitive sport at professional and amateur level, as well as in a variety of recreational physical activities.
Published: 2019

44. Heart failure prognosis over time: how the prognostic role of oxygen consumption and ventilatory efficiency during exercise has changed in the last 20 years

Author: Paolillo, S, Veglia, F, Salvioni, E, Corrà, U, Piepoli, M, Lagioia, R, Limongelli, G, Sinagra, G, Cattadori, G, Scardovi, A, Metra, M, Senni, M, Bonomi, A, Scrutinio, D, Raimondo, R, Emdin, M, Magrì, D, Parati, G, Re, F, Cicoira, M, Minà, C, Correale, M, Frigerio, M, Bussotti, M, Battaia, E, Guazzi, M, Badagliacca, R, Di Lenarda, A, Maggioni, A, Passino, C, Sciomer, S, Pacileo, G, Mapelli, M, Vignati, C, Clemenza, F, Binno, S, Lombardi, C, Perrone Filardi, P, Agostoni, P, Apostolo, A, Palermo, P, Contini, M, Farina, S, Mantegazza, V, Spadafora, E, Lattarulo, M, Giordano, A, Mezzani, A, Ricci, R, Ferraironi, A, Carubelli, V, Pietrucci, F, Malfatto, G, Caravita, S, Vigano', E, Valente, F, Vastarella, R, Gravino, R, Roselli, T, Buono, A, De Maria, R, Passantino, A, Santoro, D, Campanale, S, Caputo, D, Bertipaglia, D, Confalonieri, M, Gentile, P, Zambon, E, Morosin, M, Carriere, C, Ferraretti, A, Marchese, G, Iorio, A, Pastormerlo, L, Gargiulo, P, Villani, G, Oliva, F, Perna, E, Scardovi, AB, Lattarulo, MS, VIGANO', ELENA, Villani, GQ, Paolillo, S, Veglia, F, Salvioni, E, Corrà, U, Piepoli, M, Lagioia, R, Limongelli, G, Sinagra, G, Cattadori, G, Scardovi, A, Metra, M, Senni, M, Bonomi, A, Scrutinio, D, Raimondo, R, Emdin, M, Magrì, D, Parati, G, Re, F, Cicoira, M, Minà, C, Correale, M, Frigerio, M, Bussotti, M, Battaia, E, Guazzi, M, Badagliacca, R, Di Lenarda, A, Maggioni, A, Passino, C, Sciomer, S, Pacileo, G, Mapelli, M, Vignati, C, Clemenza, F, Binno, S, Lombardi, C, Perrone Filardi, P, Agostoni, P, Apostolo, A, Palermo, P, Contini, M, Farina, S, Mantegazza, V, Spadafora, E, Lattarulo, M, Giordano, A, Mezzani, A, Ricci, R, Ferraironi, A, Carubelli, V, Pietrucci, F, Malfatto, G, Caravita, S, Vigano', E, Valente, F, Vastarella, R, Gravino, R, Roselli, T, Buono, A, De Maria, R, Passantino, A, Santoro, D, Campanale, S, Caputo, D, Bertipaglia, D, Confalonieri, M, Gentile, P, Zambon, E, Morosin, M, Carriere, C, Ferraretti, A, Marchese, G, Iorio, A, Pastormerlo, L, Gargiulo, P, Villani, G, Oliva, F, Perna, E, Scardovi, AB, Lattarulo, MS, VIGANO', ELENA, and Villani, GQ
Abstract: Aims: Exercise-derived parameters, specifically peak exercise oxygen uptake (peak VO 2 ) and minute ventilation/carbon dioxide relationship slope (VE/VCO 2 slope), have a pivotal prognostic value in heart failure (HF). It is unknown how the prognostic threshold of peak VO 2 and VE/VCO 2 slope has changed over the last 20 years in parallel with HF prognosis improvement. Methods and results: Data from 6083 HF patients (81% male, age 61 ± 13 years), enrolled in the MECKI score database between 1993 and 2015, were retrospectively analysed. By enrolment year, four groups were generated: group 1 1993–2000 (n = 440), group 2 2001–2005 (n = 1288), group 3 2006–2010 (n = 2368), and group 4 2011–2015 (n = 1987). We compared the 10-year survival of groups and analysed how the overall risk (cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation) changed over time according to peak VO 2 and VE/VCO 2 slope and to major clinical and therapeutic variables. At 10 years, a progressively higher survival from group 1 to group 3 was observed, with no further improvement afterwards. A 20% risk for peak VO 2 15 mL/min/kg (95% confidence interval 16–13), 9 (11–8), 4 (4–2) and 5 (7–4) was observed in group 1, 2, 3, and 4, respectively, while the VE/VCO 2 slope value for a 20% risk was 32 (37–29), 47 (51–43), 59 (64–55), and 57 (63–52), respectively. Conclusions: Heart failure prognosis improved over time up to 2010 in a HF population followed by experienced centres. The peak VO 2 and VE/VCO 2 slope cut-offs identifying a definite risk progressively decreased and increased over time, respectively. The prognostic threshold of peak VO 2 and VE/VCO 2 slope must be updated whenever HF prognosis improves.
Published: 2019

45. HF progression among outpatients with HF in a community setting

Author: Iorio, A, Rea, F, Barbati, G, Scagnetto, A, Peruzzi, E, Garavaglia, A, Corrao, G, Sinagra, G, Di Lenarda, A, Iorio, A, Rea, F, Barbati, G, Scagnetto, A, Peruzzi, E, Garavaglia, A, Corrao, G, Sinagra, G, and Di Lenarda, A
Abstract: Background: Incidence and prognostic impact of heart failure (HF) progression has been not well addressed. Methods: From 2009 until 2015, consecutive ambulatory HF patients were recruited. HF progression was defined by the presence of at least two of the following criteria: step up of ≥1 New York Heart Association (NYHA) class; decrease LVEF ≥ 10 points; association of diuretics or increase ≥ 50% of furosemide dosage, or HF hospitalization. Results: 2528 met study criteria (mean age 76; 42% women). Of these, 48% had ischemic heart disease, 18% patients with LVEF ≤ 35%. During a median follow-up of 2.4 years, overall mortality was 31% (95% CI: 29%–33%), whereas rate of HF progression or death was 57% (95% CI: 55%–59%). The 4-year incidence of HF progression was 39% (95% CI: 37%–41%) whereas the competing mortality rate was 18% (95% CI: 16%–19%). Rates of HF progression and death were higher in HF patients with LVEF ≤ 35% vs >35% (HF progression: 42% vs 38%, p = 0.012; death as a competing risk: 22% vs 17%, p = 0.002). HF progression identified HF patients with a worse survival (HR = 3.16, 95% CI: 2.75–3.72). In cause-specific Cox models, age, previous HF hospitalization, chronic obstructive pulmonary disease, chronic kidney disease, anemia, sex, LVEF ≤ 35% emerged as prognostic factors of HF progression. Conclusions: Among outpatients with HF, at 4 years 39% presented a HF progression, while 18% died before any sign of HF progression. This trend was higher in patients with LVEF ≤ 35%. These findings may have implications for healthcare planning and resource allocation.
Published: 2019

46. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: Setten, J. (Jessica) van, Brody, J.A. (Jennifer A.), Jamshidi, Y. (Yalda), Swenson, B.R. (Brenton R.), Butler, A.M. (Anne M.), Campbell, H. (Harry), Del Greco, F.M. (Fabiola), Evans, D.S. (Daniel), Gibson, Q. (Quince), Gudbjartsson, D.F. (Daniel), Kerr, K.F. (Kathleen), Krijthe, B.P. (Bouwe), Lyytikäinen, L.-P. (Leo-Pekka), Müller, C. (Christian), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Ritchie, M.D. (Marylyn D.), Robino, A. (Antonietta), Smith, A.V. (Albert), Steri, M. (Maristella), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Ulivi, S. (Sheila), Verweij, N. (Niek), Yin, X. (Xiaoyan), Arnar, D.O. (David O.), Asselbergs, F.W. (Folkert W.), Bader, J.S. (Joel), Barnard, J. (John), Bis, J.C. (Joshua), Blankenberg, S. (Stefan), Boerwinkle, E. (Eric), Bradford, Y. (Yuki), Buckley, B.M. (Brendan M.), Chung, M.K. (Mina), Crawford, D. (Dana), Hoed, M. (Marcel) den, Denny, J.C. (Joshua C.), Dominiczak, A. (Anna), Ehret, G.B. (Georg B.), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Felix, S.B. (Stephan), Franco, O.H. (Oscar), Franke, L. (Lude), Harris, T.B. (Tamara), Holm, H. (Hilma), Ilaria, G. (Gandin), Iorio, A. (Annamaria), Kähönen, M. (Mika), Kolcic, I. (Ivana), Kors, J.A. (Jan), Lakatta, E. (Edward), Launer, L.J. (Lenore), Lin, H. (Honghuang), Lin, H.J. (Henry J.), Loos, R.J.F. (Ruth), Lubitz, S.A. (Steven A.), MacFarlane, P.W. (Peter), Magnani, J.W. (Jared), Leach, I.M. (Irene Mateo), Meitinger, T. (Thomas), Mitchell, B.D. (Braxton), Munzel, T. (Thomas), Papanicolaou, G.J. (George J.), Peters, A. (Annette), Pfeufer, A. (Arne), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Schlessinger, D. (David), Silva Aldana, C.T. (Claudia), Sinner, M.F. (Moritz), Smith, J.D. (Jonathan), Snieder, H. (Harold), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Stott, D.J. (David. J.), Strauch, K. (Konstantin), Tarasov, K.V. (Kirill V.), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Wagoner, D.R. (David) van, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Jan Westra, H. (Harm), Wild, P.S. (Philipp), Zeller, T. (Tanja), Alonso, A. (Alvaro), Avery, C.L., Bandinelli, S. (Stefania), Benjamin, E.J. (Emelia), Cucca, F. (Francesco), Dörr, M. (Marcus), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Gudnason, V. (Vilmundur), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Hicks, A.A. (Andrew A.), Jukema, J.W. (Jan Wouter), Kääb, S. (Stefan), Lehtimäki, T. (Terho), Liu, Y. (YongMei), Munroe, P. (Patricia), Parsa, A. (Afshin), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Roden, D.M. (Dan), Schnabel, R.B. (Renate), Sinagra, G. (Gianfranco), Zwart, J-A. (John-Anker), Stricker, B.H.Ch. (Bruno), van der Harst, P. (Pim), Duijn, C.M. (Cornelia) van, Wilson, J.F. (James F.), Gharib, S.A. (Sina), Bakker, P.I.W. (Paul) de, Isaacs, A. (Aaron), Arking, D.E. (Dan), Sotoodehnia, N. (Nona), Setten, J. (Jessica) van, Brody, J.A. (Jennifer A.), Jamshidi, Y. (Yalda), Swenson, B.R. (Brenton R.), Butler, A.M. (Anne M.), Campbell, H. (Harry), Del Greco, F.M. (Fabiola), Evans, D.S. (Daniel), Gibson, Q. (Quince), Gudbjartsson, D.F. (Daniel), Kerr, K.F. (Kathleen), Krijthe, B.P. (Bouwe), Lyytikäinen, L.-P. (Leo-Pekka), Müller, C. (Christian), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Ritchie, M.D. (Marylyn D.), Robino, A. (Antonietta), Smith, A.V. (Albert), Steri, M. (Maristella), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Ulivi, S. (Sheila), Verweij, N. (Niek), Yin, X. (Xiaoyan), Arnar, D.O. (David O.), Asselbergs, F.W. (Folkert W.), Bader, J.S. (Joel), Barnard, J. (John), Bis, J.C. (Joshua), Blankenberg, S. (Stefan), Boerwinkle, E. (Eric), Bradford, Y. (Yuki), Buckley, B.M. (Brendan M.), Chung, M.K. (Mina), Crawford, D. (Dana), Hoed, M. (Marcel) den, Denny, J.C. (Joshua C.), Dominiczak, A. (Anna), Ehret, G.B. (Georg B.), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Felix, S.B. (Stephan), Franco, O.H. (Oscar), Franke, L. (Lude), Harris, T.B. (Tamara), Holm, H. (Hilma), Ilaria, G. (Gandin), Iorio, A. (Annamaria), Kähönen, M. (Mika), Kolcic, I. (Ivana), Kors, J.A. (Jan), Lakatta, E. (Edward), Launer, L.J. (Lenore), Lin, H. (Honghuang), Lin, H.J. (Henry J.), Loos, R.J.F. (Ruth), Lubitz, S.A. (Steven A.), MacFarlane, P.W. (Peter), Magnani, J.W. (Jared), Leach, I.M. (Irene Mateo), Meitinger, T. (Thomas), Mitchell, B.D. (Braxton), Munzel, T. (Thomas), Papanicolaou, G.J. (George J.), Peters, A. (Annette), Pfeufer, A. (Arne), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Schlessinger, D. (David), Silva Aldana, C.T. (Claudia), Sinner, M.F. (Moritz), Smith, J.D. (Jonathan), Snieder, H. (Harold), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Stott, D.J. (David. J.), Strauch, K. (Konstantin), Tarasov, K.V. (Kirill V.), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Wagoner, D.R. (David) van, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Jan Westra, H. (Harm), Wild, P.S. (Philipp), Zeller, T. (Tanja), Alonso, A. (Alvaro), Avery, C.L., Bandinelli, S. (Stefania), Benjamin, E.J. (Emelia), Cucca, F. (Francesco), Dörr, M. (Marcus), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Gudnason, V. (Vilmundur), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Hicks, A.A. (Andrew A.), Jukema, J.W. (Jan Wouter), Kääb, S. (Stefan), Lehtimäki, T. (Terho), Liu, Y. (YongMei), Munroe, P. (Patricia), Parsa, A. (Afshin), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Roden, D.M. (Dan), Schnabel, R.B. (Renate), Sinagra, G. (Gianfranco), Zwart, J-A. (John-Anker), Stricker, B.H.Ch. (Bruno), van der Harst, P. (Pim), Duijn, C.M. (Cornelia) van, Wilson, J.F. (James F.), Gharib, S.A. (Sina), Bakker, P.I.W. (Paul) de, Isaacs, A. (Aaron), Arking, D.E. (Dan), and Sotoodehnia, N. (Nona)
Abstract: Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Published: 2018
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47. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Prins, B.P. (Bram P.), Mead, T.J. (Timothy J.), Brody, J.A. (Jennifer A.), Sveinbjornsson, G. (Gardar), Ntalla, I. (Ioanna), Bihlmeyer, N.A. (Nathan A.), Berg, M.E. (Marten) van den, Bork-Jensen, J. (Jette), Cappellani, S. (Stefania), Van Duijvenboden, S. (Stefan), Klena, N.T. (Nikolai T.), Gabriel, G.C. (George C.), Liu, X. (Xiaoqin), Gulec, C. (Cagri), Grarup, N. (Niels), Haessler, J. (Jeff), Hall, L.M. (Leanne M.), Iorio, A. (Annamaria), Isaacs, A. (Aaron), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Liu, C.-T. (Ching-Ti), Lyytikäinen, L.-P. (Leo-Pekka), Marten, J. (Jonathan), Mei, H. (Hao), Müller-Nurasyid, M. (Martina), Orini, M. (Michele), Padmanabhan, S. (Sandosh), Radmanesh, F. (Farid), Ramirez, J. (Julia), Robino, A. (Antonietta), Schwartz, M. (Molly), Setten, J. (Jessica) van, Smith, A.V. (Albert), Verweij, N. (Niek), Warren, H. (Helen), Weiss, S. (Stefan), Alonso, A. (Alvaro), Arnar, D.O. (David O.), Bots, M.L. (Michiel), Boer, R.A. (Rudolf) de, Dominiczak, A. (Anna), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Guo, X. (Xiuqing), Felix, S.B. (Stephan), Harris, T.B. (Tamara), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kors, J.A. (Jan), Lambiase, P.D. (Pier), Launer, L.J. (Lenore), Li, M. (Man), Linneberg, A. (Allan), Nelson, C.P. (Christopher P.), Pedersen, O. (Oluf), Perez, M. (Marco), Peters, A. (Annette), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Raitakari, O. (Olli), Rice, K.M. (Kenneth), Rotter, J.I. (Jerome I.), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Strauch, K. (Konstantin), Thorsteinsdottir, U. (Unnur), Tinker, A. (Andrew), Trompet, S. (Stella), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Meer, P. (Peter) van der, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Wilson, J.F. (James), Xie, Z. (Zhijun), Asselbergs, F.W. (Folkert W.), Dörr, M. (Marcus), Duijn, C.M. (Cornelia) van, Gasparini, P. (Paolo), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Hansen, T. (Torben), Kääb, S. (Stefan), Kanters, J.K., Kooperberg, C. (Charles), Lehtimäki, T. (Terho), Lin, H.J. (Henry J.), Lubitz, S.A. (Steven A.), Mook-Kanamori, D.O. (Dennis O.), Conti, F.J. (Francesco J.), Newton-Cheh, C. (Christopher), Rosand, J. (Jonathan), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Sinagra, G. (Gianfranco), Smith, B.H. (Blair), Holm, H. (Hilma), Stricker, B.H.Ch. (Bruno), Ulivi, S. (Sheila), Sotoodehnia, N. (Nona), Apte, S.S. (Suneel S.), van der Harst, P. (Pim), Zwart, J-A. (John-Anker), Munroe, P. (Patricia), Arking, D.E. (Dan), Lo, C.W. (Cecilia W.), Jamshidi, Y. (Yalda), Prins, B.P. (Bram P.), Mead, T.J. (Timothy J.), Brody, J.A. (Jennifer A.), Sveinbjornsson, G. (Gardar), Ntalla, I. (Ioanna), Bihlmeyer, N.A. (Nathan A.), Berg, M.E. (Marten) van den, Bork-Jensen, J. (Jette), Cappellani, S. (Stefania), Van Duijvenboden, S. (Stefan), Klena, N.T. (Nikolai T.), Gabriel, G.C. (George C.), Liu, X. (Xiaoqin), Gulec, C. (Cagri), Grarup, N. (Niels), Haessler, J. (Jeff), Hall, L.M. (Leanne M.), Iorio, A. (Annamaria), Isaacs, A. (Aaron), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Liu, C.-T. (Ching-Ti), Lyytikäinen, L.-P. (Leo-Pekka), Marten, J. (Jonathan), Mei, H. (Hao), Müller-Nurasyid, M. (Martina), Orini, M. (Michele), Padmanabhan, S. (Sandosh), Radmanesh, F. (Farid), Ramirez, J. (Julia), Robino, A. (Antonietta), Schwartz, M. (Molly), Setten, J. (Jessica) van, Smith, A.V. (Albert), Verweij, N. (Niek), Warren, H. (Helen), Weiss, S. (Stefan), Alonso, A. (Alvaro), Arnar, D.O. (David O.), Bots, M.L. (Michiel), Boer, R.A. (Rudolf) de, Dominiczak, A. (Anna), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Guo, X. (Xiuqing), Felix, S.B. (Stephan), Harris, T.B. (Tamara), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kors, J.A. (Jan), Lambiase, P.D. (Pier), Launer, L.J. (Lenore), Li, M. (Man), Linneberg, A. (Allan), Nelson, C.P. (Christopher P.), Pedersen, O. (Oluf), Perez, M. (Marco), Peters, A. (Annette), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Raitakari, O. (Olli), Rice, K.M. (Kenneth), Rotter, J.I. (Jerome I.), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Strauch, K. (Konstantin), Thorsteinsdottir, U. (Unnur), Tinker, A. (Andrew), Trompet, S. (Stella), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Meer, P. (Peter) van der, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Wilson, J.F. (James), Xie, Z. (Zhijun), Asselbergs, F.W. (Folkert W.), Dörr, M. (Marcus), Duijn, C.M. (Cornelia) van, Gasparini, P. (Paolo), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Hansen, T. (Torben), Kääb, S. (Stefan), Kanters, J.K., Kooperberg, C. (Charles), Lehtimäki, T. (Terho), Lin, H.J. (Henry J.), Lubitz, S.A. (Steven A.), Mook-Kanamori, D.O. (Dennis O.), Conti, F.J. (Francesco J.), Newton-Cheh, C. (Christopher), Rosand, J. (Jonathan), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Sinagra, G. (Gianfranco), Smith, B.H. (Blair), Holm, H. (Hilma), Stricker, B.H.Ch. (Bruno), Ulivi, S. (Sheila), Sotoodehnia, N. (Nona), Apte, S.S. (Suneel S.), van der Harst, P. (Pim), Zwart, J-A. (John-Anker), Munroe, P. (Patricia), Arking, D.E. (Dan), Lo, C.W. (Cecilia W.), and Jamshidi, Y. (Yalda)
Abstract: Background: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. Results: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. Conclusions: Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.
Published: 2018
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48. Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease

Author: Van Hagen, Iris M., Baart, Sara, Fong Soe Khioe, Rebekah, Sliwa-Hahnle, Karen, Taha, Nasser, Lelonek, Malgorzata, Tavazzi, Luigi, Maggioni, Aldo Pietro, Johnson, Mark R., Maniadakis, Nikolaos, Fordham, Richard, Hall, Roger, Roos-Hesselink, Jolien W., Ferrari, Roberto, Marelli, Ariane, Webb, Gary, Kaemmerer, Harald, Popelova, Jana, Sliwa, Karen, Parsonage, William Anthony, Stein, Joerg, Elkayam, Uri, Thilen, Ulf, Budts, Werner, Ruys, Titia, Vardas, Panos, Komajda, Michel, Pinto, Fausto, Alonso, Angeles, Wood, David, Ferreira, Thierry, Gracia, Gérard, Laroche, Cécile, Missiamenou, Viviane, Taylor, Charles, Konte, Marème, Andarala, Maryna, Fiorucci, Emanuela, Lefrancq, Elin Folkesson, Glémot, Myriam, McNeill, Patti Ann, Pommier, Caroline, Lafay, Myriam, Aquieri, A., Vega, H. Ruda, Blanco, M. Vázquez, Lust, K., Fagermo, N., Gabriel, H., Donhauser, E., Gasimov, Z., Jahangirov, T., Hasanova, I., De Backer, J., Demulier, L., de Hosson, M., Beckx, M., Moissens, M., Kovacevic-Preradovic, T., Kozic, M., Lovric, M., Freire, C. Vilas, Chilingirova, N., Kratunkov, P., Montesclaros, A. R., Beaubien, E., Gordon, E., Walter, L., Lindsay, C., Wahab, N., Vavera, Z., El Nagar, A., Ebaid, H. H., El Sayed Makled, W. A., Dardier, A., Shabaan, M., Elrakshy, Y., Eltamawey, K., Abd-El Aziz, M. Gamal, Saad, A., Aboleineen, W., Ashour, Z., Sorour, K., Mahdy, M. A.Meguid, Iserin, L., Ladouceur, M., Cohen, S., Iung, B., Maisuradze, D., Mebus, S., Gembruch, U., Hammerstingl, C., Merz, W. M., Wald, C., Baumgartner, H., Orwat, S., Schmidt, R., Motz, R., Olsson, A., Berger, F., Nagdyman, N., Frogoudaki, A., Anastasiou-Nana, M., Temesvari, A., Kohalmi, D., Balint, H., Merkely, B., Liptai, C., Bowen, M., Cullen, M., Thornton, P., Husarova, V., Blatt, A., Elbaz-Greener, G., Moravsky, G., Vered, Z., Fuhrmann, A. Vazan, Shotan, A., Goland, S., Festa, P., Ali, L. Ait, Sinagra, G., Puggia, I., Mottolese, B. D.Agata, Carmina, M. G., Romeo, C., Crepaz, R., Fesslova, V., Azzarelli, A., Baldi, D., Bovenzi, F., Donvito, V., Vasario, E., Todros, T., Niwa, K., Mussagaliyeva, A., Mekebekova, D., Sharipova, S., Zaliunas, R., Jonkaitiene, R., Petrauskaite, J., Gumbiene, L., Jovanova, S., Cassar, A., Caruana, M., Karamermer, Y., Cornette, J. M.J., van Dijk, A., Bellersen, L., Duijnhouwer, T., De Groot, C., Pieper, E. P.G., van Oppen, C., Polak, P., Wajon, E., Wagenaar, L., Estensen, M., Lesniak-Sobelga, A., Podolec, P., Wisniowska-Smialek, S., Trybuch, A., Hoffman, P., Cichocka-Radwan, A., Sobczak, S., Faflik, U., Tomaszuk-Kazberuk, A., Przepiesc, J., Gil, M., Plaskota, K., Trojnarska, O., Guerra, N., de Sousa, L., Petrescu, V., Ginghina, C., Jurcut, R., Coman, I. Mircea, Gaisin, I. Ravilevich, Shilina, L. Valeryevna, Sharashkina, N., Tkacheva, O., Ivanov, D., Irtyuga, O., Jovovic, L., Prokselj, K., Kozelj, M., Elliott, C., Galian-Gay, L., Pijuan-Domenech, A., Subirana-Domenech, M. T., Tornos, P., Murga, N., Oliver, J. M., Escribano-Subías, P., Ruiz-Cano, M. J., Delgado-Jiménez, J., Furenas, E., Dellborg, M., Thilén, U., Schwerzmann, M., Bouchardy, J., Rutz, T., Tobler, D., Sarac, L., Esen, O. Batukan, Enar, S. Catirli, Al Mulla, A., Bazargani, N., Al Hatou, E., Farook, F., Almahmeed, W., Salih, B., Clifford, P., Bowers, N., Veldtman, G., Kerr, J., Tellett, L., Hudsmith, L., Thompson, P., Thorne, S., Bowater, S., Nihoyannopoulos, P., Curry, R., Freeman, L., Schroeder, F., Wendler, R., Hammond, S., Talluto, C., Murphy, D., Perlroth, M. G., Chintala, K., Gupta, P., Pare, E., Khatri, N., Scott, N., De Faria-Yeh, D., Bhatt, A. B., Tsiaras, S., Gurvitz, M., Otto, C., Botti, J., Ting, J., Davidson, W. R., Van Hagen, Iris M., Baart, Sara, Fong Soe Khioe, Rebekah, Sliwa-Hahnle, Karen, Taha, Nasser, Lelonek, Malgorzata, Tavazzi, Luigi, Maggioni, Aldo Pietro, Johnson, Mark R., Maniadakis, Nikolaos, Fordham, Richard, Hall, Roger, Roos-Hesselink, Jolien W., Ferrari, Roberto, Marelli, Ariane, Webb, Gary, Kaemmerer, Harald, Popelova, Jana, Sliwa, Karen, Parsonage, William Anthony, Stein, Joerg, Elkayam, Uri, Thilen, Ulf, Budts, Werner, Ruys, Titia, Vardas, Panos, Komajda, Michel, Pinto, Fausto, Alonso, Angeles, Wood, David, Ferreira, Thierry, Gracia, Gérard, Laroche, Cécile, Missiamenou, Viviane, Taylor, Charles, Konte, Marème, Andarala, Maryna, Fiorucci, Emanuela, Lefrancq, Elin Folkesson, Glémot, Myriam, McNeill, Patti Ann, Pommier, Caroline, Lafay, Myriam, Aquieri, A., Vega, H. Ruda, Blanco, M. Vázquez, Lust, K., Fagermo, N., Gabriel, H., Donhauser, E., Gasimov, Z., Jahangirov, T., Hasanova, I., De Backer, J., Demulier, L., de Hosson, M., Beckx, M., Moissens, M., Kovacevic-Preradovic, T., Kozic, M., Lovric, M., Freire, C. Vilas, Chilingirova, N., Kratunkov, P., Montesclaros, A. R., Beaubien, E., Gordon, E., Walter, L., Lindsay, C., Wahab, N., Vavera, Z., El Nagar, A., Ebaid, H. H., El Sayed Makled, W. A., Dardier, A., Shabaan, M., Elrakshy, Y., Eltamawey, K., Abd-El Aziz, M. Gamal, Saad, A., Aboleineen, W., Ashour, Z., Sorour, K., Mahdy, M. A.Meguid, Iserin, L., Ladouceur, M., Cohen, S., Iung, B., Maisuradze, D., Mebus, S., Gembruch, U., Hammerstingl, C., Merz, W. M., Wald, C., Baumgartner, H., Orwat, S., Schmidt, R., Motz, R., Olsson, A., Berger, F., Nagdyman, N., Frogoudaki, A., Anastasiou-Nana, M., Temesvari, A., Kohalmi, D., Balint, H., Merkely, B., Liptai, C., Bowen, M., Cullen, M., Thornton, P., Husarova, V., Blatt, A., Elbaz-Greener, G., Moravsky, G., Vered, Z., Fuhrmann, A. Vazan, Shotan, A., Goland, S., Festa, P., Ali, L. Ait, Sinagra, G., Puggia, I., Mottolese, B. D.Agata, Carmina, M. G., Romeo, C., Crepaz, R., Fesslova, V., Azzarelli, A., Baldi, D., Bovenzi, F., Donvito, V., Vasario, E., Todros, T., Niwa, K., Mussagaliyeva, A., Mekebekova, D., Sharipova, S., Zaliunas, R., Jonkaitiene, R., Petrauskaite, J., Gumbiene, L., Jovanova, S., Cassar, A., Caruana, M., Karamermer, Y., Cornette, J. M.J., van Dijk, A., Bellersen, L., Duijnhouwer, T., De Groot, C., Pieper, E. P.G., van Oppen, C., Polak, P., Wajon, E., Wagenaar, L., Estensen, M., Lesniak-Sobelga, A., Podolec, P., Wisniowska-Smialek, S., Trybuch, A., Hoffman, P., Cichocka-Radwan, A., Sobczak, S., Faflik, U., Tomaszuk-Kazberuk, A., Przepiesc, J., Gil, M., Plaskota, K., Trojnarska, O., Guerra, N., de Sousa, L., Petrescu, V., Ginghina, C., Jurcut, R., Coman, I. Mircea, Gaisin, I. Ravilevich, Shilina, L. Valeryevna, Sharashkina, N., Tkacheva, O., Ivanov, D., Irtyuga, O., Jovovic, L., Prokselj, K., Kozelj, M., Elliott, C., Galian-Gay, L., Pijuan-Domenech, A., Subirana-Domenech, M. T., Tornos, P., Murga, N., Oliver, J. M., Escribano-Subías, P., Ruiz-Cano, M. J., Delgado-Jiménez, J., Furenas, E., Dellborg, M., Thilén, U., Schwerzmann, M., Bouchardy, J., Rutz, T., Tobler, D., Sarac, L., Esen, O. Batukan, Enar, S. Catirli, Al Mulla, A., Bazargani, N., Al Hatou, E., Farook, F., Almahmeed, W., Salih, B., Clifford, P., Bowers, N., Veldtman, G., Kerr, J., Tellett, L., Hudsmith, L., Thompson, P., Thorne, S., Bowater, S., Nihoyannopoulos, P., Curry, R., Freeman, L., Schroeder, F., Wendler, R., Hammond, S., Talluto, C., Murphy, D., Perlroth, M. G., Chintala, K., Gupta, P., Pare, E., Khatri, N., Scott, N., De Faria-Yeh, D., Bhatt, A. B., Tsiaras, S., Gurvitz, M., Otto, C., Botti, J., Ting, J., and Davidson, W. R.
Abstract: Objective Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease. Methods The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient-centre-country). Results A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate. Conclusion While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome.
Published: 2018

49. Mineralocorticoid receptor antagonists for heart failure: a real-life observational study

Author: Bruno, N, Sinagra, G, Paolillo, S, Bonomi, A, Corrà, U, Piepoli, M, Veglia, F, Salvioni, E, Lagioia, R, Metra, M, Limongelli, G, Cattadori, G, Scardovi, A, Carubelli, V, Scrutino, D, Badagliacca, R, Guazzi, M, Raimondo, R, Gentile, P, Magrì, D, Correale, M, Parati, G, Re, F, Cicoira, M, Frigerio, M, Bussotti, M, Vignati, C, Oliva, F, Mezzani, A, Vergaro, G, Di Lenarda, A, Passino, C, Sciomer, S, Pacileo, G, Ricci, R, Contini, M, Apostolo, A, Palermo, P, Mapelli, M, Carriere, C, Clemenza, F, Binno, S, Belardinelli, R, Lombardi, C, Perrone Filardi, P, Emdin, M, Agostoni, P, Bruno, Noemi, Sinagra, Gianfranco, Paolillo, Stefania, Bonomi, Alice, Corrà, Ugo, Piepoli, Massimo, Veglia, Fabrizio, Salvioni, Elisabetta, Lagioia, Rocco, Metra, Marco, Limongelli, Giuseppe, Cattadori, Gaia, Scardovi, Angela B, Carubelli, Valentina, Scrutino, Domenico, Badagliacca, Roberto, Guazzi, Marco, Raimondo, Rosa, Gentile, Piero, Magrì, Damiano, Correale, Michele, Parati, Gianfranco, Re, Federica, Cicoira, Mariantonietta, Frigerio, Maria, Bussotti, Maurizio, Vignati, Carlo, Oliva, Fabrizio, Mezzani, Alessandro, Vergaro, Giuseppe, Di Lenarda, Andrea, Passino, Claudio, Sciomer, Susanna, Pacileo, Giuseppe, Ricci, Roberto, Contini, Mauro, Apostolo, Anna, Palermo, Pietro, Mapelli, Massimo, Carriere, Cosimo, Clemenza, Francesco, Binno, Simone, Belardinelli, Romualdo, Lombardi, Carlo, Perrone Filardi, Pasquale, Emdin, Michele, Agostoni, Piergiuseppe, Bruno, N, Sinagra, G, Paolillo, S, Bonomi, A, Corrà, U, Piepoli, M, Veglia, F, Salvioni, E, Lagioia, R, Metra, M, Limongelli, G, Cattadori, G, Scardovi, A, Carubelli, V, Scrutino, D, Badagliacca, R, Guazzi, M, Raimondo, R, Gentile, P, Magrì, D, Correale, M, Parati, G, Re, F, Cicoira, M, Frigerio, M, Bussotti, M, Vignati, C, Oliva, F, Mezzani, A, Vergaro, G, Di Lenarda, A, Passino, C, Sciomer, S, Pacileo, G, Ricci, R, Contini, M, Apostolo, A, Palermo, P, Mapelli, M, Carriere, C, Clemenza, F, Binno, S, Belardinelli, R, Lombardi, C, Perrone Filardi, P, Emdin, M, Agostoni, P, Bruno, Noemi, Sinagra, Gianfranco, Paolillo, Stefania, Bonomi, Alice, Corrà, Ugo, Piepoli, Massimo, Veglia, Fabrizio, Salvioni, Elisabetta, Lagioia, Rocco, Metra, Marco, Limongelli, Giuseppe, Cattadori, Gaia, Scardovi, Angela B, Carubelli, Valentina, Scrutino, Domenico, Badagliacca, Roberto, Guazzi, Marco, Raimondo, Rosa, Gentile, Piero, Magrì, Damiano, Correale, Michele, Parati, Gianfranco, Re, Federica, Cicoira, Mariantonietta, Frigerio, Maria, Bussotti, Maurizio, Vignati, Carlo, Oliva, Fabrizio, Mezzani, Alessandro, Vergaro, Giuseppe, Di Lenarda, Andrea, Passino, Claudio, Sciomer, Susanna, Pacileo, Giuseppe, Ricci, Roberto, Contini, Mauro, Apostolo, Anna, Palermo, Pietro, Mapelli, Massimo, Carriere, Cosimo, Clemenza, Francesco, Binno, Simone, Belardinelli, Romualdo, Lombardi, Carlo, Perrone Filardi, Pasquale, Emdin, Michele, and Agostoni, Piergiuseppe
Abstract: AIMS: Mineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population-based analysis, the long-term effects of MRA treatment in HFrEF patients. METHODS AND RESULTS: We analysed data of 6046 patients included in the Metabolic Exercise Cardiac Kidney Index score dataset. Analysis was performed in patients treated (n = 3163) and not treated (n = 2883) with MRA. The study endpoint was a composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Ten years' survival was analysed through Kaplan-Meier, compared by log-rank test and propensity score matching. At 10 years' follow-up, the MRA-untreated group had a significantly lower number of events than the MRA-treated group (P < 0.001). MRA-treated patients had more severe heart failure (higher New York Heart Association class and lower left ventricular ejection fraction, kidney function, and peak VO2 ). At a propensity-score-matching analysis performed on 1587 patients, MRA-treated and MRA-untreated patients showed similar study endpoint values. CONCLUSIONS: In conclusion, MRA treatment does not affect the composite of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation in a real-life setting. A meticulous patient follow-up, as performed in trials, is likely needed to match the positive MRA-related benefits observed in clinical trials
Published: 2018

50. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Prins, BP, Mead, TJ, Brody, JA, Sveinbjornsson, G, Ntalla, I, Bihlmeyer, NA, van den Berg, Marten, Bork-Jensen, J, Cappellani, S, Van Duijvenboden, S, Klena, NT, Gabriel, GC, Liu, XQ, Gulec, C, Grarup, N, Haessler, J, Hall, LM, Iorio, A, Isaacs, Aaron, Li-Gao, RF, Lin, HH, Liu, CT, Lyytikainen, LP, Marten, J, Mei, H, Muller-Nurasyid, M, Orini, M, Padmanabhan, S, Radmanesh, F, Ramirez, J, Robino, A, Schwartz, M, van Setten, J, Smith, AV, Verweij, N, Warren, HR, Weiss, S, Alonso, A, Arnar, DO, Bots, ML, de Boer, RA, Dominiczak, AF, Eijgelsheim, Mark, Ellinor, PT, Guo, XQ, Felix, SB, Harris, TB, Hayward, C, Heckbert, SR, Huang, PL, Jukema, JW, Kahonen, M, Kors, Jan, Lambiase, PD, Launer, LJ, Li, M, Linneberg, A, Nelson, CP, Pedersen, O, Perez, M, Peters, A, Polasek, O, Psaty, BM, Raitakari, OT, Rice, KM, Rotter, JI, Sinner, MF, Soliman, EZ, Spector, TD, Strauch, K, Thorsteinsdottir, U, Tinker, A, Trompet, S, Uitterlinden, André, Vaartjes, I, Meer, P, Volker, U, Volzke, H, Waldenberger, M, Wilson, JG, Xie, ZJ, Asselbergs, FW, Dorr, M, Duijn, Cornelia, Gasparini, P, Gudbjartsson, DF, Gudnason, V, Hansen, T, Kaab, S, Kanters, JK, Kooperberg, C, Lehtimaki, T, Lin, H J, Lubitz, SA, Mook, Dennis, Conti, FJ, Newton-Cheh, CH, Rosand, J, Rudan, I, Samani, NJ, Sinagra, G, Smith, BH, Holm, H, Stricker, Bruno, Ulivi, S, Sotoodehnia, N, Apte, SS, van der Harst, P, Stefansson, K, Munroe, PB, Arking, DE, Lo, CW, Jamshidi, Y, Prins, BP, Mead, TJ, Brody, JA, Sveinbjornsson, G, Ntalla, I, Bihlmeyer, NA, van den Berg, Marten, Bork-Jensen, J, Cappellani, S, Van Duijvenboden, S, Klena, NT, Gabriel, GC, Liu, XQ, Gulec, C, Grarup, N, Haessler, J, Hall, LM, Iorio, A, Isaacs, Aaron, Li-Gao, RF, Lin, HH, Liu, CT, Lyytikainen, LP, Marten, J, Mei, H, Muller-Nurasyid, M, Orini, M, Padmanabhan, S, Radmanesh, F, Ramirez, J, Robino, A, Schwartz, M, van Setten, J, Smith, AV, Verweij, N, Warren, HR, Weiss, S, Alonso, A, Arnar, DO, Bots, ML, de Boer, RA, Dominiczak, AF, Eijgelsheim, Mark, Ellinor, PT, Guo, XQ, Felix, SB, Harris, TB, Hayward, C, Heckbert, SR, Huang, PL, Jukema, JW, Kahonen, M, Kors, Jan, Lambiase, PD, Launer, LJ, Li, M, Linneberg, A, Nelson, CP, Pedersen, O, Perez, M, Peters, A, Polasek, O, Psaty, BM, Raitakari, OT, Rice, KM, Rotter, JI, Sinner, MF, Soliman, EZ, Spector, TD, Strauch, K, Thorsteinsdottir, U, Tinker, A, Trompet, S, Uitterlinden, André, Vaartjes, I, Meer, P, Volker, U, Volzke, H, Waldenberger, M, Wilson, JG, Xie, ZJ, Asselbergs, FW, Dorr, M, Duijn, Cornelia, Gasparini, P, Gudbjartsson, DF, Gudnason, V, Hansen, T, Kaab, S, Kanters, JK, Kooperberg, C, Lehtimaki, T, Lin, H J, Lubitz, SA, Mook, Dennis, Conti, FJ, Newton-Cheh, CH, Rosand, J, Rudan, I, Samani, NJ, Sinagra, G, Smith, BH, Holm, H, Stricker, Bruno, Ulivi, S, Sotoodehnia, N, Apte, SS, van der Harst, P, Stefansson, K, Munroe, PB, Arking, DE, Lo, CW, and Jamshidi, Y
Published: 2018

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