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202. Cardiovascular Risk Factors Associated With the Metabolically Healthy Obese (MHO) Phenotype Compared to the Metabolically Unhealthy Obese (MUO) Phenotype in Children

Author

Genovesi, S, Antolini, L, Orlando, A, Gilardini, L, Bertoli, S, Giussani, M, Invitti, C, Nava, E, Battaglino, M, Leone, A, Valsecchi, M, Parati, G, Genovesi S., Antolini L., Orlando A., Gilardini L., Bertoli S., Giussani M., Invitti C., Nava E., Battaglino M. G., Leone A., Valsecchi M. G., Parati G., Genovesi, S, Antolini, L, Orlando, A, Gilardini, L, Bertoli, S, Giussani, M, Invitti, C, Nava, E, Battaglino, M, Leone, A, Valsecchi, M, Parati, G, Genovesi S., Antolini L., Orlando A., Gilardini L., Bertoli S., Giussani M., Invitti C., Nava E., Battaglino M. G., Leone A., Valsecchi M. G., and Parati G.

Abstract

Background: In pediatric age the prevalence of obesity is high. Obese children who do not have other risk factors than excess weight have been defined as “metabolically healthy obese” (MHO). Aim: The aim of this study is to evaluate, in a population of obese children, the prevalence of the MHO and “metabolically unhealthy obese” (MUO) phenotype. Furthermore, we evaluated the distribution of Uric Acid, HOMA index and Waist-Height ratio (W-Hr) in the MHO and MUO sub-groups and the impact of these non-traditional risk factors on the probability to be MUO. Methods: In 1201 obese children and adolescents [54% males, age (±SD) 11.9 (±3.0) years] weight, height, waist circumference, systolic (SBP) and diastolic (DBP) blood pressure, pubertal status, glucose, insulin, HDL cholesterol, triglycerides and Uric Acid serum values were assessed. MUO phenotype was defined as the presence of at least one of the following risk factors: SBP or DBP ≥ 90th percentile, glycaemia ≥ 100 mg/dl, HDL cholesterol <40 mg/dl, triglycerides ≥100 mg/dl (children <10 years) or ≥130 mg/dl (children ≥10 years). A multivariate logistic regression analysis was used to estimate the association between MUO phenotype and non-traditional cardiovascular risk factors. Results: The prevalence of the MUO status was high (61%). MUO subjects were more often male, older and pubertal (p < 0.001). The levels of the three non-traditional risk factors were significantly higher in MUO children compared to MHO children (p < 0.001) and all of them were independent predictors of the fact of being MUO [OR 1.41 (95% CI 1.24–1.69); 1.15 (95% CI 1.06–1.23) and 1.03 (95% CI1.01–1.05) for Uric Acid, HOMA index and W-Hr, respectively]. About 15% of MHO subjects had serum Uric Acid, HOMA index and W-Hr values within the highest quartile of the study population. Conclusion: The prevalence of MUO subjects in a large pediatric population is high and serum Uric Acid, HOMA index and W-Hr values are independent predictors of the prob

Published
2020

203. Haemodynamic characteristics of COVID-19 patients with acute respiratory distress syndrome requiring mechanical ventilation. An invasive assessment using right heart catheterization

Author

Caravita, S, Baratto, C, Di Marco, F, Calabrese, A, Balestrieri, G, Russo, F, Faini, A, Soranna, D, Perego, G, Badano, L, Grazioli, L, Lorini, F, Parati, G, Senni, M, Caravita S., Baratto C., Di Marco F., Calabrese A., Balestrieri G., Russo F., Faini A., Soranna D., Perego G. B., Badano L, Grazioli L., Lorini F. L., Parati G., Senni M., Caravita, S, Baratto, C, Di Marco, F, Calabrese, A, Balestrieri, G, Russo, F, Faini, A, Soranna, D, Perego, G, Badano, L, Grazioli, L, Lorini, F, Parati, G, Senni, M, Caravita S., Baratto C., Di Marco F., Calabrese A., Balestrieri G., Russo F., Faini A., Soranna D., Perego G. B., Badano L, Grazioli L., Lorini F. L., Parati G., and Senni M.

Abstract

Aims: Interstitial pneumonia due to coronavirus disease 2019 (COVID-19) is often complicated by severe respiratory failure. In addition to reduced lung compliance and ventilation/perfusion mismatch, a blunted hypoxic pulmonary vasoconstriction has been hypothesized, that could explain part of the peculiar pathophysiology of the COVID-19 cardiorespiratory syndrome. However, no invasive haemodynamic characterization of COVID-19 patients has been reported so far. Methods and results: Twenty-one mechanically-ventilated COVID-19 patients underwent right heart catheterization. Their data were compared both with those obtained from non-mechanically ventilated paired control subjects matched for age, sex and body mass index, and with pooled data of 1937 patients with ‘typical’ acute respiratory distress syndrome (ARDS) from a systematic literature review. Cardiac index was higher in COVID-19 patients than in controls [3.8 (2.7–4.5) vs. 2.4 (2.1–2.8) L/min/m2, P < 0.001], but slightly lower than in ARDS patients (P = 0.024). Intrapulmonary shunt and lung compliance were inversely related in COVID-19 patients (r = −0.57, P = 0.011) and did not differ from ARDS patients. Despite this, pulmonary vascular resistance of COVID-19 patients was normal, similar to that of control subjects [1.6 (1.1–2.5) vs. 1.6 (0.9–2.0) WU, P = 0.343], and lower than reported in ARDS patients (P < 0.01). Pulmonary hypertension was present in 76% of COVID-19 patients and in 19% of control subjects (P < 0.001), and it was always post-capillary. Pulmonary artery wedge pressure was higher in COVID-19 than in ARDS patients, and inversely related to lung compliance (r = −0.46, P = 0.038). Conclusions: The haemodynamic profile of COVID-19 patients needing mechanical ventilation is characterized by combined cardiopulmonary alterations. Low pulmonary vascular resistance, coherent with a blunted hypoxic vasoconstriction, is associated with high c

Published
2020

205. Sudden Cardiac Death in Children Affected by Cardiomyopathies: An Update on Risk Factors and Indications at Transvenous or Subcutaneous Implantable Defibrillators

Author

Rella, V, Parati, G, Crotti, L, Rella V., Parati G., Crotti L., Rella, V, Parati, G, Crotti, L, Rella V., Parati G., and Crotti L.

Abstract

In the present paper, we will discuss the main cardiomyopathies affecting children with a specific focus on risk stratification and prevention of sudden cardiac death (SCD). We will discuss the main clinical features of hypertrophic cardiomyopathy (HCM), dilated and restrictive cardiomyopathies, left ventricular non-compaction (LVNC) and arrhythmogenic cardiomyopathy (AC), always highlighting their peculiarities in the pediatric age. Since sudden cardiac death may be the first manifestation of the disease, even in children, the identification of the specific underlying condition and of risk factors are pivotal to carry out the appropriate preventing strategies. ICD recommendations in children are similar to adults, but supporting evidences are not so solid, being based on registries or single center studies. Furthermore, children and young patients are most likely to manifest long term complications related to an implanted ICD, and this should be taken into account when evaluating the risk benefit ratio. In this perspective, subcutaneous ICDs (S-ICDs) could carry an advantage; however, they cannot be considered in small children for technical reasons. Data on effectiveness and safety of S-ICDs in a pediatric population is still lacking, although some limited experiences are reported and will be discussed in the current review.

Published
2020

206. Editorial cardiovascular risk in children: Focus on pathophysiological aspects

Author

Genovesi, S, Parati, G, Genovesi S., Parati G., Genovesi, S, Parati, G, Genovesi S., and Parati G.

Abstract

Cardiovascular diseases are the leading cause of death, disability, and health care costs in industrialized countries. In general, cardiovascular diseases occur in adulthood, but cardiovascular damage, including stiffening of the arteries, begins very early. Already in the first decade of life, alterations that will favor the formation of atherosclerotic plaques may be present. Cardiovascular risk factors, associated with genetic predisposition, may trigger a sequence of pathophysiological changes which are associated with the progression of the atherosclerosis process. In this frame, the role of obesity has been increasingly emphasized. Different mechanisms linking obesity to cardiovascular disease have been postulated. Endothelial dysfunction and subclinical inflammation seem to be related to the worsening of cardiovascular risk factors in obese subjects and might have an essential role in the development of insulin resistance and the initiation and progression of atherosclerotic lesions. Excess weight, and in particular visceral adiposity, are associated with hypertrophy and hyperplasia of the adipocytes, increased secretion of adipokines and inflammatory cytokines and increase in serum uric acid levels. The list of obesity-related biomarkers associated with cardiovascular damage is rapidly expanding and their importance has already been described in children as well. Pathophysiological changes involved in determining early cardiovascular damage starting from childhood are discussed in this Special Issue.

Published
2020

207. Automated office blood pressure measurements in primary care are misleading in more than one third of treated hypertensives: The VALENTINE-Greece Home Blood Pressure Monitoring study

Author

Kollias, A, Papadatos, S, Dominiczak, A, Parati, G, Stergiou, G, Demerouti, E, Voulgaris, D, Papadakis, I, Karsanidis, A, Triantafillou, A, Garzonis, S, Gourgoulis, G, Trikalinou, A, Karidas, P, Savvalas, D, Aggelopoulos, T, Alevizos, A, Moraiti, A, Rosmarakis, E, Chatzigeorgiou, G, Antonakis, V, Alexandropoulou-Tsirka, A, Markaki, I, Astrinakis, S, Roilidis, V, Polymeros, S, Chariatis, E, Panageas, V, Kontoriga, A, Patsioura, M, Kleftaki-Manta, A, Kalantaridou, A, Kourouklis, S, Papakonstantinos, G, Barouni, P, Grekidou, E, Sklaveniti, A, Kolovou, I, Antoniadis, A, Pelekanos, I, Zervaki Drakou, N, Tikka-Zoumpou, K, Dalaklidou, V, Menti, A, Christofeli, A, Androutsakos, T, Doulgerakis, D, Oikonomopoulou, I, Moschos, M, Koutras, D, Skias, I, Boutsikos, P, Matsaggoura-Sameli, M, Riga, M, Sainis, P, Mitilinaiou-Karakozi, E, Mainas, K, Nikolaou, K, Chatziparaskevas, S, Ozai, O, Vogiatzis, G, Lilis, L, Plaskas, D, Chatzizisi, S, Gianasmidis, A, Petrovitsos, E, Koykoyfikis, G, Pittas, A, Rovithis, D, Ioannidis, A, Dalamaga, E, Kladas, G, Afthonidis, N, Pourou, E, Katainidis, S, Gavrilidou, M, Kourtidou, P, Tsamopoulos, L, Kairis, K, Arampatzi, S, Basoukos, C, Daskalakis, K, Megianis, V, Simintiridou, D, Christoforidis, T, Lafazanis, G, Chatzioannidis, L, Stephopoulos, C, Karanika-Chandolia, K, Teneketzi, E, Mellidis, C, Tsepelis, P, Louspas, C, Biternas, M, Xionis, T, Tsantilas, D, Kosmanou, M, Gougousis, I, Chatzi, F, Vassos, A, Bitchavas, S, Dalaveris, E, Spiroulias, G, Anastasopoulos, I, Karlis, D, Chiotis, D, Christodoulou, G, Arfanakis, D, Psarogianni-Sinou, V, Kokkinos, S, Anifantis, I, Alogogianni, P, Michas, A, Oikonomou, A, Charalampous, A, Papadopoulos, P, Philipoiou Kotsoni, M, Dragonas, P, Laskari, E, Tsiamtsiouri, G, Kritsova-Avgerou, V, Tiligadas, T, Vrettos, N, Vernardos, N, Melessanakis, M, Melidoniotis, A, Liodakis, E, Manousakis, A, Galanakis, C, Lampousakis, I, Vyzoukakis, E, Strimpouli, G, Patramanis, I, Chatziliadou, D, Nioti, K, Koynalakis, D, Tserkis, I, Androutsopoulou, C, Liavvas, C, Karaoglanidou, D, Kollias A., Papadatos S. S., Dominiczak A. F., Parati G., Stergiou G. S., Demerouti E., Voulgaris D., Papadakis I., Karsanidis A., Triantafillou A., Garzonis S., Gourgoulis G., Trikalinou A., Karidas P., Savvalas D., Aggelopoulos T., Alevizos A., Moraiti A., Rosmarakis E., Chatzigeorgiou G., Antonakis V., Alexandropoulou-Tsirka A., Markaki I., Astrinakis S., Roilidis V., Polymeros S., Chariatis E., Panageas V., Kontoriga A., Patsioura M., Kleftaki-Manta A., Kalantaridou A., Kourouklis S., Papakonstantinos G., Barouni P., Grekidou E., Sklaveniti A., Kolovou I., Antoniadis A., Pelekanos I., Zervaki Drakou N., Tikka-Zoumpou K., Dalaklidou V., Menti A., Christofeli A., Androutsakos T., Doulgerakis D., Oikonomopoulou I., Moschos M., Koutras D., Skias I., Boutsikos P., Matsaggoura-Sameli M., Riga M., Sainis P., Mitilinaiou-Karakozi E., Mainas K., Nikolaou K., Chatziparaskevas S., Ozai O., Vogiatzis G., Lilis L., Plaskas D., Chatzizisi S., Gianasmidis A., Petrovitsos E., Koykoyfikis G., Pittas A., Rovithis D., Ioannidis A., Dalamaga E., Kladas G., Afthonidis N., Pourou E., Katainidis S., Gavrilidou M., Kourtidou P., Tsamopoulos L., Kairis K., Arampatzi S., Basoukos C., Daskalakis K., Megianis V., Simintiridou D., Christoforidis T., Lafazanis G., Chatzioannidis L., Stephopoulos C., Karanika-Chandolia K., Teneketzi E., Mellidis C., Tsepelis P., Louspas C., Biternas M., Xionis T., Tsantilas D., Kosmanou M., Gougousis I., Chatzi F., Vassos A., Bitchavas S., Dalaveris E., Spiroulias G., Anastasopoulos I., Karlis D., Chiotis D., Christodoulou G., Arfanakis D., Psarogianni-Sinou V., Kokkinos S., Anifantis I., Alogogianni P., Michas A., Oikonomou A., Charalampous A., Papadopoulos P., Philipoiou Kotsoni M., Dragonas P., Laskari E., Tsiamtsiouri G., Kritsova-Avgerou V., Tiligadas T., Vrettos N., Vernardos N., Melessanakis M., Melidoniotis A., Liodakis E., Manousakis A., Galanakis C., Lampousakis I., Vyzoukakis E., Strimpouli G., Patramanis I., Chatziliadou D., Nioti K., Koynalakis D., Tserkis I., Androutsopoulou C., Liavvas C., Karaoglanidou D., Kollias, A, Papadatos, S, Dominiczak, A, Parati, G, Stergiou, G, Demerouti, E, Voulgaris, D, Papadakis, I, Karsanidis, A, Triantafillou, A, Garzonis, S, Gourgoulis, G, Trikalinou, A, Karidas, P, Savvalas, D, Aggelopoulos, T, Alevizos, A, Moraiti, A, Rosmarakis, E, Chatzigeorgiou, G, Antonakis, V, Alexandropoulou-Tsirka, A, Markaki, I, Astrinakis, S, Roilidis, V, Polymeros, S, Chariatis, E, Panageas, V, Kontoriga, A, Patsioura, M, Kleftaki-Manta, A, Kalantaridou, A, Kourouklis, S, Papakonstantinos, G, Barouni, P, Grekidou, E, Sklaveniti, A, Kolovou, I, Antoniadis, A, Pelekanos, I, Zervaki Drakou, N, Tikka-Zoumpou, K, Dalaklidou, V, Menti, A, Christofeli, A, Androutsakos, T, Doulgerakis, D, Oikonomopoulou, I, Moschos, M, Koutras, D, Skias, I, Boutsikos, P, Matsaggoura-Sameli, M, Riga, M, Sainis, P, Mitilinaiou-Karakozi, E, Mainas, K, Nikolaou, K, Chatziparaskevas, S, Ozai, O, Vogiatzis, G, Lilis, L, Plaskas, D, Chatzizisi, S, Gianasmidis, A, Petrovitsos, E, Koykoyfikis, G, Pittas, A, Rovithis, D, Ioannidis, A, Dalamaga, E, Kladas, G, Afthonidis, N, Pourou, E, Katainidis, S, Gavrilidou, M, Kourtidou, P, Tsamopoulos, L, Kairis, K, Arampatzi, S, Basoukos, C, Daskalakis, K, Megianis, V, Simintiridou, D, Christoforidis, T, Lafazanis, G, Chatzioannidis, L, Stephopoulos, C, Karanika-Chandolia, K, Teneketzi, E, Mellidis, C, Tsepelis, P, Louspas, C, Biternas, M, Xionis, T, Tsantilas, D, Kosmanou, M, Gougousis, I, Chatzi, F, Vassos, A, Bitchavas, S, Dalaveris, E, Spiroulias, G, Anastasopoulos, I, Karlis, D, Chiotis, D, Christodoulou, G, Arfanakis, D, Psarogianni-Sinou, V, Kokkinos, S, Anifantis, I, Alogogianni, P, Michas, A, Oikonomou, A, Charalampous, A, Papadopoulos, P, Philipoiou Kotsoni, M, Dragonas, P, Laskari, E, Tsiamtsiouri, G, Kritsova-Avgerou, V, Tiligadas, T, Vrettos, N, Vernardos, N, Melessanakis, M, Melidoniotis, A, Liodakis, E, Manousakis, A, Galanakis, C, Lampousakis, I, Vyzoukakis, E, Strimpouli, G, Patramanis, I, Chatziliadou, D, Nioti, K, Koynalakis, D, Tserkis, I, Androutsopoulou, C, Liavvas, C, Karaoglanidou, D, Kollias A., Papadatos S. S., Dominiczak A. F., Parati G., Stergiou G. S., Demerouti E., Voulgaris D., Papadakis I., Karsanidis A., Triantafillou A., Garzonis S., Gourgoulis G., Trikalinou A., Karidas P., Savvalas D., Aggelopoulos T., Alevizos A., Moraiti A., Rosmarakis E., Chatzigeorgiou G., Antonakis V., Alexandropoulou-Tsirka A., Markaki I., Astrinakis S., Roilidis V., Polymeros S., Chariatis E., Panageas V., Kontoriga A., Patsioura M., Kleftaki-Manta A., Kalantaridou A., Kourouklis S., Papakonstantinos G., Barouni P., Grekidou E., Sklaveniti A., Kolovou I., Antoniadis A., Pelekanos I., Zervaki Drakou N., Tikka-Zoumpou K., Dalaklidou V., Menti A., Christofeli A., Androutsakos T., Doulgerakis D., Oikonomopoulou I., Moschos M., Koutras D., Skias I., Boutsikos P., Matsaggoura-Sameli M., Riga M., Sainis P., Mitilinaiou-Karakozi E., Mainas K., Nikolaou K., Chatziparaskevas S., Ozai O., Vogiatzis G., Lilis L., Plaskas D., Chatzizisi S., Gianasmidis A., Petrovitsos E., Koykoyfikis G., Pittas A., Rovithis D., Ioannidis A., Dalamaga E., Kladas G., Afthonidis N., Pourou E., Katainidis S., Gavrilidou M., Kourtidou P., Tsamopoulos L., Kairis K., Arampatzi S., Basoukos C., Daskalakis K., Megianis V., Simintiridou D., Christoforidis T., Lafazanis G., Chatzioannidis L., Stephopoulos C., Karanika-Chandolia K., Teneketzi E., Mellidis C., Tsepelis P., Louspas C., Biternas M., Xionis T., Tsantilas D., Kosmanou M., Gougousis I., Chatzi F., Vassos A., Bitchavas S., Dalaveris E., Spiroulias G., Anastasopoulos I., Karlis D., Chiotis D., Christodoulou G., Arfanakis D., Psarogianni-Sinou V., Kokkinos S., Anifantis I., Alogogianni P., Michas A., Oikonomou A., Charalampous A., Papadopoulos P., Philipoiou Kotsoni M., Dragonas P., Laskari E., Tsiamtsiouri G., Kritsova-Avgerou V., Tiligadas T., Vrettos N., Vernardos N., Melessanakis M., Melidoniotis A., Liodakis E., Manousakis A., Galanakis C., Lampousakis I., Vyzoukakis E., Strimpouli G., Patramanis I., Chatziliadou D., Nioti K., Koynalakis D., Tserkis I., Androutsopoulou C., Liavvas C., and Karaoglanidou D.

Abstract

Background: This study assessed the diagnostic reliability of automated office blood pressure (OBP) measurements in treated hypertensive patients in primary care by evaluating the prevalence of white coat hypertension (WCH) and masked uncontrolled hypertension (MUCH) phenomena. Methods: Primary care physicians, nationwide in Greece, assessed consecutive hypertensive patients on stable treatment using OBP (1 visit, triplicate measurements) and home blood pressure (HBP) measurements (7 days, duplicate morning and evening measurements). All measurements were performed using validated automated devices with bluetooth capacity (Omron M7 Intelli-IT). Uncontrolled OBP was defined as ≥140/90 mmHg, and uncontrolled HBP was defined as ≥135/85 mmHg. Results: A total of 790 patients recruited by 135 doctors were analyzed (age: 64.5 ± 14.4 years, diabetics: 21.4%, smokers: 20.6%, and average number of antihypertensive drugs: 1.6 ± 0.8). OBP (137.5 ± 9.4/84.3 ± 7.7 mmHg, systolic/diastolic) was higher than HBP (130.6 ± 11.2/79.9 ± 8 mmHg; difference 6.9 ± 11.6/4.4 ± 7.6 mmHg, p < 0.001). WCH phenomenon (high OBP with low HBP) was observed in 22.7% of the patients, MUCH (low OBP with high HBP) in 15.8%, uncontrolled hypertension (high OBP with high HBP) in 29.9%, and controlled hypertension (low OBP with low HBP) in 31.6%. In multivariate logistic regression analysis, WCH was determined by stage-1 systolic hypertension (odds ratio [OR] 8.6, 95% confidence intervals [CI] 5.7, 13.1) and female gender (OR 1.6, 95% CI 1.1, 2.4), whereas MUCH was determined by high-normal systolic OBP (OR 6.2, 95% CI 3.8, 10.1) and male gender (OR 2.0, 95% CI 1.2, 3.1). Conclusions: In primary care, automated OBP measurements are misleading in approximately 40% of treated hypertensive patients. HBP monitoring is mandatory to avoid overtreatment of subjects with WCH phenomenon and prevent undertreatment and subsequent excess cardiovascular disease in MUCH.

Published
2020

208. How to Apply European and American Guidelines on High Blood Pressure in Children and Adolescents. A Position Paper Endorsed by the Italian Society of Hypertension and the Italian Society of Pediatrics

Author

Genovesi, S, Parati, G, Giussani, M, Bona, G, Fava, C, Maffeis, C, Ferri, C, Giordano, U, Genovesi S., Parati G., Giussani M., Bona G., Fava C., Maffeis C., Ferri C., Giordano U., Genovesi, S, Parati, G, Giussani, M, Bona, G, Fava, C, Maffeis, C, Ferri, C, Giordano, U, Genovesi S., Parati G., Giussani M., Bona G., Fava C., Maffeis C., Ferri C., and Giordano U.

Abstract

Children are defined as hypertensive when their blood pressure values equal or exceed the 95th percentile of the blood pressure value distribution in a pediatric population, according to gender, age and height. The population on which reference tables are based is of fundamental importance to establish the threshold values for the diagnosis of hypertension in pediatric age. Before 2017, both American and European guidelines used nomograms created in the same reference population which included children of all weight classes. Given the close and well-known association between hypertension and excess weight in childhood, the 2017 American guidelines proposed new reference nomograms excluding subjects with overweight and obesity from the “historical” reference population. Furthermore, the new American guidelines suggested a fixed cut-off of 130/80 mmHg, starting from 13 years and regardless of gender and height, to make the diagnosis of hypertension. In this document, the Italian Hypertension Society (SIIA) and the Italian Pediatric Society (SIP) jointly discuss a number of issues raised by the new American guidelines that involve the entire medical community, and also address the definition of arterial hypertension in the transition phase between childhood and adulthood.

Published
2020

209. Risk factors for primary ventricular fibrillation during a first myocardial infarction: Clinical findings from PREDESTINATION (PRimary vEntricular fibrillation and suDden dEath during firST myocardIal iNfArcTION).

Author

De Ferrari, G, Dusi, V, Ruffinazzi, M, Masiello, L, Ruffino, E, Cacciavillani, L, Noussan, P, Zacà, V, Sanna, T, Lazzarotti, M, Usmiani, T, Gnecchi, M, Parati, G, Crotti, L, Schwartz, P, ESCAPE-NET, I, De Ferrari GM, Dusi V, Ruffinazzi M, Masiello LC, Ruffino E, Cacciavillani L, Noussan P, Zacà V, Sanna T, Lazzarotti ML, Usmiani T, Gnecchi M, Parati G, Crotti L, Schwartz PJ, ESCAPE-NET Investigators., De Ferrari, G, Dusi, V, Ruffinazzi, M, Masiello, L, Ruffino, E, Cacciavillani, L, Noussan, P, Zacà, V, Sanna, T, Lazzarotti, M, Usmiani, T, Gnecchi, M, Parati, G, Crotti, L, Schwartz, P, ESCAPE-NET, I, De Ferrari GM, Dusi V, Ruffinazzi M, Masiello LC, Ruffino E, Cacciavillani L, Noussan P, Zacà V, Sanna T, Lazzarotti ML, Usmiani T, Gnecchi M, Parati G, Crotti L, Schwartz PJ, and ESCAPE-NET Investigators.

Abstract

Background: Few studies prospectively assessed risk factors for ventricular fibrillation (VF) during a first myocardial infarction (MI). We designed a nation-wide study aiming to identify clinical and genetic characteristics associated with primary VF; and report here about clinical features. Methods: PREDESTINATION (PRimary vEntricular fibrillation and suDden dEath during a firST myocardIal iNfArcTION) is an Italian case-control, prospective multicentre study. Cases are patients aged 18–80 years with a first MI and at least one VF episodes occurring within 24 h of symptoms onset, before reperfusion. Cases and controls are paired 1: 2 by gender and age (±5 years). Results: Among 1026 patients enrolled between 2007 and 2017, 970 entered the primary analysis: 375 cases and 595 controls (mean age 59 years, 85% males). Multivariable analysis identified 5 independent predictors of primary VF: systolic blood pressure (OR 0.982, 95% CI: 0.98–0.99 for each mm Hg) and K+ levels <3.5 mEq/L at presentation (OR 2.28, 95% CI: 1.6–3.3), family history of sudden death (OR 1.80, 95% CI: 1.1–3.0), physical inactivity (OR 1.73, 95% CI: 1.1–2.8) and anterior MI (OR 1.52, 95% CI: 1.1–2.1). Excluding K+ levels obtained after VF, the OR associated with K+ levels <3.5 mEq/L was1.99 (95 CI 1.22–3.21). Conclusions: The present study identified 5 independent predictors of primary VF: familiarity, anterior MI, low systolic blood pressure, physical inactivity and hypokalaemia. Importantly, the last two risk factors are modifiable and, especially in the presence of a family history of sudden death, they should be avoided as much as possible.

Published
2020

210. Blood Pressure-Lowering Profiles and Clinical Effects of Angiotensin Receptor Blockers Versus Calcium Channel Blockers

Author

Mehlum, M, Liestol, K, Kjeldsen, S, Wyller, T, Julius, S, Rothwell, P, Mancia, G, Parati, G, Weber, M, Berge, E, Mehlum M. H., Liestol K., Kjeldsen S. E., Wyller T. B., Julius S., Rothwell P. M., Mancia G., Parati G., Weber M. A., Berge E., Mehlum, M, Liestol, K, Kjeldsen, S, Wyller, T, Julius, S, Rothwell, P, Mancia, G, Parati, G, Weber, M, Berge, E, Mehlum M. H., Liestol K., Kjeldsen S. E., Wyller T. B., Julius S., Rothwell P. M., Mancia G., Parati G., Weber M. A., and Berge E.

Abstract

Blood pressure-lowering drugs have different blood pressure-lowering profiles. We studied if differences in blood pressure mean and variability can explain the differences in risks of cardiovascular events and death among 15 245 high-risk hypertensive patients randomized to valsartan or amlodipine and followed for 4.2 years in the VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation). We selected patients with ≥3 visits and performed Cox regression analyses, defining mean blood pressure as a time-dependent covariate and visit-to-visit and within-visit blood pressure variability as the SD. Of 14 996 eligible patients, participants in the valsartan group had higher systolic mean blood pressure by 2.2 mm Hg, higher visit-to-visit systolic variability by 1.4 mm Hg, and higher within-visit systolic variability by 0.2 mm Hg (P values <0.0001). The higher risks of myocardial infarction and stroke in the valsartan group was attenuated after adjustment for mean and variability of systolic blood pressure, from HR 1.19 (95% CI, 1.02-1.39) to 1.11 (0.96-1.30) and from HR 1.13 (0.96-1.33) to 1.00 (0.85-1.18), respectively. The lower risk of congestive heart failure in the valsartan group was accentuated after adjustment, from HR 0.86 (0.74-1.00) to 0.76 (0.65-0.89). A smaller effect was seen on risk of death, from 1.01 (0.92-1.12) to 0.94 (0.85-1.04). In conclusion, the higher risks of myocardial infarction and stroke in patients randomized to valsartan versus amlodipine were related to the drugs' different blood pressure modulating profiles. The risk of congestive heart failure with valsartan was lower, independent of the less favorable blood pressure modulating profile.

Published
2020

211. Nocturnal arrhythmias and heart-rate swings in patients with obstructive sleep apnea syndrome treated with beta blockers

Author

Lombardi, C, Faini, A, Mariani, D, Gironi, F, Castiglioni, P, Parati, G, Lombardi C., Faini A., Mariani D., Gironi F., Castiglioni P., Parati G., Lombardi, C, Faini, A, Mariani, D, Gironi, F, Castiglioni, P, Parati, G, Lombardi C., Faini A., Mariani D., Gironi F., Castiglioni P., and Parati G.

Abstract

BACKGROUND: The higher cardiovascular variability and the increased prevalence of arrhythmias in patients with obstructive sleep apneas may contribute to their higher rate of fatal events during sleep. In this regard, the use of beta blockers (BB) is debated because they may induce bradyarrhythmias and alter the pattern of heart rate changes induced by apneas. Thus, the aim of our study is to quantify peri-apneic heart-rate swings and prevalence of nocturnal bradyarrhythmias in BB-treated and BB-naïve patients with obstructive sleep apnea. METHODS AND RESULTS: Our real-life, retrospective, cohort study analyzed data from patients with obstructive sleep apnea after a basal cardiorespiratory polysomnography. Among 228 eligible participants, we enrolled 78 BB-treated and 88 BBnaïve patients excluding those treated with antiarrhythmic drugs or pacemakers, or with uninterpretable ECG traces during polysomnography. In each patient, type and frequency of arrhythmias were identified and peri-apneic changes of RR intervals were evaluated for each apnea. BB-treated patients were older and with more comorbidities than BB-naïve patients, but had similar obstructive sleep apnea severity, similar frequency of arrhythmic episodes, and similar prevalence of bradyarrhythmias. Apnea-induced heart-rate swings, unadjusted for age, showed lower RR interval changes in BB-treated (133.5±63.8 ms) than BB-naïve patients (171.3±87.7 ms, P=0.01), lower RR interval increases during apneas (58.5±28.5 versus 74.6±40.2 ms, P=0.01), and lower RR interval decreases after apneas (75.0±42.4 versus 96.7±55.5 ms, P<0.05). CONCLUSIONS: BB appear to be safe in patients with obstructive sleep apnea because they are not associated with worse episodes of nocturnal bradyarrhythmias and even seem protective in terms of apnea-induced changes of heart rate.

Published
2020

212. Sleep apnoea management in Europe during the COVID-19 pandemic – Data from the European Sleep Apnoea Database (ESADA)

Author

Grote, L, Mcnicholas, W, Hedner, J, Anttalainen, U, Saaresranta, T, Basoglu, O, Gunduz, C, Tasbakan, S, Bouloukaki, I, Schiza, S, Bonsignore, M, Marrone, O, Petitjean, M, Roisman, G, Fietze, I, Laharnar, N, Penzel, T, Zou, D, Kent, B, Ryan, S, Kvamme, J, Bailly, S, Pepin, J, Tamisier, R, Lombardi, C, Parati, G, Pataka, A, Plywaczewski, R, Sliwinski, P, Pretl, M, Riha, R, Staats, R, Steiropoulos, P, Joppa, P, Verbraecken, J, Petiet, E, Trakada, G, Ludka, O, Buskova, J, Hein, H, Drummond, M, van Zeller, M, Dogas, Z, Galic, T, Gouveris, H, Mihaicuta, S, Randerath, W, Herkenrath, S, Fanfulla, F, Testelmans, D, Grote L., McNicholas W. T., Hedner J., Anttalainen U., Saaresranta T., Basoglu O. K., Gunduz C., Tasbakan S., Bouloukaki I., Schiza S. E., Bonsignore M. R., Marrone O., Petitjean M., Roisman G., Fietze I., Laharnar N., Penzel T., Zou D., Kent B. D., Ryan S., Kvamme J. A., Bailly S., Pepin J. -L., Tamisier R., Lombardi C., Parati G., Pataka A., Plywaczewski R., Sliwinski P., Pretl M., Riha R., Staats R., Steiropoulos P., Joppa P., Verbraecken J., Petiet E., Trakada G., Ludka O., Buskova J., Hein H., Drummond M., van Zeller M., Dogas Z., Galic T., Gouveris H., Mihaicuta S., Randerath W., Herkenrath S., Fanfulla F., Testelmans D., Grote, L, Mcnicholas, W, Hedner, J, Anttalainen, U, Saaresranta, T, Basoglu, O, Gunduz, C, Tasbakan, S, Bouloukaki, I, Schiza, S, Bonsignore, M, Marrone, O, Petitjean, M, Roisman, G, Fietze, I, Laharnar, N, Penzel, T, Zou, D, Kent, B, Ryan, S, Kvamme, J, Bailly, S, Pepin, J, Tamisier, R, Lombardi, C, Parati, G, Pataka, A, Plywaczewski, R, Sliwinski, P, Pretl, M, Riha, R, Staats, R, Steiropoulos, P, Joppa, P, Verbraecken, J, Petiet, E, Trakada, G, Ludka, O, Buskova, J, Hein, H, Drummond, M, van Zeller, M, Dogas, Z, Galic, T, Gouveris, H, Mihaicuta, S, Randerath, W, Herkenrath, S, Fanfulla, F, Testelmans, D, Grote L., McNicholas W. T., Hedner J., Anttalainen U., Saaresranta T., Basoglu O. K., Gunduz C., Tasbakan S., Bouloukaki I., Schiza S. E., Bonsignore M. R., Marrone O., Petitjean M., Roisman G., Fietze I., Laharnar N., Penzel T., Zou D., Kent B. D., Ryan S., Kvamme J. A., Bailly S., Pepin J. -L., Tamisier R., Lombardi C., Parati G., Pataka A., Plywaczewski R., Sliwinski P., Pretl M., Riha R., Staats R., Steiropoulos P., Joppa P., Verbraecken J., Petiet E., Trakada G., Ludka O., Buskova J., Hein H., Drummond M., van Zeller M., Dogas Z., Galic T., Gouveris H., Mihaicuta S., Randerath W., Herkenrath S., Fanfulla F., and Testelmans D.

Published
2020

213. Long-term positive airway pressure therapy is associated with reduced total cholesterol levels in patients with obstructive sleep apnea: data from the European Sleep Apnea Database (ESADA)

Author

Gunduz, C, Basoglu, O, Kvamme, J, Verbraecken, J, Anttalainen, U, Marrone, O, Steiropoulos, P, Roisman, G, Joppa, P, Hein, H, Trakada, G, Hedner, J, Grote, L, Petiet, E, Montserrat, J, Fietze, I, Penzel, T, Ludka, O, Rodenstein, D, Masa, J, Bouloukaki, I, Schiza, S, Kent, B, Mcnicholas, W, Ryan, S, Riha, R, Schulz, R, Zou, D, Pepin, J, Levy, P, Bailly, S, Lavie, L, Lavie, P, Tasbakan, M, Varoneckas, G, Tkacova, R, Staats, R, Barbe, F, Lombardi, C, Parati, G, Drummond, M, van Zeller, M, Bonsignore, M, Petitjean, M, Pretl, M, Vitols, A, Dogas, Z, Galic, T, Pataka, A, Saaresranta, T, Plywaczewski, R, Sliwinski, P, Bielicki, P, Gunduz C., Basoglu O. K., Kvamme J. A., Verbraecken J., Anttalainen U., Marrone O., Steiropoulos P., Roisman G., Joppa P., Hein H., Trakada G., Hedner J., Grote L., Petiet E., Montserrat J. M., Fietze I., Penzel T., Ludka O., Rodenstein D., Masa J. F., Bouloukaki I., Schiza S., Kent B., McNicholas W. T., Ryan S., Riha R. L., Schulz R., Zou D., Pepin J. L., Levy P., Bailly S., Lavie L., Lavie P., Tasbakan M. S., Varoneckas G., Tkacova R., Staats R., Barbe F., Lombardi C., Parati G., Drummond M., van Zeller M., Bonsignore M. R., Petitjean M., Pretl M., Vitols A., Dogas Z., Galic T., Pataka A., Saaresranta T., Plywaczewski R., Sliwinski P., Bielicki P., Gunduz, C, Basoglu, O, Kvamme, J, Verbraecken, J, Anttalainen, U, Marrone, O, Steiropoulos, P, Roisman, G, Joppa, P, Hein, H, Trakada, G, Hedner, J, Grote, L, Petiet, E, Montserrat, J, Fietze, I, Penzel, T, Ludka, O, Rodenstein, D, Masa, J, Bouloukaki, I, Schiza, S, Kent, B, Mcnicholas, W, Ryan, S, Riha, R, Schulz, R, Zou, D, Pepin, J, Levy, P, Bailly, S, Lavie, L, Lavie, P, Tasbakan, M, Varoneckas, G, Tkacova, R, Staats, R, Barbe, F, Lombardi, C, Parati, G, Drummond, M, van Zeller, M, Bonsignore, M, Petitjean, M, Pretl, M, Vitols, A, Dogas, Z, Galic, T, Pataka, A, Saaresranta, T, Plywaczewski, R, Sliwinski, P, Bielicki, P, Gunduz C., Basoglu O. K., Kvamme J. A., Verbraecken J., Anttalainen U., Marrone O., Steiropoulos P., Roisman G., Joppa P., Hein H., Trakada G., Hedner J., Grote L., Petiet E., Montserrat J. M., Fietze I., Penzel T., Ludka O., Rodenstein D., Masa J. F., Bouloukaki I., Schiza S., Kent B., McNicholas W. T., Ryan S., Riha R. L., Schulz R., Zou D., Pepin J. L., Levy P., Bailly S., Lavie L., Lavie P., Tasbakan M. S., Varoneckas G., Tkacova R., Staats R., Barbe F., Lombardi C., Parati G., Drummond M., van Zeller M., Bonsignore M. R., Petitjean M., Pretl M., Vitols A., Dogas Z., Galic T., Pataka A., Saaresranta T., Plywaczewski R., Sliwinski P., and Bielicki P.

Abstract

Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies.

Published
2020

214. Mild obstructive sleep apnea increases hypertension risk, challenging traditional severity classification

Author

Bouloukaki, I, Grote, L, Mcnicholas, W, Hedner, J, Verbraecken, J, Parati, G, Lombardi, C, Basoglu, O, Pataka, A, Marrone, O, Steiropoulos, P, Bonsignore, M, Schiza, S, Bouloukaki I., Grote L., McNicholas W. T., Hedner J., Verbraecken J., Parati G., Lombardi C., Basoglu O. K., Pataka A., Marrone O., Steiropoulos P., Bonsignore M. R., Schiza S. E., Bouloukaki, I, Grote, L, Mcnicholas, W, Hedner, J, Verbraecken, J, Parati, G, Lombardi, C, Basoglu, O, Pataka, A, Marrone, O, Steiropoulos, P, Bonsignore, M, Schiza, S, Bouloukaki I., Grote L., McNicholas W. T., Hedner J., Verbraecken J., Parati G., Lombardi C., Basoglu O. K., Pataka A., Marrone O., Steiropoulos P., Bonsignore M. R., and Schiza S. E.

Abstract

Study Objectives: The association of mild obstructive sleep apnea (OSA) with important clinical outcomes remains unclear. We aimed to investigate the association between mild OSA and systemic arterial hypertension (SAH) in the European Sleep Apnea Database cohort. Methods: In a multicenter sample of 4,732 participants, we analyzed the risk of mild OSA (subclassified into 2 groups: MildAHI 5-<11/h (apnea-hypopnea index [AHI], 5 to <11 events/h) and mildAHI 11-<15/h (AHI, .11 to <15 events/h) compared with nonapneic snorers for prevalent SAH after adjustment for relevant confounding factors including sex, age, smoking, obesity, daytime sleepiness, dyslipidemia, chronic obstructive pulmonary disease, type 2 diabetes, and sleep test methodology (polygraphy or polysomnography). Results: SAH prevalence was higher in the mildAHI 11-<15/h OSA group compared with the mildAHI 5-<11/h group and nonapneic snorers (52% vs 45% vs 30%; P < -001). Corresponding adjusted odds ratios for SAH were 1.789 (mildAHI 11-<15/h; 95% confidence interval [CI], 1.49.2.15) and 1.558 (mildAHI 5-<11/h; 95%, CI, 1.34.1.82), respectively (P <.001). In sensitivity analysis, mildAHI 11-<15/h OSA remained a significant predictor for SAH both in the polygraphy (odds ratio, 1.779; 95% CI, 1.403.2.256; P < -001) and polysomnography groups (odds ratio, 1.424; 95% CI, 1.047.1.939; P = .025). Conclusions: Our data suggest a dose-response relationship betweenmild OSA and SAH risk, starting from 5 events/h in polygraphy recordings and continuing with a further risk increase in the 11-to <150-events/h range. These findings potentially introduce a challenge to traditional thresholds of OSA severity and may help to stratify participants with OSA according to cardiovascular risk.

Published
2020

215. Treating sleep disorders to improve blood pressure control and cardiovascular prevention: A dream come true?—a narrative review

Author

Maiolino, G, Bisogni, V, Silvani, A, Pengo, M, Lombardi, C, Parati, G, Maiolino G., Bisogni V., Silvani A., Pengo M., Lombardi C., Parati G., Maiolino, G, Bisogni, V, Silvani, A, Pengo, M, Lombardi, C, Parati, G, Maiolino G., Bisogni V., Silvani A., Pengo M., Lombardi C., and Parati G.

Abstract

Hypertension is one of the primary risk factors for heart disease and stroke, the leading causes of death worldwide. Current evidence supports the treatment of high blood pressure (BP) values in order to obtain a substantial reduction of cardiovascular burden. Sleep plays an important role in maintaining nocturnal BP control and nocturnal hypertension which, in turn, can be affected by the presence of sleep disorders. Whilst respiratory disturbances have been extensively studied and their causal role in the development of nocturnal hypertension has been demonstrated in both cross sectional and prospective studies, less is known about the impact of other sleep disorders such as insomnia. In this review, we aim to describe the role of sleep disorders in the development of nocturnal and diurnal hypertension. Furthermore, we aim to discuss the potential impact of the treatment of such sleep disorders on BP values as an adjunct treatment for patients with hypertension.

Published
2020

216. Adenosine and the Cardiovascular System: The Good and the Bad.

Author

Guieu, R, Deharo, J, Maille, B, Crotti, L, Torresani, E, Brignole, M, Parati, G, Guieu R, Deharo JC, Maille B, Crotti L, Torresani E, Brignole M, Parati G., Guieu, R, Deharo, J, Maille, B, Crotti, L, Torresani, E, Brignole, M, Parati, G, Guieu R, Deharo JC, Maille B, Crotti L, Torresani E, Brignole M, and Parati G.

Abstract

Adenosine is a nucleoside that impacts the cardiovascular system via the activation of its membrane receptors, named A1R, A2AR, A2BR and A3R. Adenosine is released during hypoxia, ischemia, beta-adrenergic stimulation or inflammation and impacts heart rhythm and produces strong vasodilation in the systemic, coronary or pulmonary vascular system. This review summarizes the main role of adenosine on the cardiovascular system in several diseases and conditions. Adenosine release participates directly in the pathophysiology of atrial fibrillation and neurohumoral syncope. Adenosine has a key role in the adaptive response in pulmonary hypertension and heart failure, with the most relevant effects being slowing of heart rhythm, coronary vasodilation and decreasing blood pressure. In other conditions, such as altitude or apnea-induced hypoxia, obstructive sleep apnea, or systemic hypertension, the adenosinergic system activation appears in a context of an adaptive response. Due to its short half-life, adenosine allows very rapid adaptation of the cardiovascular system. Finally, the effects of adenosine on the cardiovascular system are sometimes beneficial and other times harmful. Future research should aim to develop modulating agents of adenosine receptors to slow down or conversely amplify the adenosinergic response according to the occurrence of different pathologic conditions.

Published
2020

217. Seasonal variation in blood pressure: Evidence, consensus and recommendations for clinical practice. Consensus statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability

Author

Stergiou, G, Palatini, P, Modesti, P, Asayama, K, Asmar, R, Bilo, G, De La Sierra, A, Dolan, E, Head, G, Kario, K, Kollias, A, Manios, E, Mihailidou, A, Myers, M, Niiranen, T, Ohkubo, T, Protogerou, A, Wang, J, O'Brien, E, Parati, G, Stergiou G. S., Palatini P., Modesti P. A., Asayama K., Asmar R., Bilo G., De La Sierra A., Dolan E., Head G., Kario K., Kollias A., Manios E., Mihailidou A. S., Myers M., Niiranen T., Ohkubo T., Protogerou A., Wang J., O'Brien E., Parati G., Stergiou, G, Palatini, P, Modesti, P, Asayama, K, Asmar, R, Bilo, G, De La Sierra, A, Dolan, E, Head, G, Kario, K, Kollias, A, Manios, E, Mihailidou, A, Myers, M, Niiranen, T, Ohkubo, T, Protogerou, A, Wang, J, O'Brien, E, Parati, G, Stergiou G. S., Palatini P., Modesti P. A., Asayama K., Asmar R., Bilo G., De La Sierra A., Dolan E., Head G., Kario K., Kollias A., Manios E., Mihailidou A. S., Myers M., Niiranen T., Ohkubo T., Protogerou A., Wang J., O'Brien E., and Parati G.

Abstract

Blood pressure (BP) exhibits seasonal variation with lower levels at higher environmental temperatures and higher at lower temperatures. This is a global phenomenon affecting both sexes, all age groups, normotensive individuals, and hypertensive patients. In treated hypertensive patients it may result in excessive BP decline in summer, or rise in winter, possibly deserving treatment modification. This Consensus Statement by the European Society of Hypertension Working Group on BP Monitoring and Cardiovascular Variability provides a review of the evidence on the seasonal BP variation regarding its epidemiology, pathophysiology, relevance, magnitude, and the findings using different measurement methods. Consensus recommendations are provided for health professionals on how to evaluate the seasonal BP changes in treated hypertensive patients and when treatment modification might be justified. (i) In treated hypertensive patients symptoms appearing with temperature rise and suggesting overtreatment must be investigated for possible excessive BP drop due to seasonal variation. On the other hand, a BP rise during cold weather, might be due to seasonal variation. (ii) The seasonal BP changes should be confirmed by repeated office measurements; preferably with home or ambulatory BP monitoring. Other reasons for BP change must be excluded. (iii) Similar issues might appear in people traveling from cold to hot places, or the reverse. (iv) BP levels below the recommended treatment goal should be considered for possible down-titration, particularly if there are symptoms suggesting overtreatment. SBP less than 110 mmHg requires consideration for treatment down-titration, even in asymptomatic patients. Further research is needed on the optimal management of the seasonal BP changes.

Published
2020

218. Office and Ambulatory Arterial Hypertension in Highlanders: HIGHCARE-ANDES Highlanders Study

Author

Bilo, G, Acone, L, Anza-Ramire, C, Macarlupu, J, Soranna, D, Zambon, A, Vizcardo-Galindo, G, Pengo, M, Villafuerte, F, Parati, G, Bilo G., Acone L., Anza-Ramire C., MacArlupu J. L., Soranna D., Zambon A., Vizcardo-Galindo G., Pengo M. F., Villafuerte F. C., Parati G., Bilo, G, Acone, L, Anza-Ramire, C, Macarlupu, J, Soranna, D, Zambon, A, Vizcardo-Galindo, G, Pengo, M, Villafuerte, F, Parati, G, Bilo G., Acone L., Anza-Ramire C., MacArlupu J. L., Soranna D., Zambon A., Vizcardo-Galindo G., Pengo M. F., Villafuerte F. C., and Parati G.

Abstract

Millions of people worldwide live at high altitude, being chronically exposed to hypobaric hypoxia. Hypertension is a major cardiovascular risk factor but data on its prevalence and determinants in highlanders are limited, and systematic studies with ambulatory blood pressure monitoring are not available. Aim of this study was to assess the prevalence of clinic and ambulatory hypertension and the associated factors in a sample of Andean highlanders. Hypertension prevalence and phenotypes were assessed with office and ambulatory blood pressure measurement in a sample of adults living in Cerro de Pasco, Peru (altitude 4340 m). Basic clinical data, blood oxygen saturation, hematocrit, and Qinghai Chronic Mountain Sickness score were obtained. Participants were classified according to the presence of excessive erythrocytosis and chronic mountain sickness diagnosis. Data of 289 participants (143 women, 146 men, mean age 38.3 years) were analyzed. Office hypertension was present in 20 (7%) participants, while ambulatory hypertension was found in 58 (20%) participants. Masked hypertension was common (15%), and white coat hypertension was rare (2%). Among participants with ambulatory hypertension, the most prevalent phenotypes included isolated nocturnal hypertension, isolated diastolic hypertension, and systodiastolic hypertension. Ambulatory hypertension was associated with male gender, age, overweight/obesity, 24-hour heart rate, and excessive erythrocytosis. Prevalence of hypertension among Andean highlanders may be significantly underestimated when based on conventional blood pressure measurements, due to the high prevalence of masked hypertension. In highlanders, ambulatory hypertension may be independently associated with excessive erythrocytosis.

Published
2020

219. Advanced imaging of right ventricular anatomy and function

Author

Badano, L, Addetia, K, Pontone, G, Torlasco, C, Lang, R, Parati, G, Muraru, D, Badano L., Addetia K., Pontone G., Torlasco C., Lang R. M., Parati G., Muraru D., Badano, L, Addetia, K, Pontone, G, Torlasco, C, Lang, R, Parati, G, Muraru, D, Badano L., Addetia K., Pontone G., Torlasco C., Lang R. M., Parati G., and Muraru D.

Abstract

Right ventricular (RV) size and function are important predictors of cardiovascular morbidity and mortality in patients with various conditions. However, non-invasive assessment of the RV is a challenging task due to its complex anatomy and location in the chest. Although conventional echocardiography is widely used, its limitations in RV assessment are well recognised. New techniques such as three-dimensional and speckle tracking echocardiography have overcome the limitations of conventional echocardiography allowing a comprehensive, quantitative assessment of RV geometry and function without geometric assumptions. Cardiac magnetic resonance (CMR) and CT provide accurate assessment of RV geometry and function, too. In addition, tissue characterisation imaging for myocardial scar and fat using CMR and CT provides important information regarding the RV that has clinical applications for diagnosis and prognosis in a broad range of cardiac conditions. Limitations also exist for these two advanced modalities including availability and patient suitability for CMR and need for contrast and radiation exposure for CT. Hybrid imaging, which is able to integrate anatomical information (usually obtained by CT or CMR) with physiological and molecular data (usually obtained with positron emission tomography), can provide optimal in vivo evaluation of Rv functional impairment. This review summarises the clinically useful applications of advanced echocardiography techniques, CMR and CT for comprehensive assessment of RV size, function and mechanics.

Published
2020

220. Artificial Intelligence and Cardiovascular Imaging. A win-win Combination

Author

Badano, L, Keller, D, Torlasco, C, Muraru, D, Parati, G, Badano L, Keller D. M, Torlasco C, Muraru D, Parati G, Badano, L, Keller, D, Torlasco, C, Muraru, D, Parati, G, Badano L, Keller D. M, Torlasco C, Muraru D, and Parati G

Abstract

Rapid development of artificial intelligence (AI) is gaining grounds in medicine. Its huge impact and inevitable necessity are also reflected in cardiovascular imaging. Although AI would probably never replace doctors, it can significantly support and improve their productivity and diagnostic performance. Many algorithms have already proven useful at all stages of the cardiac imaging chain. Their crucial practical applications include classification, automatic quantification, notification, diagnosis, and risk prediction. Consequently, more reproducible and repeatable studies are obtained, and personalized reports may be available to any patient. Utilization of AI also increases patient safety and decreases healthcare costs. Furthermore, AI is particularly useful for beginners in the field of cardiac imaging as it provides anatomic guidance and interpretation of complex imaging results. In contrast, lack of interpretability and explainability in AI carries a risk of harmful recommendations. This review was aimed at summarizing AI principles, essential execution requirements, and challenges as well as its recent applications in cardiovascular imaging.

Published
2020

221. Obstructive sleep apnoea treatment and blood pressure: Which phenotypes predict a response? A systematic review and meta-analysis

Author

Pengo, M, Soranna, D, Giontella, A, Perger, E, Mattaliano, P, Schwarz, E, Lombardi, C, Bilo, G, Zambon, A, Steier, J, Parati, G, Minuz, P, Fava, C, Pengo M. F., Soranna D., Giontella A., Perger E., Mattaliano P., Schwarz E. I., Lombardi C., Bilo G., Zambon A., Steier J., Parati G., Minuz P., Fava C., Pengo, M, Soranna, D, Giontella, A, Perger, E, Mattaliano, P, Schwarz, E, Lombardi, C, Bilo, G, Zambon, A, Steier, J, Parati, G, Minuz, P, Fava, C, Pengo M. F., Soranna D., Giontella A., Perger E., Mattaliano P., Schwarz E. I., Lombardi C., Bilo G., Zambon A., Steier J., Parati G., Minuz P., and Fava C.

Abstract

The treatment for obstructive sleep apnoea (OSA) with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is associated with blood pressure (BP) reduction; however, the overall effect is modest. The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effect of such treatments on BP was to identify subgroups of patients who respond best to treatment. The article search was performed in three different databases with specific search terms and selection criteria. From 2289 articles, we included 68 RCTs that compared CPAP or MADs with either passive or active treatment. When all the studies were pooled together, CPAP and MADs were associated with a mean BP reduction of 2.09 (95% CI 2.78-1.40) mmHg for systolic BP and 1.92 (95% CI 2.40-1.43) mmHg for diastolic BP and 1.27 (95% CI 2.34-0.20) mmHg for systolic BP and 1.11 (95% CI 1.82-0.41) mmHg for diastolic BP, respectively. The subgroups of patients who showed a greater response were those aged <60 years (systolic BP 2.93 mmHg), with uncontrolled BP at baseline (systolic BP 4.14 mmHg) and with severe oxygen desaturations (minimum arterial oxygen saturation measured by pulse oximetry <77%) at baseline (24-h systolic BP 7.57 mmHg). Although this meta-analysis shows that the expected reduction of BP by CPAP/MADs is modest, it identifies specific characteristics that may predict a pronounced benefit from CPAP in terms of BP control. These findings should be interpreted with caution; however, they are particularly important in identifying potential phenotypes associated with BP reduction in patients treated for OSA.

Published
2020

223. Prolonged QRS associated with left bundle branch conduction defect is a prognostic red flag in asymptomatic patients at risk for heart failure (ACCF/AHA stages A and B): Insights from the DAVID-Berg study

Author

Pozzi, A, Gori, M, Iorio, A, Iacovoni, A, Carobbio, A, Cioffi, G, De Maria, R, Grosu, A, Fontana, A, Canova, P, Calabrese, A, Ferrari, P, Parati, G, Lorini, F, Senni, M, Gavazzi, A, Pozzi A., Gori M., Iorio A., Iacovoni A., Carobbio A., Cioffi G., De Maria R., Grosu A., Fontana A., Canova P. A., Calabrese A., Ferrari P., Parati G., Lorini F. L., Senni M., Gavazzi A., Pozzi, A, Gori, M, Iorio, A, Iacovoni, A, Carobbio, A, Cioffi, G, De Maria, R, Grosu, A, Fontana, A, Canova, P, Calabrese, A, Ferrari, P, Parati, G, Lorini, F, Senni, M, Gavazzi, A, Pozzi A., Gori M., Iorio A., Iacovoni A., Carobbio A., Cioffi G., De Maria R., Grosu A., Fontana A., Canova P. A., Calabrese A., Ferrari P., Parati G., Lorini F. L., Senni M., and Gavazzi A.

Published
2020

224. Improvement of functional capacity in sacubitril-valsartan treated patients assessed by cardiopulmonary exercise test

Author

Malfatto, G, Ravaro, S, Caravita, S, Baratto, C, Sorropago, A, Giglio, A, Tomaselli, M, Parati, G, Villani, A, Malfatto G., Ravaro S., Caravita S., Baratto C., Sorropago A., Giglio A., Tomaselli M., Parati G., Villani A., Malfatto, G, Ravaro, S, Caravita, S, Baratto, C, Sorropago, A, Giglio, A, Tomaselli, M, Parati, G, Villani, A, Malfatto G., Ravaro S., Caravita S., Baratto C., Sorropago A., Giglio A., Tomaselli M., Parati G., and Villani A.

Abstract

Neprilisin and angiotensin receptor inhibition (Sacubitril/Valsartan, i.e. ARNI) is recommended in heart failure guidelines for patients in NYHA class II-III with reduced left ventricular ejection fraction (LVEF). ARNI increase survival and quality of life; due to their hemodynamic effects, ARNI could also affect exercise tolerance. We studied the effects of ARNI on cardiopulmonary test (CPET) after six months of treatment in 35 patients [67 ± 11 years; LVEF 31 ± 6%; NT-proBNP 1822 ± 1651 pg/ml; ICD/CRT since at least 6 months in 26/35], treated with increasing doses of Sacubitril/Valsartan up to 318 ± 36 mg/die. In addition, levels of NT-proBNP, renal function, electrolytes, and echocardiocolorDoppler were assessed in the same time periods. No variations of renal function and/or potassium levels were observed; NT-proBNP decreased. Most CPET variables were improved by ARNI (p <.05): peak VO2 and O2 pulse increased (from 15.8 ± 3.4 to 17.0 ± 4.0 ml/kg/min and from 11.5 ± 2.5 to 12.6 ± 2.4 ml/beat, respectively), while VEVCO2 slope decreased from 35.2 ± 11.2 to 33.1 ± 12.3. A significant relationship (p <.05) was observed between the amount of increase in LVEF and that of O2 pulse in all patients, and between the amount of decrease in PAPs and that of VEVCO2 slope in patients showing pulmonary hypertension in baseline. In a subgroup of 22 patients who already completed A 1 year follow-up, overall CPET improvement was maintained. In conclusion, already in the short term ARNI favourably affect cardiopulmonary response to exercise in heart failure patients; such a change seems to be preserved on a longer period.

Published
2020

226. Italian Society of Arterial Hypertension (SIIA) Position Paper on the Role of Renal Denervation in the Management of the Difficult-to-Treat Hypertensive Patient

Author

Bruno, R, Taddei, S, Borghi, C, Colivicchi, F, Desideri, G, Grassi, G, Mazza, A, Muiesan, M, Parati, G, Pontremoli, R, Trimarco, B, Volpe, M, Ferri, C, Bruno R. M., Taddei S., Borghi C., Colivicchi F., Desideri G., Grassi G., Mazza A., Muiesan M. L., Parati G., Pontremoli R., Trimarco B., Volpe M., Ferri C., Bruno, R, Taddei, S, Borghi, C, Colivicchi, F, Desideri, G, Grassi, G, Mazza, A, Muiesan, M, Parati, G, Pontremoli, R, Trimarco, B, Volpe, M, Ferri, C, Bruno R. M., Taddei S., Borghi C., Colivicchi F., Desideri G., Grassi G., Mazza A., Muiesan M. L., Parati G., Pontremoli R., Trimarco B., Volpe M., and Ferri C.

Abstract

Renal denervation is a device-based procedure for hypertension for which safety and efficacy has been demonstrated. At present, its clinical use is still matter of debate, despite the most recent clinical trials have shown promising results with new-generation devices in various hypertensive populations. This position paper was deemed necessary by the Italian Society of Arterial Hypertension, in order to provide indications about the applications of renal denervation in the clinical setting. A state-of-the art review of the literature, focusing on safety and efficacy data, is provided. Furthermore, based on current evidence and expert consensus, clinical profiles of possible candidates for renal denervation are proposed. The selection process should take into account not only blood pressure values, global cardiovascular risk profile, but also drug adherence and tolerability and patient preferences. This position paper also defines minimum requirements for renal denervation selection centers and a flowchart for the difficult-to-treat hypertensive patient. Further studies are needed to support these preliminary indications, which are based on expert-consensus only.

Published
2020

227. Strategies for prevention of cardiovascular disease in adults with hypertension

Author

Whelton, P, Campbell, N, Lackland, D, Parati, G, Ram, C, Weber, M, Zhang, X, Whelton P. K., Campbell N. R. C., Lackland D. T., Parati G., Ram C. V. S., Weber M. A., Zhang X. -H., Whelton, P, Campbell, N, Lackland, D, Parati, G, Ram, C, Weber, M, Zhang, X, Whelton P. K., Campbell N. R. C., Lackland D. T., Parati G., Ram C. V. S., Weber M. A., and Zhang X. -H.

Published
2020

229. Partial Pericardial Agenesis Mimicking Arrhythmogenic Right Ventricular Cardiomyopathy

Author

Castelletti, S, Crotti, L, Dagradi, F, Rella, V, Salerno, S, Parati, G, Cecchi, F, Castelletti S, Crotti L, Dagradi F, Rella V, Salerno S, Parati G, Cecchi F., Castelletti, S, Crotti, L, Dagradi, F, Rella, V, Salerno, S, Parati, G, Cecchi, F, Castelletti S, Crotti L, Dagradi F, Rella V, Salerno S, Parati G, and Cecchi F.

Abstract

Absence of the pericardium is a rare congenital disease in which the fibroserum membrane covering the heart is partially or totally absent. It is characterized by few echocardiography (ECG) and imaging features that can mislead the diagnosis to an inherited cardiac disease, such as arrhythmogenic right ventricular cardiomyopathy. Although it has often a benign course, this congenital defect should be identified as in some cases herniation and strangulation can be life-threatening and cause sudden cardiac death. Red flags on ECG (sinus bradycardia, variable T-wave inversion), chest x-ray (Snoopy sign, absence of tracheal deviation, and esophagus impression), and transthoracic echocardiogram (unusual windows, teardrop left ventricle, and elongated atria) should rise the suspicion of pericardium absence. The correct diagnosis, confirmed by cardiac magnetic resonance, is mandatory as the consequences on the sport activity certification, the management, and the treatment are extremely different.

Published
2020

230. Prevalence of cardiac amyloidosis among adult patients referred to tertiary centres with an initial diagnosis of hypertrophic cardiomyopathy

Author

Maurizi, N, Rella, V, Fumagalli, C, Salerno, S, Castelletti, S, Dagradi, F, Torchio, M, Marceca, A, Meda, M, Gasparini, M, Boschi, B, Girolami, F, Parati, G, Olivotto, I, Crotti, L, Cecchi, F, Maurizi N., Rella V., Fumagalli C., Salerno S., Castelletti S., Dagradi F., Torchio M., Marceca A., Meda M., Gasparini M., Boschi B., Girolami F., Parati G., Olivotto I., Crotti L., Cecchi F., Maurizi, N, Rella, V, Fumagalli, C, Salerno, S, Castelletti, S, Dagradi, F, Torchio, M, Marceca, A, Meda, M, Gasparini, M, Boschi, B, Girolami, F, Parati, G, Olivotto, I, Crotti, L, Cecchi, F, Maurizi N., Rella V., Fumagalli C., Salerno S., Castelletti S., Dagradi F., Torchio M., Marceca A., Meda M., Gasparini M., Boschi B., Girolami F., Parati G., Olivotto I., Crotti L., and Cecchi F.

Abstract

Background: Differential diagnosis of genetic causes of left ventricular hypertrophy (LVH) is crucial for disease-specific therapy. We aim to describe the prevalence of Cardiac Amyloidosis (CA) among patients ≥40 years with an initial diagnosis of HCM referred for second opinion to national cardiomyopathy centres. Methods: Consecutive patients aged ≥40 years referred with a tentative HCM diagnosis in the period 2014–2017 underwent clinical evaluation and genetic testing for HCM (including trans-thyretin-TTR). Patients with at least one red flag for CA underwent blood/urine tests, abdominal fat biopsy and/or bone-scintigraphy tracing and eventually ApoAI sequencing. Results: Out of 343 patients (age 60 ± 13 years), 251 (73%) carried a likely/pathogenic gene variant, including 12 (3.5%) in the CA-associated genes TTR (n = 11) and ApoAI (n = 1). Furthermore, 6 (2%) patients had a mutation in GLA. Among the remaining, mutation-negative patients, 26 with ≥1 CA red-flag were investigated further: 3 AL-CA and 17 wild-type-TTR-CA were identified. Ultimately, 32(9%) patients were diagnosed with CA. Prevalence of CA increased with age: 1/75 (1%) at age 40–49, 2/86 (2%) at age 50–59, 8/84 (9%) at age 60–69, 13/61 (21%) at age 70–79, 8/31 (26%) at age ≥80 (p for trend <0.01). Conclusions: Among patients referred with and initial diagnosis of HCM, CA was the most common unrecognized mimic (9% prevalence) and increased with age (from 1% at ages 40–49 years to 26% >80 years). Age at diagnosis should be considered one of the most relevant red flags for CA in patients with HCM phenotypes; however, there is no clear age cut-off mandating scintigraphy and other second level investigations in the absence of other features suggestive of CA

Published
2020

231. Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database

Author

Lombardi, C, Parati, G, Soranna, D, Zambon, A, Sliwinski, P, Roisman, G, Pepin, J, Schiza, S, Riha, R, Joppa, P, Fietze, I, Hedner, J, Grote, L, Anttalainen, U, Barbe, F, Bonsignore, M, Basoglu, O, Bielicki, P, Dogas, Z, Dorkova, Z, Escourrou, P, Hein, H, Kvamme, J, Levy, P, Marrone, O, Masa, J, Mcnicholas, W, Montserrat, J, Pataka, A, Penzel, T, Petiet, E, Plywaczewski, R, Pretl, M, Ryan, S, Saaresranta, T, Schulz, R, Tasbakan, M, Tkacova, R, Staats, R, Steiropoulos, P, Varoneckas, G, Verbraecken, J, Lombardi C., Parati G., Soranna D., Zambon A., Sliwinski P., Roisman G., Pepin J. -L., Schiza S., Riha R., Joppa P., Fietze I., Hedner J., Grote L., Anttalainen U., Barbe F., Bonsignore M. R., Basoglu O. K., Bielicki P., Dogas Z., Dorkova Z., Escourrou P., Hein H., Kvamme J. A., Levy P., Marrone O., Masa J. F., McNicholas W. T., Montserrat J. M., Pataka A., Penzel T., Petiet E., Pepin J. L., Plywaczewski R., Pretl M., Riha R. L., Ryan S., Saaresranta T., Schulz R., Tasbakan M. S., Tkacova R., Staats R., Steiropoulos P., Varoneckas G., Verbraecken J., Lombardi, C, Parati, G, Soranna, D, Zambon, A, Sliwinski, P, Roisman, G, Pepin, J, Schiza, S, Riha, R, Joppa, P, Fietze, I, Hedner, J, Grote, L, Anttalainen, U, Barbe, F, Bonsignore, M, Basoglu, O, Bielicki, P, Dogas, Z, Dorkova, Z, Escourrou, P, Hein, H, Kvamme, J, Levy, P, Marrone, O, Masa, J, Mcnicholas, W, Montserrat, J, Pataka, A, Penzel, T, Petiet, E, Plywaczewski, R, Pretl, M, Ryan, S, Saaresranta, T, Schulz, R, Tasbakan, M, Tkacova, R, Staats, R, Steiropoulos, P, Varoneckas, G, Verbraecken, J, Lombardi C., Parati G., Soranna D., Zambon A., Sliwinski P., Roisman G., Pepin J. -L., Schiza S., Riha R., Joppa P., Fietze I., Hedner J., Grote L., Anttalainen U., Barbe F., Bonsignore M. R., Basoglu O. K., Bielicki P., Dogas Z., Dorkova Z., Escourrou P., Hein H., Kvamme J. A., Levy P., Marrone O., Masa J. F., McNicholas W. T., Montserrat J. M., Pataka A., Penzel T., Petiet E., Pepin J. L., Plywaczewski R., Pretl M., Riha R. L., Ryan S., Saaresranta T., Schulz R., Tasbakan M. S., Tkacova R., Staats R., Steiropoulos P., Varoneckas G., and Verbraecken J.

Abstract

Background and objective: OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort. Methods: This cross-sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5 years, mean BMI: 30.5 kg/m2) with significant OSA (defined as AHI ≥ 10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI > 25 events/hour of sleep) and patients without significant PLMS (PLMSI < 25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency). Results: The univariate analysis of SBP showed an increment of BP equal to 4.70 mm Hg (P < 0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64 mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP. Conclusion: PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.

Published
2020

232. Comorbidities in chronic heart failure: An update from Italian Society of Cardiology (SIC) Working Group on Heart Failure

Author

Correale, M, Paolillo, S, Mercurio, V, Limongelli, G, Barilla, F, Ruocco, G, Palazzuoli, A, Scrutinio, D, Lagioia, R, Lombardi, C, Lupi, L, Magri, D, Masarone, D, Pacileo, G, Scicchitano, P, Matteo Ciccone, M, Parati, G, Tocchetti, C, Nodari, S, Correale M., Paolillo S., Mercurio V., Limongelli G., Barilla F., Ruocco G., Palazzuoli A., Scrutinio D., Lagioia R., Lombardi C., Lupi L., Magri D., Masarone D., Pacileo G., Scicchitano P., Matteo Ciccone M., Parati G., Tocchetti C. G., Nodari S., Correale, M, Paolillo, S, Mercurio, V, Limongelli, G, Barilla, F, Ruocco, G, Palazzuoli, A, Scrutinio, D, Lagioia, R, Lombardi, C, Lupi, L, Magri, D, Masarone, D, Pacileo, G, Scicchitano, P, Matteo Ciccone, M, Parati, G, Tocchetti, C, Nodari, S, Correale M., Paolillo S., Mercurio V., Limongelli G., Barilla F., Ruocco G., Palazzuoli A., Scrutinio D., Lagioia R., Lombardi C., Lupi L., Magri D., Masarone D., Pacileo G., Scicchitano P., Matteo Ciccone M., Parati G., Tocchetti C. G., and Nodari S.

Abstract

The increasing number of patients with heart failure HF and comorbidities is due to aging population and increase of life expectancy of patients with cardiovascular disease. Encouraging results derived by recent trials may suggest some comorbidities as new targets for new drugs, highlighting the need for a better understanding of the comorbidities’ effects in HF patients and the need of a multidisciplinary approach for the management of chronic HF with comorbidities. We report a brief review about main cardiovascular and non-cardiovascular comorbidities in HF patients in order to update physicians and researchers engaged in the HF research or in “fight against heart failure.”

Published
2020

233. Comorbidities, cardiovascular therapies, and COVID-19 mortality: A nationwide, italian observational study (ItaliCO)

Author

Polverino, F, Stern, D, Ruocco, G, Balestro, E, Bassetti, M, Candelli, M, Cirillo, B, Contoli, M, Corsico, A, D'Amico, F, D'Elia, E, Falco, G, Gasparini, S, Guerra, S, Harari, S, Kraft, M, Mennella, L, Papi, A, Parrella, R, Pelosi, P, Poletti, V, Polverino, M, Tana, C, Terribile, R, Woods, J, Di Marco, F, Martinez, F, Zhang, S, Geelhoed, B, Sinning, C, Agarossi, A, Agati, S, Agosteo, E, Ando', F, Andreoni, M, Angelillo, I, Arcoleo, G, Arena, C, Baiamonte, P, Ball, L, Banfi, P, Bartoletti, G, Bartolotta, R, Battaglini, D, Bellan, M, Benzoni, I, Bertolini, R, Bevilacqua, M, Bezzi, M, Bianco, A, Bisbano, A, Bobbio, F, Bocchialini, G, Bonetti, F, Boni, F, Bonifazi, M, Borgonovo, G, Borre', S, Bosio, M, Brachini, G, Brunetti, I, Calagna, L, Calo, F, Capuozzo, A, Carr, T, Castellani, A, Catalano, F, Catania, G, Catena, E, Cattaneo, M, Cattelan, A, Ceruti, V, Chiumiento, F, Cicchitto, G, Confalonieri, M, Confalonieri, P, Coppola, N, Cosentina, R, Costantino, R, Crimi, C, Curra, A, D'Abbraccio, M, Dalbeni, A, Daleffe, F, Davide, R, Del Donno, M, Di Pastena, F, Di Perna, F, Di Rosa, Z, Di Sabatino, A, Elesbani, O, Elia, D, Esposito, V, Fabiani, L, Falo, G, Fanelli, C, Fantin, A, Ferrigno, F, Fiorentino, G, Franceschi, F, Fronza, M, Gardenghi, G, Giacobbe, D, Giannotti, C, Giannotti, G, Gidari, A, Giovanardi, F, Gnerre, P, Gonnelli, F, Graziano, M, Greco, S, Grosso, A, Guarino, S, Iannarelli, A, Imitazione, P, Inglese, F, Iodice, V, Izzo, A, La Greca, C, Lax, A, Legittimo, F, Leo, A, Leone, S, Lepidini, V, Leto, M, Licata, F, Locati, F, Lorini, L, Lucchetti, B, Maida, I, Macera, M, Manzillo, E, March, A, Mascheroni, D, Mastroianni, A, Mauro, I, Mazzitelli, M, Mazzuca, E, Micheletto, C, Mingoli, A, Minuz, P, Moioli, M, Monti, L, Morgagni, R, Mucci, L, Muselli, M, Negri, S, Nobile, C, Oldani, S, Olivieri, C, Parati, G, Parodi, L, Pastorelli, E, Patruno, V, Pellegrino, F, Pengo, M, Pepe, D, Perotti, A, Petrino, R, Petrucci, M, Piane, R, Pignataro, G, Pino, M, Pirisi, M, Porru, F, Pugliese, F, Punzi, R, Ramaroli, D, Robba, C, Rostagno, R, Sabatini, U, Sainaghi, P, Salton, F, Salzano, C, Sanduzzi, A, Zamparelli, S, Sangiovanni, V, Santopuoli, D, Sapienza, P, Sarmati, L, Schiaroli, E, Scienza, F, Senni, M, Serchisu, L, Sgherzi, S, Soddu, D, Soranna, D, Sorino, C, Spadaro, S, Stirpe, E, Tardivo, S, Tartaglia, S, Teopompi, E, Tomchaney, M, Torelli, E, Torlasco, C, Torti, C, Tupputi, E, Ugolinelli, C, Vatrella, A, Versace, A, Villani, M, Vincenzo, L, Volta, C, Voraphani, N, Zekaj, E, Zoppellari, R, Polverino F., Stern D. A., Ruocco G., Balestro E., Bassetti M., Candelli M., Cirillo B., Contoli M., Corsico A., D'Amico F., D'Elia E., Falco G., Gasparini S., Guerra S., Harari S., Kraft M., Mennella L., Papi A., Parrella R., Pelosi P., Poletti V., Polverino M., Tana C., Terribile R., Woods J. C., Di Marco F., Martinez F. D., Zhang S., Geelhoed B., Sinning C., Agarossi A., Agati S., Agosteo E., Ando' F., Andreoni M., Angelillo I. F., Arcoleo G., Arena C., Baiamonte P., Ball L., Banfi P., Bartoletti G., Bartolotta R., Battaglini D., Bellan M., Benzoni I., Bertolini R., Bevilacqua M., Bezzi M., Bianco A., Bisbano A., Bobbio F., Bocchialini G., Bonetti F., Boni F., Bonifazi M., Borgonovo G., Borre' S., Bosio M., Brachini G., Brunetti I., Calagna L., Calo F., Capuozzo A., Carr T., Castellani A., Catalano F., Catania G., Catena E., Cattaneo M., Cattelan A., Ceruti V., Chiumiento F., Cicchitto G., Confalonieri M., Confalonieri P., Coppola N., Cosentina R., Costantino R., Crimi C., Curra A., D'Abbraccio M., Dalbeni A., Daleffe F., Davide R., Del Donno M., Di Pastena F., Di Perna F., Di Rosa Z., Di Sabatino A., Elesbani O., Elia D., Esposito V., Fabiani L., Falo G., Fanelli C., Fantin A., Ferrigno F., Fiorentino G., Franceschi F., Fronza M., Gardenghi G. G., Giacobbe D. R., Giannotti C., Giannotti G., Gidari A., Giovanardi F., Gnerre P., Gonnelli F., Graziano M., Greco S., Grosso A., Guarino S., Iannarelli A., Imitazione P., Inglese F., Iodice V., Izzo A., La Greca C., Lax A., Legittimo F., Leo A., Leone S., Lepidini V., Leto M., Licata F., Locati F., Lorini L., Lucchetti B., Maida I., Macera M., Manzillo E., March A., Mascheroni D., Mastroianni A., Mauro I., Mazzitelli M., Mazzuca E., Micheletto C., Mingoli A., Minuz P., Moioli M., Monti L., Morgagni R., Mucci L., Muselli M., Negri S., Nobile C. G. A., Oldani S., Olivieri C., Parati G., Parodi L., Pastorelli E., Patruno V., Pellegrino F., Pengo M. F., Pepe D., Perotti A., Petrino R., Petrucci M., Piane R. M., Pignataro G., Pino M., Pirisi M., Porru F., Pugliese F., Punzi R., Ramaroli D. A., Robba C., Rostagno R., Sabatini U., Sainaghi P. P., Salton F., Salzano C., Sanduzzi A., Zamparelli S. S., Sangiovanni V., Santopuoli D., Sapienza P., Sarmati L., Schiaroli E., Scienza F., Senni M., Serchisu L., Sgherzi S., Soddu D., Soranna D., Sorino C., Spadaro S., Stirpe E., Tardivo S., Tartaglia S., Teopompi E., Tomchaney M., Torelli E., Torlasco C., Torti C., Tupputi E., Ugolinelli C., Vatrella A., Versace A. G., Villani M., Vincenzo L., Volta C. A., Voraphani N., Zekaj E., Zoppellari R., Polverino, F, Stern, D, Ruocco, G, Balestro, E, Bassetti, M, Candelli, M, Cirillo, B, Contoli, M, Corsico, A, D'Amico, F, D'Elia, E, Falco, G, Gasparini, S, Guerra, S, Harari, S, Kraft, M, Mennella, L, Papi, A, Parrella, R, Pelosi, P, Poletti, V, Polverino, M, Tana, C, Terribile, R, Woods, J, Di Marco, F, Martinez, F, Zhang, S, Geelhoed, B, Sinning, C, Agarossi, A, Agati, S, Agosteo, E, Ando', F, Andreoni, M, Angelillo, I, Arcoleo, G, Arena, C, Baiamonte, P, Ball, L, Banfi, P, Bartoletti, G, Bartolotta, R, Battaglini, D, Bellan, M, Benzoni, I, Bertolini, R, Bevilacqua, M, Bezzi, M, Bianco, A, Bisbano, A, Bobbio, F, Bocchialini, G, Bonetti, F, Boni, F, Bonifazi, M, Borgonovo, G, Borre', S, Bosio, M, Brachini, G, Brunetti, I, Calagna, L, Calo, F, Capuozzo, A, Carr, T, Castellani, A, Catalano, F, Catania, G, Catena, E, Cattaneo, M, Cattelan, A, Ceruti, V, Chiumiento, F, Cicchitto, G, Confalonieri, M, Confalonieri, P, Coppola, N, Cosentina, R, Costantino, R, Crimi, C, Curra, A, D'Abbraccio, M, Dalbeni, A, Daleffe, F, Davide, R, Del Donno, M, Di Pastena, F, Di Perna, F, Di Rosa, Z, Di Sabatino, A, Elesbani, O, Elia, D, Esposito, V, Fabiani, L, Falo, G, Fanelli, C, Fantin, A, Ferrigno, F, Fiorentino, G, Franceschi, F, Fronza, M, Gardenghi, G, Giacobbe, D, Giannotti, C, Giannotti, G, Gidari, A, Giovanardi, F, Gnerre, P, Gonnelli, F, Graziano, M, Greco, S, Grosso, A, Guarino, S, Iannarelli, A, Imitazione, P, Inglese, F, Iodice, V, Izzo, A, La Greca, C, Lax, A, Legittimo, F, Leo, A, Leone, S, Lepidini, V, Leto, M, Licata, F, Locati, F, Lorini, L, Lucchetti, B, Maida, I, Macera, M, Manzillo, E, March, A, Mascheroni, D, Mastroianni, A, Mauro, I, Mazzitelli, M, Mazzuca, E, Micheletto, C, Mingoli, A, Minuz, P, Moioli, M, Monti, L, Morgagni, R, Mucci, L, Muselli, M, Negri, S, Nobile, C, Oldani, S, Olivieri, C, Parati, G, Parodi, L, Pastorelli, E, Patruno, V, Pellegrino, F, Pengo, M, Pepe, D, Perotti, A, Petrino, R, Petrucci, M, Piane, R, Pignataro, G, Pino, M, Pirisi, M, Porru, F, Pugliese, F, Punzi, R, Ramaroli, D, Robba, C, Rostagno, R, Sabatini, U, Sainaghi, P, Salton, F, Salzano, C, Sanduzzi, A, Zamparelli, S, Sangiovanni, V, Santopuoli, D, Sapienza, P, Sarmati, L, Schiaroli, E, Scienza, F, Senni, M, Serchisu, L, Sgherzi, S, Soddu, D, Soranna, D, Sorino, C, Spadaro, S, Stirpe, E, Tardivo, S, Tartaglia, S, Teopompi, E, Tomchaney, M, Torelli, E, Torlasco, C, Torti, C, Tupputi, E, Ugolinelli, C, Vatrella, A, Versace, A, Villani, M, Vincenzo, L, Volta, C, Voraphani, N, Zekaj, E, Zoppellari, R, Polverino F., Stern D. A., Ruocco G., Balestro E., Bassetti M., Candelli M., Cirillo B., Contoli M., Corsico A., D'Amico F., D'Elia E., Falco G., Gasparini S., Guerra S., Harari S., Kraft M., Mennella L., Papi A., Parrella R., Pelosi P., Poletti V., Polverino M., Tana C., Terribile R., Woods J. C., Di Marco F., Martinez F. D., Zhang S., Geelhoed B., Sinning C., Agarossi A., Agati S., Agosteo E., Ando' F., Andreoni M., Angelillo I. F., Arcoleo G., Arena C., Baiamonte P., Ball L., Banfi P., Bartoletti G., Bartolotta R., Battaglini D., Bellan M., Benzoni I., Bertolini R., Bevilacqua M., Bezzi M., Bianco A., Bisbano A., Bobbio F., Bocchialini G., Bonetti F., Boni F., Bonifazi M., Borgonovo G., Borre' S., Bosio M., Brachini G., Brunetti I., Calagna L., Calo F., Capuozzo A., Carr T., Castellani A., Catalano F., Catania G., Catena E., Cattaneo M., Cattelan A., Ceruti V., Chiumiento F., Cicchitto G., Confalonieri M., Confalonieri P., Coppola N., Cosentina R., Costantino R., Crimi C., Curra A., D'Abbraccio M., Dalbeni A., Daleffe F., Davide R., Del Donno M., Di Pastena F., Di Perna F., Di Rosa Z., Di Sabatino A., Elesbani O., Elia D., Esposito V., Fabiani L., Falo G., Fanelli C., Fantin A., Ferrigno F., Fiorentino G., Franceschi F., Fronza M., Gardenghi G. G., Giacobbe D. R., Giannotti C., Giannotti G., Gidari A., Giovanardi F., Gnerre P., Gonnelli F., Graziano M., Greco S., Grosso A., Guarino S., Iannarelli A., Imitazione P., Inglese F., Iodice V., Izzo A., La Greca C., Lax A., Legittimo F., Leo A., Leone S., Lepidini V., Leto M., Licata F., Locati F., Lorini L., Lucchetti B., Maida I., Macera M., Manzillo E., March A., Mascheroni D., Mastroianni A., Mauro I., Mazzitelli M., Mazzuca E., Micheletto C., Mingoli A., Minuz P., Moioli M., Monti L., Morgagni R., Mucci L., Muselli M., Negri S., Nobile C. G. A., Oldani S., Olivieri C., Parati G., Parodi L., Pastorelli E., Patruno V., Pellegrino F., Pengo M. F., Pepe D., Perotti A., Petrino R., Petrucci M., Piane R. M., Pignataro G., Pino M., Pirisi M., Porru F., Pugliese F., Punzi R., Ramaroli D. A., Robba C., Rostagno R., Sabatini U., Sainaghi P. P., Salton F., Salzano C., Sanduzzi A., Zamparelli S. S., Sangiovanni V., Santopuoli D., Sapienza P., Sarmati L., Schiaroli E., Scienza F., Senni M., Serchisu L., Sgherzi S., Soddu D., Soranna D., Sorino C., Spadaro S., Stirpe E., Tardivo S., Tartaglia S., Teopompi E., Tomchaney M., Torelli E., Torlasco C., Torti C., Tupputi E., Ugolinelli C., Vatrella A., Versace A. G., Villani M., Vincenzo L., Volta C. A., Voraphani N., Zekaj E., and Zoppellari R.

Abstract

Background: Italy has one of the world’s oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertensionmedicationsmay increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were ≥65 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p < 0.001]. Use of ACE inhibitors, ARBs, beta-blockers or Ca-antagonists was not associated with significantly increased risk of death. There was a marginal negative association between ARB use and death, and a marginal positive association between diuretic use and death. Conclusions: This Italian nationwide observational study of COVID-19 inpatients, the majority of which ≥65 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide.

Published
2020

234. 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

235. Risk stratification in heart failure with mild reduced ejection fraction

Author

Magrì, D, Gallo, G, Parati, G, Cicoira, M, Senni, M, Magrì D, Gallo G, Parati G, Cicoira M, Senni M, Magrì, D, Gallo, G, Parati, G, Cicoira, M, Senni, M, Magrì D, Gallo G, Parati G, Cicoira M, and Senni M

Abstract

Heart failure with mid-range ejection fraction represents a heterogeneous and relatively young heart failure category accounting for nearly 20–30% of the overall heart failure population. Due to its complex phenotype, a reliable clinical picture of heart failure with mid-range ejection fraction patients as well as a definite risk stratification are still relevant unsolved issues. In such a context, there is growing interest in a comprehensive functional assessment by means of a cardiopulmonary exercise test, yet considered a cornerstone in the clinical management of patients with heart failure and reduced ejection fraction. Indeed, the cardiopulmonary exercise test has also been found to be particularly useful in the heart failure with mid-range ejection fraction category, several cardiopulmonary exercise test-derived parameters being associated with a poor outcome. In particular, a recent contribution by the metabolic exercise combined with cardiac and kidney indexes research group showed an independent association between the peak oxygen uptake and pure cardiovascular mortality in a large cohort of recovered heart failure with mid-range ejection fraction patients. Contextually, the same study supplied an easy approach to identify a high-risk heart failure with mid-range ejection fraction subset by using a combination of peak oxygen uptake and ventilatory efficiency cut-off values, namely 55% of the maximum predicted and 31, respectively. Thus, looking at the above-mentioned promising results and waiting for specific trials, it is reasonable to consider cardiopulmonary exercise test assessment as part of the heart failure with mid-range ejection fraction work-up in order to identify those patients with an unfavourable functional profile who probably deserve a close clinical follow-up and, probably, more aggressive therapeutic strategies.

Published
2020

236. Cardiac magnetic resonance in heart failure with preserved ejection fraction: myocyte, interstitium, microvascular, and metabolic abnormalities

Author

Quarta, G, Gori, M, Iorio, A, D'Elia, E, Moon, J, Iacovoni, A, Burocchi, S, Schelbert, E, Brambilla, P, Sironi, S, Caravita, S, Parati, G, Gavazzi, A, Maisel, A, Butler, J, Lam, C, Senni, M, Quarta G., Gori M., Iorio A., D'Elia E., Moon J. C., Iacovoni A., Burocchi S., Schelbert E. B., Brambilla P., Sironi S., Caravita S., Parati G., Gavazzi A., Maisel A. S., Butler J., Lam C. S. P., Senni M., Quarta, G, Gori, M, Iorio, A, D'Elia, E, Moon, J, Iacovoni, A, Burocchi, S, Schelbert, E, Brambilla, P, Sironi, S, Caravita, S, Parati, G, Gavazzi, A, Maisel, A, Butler, J, Lam, C, Senni, M, Quarta G., Gori M., Iorio A., D'Elia E., Moon J. C., Iacovoni A., Burocchi S., Schelbert E. B., Brambilla P., Sironi S., Caravita S., Parati G., Gavazzi A., Maisel A. S., Butler J., Lam C. S. P., and Senni M.

Abstract

Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose prevalence continues to rise, with high social and economic burden, but with no specific approved treatment. Patients diagnosed with HFpEF have a high prevalence of comorbidities and exhibit a high misdiagnosis rate. True HFpEF is likely to have multiple pathophysiological causes – with these causes being clinically ill-defined due to limitations of current measurement techniques. Myocyte, interstitium, microvascular, and metabolic abnormalities have been regarded as key components of the pathophysiology and potential therapeutic targets. Cardiac magnetic resonance (CMR) has the capability to look deeper with a number of tissue characterization techniques which are closer to the underlying specific abnormalities and which could be linked to personalized medicine for HFpEF. This review aims to discuss the potential role of CMR to better define HFpEF phenotypes and to infer measurable therapeutic targets.

Published
2020

237. Comorbidities, cardiovascular therapies, and COVID-19 mortality: A nationwide, italian observational study (ItaliCO)

Author

Polverino, F., Phd, Md, Stern, D., Polverino, M., D'Amico, F., D'Elia, E., Agarossi, A., Agati, S., Agosteo, E., Ando', F., Andreoni, M., Angelillo, If., Dds, Mph, Arcoleo, G., Arena, C., Baiamonte, P., Balestro, E., Ball, L., Banfi, P., Bartoletti, G., Bartolotta, R., Bassetti, M., Battaglini, D., Bellan, M., Benzoni, I., Bertolini, R., Bevilacqua, M., Bezzi, M., Bianco, A., Bisbano, A., Bobbio, F., Bocchialini, G., Bonetti, F., Boni, F., Bonifazi, M., Borgonovo, G., Borre', S., Bosio, M., Brachini, G., Brunetti, I., Calagna, L., Calò, F., Candelli, M., Capuozzo, A., Carr, T., Castellani, A., Catalano, F., Catania, G., Catena, E., Cattaneo, M., Cattelan, A., Ceruti, V., Chiumiento, F., Cicchitto, G., Cirillo, B., Confalonieri, M., Confalonieri, P., Contoli, M., Coppola, N., Corsico, A., Cosentina, R., Costantino, R., Crimi, C., Currà, A., D'Abbraccio, M., Dalbeni, A., Daleffe, F., Davide, R., Del Donno, M., Di Marco, F., Di Pastena, F., Di Perna, F., Di Rosa, Z., Di Sabatino, A., Elesbani, O., Elia, D., Esposito, V., Fabiani, L., Falco, G., Falo, G., Fanelli, C., Fantin, A., Ferrigno, F., Fiorentino, G., Franceschi, F., Fronza, M., Gardini Gardenghi, G., Gasparini, S., Giacobbe, D. R., Giannotti, C., Giannotti, G., Gidari, A., Giovanardi, F., Gnerre, P., Gonnelli, F., Graziano, M., Greco, S., Grosso, A., Phd, Guarino, S., Guerra, S., Harari, S., Iannarelli, A., Imitazione, P., Inglese, F., Iodice, V., Izzo, A., La Greca, C., Kraft, M., Lax, A., Legittimo, F., Leo, A., Leone, S., Lepidini, V., Leto, M., Licata, F., Locati, F., Lorini, L., Lucchetti, B., Maida, I., Macera, M., Manzillo, E., March, A., Mascheroni, D., Mastroianni, A., Mauro, I., Mazzitelli, M., Mazzuca, E., Mennella, L., Micheletto, C., Mingoli, A., Minuz, P., Moioli, M., Monti, L., Morgagni, R., Mucci, L., Muselli, M., Negri, S., Nobile, C. G. A., Oldani, S., Olivieri, C., Papi, A., Parati, G., Parodi, L., Parrella, R., Pastorelli, E., Patruno, V., Pellegrino, F., Pelosi, P., Fers, Md, Pengo, M. F., Pepe, D., Perotti, A., Petrino, R., Petrucci, M., Piane, R. M., Pignataro, G., Pino, M., Pirisi, M., Poletti, V., Porru, F., Pugliese, F., Punzi, R., Ramaroli, D. A., Robba, C., Rostagno, R., Ruocco, G., Sabatini, U., Sainaghi, P. P., Salton, F., Salzano, C., Sanduzzi, A., Sanduzzi Zamparelli, S., Sangiovanni, V., Santopuoli, D., Sapienza, P., Sarmati, L., Schiaroli, E., Scienza, F., Senni, M., Serchisu, L., Sgherzi, S., Soddu, D., Soranna, D., Sorino, C., Spadaro, S., Stirpe, E., Tana, C., Tardivo, S., Tartaglia, S., Teopompi, E., Terribile, R., Tomchaney, M., Torelli, E., Torlasco, C., Torti, C., Tupputi, E., Ugolinelli, C., Vatrella, A., Versace, A. G., Villani, M., Vincenzo, L., Volta, C. A., Voraphani, N., Woods, J. C., Zekaj, E., Zoppellari, R., Martinez, and F. D., Polverino, Francesca, Stern, Debra A, Ruocco, Gaetano, Balestro, Elisabetta, Bassetti, Matteo, Candelli, Marcello, Cirillo, Bruno, Contoli, Marco, Corsico, Angelo, D'Amico, Filippo, D'Elia, Emilia, Falco, Giuseppe, Gasparini, Stefano, Guerra, Stefano, Harari, Sergio, Kraft, Monica, Mennella, Luigi, Papi, Alberto, Parrella, Roberto, Pelosi, Paolo, Poletti, Venerino, Polverino, Mario, Tana, Claudio, Terribile, Roberta, Woods, Jason C, Di Marco, Fabiano, Martinez, Fernando D, Angelillo, Italo Francesco, Stern, Debra A., C Woods, Jason, Martinez, Fernando D., Polverino, F., Stern, D., Polverino, M., D'Amico, F., D'Elia, E., Agarossi, A., Agati, S., Agosteo, E., Ando', F., Andreoni, M., Angelillo, If., Arcoleo, G., Arena, C., Baiamonte, P., Balestro, E., Ball, L., Banfi, P., Bartoletti, G., Bartolotta, R., Bassetti, M., Battaglini, D., Bellan, M., Benzoni, I., Bertolini, R., Bevilacqua, M., Bezzi, M., Bianco, A., Bisbano, A., Bobbio, F., Bocchialini, G., Bonetti, F., Boni, F., Bonifazi, M., Borgonovo, G., Borre', S., Bosio, M., Brachini, G., Brunetti, I., Calagna, L., Calò, F., Candelli, M., Capuozzo, A., Carr, T., Castellani, A., Catalano, F., Catania, G., Catena, E., Cattaneo, M., Cattelan, A., Ceruti, V., Chiumiento, F., Cicchitto, G., Cirillo, B., Confalonieri, M., Confalonieri, P., Contoli, M., Coppola, N., Corsico, A., Cosentina, R., Costantino, R., Crimi, C., Currà, A., D'Abbraccio, M., Dalbeni, A., Daleffe, F., Davide, R., Del Donno, M., Di Marco, F., Di Pastena, F., Di Perna, F., Di Rosa, Z., Di Sabatino, A., Elesbani, O., Elia, D., Esposito, V., Fabiani, L., Falco, G., Falo, G., Fanelli, C., Fantin, A., Ferrigno, F., Fiorentino, G., Franceschi, F., Fronza, M., Gardini Gardenghi, G., Gasparini, S., Giacobbe, D. R., Giannotti, C., Giannotti, G., Gidari, A., Giovanardi, F., Gnerre, P., Gonnelli, F., Graziano, M., Greco, S., Grosso, A., Guarino, S., Guerra, S., Harari, S., Iannarelli, A., Imitazione, P., Inglese, F., Iodice, V., Izzo, A., La Greca, C., Kraft, M., Lax, A., Legittimo, F., Leo, A., Leone, S., Lepidini, V., Leto, M., Licata, F., Locati, F., Lorini, L., Lucchetti, B., Maida, I., Macera, M., Manzillo, E., March, A., Mascheroni, D., Mastroianni, A., Mauro, I., Mazzitelli, M., Mazzuca, E., Mennella, L., Micheletto, C., Mingoli, A., Minuz, P., Moioli, M., Monti, L., Morgagni, R., Mucci, L., Muselli, M., Negri, S., Nobile, C. G. A., Oldani, S., Olivieri, C., Papi, A., Parati, G., Parodi, L., Parrella, R., Pastorelli, E., Patruno, V., Pellegrino, F., Pelosi, P., Pengo, M. F., Pepe, D., Perotti, A., Petrino, R., Petrucci, M., Piane, R. M., Pignataro, G., Pino, M., Pirisi, M., Poletti, V., Porru, F., Pugliese, F., Punzi, R., Ramaroli, D. A., Robba, C., Rostagno, R., Ruocco, G., Sabatini, U., Sainaghi, P. P., Salton, F., Salzano, C., Sanduzzi, A., Sanduzzi Zamparelli, S., Sangiovanni, V., Santopuoli, D., Sapienza, P., Sarmati, L., Schiaroli, E., Scienza, F., Senni, M., Serchisu, L., Sgherzi, S., Soddu, D., Soranna, D., Sorino, C., Spadaro, S., Stirpe, E., Tana, C., Tardivo, S., Tartaglia, S., Teopompi, E., Terribile, R., Tomchaney, M., Torelli, E., Torlasco, C., Torti, C., Tupputi, E., Ugolinelli, C., Vatrella, A., Versace, A. G., Villani, M., Vincenzo, L., Volta, C. A., Voraphani, N., Woods, J. C., Zekaj, E., Zoppellari, R., Martinez, F. D., Public Health, Polverino, F, Stern, D, Ruocco, G, Balestro, E, Bassetti, M, Candelli, M, Cirillo, B, Contoli, M, Corsico, A, D'Amico, F, D'Elia, E, Falco, G, Gasparini, S, Guerra, S, Harari, S, Kraft, M, Mennella, L, Papi, A, Parrella, R, Pelosi, P, Poletti, V, Polverino, M, Tana, C, Terribile, R, Woods, J, Di Marco, F, Martinez, F, Zhang, S, Geelhoed, B, Sinning, C, Agarossi, A, Agati, S, Agosteo, E, Ando', F, Andreoni, M, Angelillo, I, Arcoleo, G, Arena, C, Baiamonte, P, Ball, L, Banfi, P, Bartoletti, G, Bartolotta, R, Battaglini, D, Bellan, M, Benzoni, I, Bertolini, R, Bevilacqua, M, Bezzi, M, Bianco, A, Bisbano, A, Bobbio, F, Bocchialini, G, Bonetti, F, Boni, F, Bonifazi, M, Borgonovo, G, Borre', S, Bosio, M, Brachini, G, Brunetti, I, Calagna, L, Calo, F, Capuozzo, A, Carr, T, Castellani, A, Catalano, F, Catania, G, Catena, E, Cattaneo, M, Cattelan, A, Ceruti, V, Chiumiento, F, Cicchitto, G, Confalonieri, M, Confalonieri, P, Coppola, N, Cosentina, R, Costantino, R, Crimi, C, Curra, A, D'Abbraccio, M, Dalbeni, A, Daleffe, F, Davide, R, Del Donno, M, Di Pastena, F, Di Perna, F, Di Rosa, Z, Di Sabatino, A, Elesbani, O, Elia, D, Esposito, V, Fabiani, L, Falo, G, Fanelli, C, Fantin, A, Ferrigno, F, Fiorentino, G, Franceschi, F, Fronza, M, Gardenghi, G, Giacobbe, D, Giannotti, C, Giannotti, G, Gidari, A, Giovanardi, F, Gnerre, P, Gonnelli, F, Graziano, M, Greco, S, Grosso, A, Guarino, S, Iannarelli, A, Imitazione, P, Inglese, F, Iodice, V, Izzo, A, La Greca, C, Lax, A, Legittimo, F, Leo, A, Leone, S, Lepidini, V, Leto, M, Licata, F, Locati, F, Lorini, L, Lucchetti, B, Maida, I, Macera, M, Manzillo, E, March, A, Mascheroni, D, Mastroianni, A, Mauro, I, Mazzitelli, M, Mazzuca, E, Micheletto, C, Mingoli, A, Minuz, P, Moioli, M, Monti, L, Morgagni, R, Mucci, L, Muselli, M, Negri, S, Nobile, C, Oldani, S, Olivieri, C, Parati, G, Parodi, L, Pastorelli, E, Patruno, V, Pellegrino, F, Pengo, M, Pepe, D, Perotti, A, Petrino, R, Petrucci, M, Piane, R, Pignataro, G, Pino, M, Pirisi, M, Porru, F, Pugliese, F, Punzi, R, Ramaroli, D, Robba, C, Rostagno, R, Sabatini, U, Sainaghi, P, Salton, F, Salzano, C, Sanduzzi, A, Zamparelli, S, Sangiovanni, V, Santopuoli, D, Sapienza, P, Sarmati, L, Schiaroli, E, Scienza, F, Senni, M, Serchisu, L, Sgherzi, S, Soddu, D, Soranna, D, Sorino, C, Spadaro, S, Stirpe, E, Tardivo, S, Tartaglia, S, Teopompi, E, Tomchaney, M, Torelli, E, Torlasco, C, Torti, C, Tupputi, E, Ugolinelli, C, Vatrella, A, Versace, A, Villani, M, Vincenzo, L, Volta, C, Voraphani, N, Zekaj, E, and Zoppellari, R

Subjects
0301 basic medicine, COVID-19, comorbidities, ACE inhibitors, mortality, cohort study, medicine.medical_specialty, comorbiditie, lcsh:Diseases of the circulatory (Cardiovascular) system, ACE inhibitors, Coronavirus disease 2019 (COVID-19), COVID-19, cohort study, comorbidities, mortality, Cardiomyopathy, Socio-culturale, Disease, 030204 cardiovascular system & hematology, Cardiovascular Medicine, Logistic regression, Older population, Comorbidities, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Internal medicine, ACE inhibitor, medicine, Mortality, Original Research, business.industry, Cohort study, medicine.disease, Comorbidity, 030104 developmental biology, lcsh:RC666-701, Observational study, Erratum, Cardiology and Cardiovascular Medicine, business
Abstract

Background: Italy has one of the world’s oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertensionmedicationsmay increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were ≥65 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p < 0.001]. Use of ACE inhibitors, ARBs, beta-blockers or Ca-antagonists was not associated with significantly increased risk of death. There was a marginal negative association between ARB use and death, and a marginal positive association between diuretic use and death. Conclusions: This Italian nationwide observational study of COVID-19 inpatients, the majority of which ≥65 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide.

Published
2020

238. Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database

Author

Lombardi C, Parati G, Soranna D, Zambon A, Sliwinski P, Roisman G, Pepin JL, Schiza S, Riha R, Joppa P, Fietze I, Hedner J, Grote L, European Sleep Apnoea Database (ESADA) Collaborators (ESADA Collaborators: Anttalainen U, Barbé F, Bonsignore MR, Basoglu OK, Bielicki P, Dogas Z, Dorkova Z, Escourrou P, Hein H, Kvamme JA, Levy P, Marrone O, Masa JF, McNicholas WT, Montserrat JM, Pataka A, Penzel T, Petiet E, Pépin JL, Plywaczewski R, Pretl M, Riha RL, Ryan S, Saaresranta T, Schulz R, Tasbakan MS, Tkacova R, Staats R, Steiropoulos P, Varoneckas G, Verbraecken J), Lombardi C., Parati G., Soranna D., Zambon A., Sliwinski P., Roisman G., Pepin J.-L., Schiza S., Riha R., Joppa P., Fietze I., Hedner J., Grote L., Anttalainen U., Barbe F., Bonsignore M.R., Basoglu O.K., Bielicki P., Dogas Z., Dorkova Z., Escourrou P., Hein H., Kvamme J.A., Levy P., Marrone O., Masa J.F., McNicholas W.T., Montserrat J.M., Pataka A., Penzel T., Petiet E., Pepin J.L., Plywaczewski R., Pretl M., Riha R.L., Ryan S., Saaresranta T., Schulz R., Tasbakan M.S., Tkacova R., Staats R., Steiropoulos P., Varoneckas G., Verbraecken J., Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Institute of Tuberculosis and Lung Diseases [Warsaw, Poland] (ITLD), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), University of Crete [Heraklion] (UOC), Royal Infirmary of Edinburgh, Univerzitnej nemocnice L. Pasteura Košice [Košice, Slovakia]. (UNLPK), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Gothenburg (GU), Sahlgrenska Academy at University of Gothenburg [Göteborg], European Sleep Apnoea Database (ESADA) Collaborators: Anttalainen U, Barbé F, Bonsignore Mr, Basoglu Ok, Bielicki P, Dogas Z, Dorkova Z, Escourrou P, Fietze I, Grote L, Hedner J, Hein H, Joppa P, Kvamme Ja, Levy P, Lombardi C, Marrone O, Masa Jf, McNicholas Wt, Montserrat Jm, Parati G, Pataka A, Penzel T, Petiet E, Pépin Jl, Plywaczewski R, Pretl M, Riha Rl, Roisman G, Ryan S, Saaresranta T, Schiza S, Schulz R, Sliwinski P, Pepin Jl, Tasbakan Ms, Tkacova R, Staats R, Steiropoulos P, Varoneckas G, Verbraecken J, SALAS, Danielle, Lombardi, C, Parati, G, Soranna, D, Zambon, A, Sliwinski, P, Roisman, G, Pepin, J, Schiza, S, Riha, R, Joppa, P, Fietze, I, Hedner, J, Grote, L, Anttalainen, U, Barbe, F, Bonsignore, M, Basoglu, O, Bielicki, P, Dogas, Z, Dorkova, Z, Escourrou, P, Hein, H, Kvamme, J, Levy, P, Marrone, O, Masa, J, Mcnicholas, W, Montserrat, J, Pataka, A, Penzel, T, Petiet, E, Plywaczewski, R, Pretl, M, Ryan, S, Saaresranta, T, Schulz, R, Tasbakan, M, Tkacova, R, Staats, R, Steiropoulos, P, Varoneckas, G, and Verbraecken, J

Subjects
Male, Pulmonary and Respiratory Medicine, Multivariate statistics, medicine.medical_specialty, obstructive sleep apnoea, Systole, Movement, [SDV]Life Sciences [q-bio], Blood Pressure, Comorbidity, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Cohort Studies, 03 medical and health sciences, Sleep Apnea Syndromes, 0302 clinical medicine, Diastole, cardiovascular disease, Diabetes mellitus, Internal medicine, medicine, Humans, 030212 general & internal medicine, sleep disorder, Sleep disorder, Univariate analysis, business.industry, Confounding, Extremities, clinical epidemiology, Middle Aged, medicine.disease, Sleep in non-human animals, Europe, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Blood pressure, Databases as Topic, 030228 respiratory system, Cohort, Female, Sleep, business
Abstract

International audience; Background and objective: OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort.Methods: This cross-sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5 years, mean BMI: 30.5 kg/m2 ) with significant OSA (defined as AHI ≥ 10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI > 25 events/hour of sleep) and patients without significant PLMS (PLMSI < 25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency).Results: The univariate analysis of SBP showed an increment of BP equal to 4.70 mm Hg (P < 0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64 mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP.Conclusion: PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.

Published
2020

239. Serum uric acid and fatal myocardial infarction: Detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study

Author

Casiglia E, Tikhonoff V, Virdis A, Masi S, Barbagallo CM, Bombelli M, Bruno B, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Lippa L, Mallamaci F, Maloberti A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Grassi G, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)., Casiglia E, Tikhonoff V, Virdis A, Masi S, Barbagallo CM, Bombelli M, Bruno B, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Lippa L, Mallamaci F, Maloberti A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Grassi G, Borghi C, Casiglia, E, Tikhonoff, V, Virdis, A, Masi, S, Barbagallo, C, Bombelli, M, Bruno, B, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)., Casiglia, Edoardo, Tikhonoff, Valérie, Virdis, Agostino, Masi, Stefano, Barbagallo, Carlo M, Bombelli, Michele, Bruno, Bernardino, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Grassi, Guido, and Borghi, Claudio

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Physiology, cut-off value, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, uric acid, Internal medicine, Internal Medicine, medicine, ORIGINAL PAPERS: Epidemiology, Humans, sex, 030212 general & internal medicine, Hyperuricemia, Myocardial infarction, Risk factor, Aged, Aged, 80 and over, uric acid, cardiovascular, arterial hypertension, cut-off value, mortality, myocardial infarction,sex, uric acid, Proportional hazards model, business.industry, cut-off value, mortality, myocardial infarction, sex, uric acid, Hazard ratio, Middle Aged, medicine.disease, Prognosis, mortality, Confidence interval, Uric acid, myocardial infarction, epidemiology, myocardial infarction, chemistry, Italy, Hypertension, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Uric acid, Female, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract

Supplemental Digital Content is available in the text, Objective: The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men. Methods: The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18–95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months. Results: A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096–1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105–2.075, P

Published
2020

240. Atrial Functional Tricuspid Regurgitation as a Distinct Pathophysiological and Clinical Entity: No Idiopathic Tricuspid Regurgitation Anymore

Author

Florescu, D, Muraru, D, Volpato, V, Gavazzoni, M, Caravita, S, Tomaselli, M, Ciampi, P, Florescu, C, Balseanu, T, Parati, G, Badano, L, Florescu, D, Muraru, D, Volpato, V, Gavazzoni, M, Caravita, S, Tomaselli, M, Ciampi, P, Florescu, C, Balseanu, T, Parati, G, and Badano, L

Abstract

Functional tricuspid regurgitation (FTR) is a strong and independent predictor of patient morbidity and mortality if left untreated. The development of transcatheter procedures to either repair or replace the tricuspid valve (TV) has fueled the interest in the pathophysiology, severity assessment, and clinical consequences of FTR. FTR has been considered to be secondary to tricuspid annulus (TA) dilation and leaflet tethering, associated to right ventricular (RV) dilation and/or dysfunction (the “classical”, ventricular form of FTR, V-FTR) for a long time. Atrial FTR (A-FTR) has recently emerged as a distinct pathophysiological entity. A-FTR typically occurs in patients with persistent/permanent atrial fibrillation, in whom an imbalance between the TA and leaflet areas results in leaflets malcoaptation, associated with the dilation and loss of the sphincter-like function of the TA, due to right atrium enlargement and dysfunction. According to its distinct pathophysiology, A-FTR poses different needs of clinical management, and the various interventional treatment options will likely have different outcomes than in V-FTR patients. This review aims to provide an insight into the anatomy of the TV, and the distinct pathophysiology of A-FTR, which are key concepts to understanding the objectives of therapy, the choice of transcatheter TV interventions, and to properly use pre-, intra-, and post-procedural imaging.

Published
2022

241. Reboxetine plus Oxybutynin for Obstructed Sleep Apnea Treatment A 1-week Randomized, Placebo-controlled, Double-Blind Crossover Trial

Author

Perger, E, Montemurro, L, Rosa, D, Vicini, S, Marconi, M, Zanotti, L, Meriggi, P, Azarbarzin, A, Sands, S, Wellman, A, Lombardi, C, Parati, G, Perger, Elisa, Montemurro, Luigi Taranto, Rosa, Debora, Vicini, Stefano, Marconi, Mariapaola, Zanotti, Lucia, Meriggi, Paolo, Azarbarzin, Ali, Sands, Scott A, Wellman, Andrew, Lombardi, Carolina, Parati, Gianfranco, Perger, E, Montemurro, L, Rosa, D, Vicini, S, Marconi, M, Zanotti, L, Meriggi, P, Azarbarzin, A, Sands, S, Wellman, A, Lombardi, C, Parati, G, Perger, Elisa, Montemurro, Luigi Taranto, Rosa, Debora, Vicini, Stefano, Marconi, Mariapaola, Zanotti, Lucia, Meriggi, Paolo, Azarbarzin, Ali, Sands, Scott A, Wellman, Andrew, Lombardi, Carolina, and Parati, Gianfranco

Abstract

Background: The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced OSA severity has revitalized interest in pharmacologic therapies for OSA. Research Question: Would 1 week of reboxetine plus oxybutynin (Reb-Oxy) be effective on OSA severity? Study Design and Methods: A randomized, placebo-controlled, double-blind, crossover trial was performed comparing 4 mg reboxetine plus 5 mg oxybutynin (Reb-Oxy) vs placebo in patients with OSA. After a baseline in-laboratory polysomnogram (PSG), patients underwent PSGs after 7 nights of Reb-Oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI), which was the primary outcome. Response rate was based on the percentage of subjects with a ≥ 50% reduction in AHI from baseline. Secondary outcomes included Epworth Sleepiness Scale (ESS) score and psychomotor vigilance test (PVT) values. Home oximetry evaluated overnight oxygen desaturation index (ODI) throughout treatment. Results: Sixteen subjects aged 57 [51-61] years (median [interquartile range]) with a BMI of 30 [26-36] kg/m2 completed the study. Reb-Oxy lowered AHI from 49 [35-57] events per hour at baseline to 18 [13-21] events per hour (59% median reduction) compared with 39 [29-48] events per hour (6% median reduction) with placebo (P <.001). Response rate for Reb-Oxy was 81% vs 13% for placebo (P <.001). Although ESS scores were not significantly lowered, PVT median reaction time decreased from 250 [239-312] ms at baseline to 223 [172-244] ms on Reb-Oxy vs 264 [217-284] ms on placebo (P <.001). Home oximetry illustrated acute and sustained improvement in the oxygen desaturation index on Reb-Oxy vs placebo. Interpretation: The administration of Reb-Oxy greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacologic treatment of OSA. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04449133; URL: www.cl

Published
2022

242. World Hypertension Day 2021 in Italy: Results of a Nationwide Survey

Author

Del Pinto, R, Grassi, G, Lorenza Muiesan, M, Borghi, C, Carugo, S, Cicero, A, Di Meo, L, Iaccarino, G, Minuz, P, Mulatero, P, Mulè, G, Parati, G, Pucci, G, Salvetti, M, Sarzani, R, Savoia, C, Sechi, L, Tocci, G, Volpe, M, Vulpis, V, Ferri, C, Rita Del Pinto, Guido Grassi, Maria Lorenza Muiesan, Claudio Borghi, Stefano Carugo, Arrigo F. G. Cicero, Luciano Di Meo, Guido Iaccarino, Pietro Minuz, Paolo Mulatero, Giuseppe Mulè, Gianfranco Parati, Giacomo Pucci, Massimo Salvetti, Riccardo Sarzani, Carmine Savoia, Leonardo Sechi, Giuliano Tocci, Massimo Volpe, Vito Vulpis, Claudio Ferri, Del Pinto, R, Grassi, G, Lorenza Muiesan, M, Borghi, C, Carugo, S, Cicero, A, Di Meo, L, Iaccarino, G, Minuz, P, Mulatero, P, Mulè, G, Parati, G, Pucci, G, Salvetti, M, Sarzani, R, Savoia, C, Sechi, L, Tocci, G, Volpe, M, Vulpis, V, Ferri, C, Rita Del Pinto, Guido Grassi, Maria Lorenza Muiesan, Claudio Borghi, Stefano Carugo, Arrigo F. G. Cicero, Luciano Di Meo, Guido Iaccarino, Pietro Minuz, Paolo Mulatero, Giuseppe Mulè, Gianfranco Parati, Giacomo Pucci, Massimo Salvetti, Riccardo Sarzani, Carmine Savoia, Leonardo Sechi, Giuliano Tocci, Massimo Volpe, Vito Vulpis, and Claudio Ferri

Abstract

Introduction: Hypertension is the biggest contributor to the global burden of cardiovascular diseases and related death, but the rates of hypertension awareness, treatment, and control remain largely perfectible. Methods: During the XVII World Hypertension Day (May 17th, 2021), a nationwide cross-sectional opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of high blood pressure (BP). A questionnaire on major demographic/clinical features (sex, age, employment, education, BP status awareness, hypertension family/personal history, antihypertensive medications use) and BP measurement habits (≥1 BP measurement in the previous month/week) was administered. Due to the ongoing SARS-CoV-2 pandemic, BP was measured with standard procedures in a subset of participants (24.4%). Results: A total of 1354 participants (mean age 56.3 ± 15.3 years; 57.3% women; mean BP: 131.2 ± 17.5/81.6 ± 10.5 mmHg; 42.3% self-declared hypertensive; 41.4% on antihypertensive medications) were enrolled; 73.6% declared being aware of their BP status. Among treated individuals with measured BP, 26.9% showed BP levels within the predefined therapeutic goals. Interestingly, BP status awareness rates were the highest among individuals with uncontrolled hypertension (85.1%) and the lowest among those with normal measured BP (54.4%). Conclusions: This survey provides an updated insight into hypertension awareness and control in a setting of daily clinical practice, emphasizing the centricity of patients in the therapeutic alliance for a successful reduction of cardiovascular risk.

Published
2022

243. Reference ranges of tricuspid annulus geometry in healthy adults using a dedicated three-dimensional echocardiography software package

Author

Muraru, D, Gavazzoni, M, Heilbron, F, Mihalcea, D, Guta, A, Radu, N, Muscogiuri, G, Tomaselli, M, Sironi, S, Parati, G, Badano, L, Muraru, Denisa, Gavazzoni, Mara, Heilbron, Francesca, Mihalcea, Diana J, Guta, Andrada C, Radu, Noela, Muscogiuri, Giuseppe, Tomaselli, Michele, Sironi, Sandro, Parati, Gianfranco, Badano, Luigi, Muraru, D, Gavazzoni, M, Heilbron, F, Mihalcea, D, Guta, A, Radu, N, Muscogiuri, G, Tomaselli, M, Sironi, S, Parati, G, Badano, L, Muraru, Denisa, Gavazzoni, Mara, Heilbron, Francesca, Mihalcea, Diana J, Guta, Andrada C, Radu, Noela, Muscogiuri, Giuseppe, Tomaselli, Michele, Sironi, Sandro, Parati, Gianfranco, and Badano, Luigi

Abstract

Background: Tricuspid annulus (TA) sizing is essential for planning percutaneous or surgical tricuspid procedures. According to current guidelines, TA linear dimension should be assessed using two-dimensional echocardiography (2DE). However, TA is a complex three-dimensional (3D) structure. Aim: Identify the reference values for TA geometry and dynamics and its physiological determinants using a commercially available three-dimensional echocardiography (3DE) software package dedicated to the tricuspid valve (4D AutoTVQ, GE). Methods: A total of 254 healthy volunteers (113 men, 47 ± 11 years) were evaluated using 2DE and 3DE. TA 3D area, perimeter, diameters, and sphericity index were assessed at mid-systole, early- and end-diastole. Right atrial (RA) and ventricular (RV) end-diastolic and end-systolic volumes were also measured by 3DE. Results: The feasibility of the 3DE analysis of TA was 90%. TA 3D area, perimeter, and diameters were largest at end-diastole and smallest at mid-systole. Reference values of TA at end-diastole were 9.6 ± 2.1 cm2 for the area, 11.2 ± 1.2 cm for perimeter, and 38 ± 4 mm, 31 ± 4 mm, 33 ± 4 mm, and 34 ± 5 mm for major, minor, 4-chamber and 2-chamber diameters, respectively. TA end-diastolic sphericity index was 81 ± 11%. All TA parameters were correlated with body surface area (BSA) (r from 0.42 to 0.58, p < 0.001). TA 3D area and 4-chamber diameter were significantly larger in men than in women, independent of BSA (p < 0.0001). There was no significant relationship between TA metrics with age, except for the TA minor diameter (r = −0.17, p < 0.05). When measured by 2DE in 4-chamber (29 ± 5 mm) and RV-focused (30 ± 5 mm) views, both TA diameters resulted significantly smaller than the 4-chamber (33 ± 4 mm; p < 0.0001), and the major TA diameters (38 ± 4 mm; p < 0.0001) measured by 3DE. At multivariable linear regression analysis, RA maximal volume was independently associated with both TA 3D area at mid-systole (R2 = 0.511

Published
2022

244. An explainable model of host genetic interactions linked to COVID-19 severity

Author

Onoja, A., Picchiotti, N., Fallerini, C., Baldassarri, M., Fava, F., Mari, F., Daga, S., Benetti, E., Bruttini, M., Palmieri, Marco, Croci, S., Amitrano, S., Meloni, I., Frullanti, E., Doddato, G., Lista, Maddalena, Beligni, G., Valentino, Francesca, Zguro, K., Tita, R., Giliberti, A., Mencarelli, Marta, Rizzo, C. L., Pinto, A. M., Ariani, F., Di Sarno, Lorenzo, Montagnani, F., Tumbarello, Mario, Rancan, I., Fabbiani, M., Rossetti, Barbara, Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Raffaelli, C. S., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Romani, D., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Pisani, M., Ognibene, A., Pancrazzi, A., Lorubbio, M., Vaghi, M., D'Arminio Monforte, A., Miraglia, F. G., Bruno, R., Vecchia, M., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, Armando, Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Paciosi, F., Tommasi, A., Zuccon, U., Vietri, L., Scotton, P. G., Andretta, F., Panese, S., Baratti, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, E., Antoni, M. D., Zanella, I., Della Monica, M., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Aucella, F., Raggi, P., Perna, Raffaella, Bassetti, M., Di Biagio, Anna, Sanguinetti, Maurizio, Masucci, Luca, Guarnaccia, A., Valente, S., De Vivo, O., Bargagli, E., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Lacerenza, G., Coviello, D. A., Mussini, C., Martinelli, E., Tavecchia, L., Belli, M. A., Crotti, L., Parati, G., Sanarico, M., Biscarini, F., Stella, A., Rizzi, M., Maggiolo, F., Ripamonti, D., Suardi, C., Bachetti, T., La Rovere, M. T., Sarzi-Braga, S., Bussotti, M., Capitani, K., Dei, S., Ravaglia, S., Artuso, R., Andreucci, E., Gori, Giovanni Cristiano, Pagliazzi, A., Fiorentini, E., Perrella, A., Bianchi, F., Bergomi, P., Catena, E., Colombo, R., Luchi, S., Morelli, G., Petrocelli, Paolo, Iacopini, S., Modica, S., Baroni, Silvia, Segala, F. V., Menichetti, F., Falcone, M., Tiseo, G., Barbieri, Cristiano, Matucci, T., Grassi, D., Ferri, C., Marinangeli, F., Brancati, F., Vincenti, A., Borgo, V., Lombardi, S., Lenzi, M., Di Pietro, Maria Luisa, Vichi, F., Romanin, B., Attala, L., Costa, C., Gabbuti, A., Mene, R., Colaneri, M., Casprini, P., Merla, G., Squeo, G. M., Maffezzoni, M., Mantovani, Susanna, Mondelli, M. U., Ludovisi, S., Colombo, F., Chiaromonte, F., Renieri, A., Furini, S., Raimondi, F., Palmieri M. (ORCID:0000-0001-8263-336X), Lista M., Valentino F., Mencarelli M. A., Di Sarno L., Tumbarello M. (ORCID:0000-0002-9519-8552), Rossetti B., D'Alessandro M., Franchi F., Donati A., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Di Biagio A., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Gori G. (ORCID:0000-0002-3308-5309), Petrocelli P., Barbieri C., Di Pietro M. A. (ORCID:0000-0002-3893-8788), Mantovani S., Onoja, A., Picchiotti, N., Fallerini, C., Baldassarri, M., Fava, F., Mari, F., Daga, S., Benetti, E., Bruttini, M., Palmieri, Marco, Croci, S., Amitrano, S., Meloni, I., Frullanti, E., Doddato, G., Lista, Maddalena, Beligni, G., Valentino, Francesca, Zguro, K., Tita, R., Giliberti, A., Mencarelli, Marta, Rizzo, C. L., Pinto, A. M., Ariani, F., Di Sarno, Lorenzo, Montagnani, F., Tumbarello, Mario, Rancan, I., Fabbiani, M., Rossetti, Barbara, Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Raffaelli, C. S., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Romani, D., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Pisani, M., Ognibene, A., Pancrazzi, A., Lorubbio, M., Vaghi, M., D'Arminio Monforte, A., Miraglia, F. G., Bruno, R., Vecchia, M., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, Armando, Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Paciosi, F., Tommasi, A., Zuccon, U., Vietri, L., Scotton, P. G., Andretta, F., Panese, S., Baratti, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, E., Antoni, M. D., Zanella, I., Della Monica, M., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Aucella, F., Raggi, P., Perna, Raffaella, Bassetti, M., Di Biagio, Anna, Sanguinetti, Maurizio, Masucci, Luca, Guarnaccia, A., Valente, S., De Vivo, O., Bargagli, E., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Lacerenza, G., Coviello, D. A., Mussini, C., Martinelli, E., Tavecchia, L., Belli, M. A., Crotti, L., Parati, G., Sanarico, M., Biscarini, F., Stella, A., Rizzi, M., Maggiolo, F., Ripamonti, D., Suardi, C., Bachetti, T., La Rovere, M. T., Sarzi-Braga, S., Bussotti, M., Capitani, K., Dei, S., Ravaglia, S., Artuso, R., Andreucci, E., Gori, Giovanni Cristiano, Pagliazzi, A., Fiorentini, E., Perrella, A., Bianchi, F., Bergomi, P., Catena, E., Colombo, R., Luchi, S., Morelli, G., Petrocelli, Paolo, Iacopini, S., Modica, S., Baroni, Silvia, Segala, F. V., Menichetti, F., Falcone, M., Tiseo, G., Barbieri, Cristiano, Matucci, T., Grassi, D., Ferri, C., Marinangeli, F., Brancati, F., Vincenti, A., Borgo, V., Lombardi, S., Lenzi, M., Di Pietro, Maria Luisa, Vichi, F., Romanin, B., Attala, L., Costa, C., Gabbuti, A., Mene, R., Colaneri, M., Casprini, P., Merla, G., Squeo, G. M., Maffezzoni, M., Mantovani, Susanna, Mondelli, M. U., Ludovisi, S., Colombo, F., Chiaromonte, F., Renieri, A., Furini, S., Raimondi, F., Palmieri M. (ORCID:0000-0001-8263-336X), Lista M., Valentino F., Mencarelli M. A., Di Sarno L., Tumbarello M. (ORCID:0000-0002-9519-8552), Rossetti B., D'Alessandro M., Franchi F., Donati A., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Di Biagio A., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Gori G. (ORCID:0000-0002-3308-5309), Petrocelli P., Barbieri C., Di Pietro M. A. (ORCID:0000-0002-3893-8788), and Mantovani S.

Abstract

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as “Respiratory or thoracic disease”, supporting their link with COVID-19 severity outcome.

Published
2022

245. PROGNOSTIC CUTOFF OF TRIGLYCERIDES PREDICTING CARDIOVASCULAR OUTCOME IN A LARGE REGIONAL-BASED ITALIAN DATABASE

Author

Tikhonoff, V, Casiglia, E, Virdis, A, Barbagallo, C, Cirillo, M, Desideri, G, Ferri, C, Galletti, F, Grassi, G, Giannattasio, C, Iaccarino, G, Mazza, A, Muiesan, M, Palatini, P, Parati, G, Pontremoli, R, Verdecchia, P, Volpe, M, Ungar, A, Borghi, C, Tikhonoff, Valerie, Casiglia, Edoardo, Virdis, Agostino, Barbagallo, Carlo, Cirillo, Massimo, Desideri, Giambattista, Ferri, Claudio, Galletti, Ferruccio, Grassi, Guido, Giannattasio, Cristina, Iaccarino, Guido, Mazza, Alberto, Muiesan, Maria Lorenza, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Verdecchia, Paolo, Volpe, Massimo, Ungar, Andrea, Borghi, Caludio, Tikhonoff, V, Casiglia, E, Virdis, A, Barbagallo, C, Cirillo, M, Desideri, G, Ferri, C, Galletti, F, Grassi, G, Giannattasio, C, Iaccarino, G, Mazza, A, Muiesan, M, Palatini, P, Parati, G, Pontremoli, R, Verdecchia, P, Volpe, M, Ungar, A, Borghi, C, Tikhonoff, Valerie, Casiglia, Edoardo, Virdis, Agostino, Barbagallo, Carlo, Cirillo, Massimo, Desideri, Giambattista, Ferri, Claudio, Galletti, Ferruccio, Grassi, Guido, Giannattasio, Cristina, Iaccarino, Guido, Mazza, Alberto, Muiesan, Maria Lorenza, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Verdecchia, Paolo, Volpe, Massimo, Ungar, Andrea, and Borghi, Caludio

Abstract

Objective: Searching for a prognostic cut-off value of triglycerides (TG) in predicting cardiovascular (CV) outcome in a large regional-based Italian database of men and women. Design and method: A nationwide multicentre database collects data on subjects aged 18 to 95 years recruited on a regional community basis from all the territory of Italy with at least 1 measure of TG and a mean follow-up of 110.1 ± 64.3 months. A total of 18,784 subjects were included in the analysis. CV outcome was defined on the basis of ICD10 codes and double-checked with general practitioners and hospital files. Multivariate dichotomic Cox regression models having CV outcome as dependent variable, adjusted for age, sex, serum uric acid, body mass index, total and HDL-cholesterol, arterial hypertension, diabetes, chronic renal disease, smoking habit, use of antihypertensive and lipid lowering drugs were preliminarily used to search for an association between TG log-transformed as a continuous variable and CV event. The conventional cut-off value of TG (150 mg/d) and the prognostic cut-off value of TG identified by means of receiver operating characteristics (ROC) curves, both able to discriminate between subjects developing a CV event, were used as independent predictors in further multivariate Cox models adjusted for the confounders listed above. Results: During 172,329 person-years of follow-up, 1910 participants experienced CV events (11.1 per 1000 age-adjusted person-years). In Cox analysis, TG as a continuous variable was a significant predictor of CV event [odds ratio, OR, 1.189 (1.060-1.334), p = 0.003]. ROC curve showed that > 105 mg/dl (95%CI 75.8-129.3, sensitivity 61.7, specificity 48.8, p < 0.0001) was the prognostic cut-off value for CV event. The conventional cut-off (150 mg/dl) and that identified by ROC curve (105 mg/dl) were both accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.157 (95%CI 1.037-1.290, p = 0.009) and 1.137 (95%C

Published
2022

246. Hypertension in children and adolescents

Author

de Simone, G, Mancusi, C, Hanssen, H, Genovesi, S, Lurbe, E, Parati, G, Sendzikaite, S, Valerio, G, Di Bonito, P, Di Salvo, G, Ferrini, M, Leeson, P, Moons, P, Weismann, C, Williams, B, de Simone, Giovanni, Mancusi, Costantino, Hanssen, Henner, Genovesi, Simonetta, Lurbe, Empar, Parati, Gianfranco, Sendzikaite, Skaiste, Valerio, Giuliana, Di Bonito, Procolo, Di Salvo, Giovanni, Ferrini, Marc, Leeson, Paul, Moons, Philip, Weismann, Constance G, Williams, Bryan, de Simone, G, Mancusi, C, Hanssen, H, Genovesi, S, Lurbe, E, Parati, G, Sendzikaite, S, Valerio, G, Di Bonito, P, Di Salvo, G, Ferrini, M, Leeson, P, Moons, P, Weismann, C, Williams, B, de Simone, Giovanni, Mancusi, Costantino, Hanssen, Henner, Genovesi, Simonetta, Lurbe, Empar, Parati, Gianfranco, Sendzikaite, Skaiste, Valerio, Giuliana, Di Bonito, Procolo, Di Salvo, Giovanni, Ferrini, Marc, Leeson, Paul, Moons, Philip, Weismann, Constance G, and Williams, Bryan

Abstract

Definition and management of arterial hypertension in children and adolescents are uncertain, due to different positions of current guidelines. The European Society of Cardiology task-force, constituted by Associations and Councils with interest in arterial hypertension, has reviewed current literature and evidence, to produce a Consensus Document focused on aspects of hypertension in the age range of 6-16 years, including definition, methods of measurement of blood pressure, clinical evaluation, assessment of hypertension-mediated target organ damage, evaluation of possible vascular, renal and hormonal causes, assessment and management of concomitant risk factors with specific attention for obesity, and anti-hypertensive strategies, especially focused on life-style modifications. The Consensus Panel also suggests aspects that should be studied with high priority, including generation of multi-ethnic sex, age and height specific European normative tables, implementation of randomized clinical trials on different diagnostic and therapeutic aspects, and long-term cohort studies to link with adult cardiovascular risk. Finally, suggestions for the successful implementation of the contents of the present Consensus document are also given.

Published
2022

247. Exercise haemodynamics in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Author

Baratto, C, Caravita, S, Soranna, D, Dewachter, C, Bondue, A, Zambon, A, Badano, L, Parati, G, Vachiéry, J, Baratto, Claudia, Caravita, Sergio, Soranna, Davide, Dewachter, Céline, Bondue, Antoine, Zambon, Antonella, Badano, Luigi, Parati, Gianfranco, Vachiéry, Jean-Luc, Baratto, C, Caravita, S, Soranna, D, Dewachter, C, Bondue, A, Zambon, A, Badano, L, Parati, G, Vachiéry, J, Baratto, Claudia, Caravita, Sergio, Soranna, Davide, Dewachter, Céline, Bondue, Antoine, Zambon, Antonella, Badano, Luigi, Parati, Gianfranco, and Vachiéry, Jean-Luc

Abstract

Aims: Exercise right heart catheterization (RHC) is considered the gold-standard test to diagnose heart failure with preserved ejection fraction (HFpEF). However, exercise RHC is an insufficiently standardized technique, and current haemodynamic thresholds to define HFpEF are not universally accepted. We sought to describe the exercise haemodynamics profile of HFpEF cohorts reported in literature, as compared with control subjects. Methods and results: We performed a systematic literature review until December 2020. Studies reporting pulmonary artery wedge pressure (PAWP) at rest and peak exercise were extracted. Summary estimates of all haemodynamic variables were evaluated, stratified according to body position (supine/upright exercise). The PAWP/cardiac output (CO) slope during exercise was extrapolated. Twenty-seven studies were identified, providing data for 2180 HFpEF patients and 682 controls. At peak exercise, patients with HFpEF achieved higher PAWP (30 [29–31] vs. 16 [15–17] mmHg, P < 0.001) and mean right atrial pressure (P < 0.001) than controls. These differences persisted after adjustment for age, sex, body mass index, and body position. However, peak PAWP values were highly heterogeneous among the cohorts (I2 = 93%), with a relative overlap with controls. PAWP/CO slope was steeper in HFpEF than in controls (3.75 [3.20–4.28] vs. 0.95 [0.30–1.59] mmHg/L/min, P value < 0.0001), even after adjustment for covariates (P = 0.007). Conclusions: Despite methodological heterogeneity, as well as heterogeneity of pooled haemodynamic estimates, the exercise haemodynamic profile of HFpEF patients is consistent across studies and characterized by a steep PAWP rise during exercise. More standardization of exercise haemodynamics may be advisable for a wider application in clinical practice.

Published
2022

248. Impact of correcting the 2D PISA method on the quantification of functional tricuspid regurgitation severity

Author

Tomaselli, M, Badano, L, Menè, R, Gavazzoni, M, Heilbron, F, Radu, N, Caravita, S, Baratto, C, Oliverio, G, Florescu, D, Parati, G, Muraru, D, Tomaselli, Michele, Badano, Luigi, Menè, Roberto, Gavazzoni, Mara, Heilbron, Francesca, Radu, Noela, Caravita, Sergio, Baratto, Claudia, Oliverio, Giorgio, Florescu, Diana R, Parati, Gianfranco, Muraru, Denisa, Tomaselli, M, Badano, L, Menè, R, Gavazzoni, M, Heilbron, F, Radu, N, Caravita, S, Baratto, C, Oliverio, G, Florescu, D, Parati, G, Muraru, D, Tomaselli, Michele, Badano, Luigi, Menè, Roberto, Gavazzoni, Mara, Heilbron, Francesca, Radu, Noela, Caravita, Sergio, Baratto, Claudia, Oliverio, Giorgio, Florescu, Diana R, Parati, Gianfranco, and Muraru, Denisa

Abstract

AIMS: In functional tricuspid regurgitation (FTR) patients, tricuspid leaflet tethering and relatively low jet velocity could result in proximal flow geometry distortions that lead to underestimation of TR. Application of correction factors on two-dimensional (2D) proximal isovelocity surface area (PISA) equation may increase its reliability. This study sought to evaluate the impact of the corrected 2D PISA method in quantifying FTR severity. METHODS AND RESULTS: In 102 patients with FTR, we compared both conventional and corrected 2D PISA measurements of effective regurgitant orifice area [EROA vs. corrected (EROAc)] and regurgitant volume (RegVol vs. RegVolc) with those obtained by volumetric method (VM) using three-dimensional echocardiography (3DE), as reference. Both EROAc and RegVolc were larger than EROA (0.29 ± 0.26 vs. 0.22 ± 0.21 cm2; P < 0.001) and RegVol (24.5 ± 20 vs. 18.5 ± 14.25 mL; P < 0.001), respectively. Compared with VM, both EROAc and RegVolc resulted more accurate than EROA [bias = -0.04 cm2, limits of agreement (LOA) ± 0.02 cm2 vs. bias = -0.15 cm2, LOA ± 0.31 cm2] and RegVol (bias = -3.29 mL, LOA ± 2.19 mL vs. bias = -10.9 mL, LOA ± 13.5 mL). Using EROAc and RegVolc, 37% of patients were reclassified in higher grades of FTR severity. Corrected 2D PISA method led to a higher concordance of TR severity grade with the VM method (ĸ = 0.84 vs. ĸ = 0.33 for uncorrected PISA, P < 0.001). CONCLUSION: Compared with VM by 3DE, the conventional PISA underestimated FTR severity in about 50% of patients. Correction for TV leaflets tethering angle and lower velocity of FTR jet improved 2D PISA accuracy and reclassified more than one-third of the patients.

Published
2022

249. An explainable model of host genetic interactions linked to COVID-19 severity

Author

Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &amp, M, Ludovisi, S, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi Francesco, Francesca Mari, Sergio Daga, Elisa Benetti, Mirella Bruttini, Maria Palmieri, Susanna Croci, Sara Amitrano, Ilaria Meloni, Elisa Frullanti, Gabriella Doddato, Mirjam Lista, Giada Beligni, Floriana Valentino, Kristina Zguro, Rossella Tita, Annarita Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Ariani, Laura Di Sarno, Francesca Montagnani, Mario Tumbarello, Ilaria Rancan, Massimiliano Fabbiani, Barbara Rossetti, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli Raffaelli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Davide Romani, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Manola Pisani, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Massimo Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Raffaele Bruno, Marco Vecchia, Massimo Girardis, Sophie Venturelli, Stefano Busani, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Emiliozzi, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Andrea Tommasi, Umberto Zuccon, Lucia Vietri, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Stefano Baratti, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Filippo Aucella, Pamela Raggi, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Alessandra Guarnaccia, Serafina Valente, Oreste De Vivo, Elena Bargagli, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Gianluca Lacerenza, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Luisa Tavecchia, Mary Ann Belli, Lia Crotti, Gianfranco Parati, Maurizio Sanarico, Filippo Biscarini, Alessandra Stella, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Claudia Suardi, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Katia Capitani, Simona Dei, Sabrina Ravaglia, Rosangela Artuso, Elena Andreucci, Giulia Gori, Angelica Pagliazzi, Erika Fiorentini, Antonio Perrella, Francesco Bianchi, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Sauro Luchi, Giovanna Morelli, Paola Petrocelli, Sarah Iacopini, Sara Modica, Silvia Baroni, Francesco Vladimiro Segala, Francesco Menichetti, Marco Falcone, Giusy Tiseo, Chiara Barbieri, Tommaso Matucci, Davide Grassi, Claudio Ferri, Franco Marinangeli, Francesco Brancati, Antonella Vincenti, Valentina Borgo, Stefania Lombardi, Mirco Lenzi, Massimo Antonio Di Pietro, Francesca Vichi, Benedetta Romanin, Letizia Attala, Cecilia Costa, Andrea Gabbuti, Roberto Menè, Marta Colaneri, Patrizia Casprini, Giuseppe Merla, Gabriella Maria Squeo, Marcello Maffezzoni, Stefania Mantovani, Mario U. Mondelli &, Serena Ludovisi, Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &amp, M, Ludovisi, S, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi Francesco, Francesca Mari, Sergio Daga, Elisa Benetti, Mirella Bruttini, Maria Palmieri, Susanna Croci, Sara Amitrano, Ilaria Meloni, Elisa Frullanti, Gabriella Doddato, Mirjam Lista, Giada Beligni, Floriana Valentino, Kristina Zguro, Rossella Tita, Annarita Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Ariani, Laura Di Sarno, Francesca Montagnani, Mario Tumbarello, Ilaria Rancan, Massimiliano Fabbiani, Barbara Rossetti, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli Raffaelli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Davide Romani, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Manola Pisani, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Massimo Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Raffaele Bruno, Marco Vecchia, Massimo Girardis, Sophie Venturelli, Stefano Busani, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Emiliozzi, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Andrea Tommasi, Umberto Zuccon, Lucia Vietri, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Stefano Baratti, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Filippo Aucella, Pamela Raggi, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Alessandra Guarnaccia, Serafina Valente, Oreste De Vivo, Elena Bargagli, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Gianluca Lacerenza, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Luisa Tavecchia, Mary Ann Belli, Lia Crotti, Gianfranco Parati, Maurizio Sanarico, Filippo Biscarini, Alessandra Stella, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Claudia Suardi, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Katia Capitani, Simona Dei, Sabrina Ravaglia, Rosangela Artuso, Elena Andreucci, Giulia Gori, Angelica Pagliazzi, Erika Fiorentini, Antonio Perrella, Francesco Bianchi, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Sauro Luchi, Giovanna Morelli, Paola Petrocelli, Sarah Iacopini, Sara Modica, Silvia Baroni, Francesco Vladimiro Segala, Francesco Menichetti, Marco Falcone, Giusy Tiseo, Chiara Barbieri, Tommaso Matucci, Davide Grassi, Claudio Ferri, Franco Marinangeli, Francesco Brancati, Antonella Vincenti, Valentina Borgo, Stefania Lombardi, Mirco Lenzi, Massimo Antonio Di Pietro, Francesca Vichi, Benedetta Romanin, Letizia Attala, Cecilia Costa, Andrea Gabbuti, Roberto Menè, Marta Colaneri, Patrizia Casprini, Giuseppe Merla, Gabriella Maria Squeo, Marcello Maffezzoni, Stefania Mantovani, Mario U. Mondelli &, and Serena Ludovisi

Abstract

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as “Respiratory or thoracic disease”, supporting their link with COVID-19 severity outcome.

Published
2022

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