Search

Introduction and objectives Hereditary transthyretin amyloidosis (hATTR) is a disease caused by mutations in the transthyretin gene that frequently shows cardiac involvement due to amyloid deposition in the myocardium. Our objective was to identify cardiac involvement in a Spanish cohort. Methods Retrospective multicenter study of patients diagnosed with hATTR with cardiac involvement from Spanish centers. We collected demographic, clinical, and genetic data. Results A total of 181 patients from 26 centers were included (65.2% men, with a median age at diagnosis of 62 years). The most frequent mutations were Val50Met (67.7%) and Val142Ile (12.4%). The main reason for consultation was extracardiac symptoms (69%), mainly neurological. The mean N-terminal pro-B-type natriuretic peptide level was 2145±3586 pg/mL. The most characteristic electrocardiogram findings were a pseudoinfarct pattern (25.9%) and atrioventricular block (25.3%). Mean ventricular thickness was 15.4±4.1mm. Longitudinal strain was reduced in basal segments by 29.4%. Late diffuse subendocardial enhancement was observed in 58.8%. Perugini grade 2 or 3 uptake was observed in 75% of scintigraphy scans. During follow-up, 24.9% of the patients were admitted for heart failure, 34.3% required a pacemaker, and 31.6% required a liver transplant. One third (32.5%) died during follow-up, mainly due to heart failure (28.8%). The presence of non-Val50Met mutations was associated with a worse prognosis. Conclusions HATTR cardiac amyloidosis in Spain shows heterogeneous genetic and clinical involvement. The prognosis is poor, mainly due to cardiac complications. Consequently early diagnosis and treatment are vital.

Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene that is usually lethal without cardiac transplantation. The purpose of this study was to characterize post-transplant outcomes in a large cohort of patients with DD who underwent cardiac transplantation.The clinical phenotype and outcome data of patients with DD who underwent cardiac transplantation (n = 38; 19 males and 19 females) were obtained from 8 centers. Study outcomes included graft survival, defined as death or retransplantation, and episodes of acute cellular and antibody-mediated rejection and cardiac allograft vasculopathy at 1 year.Median follow-up time after transplantation for the entire cohort was 4.4 years (IQR: 1.5-12.8 years). The median age at transplant for the cohort was 20.2 years (15.8-27.9 years), with no difference in age between sexes. Median pretransplant left-ventricular ejection fraction for the entire cohort was 30% (range 11%-84%). Males had higher pretransplant aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase levels than females (P0.001). There were 2 deaths in the entire cohort and 2 retransplants. There was no difference in actuarial graft survival between males and females (P = 0.8965); the estimated graft survival was 87.1% (95%CI: 63.6%-95.9%) at 5 years. One episode (2.7%) of antibody-mediated rejection, grade 2, and 7 episodes (19%) of acute cellular rejection, grade 2 or 3, were reported in patients who survived to discharge (6 females and 1 male; P = 0.172).Heart transplantation outcomes are acceptable in DD with high probabilities of 5-year graft survival for males and females suggesting that cardiac transplantation is an effective treatment option for DD patients.

Instituto de Salud Carlos III (ISCIII), European Regional Development Fund/European Social Fund "A way to make Europe"/" Investing in your future" [PI18/0004, PI20/0320, PT17/0015/0043]; ISCIII; MCIN; Pro-CNIC Foundation; Severo Ochoa Centers of Excellence program [CEX2020-001041-S]; ISCIII [CM20/00101], Frutos F. de, Ochoa JP, Navarro-Peñalver M, Baas A, Bjerre JV, Zorio E, Méndez I, Lorca R, Verdonschot JAJ, García-Granja PE, Bilinska Z, Fatkin D, Fuentes-Cañamero ME, García-Pinilla JM, García-Álvarez MI, Girolami F, Barriales-Villa R, Díez-López C, Lopes LR, Wahbi K, García-Álvarez A, Rodríguez-Sánchez I, Rekondo-Olaetxea J, Rodríguez-Palomares JF, Gallego-Delgado M, Meder B, Kubanek M, Hansen FG, Restrepo-Córdoba MA, Palomino-Doza J, Ruiz-Guerrero L, Sarquella-Brugada G, Perez-Perez AJ, Bermúdez-Jiménez FJ, Ripoll-Vera T, Rasmussen TB, Jansen M, Sabater-Molina M, Elliot PM, Garcia-Pavia P; European Genetic Cardiomyopathies Initiative Investigators

INTRODUCTION AND OBJECTIVES According to the wavefront phenomenon described in the late 1970s, myocardial infarction triggered by acute coronary occlusion progresses with increasing duration of ischemia as a transmural wavefront from the subendocardium toward the subepicardium. However, whether wavefront progression of necrosis also occurs laterally has been disputed. We aimed to assess the transmural and lateral spread of myocardial damage after acute myocardial infarction in humans and to evaluate the impact of metoprolol on these. METHODS We assessed myocardial infarction in the transmural and lateral dimensions in a cohort of 220 acute ST-segment elevation myocardial infarction (STEMI) patients from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction). The patients underwent cardiac magnetic resonance imaging at 5 to 7 days and 6 months post-STEMI. RESULTS On day 5 to 7 post-STEMI cardiac magnetic resonance, there was a strong linear correlation between the transmural and lateral extent of infarction (delayed gadolinium enhancement) (r=-0.88; P

Aims: Dilated cardiomyopathy (DCM) associated with dystrophin gene (DMD) mutations in individuals with mild or absent skeletal myopathy is often indistinguishable from other DCM forms. We sought to describe the phenotype and prognosis of DMD associated DCM in DMD mutation carriers without severe skeletal myopathy. Methods and results: At 26 European centres, we retrospectively collected clinical characteristics and outcomes of 223 DMD mutation carriers (83% male, 33 ± 15 years). A total of 112 individuals (52%) had DCM at first evaluation [n = 85; left ventricular ejection fraction (LVEF) 34 ± 11.2%] or developed DCM (n = 27; LVEF 41.3 ± 7.5%) after a median follow-up of 96 months (interquartile range 5–311 months). DCM penetrance was 45% in carriers older than 40 years. DCM appeared earlier in males and was independent of the type of mutation, presence of skeletal myopathy, or elevated serum creatine kinase levels. Major adverse cardiac events (MACE) occurred in 22% individuals with DCM, 18% developed end-stage heart failure and 9% sudden cardiac death or equivalent. Skeletal myopathy was not associated with survival free of MACE in patients with DCM. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Individuals without DCM had favourable prognosis without MACE or death during follow-up. Conclusions: DMD-associated DCM without severe skeletal myopathy is characterized by incomplete penetrance but high risk of MACE, including progression to end-stage heart failure and ventricular arrhythmias. DCM onset is the major determinant of prognosis with similar survival regardless of the presence of skeletal myopathy.

Aims: Genotype and left ventricular scar on cardiac magnetic resonance (CMR) are increasingly recognized as risk markers for adverse outcomes in non-ischaemic dilated cardiomyopathy (DCM). We investigated the combined influence of genotype and late gadolinium enhancement (LGE) in assessing prognosis in a large cohort of patients with DCM. Methods and results: Outcomes of 600 patients with DCM (53.3 ± 14.1 years, 66% male) who underwent clinical CMR and genetic testing were retrospectively analysed. The primary endpoints were end-stage heart failure (ESHF) and malignant ventricular arrhythmias (MVA). During a median follow-up of 2.7 years (interquartile range 1.3–4.9), 24 (4.00%) and 48 (8.00%) patients had ESHF and MVA, respectively. In total, 242 (40.3%) patients had pathogenic/likely pathogenic variants (positive genotype) and 151 (25.2%) had LGE. In survival analysis, positive LGE was associated with MVA and ESHF (both, p < 0.001) while positive genotype was associated with ESHF (p = 0.034) but not with MVA (p = 0.102). Classification of patients according to genotype (G+/G−) and LGE presence (L+/L−) revealed progressively increasing events across L−/G−, L−/G+, L+/G− and L+/G+ groups and resulted in optimized MVA and ESHF prediction (p < 0.001 and p = 0.001, respectively). Hazard ratios for MVA and ESHF in patients with either L+ or G+ compared with those with L−/G− were 4.71 (95% confidence interval: 2.11–10.50, p < 0.001) and 7.92 (95% confidence interval: 1.86–33.78, p < 0.001), respectively. Conclusion: Classification of patients with DCM according to genotype and LGE improves MVA and ESHF prediction. Scar assessment with CMR and genotyping should be considered to select patients for primary prevention implantable cardioverter-defibrillator placement, This work was supported by grants from the Instituto de Salud Carlos III (ISCIII) (PI18/0004, PI19/01283, PI20/0320). (Co-funded by European Regional Development Fund/European Social Fund ‘A way to make Europe’/‘Investing in your future’). The Hospital Universitario Puerta de Hierro Majadahonda, the Hospital Clinic, the Hospital Vall d’Hebron, the Hospital General Universitario Gregorio Marañón and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for rare, low-prevalence, and complex diseases of the heart (ERN GUARD-Heart). The CNIC is supported by the ISCIII, MCIN, the Pro-CNIC Foundation, and the Severo Ochoa Centers of Excellence program (CEX2020-001041-S). Conflict of interest: none declared

Trasplante combinado de corazón e hígado; Cardiomiopatía Trasplantament combinat de fetge i cor; Cardiomiopatia Combined heart-liver transplant; Cardiomyopathy Background Uhl's anomaly is an extremely rare congenital heart defect characterized by absence of the right ventricle myocardium and preserved left ventricular myocardium. Although the disease has a poor prognosis and is generally fatal in the perinatal period, some patients may reach adulthood. Methods We describe a case of Uhl's anomaly complicated with heart failure and decompensated cardiac cirrhosis in a 42-year-old man treated by combined heart-liver transplant. Results The patient underwent heart transplant using the bicaval technique followed by subsequent liver transplant with the piggyback technique without venovenous bypass. Total ischemia time was 108 minutes for the heart and 360 and 25 minutes of cold and warm ischemia, respectively, for the liver. No intraoperative complications occurred. The patient was discharged without severe complications on postoperative day 22. Pathologic examination of the organs reported advanced cirrhosis of the liver and severe dilated myocardiopathy of right ventricle with absence of myocardium and a normal left ventricle. Twenty-seven months after the transplant the patient has been free from hospital admissions, with normal function of both transplanted organs. Conclusions We report the first successful combined heart-liver transplant for Uhl's anomaly indication in an adult patient. Despite of the insufficient knowledge of natural history of this exceptional disease, we successfully apply the management principles of other end-stage right heart disorders complicated with liver failure.

Heparin-induced thrombocytopaenia (HIT) complicates the management of patients in need for mechanical circulatory support awaiting heart transplantation. The limited available treatment options are fraught with complications and limitations in their applicability. We report on the combined use of therapeutic plasma exchange therapy and intravenous immunoglobulin, used in 3 consecutive heparin-induced thrombocytopaenia-positive patients on temporary mechanical circulatory support awaiting urgent heart transplant. This combined approach allowed us to use heparin safely.

BACKGROUND The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled. OBJECTIVES The study sought to assess the prognostic impact of disease-causing genetic variants in DCM. METHODS Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR) RESULTS After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.092.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction #35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene. CONCLUSIONS In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene. (J Am Coll Cardiol 2021;78:1682-1699) (c) 2021 by the American College of Cardiology Foundation.

A proper interpretation of the pathogenicity of rare variants is crucial before clinical translation. Ongoing addition of new data may modify previous variant classifications; however, how often a reanalysis is necessary remains undefined. We aimed to extensively reanalyze rare variants associated with inherited channelopathies originally classified 5 years ago and its clinical impact. In 2016, rare variants identified through genetic analysis were classified following the American College of Medical Genetics and Genomics’ recommendations. Five years later, we have reclassified the same variants following the same recommendations but including new available data. Potential clinical implications were discussed. Our cohort included 49 cases of inherited channelopathies diagnosed in 2016. Update show that 18.36% of the variants changed classification mainly due to improved global frequency data. Reclassifications mostly occurred in minority genes associated with channelopathies. Similar percentage of variants remain as deleterious nowadays, located in main known genes (SCN5A, KCNH2 and KCNQ1). In 2016, 69.38% of variants were classified as unknown significance, but now, 53.06% of variants are classified as such, remaining the most common group. No management was modified after translation of genetic data into clinics. After 5 years, nearly 20% of rare variants associated with inherited channelopathies were reclassified. This supports performing periodic reanalyses of no more than 5 years since last classification. Use of newly available data is necessary, especially concerning global frequencies and family segregation. Personalized clinical translation of rare variants can be crucial to management if a significant change in classification is identified.

The autonomic nervous system (ANS) and renin-angiotensin-aldosterone system (RAAS) are involved in many cardiovascular disorders, including pulmonary hypertension (PH). The current review focuses on the role of the ANS and RAAS activation in PH and updated evidence of potential therapies targeting both systems in this condition, particularly in Groups 1 and 2. State of the art knowledge in preclinical and clinical use of pharmacologic drugs (beta-blockers, beta-three adrenoceptor agonists, or renin-angiotensin-aldosterone signaling drugs) and invasive procedures, such as pulmonary artery denervation, is provided. This work was partially funded by Fondo Europeo de Desarrollo Regional (FEDER) Instituto de Salud Carlos III-Fondo de Investigación Sanitaria PI17/00995 and Intensificación AES2019 to Dr. García-Álvarez. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Part of this work was developed at the Centre de Recerca Biomèdica Cellex, IDIBAPS, Barcelona. The IDIBAPS belongs to the CERCA Programme and receives partial funding from the Generalitat de Catalunya. Sí

Introduction and objectives: To determine whether structural/organizational characteristics of hospitals and emergency departments (EDs) affect acute heart failure (AHF) outcomes. Methods: We performed a secondary analysis of the EAHFE Registry. Six hospital/ED characteristics were collected and were related to 7 postindex events and postdischarge outcomes, adjusted by the period of patient inclusion, baseline patient characteristics, AHF episode features, and hospital and ED characteristics. The relationship between discharge directly from the ED (DDED) and outcomes was assessed, and interaction was analyzed according to the hospital/ED characteristics. Results: We analyzed 17 974 AHF episodes included by 40 Spanish EDs. Prolonged stays were less frequent in high-technology hospitals and those with hospitalization at home and with high-inflow EDs, and were more frequent in hospitals with a heart failure unit (HFU) and an ED observation unit. In-hospital mortality was lower in high-technology hospitals (OR, 0.78; 95%CI, 0.65-0.94). Analysis of 30-day postdischarge outcomes showed that hospitals with a short-stay unit (SSU) had higher hospitalization rates (OR, 1.19; 95%CI, 1.02-1.38), high-inflow EDs had lower mortality (OR, 0.73; 95%CI, 0.56-0.96) and fewer combined events (OR, 0.87; 95%CI, 0.76-0.99), while hospitals with HFU had fewer ED reconsultations (OR, 0.83; 95%CI, 0.76-0.91), hospitalizations (OR, 0.85; 95%CI, 0.75-0.97), and combined events (OR, 0.84; 95%CI, 0.77-0.92). The higher the percentage of DDED, the fewer the prolonged stays. Among other interactions, we found that more frequent DDED was associated with more 30-day postdischarge reconsultations, hospitalizations and combined events in hospitals without SSUs, but not in hospitals with an SSU. Conclusions: AHF outcomes were significantly affected by the structural/organizational characteristics of hospitals and EDs and their aggressiveness in ED management. (C) 2020 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Chagas disease is emerging in countries to which it is not endemic. Biomarkers for earlier therapeutic response assessment in patients with chronic Chagas disease are needed. We profiled plasma-derived extracellular vesicles from a heart transplant patient with chronic Chagas disease and showed the potential of this approach for discovering such biomarkers. Barcelona Institute for Global Health (ISGlobal) receives support from the Spanish Ministry of Science, Innovation and Universities through the Centro de Excelencia Severo Ochoa 2019–2023 Program (CEX2018-000806-S). ISGlobal and Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP) are members of the Centres de Recerca de Catalunya (CERCA Program), Generalitat de Catalunya. Work in the laboratory of C.F.B. is funded by Fundació La Marató de TV3 (reference 566/U/2018) and Fundación Mundo Sano. This project was co-financed by the European Union through the European Regional Development Fund with the support of Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya. N.C., M.G., J.G., and M.J.P. receive funds from the Redes temáticas de investigación cooperativa en salud (RETICS), Spanish Tropical Diseases Network “RD12/0018/0010” and from the Agencia de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya; grant “2017 SGR 00924.” M.G., C.B., J.G., M.J.P., and I.C.A. belong to the Ibero-American Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas network. I.C.A. is partially supported by grants no. 2G12MD007592 and 5U54MD007592 from the National Institute on Minority Health and Health Disparities of the US National Institutes of Health. We are grateful to the Biomolecule Analysis Core Facility at University of Texas at El Paso, Border Biomedical Research Center, funded by National Institute on Minority Health and Health Disparities grants 2G12MD007592 and 5U54MD007592. M.T.M. received a PhD fellowship from the Science Without Borders Program, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil. Sí

Background: Accurate interpretation of rare genetic variants is a challenge for clinical translation. Updates in recommendations for rare variant classification require the reanalysis and reclassification. We aim to perform an exhaustive re-analysis of rare variants associated with inherited arrhythmogenic syndromes, which were classified ten years ago, to determine whether their classification aligns with current standards and research findings. Methods: In 2010, the rare variants identified throughout genetic analysis were classified following recommendations available at that time. Nowadays, the same variants have been reclassified following current American College of Medical Genetics and Genomics recommendations. Findings: Our cohort included 104 cases diagnosed with inherited arrhythmogenic syndromes and 17 post-mortem cases in which inherited arrhythmogenic syndromes was cause of death. 71.87% of variants change their classification. While 65.62% of variants were classified as likely pathogenic in 2010, after reanalysis, only 17.96% remain as likely pathogenic. In 2010, 18.75% of variants were classified as uncertain role but nowadays 60.15% of variants are classified of unknown significance. Interpretation: Reclassification occurred in more than 70% of rare variants associated with inherited arrhythmogenic syndromes. Our results support the periodical reclassification and personalized clinical translation of rare variants to improve diagnosis and adjust treatment. Funding Statement:This work was supported by Obra Social "La Caixa Foundation" (ID 100010434), Fondo Investigacion Sanitaria (FIS PI16/01203 and FIS, PI17/01690) from Instituto Salud Carlos III (ISCIII), Sociedad Espanola de Cardiologia (Proyecto Investigacion Basica Cardiologia 2015 de los Socios Estrategicos SEC), and “Fundacio Privada Daniel Bravo Andreu”. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: Genetic analysis was approved by the ethics committee of Hospital Josep Trueta (Girona, Spain) following the Helsinki II declaration. Written informed consent was obtained from all patients included in the study.

INTRODUCTION AND OBJECTIVES The present report updates the characteristics and results of heart transplantation in Spain, mainly focused in the 2008-2017 period. METHODS We describe the recipient and donor characteristics, surgical procedures, and outcomes of heart transplants performed in 2017. The 2017 data were compared with those obtained from 2008 to 2016. RESULTS A total of 304 cardiac transplants were performed in 2017. Between 1984 and 2017, 8173 procedures were performed, 2689 of them after 2008. Significant temporal trends were observed in recipient characteristics (lower pulmonary vascular resistance, lower use of mechanical ventilation, and a higher percentage of diabetic patients and those with previous cardiac surgery), donor characteristics (older donor age and a higher percentage of female donors and those with a prior cardiac arrest) and procedures (lower ischemia time). In 2017, 27% of patients were transplanted after undergoing mechanical ventricular assistance (P

Over the last ten years, analysis of copy number variants has increasingly been applied to the study of arrhythmogenic pathologies associated with sudden death, mainly due to significant advances in the field of massive genetic sequencing. Nevertheless, few published reports have focused on the prevalence of copy number variants associated with sudden cardiac death. As a result, the frequency of these genetic alterations in arrhythmogenic diseases as well as their genetic interpretation and clinical translation has not been established. This review summarizes the current available data concerning copy number variants in sudden cardiac death-related diseases.

BACKGROUND Pre-reperfusion administration of intravenous (IV) metoprolol reduces infarct size in ST-segment elevation myocardial infarction (STEMI). OBJECTIVES This study sought to determine how this cardioprotective effect is influenced by the timing of metoprolol therapy having either a long or short metoprolol bolus-to-reperfusion interval. METHODS We performed a post hoc analysis of the METOCARD-CNIC (effect of METOprolol of CARDioproteCtioN during an acute myocardial InfarCtion) trial, which randomized anterior STEMI patients to IV metoprolol or control before mechanical reperfusion. Treated patients were divided into short-and long-interval groups, split by the median time from 15 mg metoprolol bolus to reperfusion. We also performed a controlled validation study in 51 pigs subjected to 45 min ischemia/reperfusion. Pigs were allocated to IV metoprolol with a long (-25 min) or short (-5 min) pre-perfusion interval, IV metoprolol post-reperfusion (+60 min), or IV vehicle. Cardiac magnetic resonance (CMR) was performed in the acute and chronic phases in both clinical and experimental settings. RESULTS For 218 patients (105 receiving IV metoprolol), the median time from 15 mg metoprolol bolus to reperfusion was 53 min. Compared with patients in the short-interval group, those with longer metoprolol exposure had smaller infarcts (22.9 g vs. 28.1 g; p = 0.06) and higher left ventricular ejection fraction (LVEF) (48.3\% vs. 43.9\%; p = 0.019) on day 5 CMR. These differences occurred despite total ischemic time being significantly longer in the long-interval group (214 min vs. 160 min; p < 0.001). There was no between-group difference in the time from symptom onset to metoprolol bolus. In the animal study, the long-interval group (IV metoprolol 25 min before reperfusion) had the smallest infarcts (day 7 CMR) and highest long-term LVEF (day 45 CMR). CONCLUSIONS In anterior STEMI patients undergoing primary angioplasty, the sooner IV metoprolol is administered in the course of infarction, the smaller the infarct and the higher the LVEF. These hypothesis-generating clinical data are supported by a dedicated experimental large animal study. (C) 2016 by the American College of Cardiology Foundation. The authors thank Noemi Escalera and Maite Rodriguez, who were outstanding in the management of the clinical trial and imaging analyses. The authors are also indebted to the generous dedication of time and effort to the METOCARD-CNIC trial by all coinvestigators from SUMMA112, 061 Galicia, and SAMUR. The coordinating center at SCU-SUMMA112 was crucial for the proper conduct of the trial. Tamara Cordoba, Oscar Sanz, Ruben Mota, Santiago Rodriguez, Eugenio Fernández, and the rest of the team at the CNIC Animal Facility and farm provided outstanding animal care and support. Simon Bartlett (CNIC) provided English editing. Sí

We report a case of bioresorbable vascular scaffold restenosis which could be caused by abnormal resorption 17months after implantation.

BACKGROUND Pulmonary hypertension (PH) after heart transplantation (HT) is associated to right ventricular (RV) dysfunction and increased morbidity and mortality. We present our experience with bosentan for the treatment of PH after HT. METHODS A retrospective evaluation of patients with PH receiving bosentan post-transplant was performed. Pulmonary hemodynamics before and after bosentan (BG) and clinical outcomes were assessed and compared to a historical control group (CG) not receiving bosentan. RESULTS Between 2013 and 2016, 21 patients were treated post-transplant with bosentan. Twenty-four hours after bosentan initiation, there were significant decreases in systolic (42.5 ± 8 to 38.1 ± 8 mm Hg, P = 0.015), diastolic (21.4 ± 4 to 17.8 ± 6 mm Hg, P = 0.008) and mean (29.6 ± 5 to 25 ± 6 mm Hg, P = 0.001) pulmonary artery pressures (PAP), transpulmonary gradient (13.1 ± 3 to 9.7 ± 4 mm Hg, P

Introduction and objectives: Danon disease (DD) is caused by mutations in the LAMP2 gene. It is considered a multisystemic disease characterized by hypertrophic cardiomyopathy with pre-excitation and extreme hypertrophy, intellectual disability, myopathy, childhood presentation, and worse prognosis in men. There are scarce data on the clinical characteristics and prognosis of DD. Methods: We analyzed the clinical records of patients with DD from 10 Spanish hospitals. Results: Twenty-seven patients were included (mean age, 31 +/- 19 years; 78% women). Male patients showed a high prevalence of extracardiac manifestations: myopathy (80%), learning disorders (83%), and visual alterations (60%), which were uncommon findings in women (5%, 0%, and 27%, respectively). Although hypertrophic cardiomyopathy was the most common form of heart disease (61%), the mean maximum wall thickness was 15 +/- 7 mm and dilated cardiomyopathy was present in 12 patients (10 women). Pre-excitation was found in only 11 patients (49%). Age at presentation was older than 20 years in 16 patients (65%). After a median follow-up of 4 years (interquartile range, 2-9), 4 men (67%) and 9 women (43%) died or required a transplant. Cardiac disease and adverse events occurred later in women (37 +/- 9 vs 23 +/- 16 and 36 +/- 20 vs 20 +/- 11 years, respectively). Conclusions: The clinical characteristics of DD differ substantially from traditional descriptions: age at presentation of DD is older, the disease is not multisystemic in women, and pre-excitation is infrequent. (C) 2018 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Cardiovascular imaging has become essential to achieving a better understanding of cardiovascular diseases. Due to the advent of new technology and the refinement of existing technologies, imaging's role has extended into the biological, functional, and hemodynamic diagnosis of multiple pathophysiologic processes. Current and future trends in cardiovascular imaging will focus on improving early diagnosis of vascular disease, so as to be able to promote cardiovascular health, and on its development as a useful tool in clinical decision-making. Imaging is also increasingly used to quantify the effect of novel therapies. The rapid development of molecular imaging and fusion imaging techniques improves our understanding of cardiovascular processes from the molecular and cellular points of view and makes it possible to design and test new preventive interventions. The proliferation and integration of imaging techniques in different clinical areas and their role in “translational imaging” plays an important part in the implementation of personalized therapeutic and preventive management strategies for patients with cardiovascular disease.

Beta-3 adrenergic receptor (beta 3AR) agonists have been shown to produce vasodilation and prevention of ventricular remodeling in different conditions. Given that these biological functions are critical in pulmonary hypertension (PH), we aimed to demonstrate a beneficial effect of beta 3AR agonists in PH. An experimental study in pigs (n = 34) with chronic PH created by pulmonary vein banding was designed to evaluate the acute hemodynamic effect and the long-term effect of beta 3AR agonists on hemodynamics, vascular remodeling and RV performance in chronic PH. Ex vivo human experiments were performed to explore the expression of beta 3AR mRNA and the vasodilator response of beta 3AR agonists in pulmonary arteries. Single intravenous administration of the beta 3AR agonist BRL37344 produced a significant acute reduction in PVR, and two-weeks treatment with two different beta 3AR selective agonists, intravenous BRL37344 or oral mirabegron, resulted in a significant reduction in PVR (median of -2.0 Wood units/m(2) for BRL37344 vs. + 1.5 for vehicle, p = 0.04; and -1.8 Wood units/m(2) for mirabegron vs. + 1.6 for vehicle, p = 0.002) associated with a significant improvement in magnetic resonance-measured RV performance. Histological markers of pulmonary vascular proliferation (p27 and Ki67) were significantly attenuated in beta 3AR agonists-treated pigs. beta 3AR was expressed in human pulmonary arteries and beta 3AR agonists produced vasodilatation. beta 3AR agonists produced a significant reduction in PVR and improved RV performance in experimental PH, emerging as a potential novel approach for treating patients with chronic PH. This work was supported by Fonde Europeo de Desarrollo Regional (FEDER) Instituto de Salud Carlos III-Fondo de Investigacion Sanitaria PI13/02339 (to A. G-A), and the competitive grant ``CNIC-Translational 01-2009´´ (to BI). R F-J is recipient of a ``Rio Hortega´´ fellowship granted by the ISCIII. R F-J is recipient of the ``FICNIC´´ fellowship granted by the ``Fundacio Jesus Serra´´, ``Fundacion Interhospitalaria de Investigacion Cardiovascular (FIC)´´ and CNIC. A. G-A, B. I, L. F-F, R. F-J, M. S and JM. G-R are members of ``Red de Investigacion Cardiovascular´´ (RIC RD12/0042/0006 and RD12/0042/0054) from the Ministerio de Economia y Competitividad, ISCIII´´. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Sí

Accurate and efficient evaluation of acute chest pain remains clinically challenging because traditional diagnostic modalities have many limitations. Recent improvement in non-invasive imaging technologies could potentially improve both diagnostic efficiency and clinical outcomes of patients with acute chest pain while reducing unnecessary hospitalizations. However, there is still controversy regarding much of the evidence for these technologies. This article reviews the role of coronary artery calcium score and the coronary computed tomography in the assessment of individual coronary risk and their usefulness in the emergency department in facilitating appropriate disposition decisions. The evidence base and clinical applications for both techniques are also described, together with cost- effectiveness and radiation exposure considerations.

Objective To quantify right ventriculo-arterial coupling in pulmonary hypertension by combining standard right heart catheterisation (RHC) and cardiac magnetic resonance (CMR) and to estimate it non-invasively with CMR alone. Design Cross-sectional analysis in a retrospective cohort of consecutive patients. Setting Tertiary care centre. Patients 139 adults referred for pulmonary hypertension evaluation. Interventions CMR and RHC within 2 days (n=151 test pairs). Main outcome measures Right ventriculo-arterial coupling was quantified as the ratio of pulmonary artery (PA) effective elastance (E a , index of arterial load) to right ventricular maximal end-systolic elastance (E max , index of contractility). Right ventricular end-systolic volume (ESV) and stroke volume (SV) were obtained from CMR and adjusted to body surface area. RHC provided mean PA pressure (mPAP) as a surrogate of right ventricular end-systolic pressure, pulmonary capillary wedge pressure (PCWP) and pulmonary vascular resistance index (PVRI). E a was calculated as (mPAP − PCWP)/SV and E max as mPAP/ESV. Results E a increased linearly with advancing severity as defined by PVRI quartiles (0.19, 0.50, 0.93 and 1.63 mm Hg/ml/m 2 , respectively; p max increased initially and subsequently tended to decrease (0.52, 0.67, 0.54 and 0.56 mm Hg/ml/m 2 ; p=0.7). E a /E max was maintained early but increased markedly with severe hypertension (0.35, 0.72, 1.76 and 2.85; p a /E max approximated non-invasively with CMR as ESV/SV was 0.75, 1.17, 2.28 and 3.51, respectively (p Conclusions Right ventriculo-arterial coupling in pulmonary hypertension can be studied with standard RHC and CMR. Arterial load increases with disease severity whereas contractility cannot progress in parallel, leading to severe uncoupling.

Background Exercise testing constitutes the usual tool for decision making in chest pain units. This policy implies logistical constrains. Our aim was to evaluate a new strategy, combining a clinical risk score and N-terminal pro–B-type natriuretic peptide (NT-proBNP), in patients presenting to the emergency department with chest pain, without ischemic electrocardiogram changes or troponin elevation. Methods A total of 320 patients were randomized to either usual management, involving exercise testing, or a new strategy combining a clinical risk score and NT-proBNP without exercise testing. In the usual management, discharge decision was guided by the result of exercise test. In the new strategy, those patients with low clinical risk score and NT-proBNP were directly discharged. The primary outcome was hospitalization at the index episode. Secondary outcomes were cardiac events at 1 year. Results A total of 110 patients (69%) were hospitalized using usual management in comparison with 90 (56%) in the new strategy ( P = .03). There were no differences in death or myocardial infarction (n = 11, 6.9% vs n=6, 3.8%, P = .3) or cardiac events (n = 38, 24% vs n=28, 18%, P = .2). Revascularizations at the index episode were more frequent under usual management (18% vs 8%, P = .01), although the new strategy was associated with higher rate of planned postdischarge revascularizations (0.6% vs 5%, P = .04). Conclusions A strategy combining clinical history and NT-proBNP is simpler and reduced initial emergency hospitalizations in patients with chest pain, in comparison with the usual strategy involving exercise testing. Larger studies to assess its impact on long-term hard end points are needed. (ClinicalTrials.govNCT00493844)

The main objective of this study was to investigate the relation between brain natriuretic peptide (BNP) levels within the first 96 hours after ST-segment elevation acute myocardial infarction (STEMI) and the development of left ventricular (LV) dilatation at 6-month follow-up. Eighty-two patients with first STEMIs, reperfused within 12 hours of symptom onset, were prospectively included. Plasma BNP was determined on admission and at 1- and 6-month follow-up. Clinically significant LV dilatation, defined as a20% increase in LV end-diastolic volume at 6-month follow-up, was assessed using echocardiography and cardiac magnetic resonance. Thirty-two percent of patients developed clinically significant LV dilatation. BNP values on admission and at follow-up were significantly higher in patients who developed clinically significant LV dilatation at 6 months (182 +/- 117 vs 106 +/- 91 pmol/ml). After adjusting for age, infarct size, E-wave deceleration time, and the LV ejection fraction, BNP on admission was an independent predictor of LV dilatation, whether assessed by echocardiography (B = 0.075, p = 0.04) or cardiac magnetic resonance (B = 0.085, p = 0.04). In conclusion, high BNP levels on admission and at follow-up predict LV dilatation after STEMI. The early determination of plasma BNP upon admission for STEMI could be helpful in identifying patients at higher risk for LV dilatation, in whom aggressive management is warranted.

Cardiac resynchronization therapy (CRT) has been shown to reduce functional mitral regurgitation (MR). The aims of this study were to analyze the underlying mechanisms leading to this reduction and to identify the best candidates with functional MR for this therapy. Changes in mitral geometry, left ventricular (LV) remodeling, and LV synchrony were studied in patients who underwent CRT acutely and at 6- and 12-month follow-up. Of 151 patients (mean age 69 +/- 9 years, 82% men) who underwent CRT, 57 (38%) had nontrivial MR (regurgitant orifice areaor =10 mm(2)). The median reduction of MR with CRT was 18% acutely and 38% at 12-month follow-up. CRT induced an acute improvement in LV systolic function (LV dP/dt from 508 +/- 143 to 700 +/- 249 mm Hg, p0.05) and a reduction in dyssynchrony (interventricular delay from 51 +/- 31 to 29 +/- 27 ms, p0.05). At 12-month follow-up, additional reverse global and local LV remodeling (LV end-systolic volume from 183 +/- 77 to 151 +/- 50 ml, tenting area from 3.36 +/- 0.98 to 2.78 +/- 0.75 cm, p0.05 for both) and a reduction in LV dyssynchrony (septal-lateral delay from 90 +/- 63 to 53 +/- 42 ms, p0.05) were found. Significant reductions in MR were found in 28 patients (49%) and similarly observed in either ischemic MR or functional MR of other causes. Baseline mitral tenting area was the strongest predictor of significant MR reduction with CRT. In conclusion, CRT induced acute and sustained reductions in functional MR in almost 50% of patients by initially improving LV systolic function and dyssynchrony; long-term reverse LV remodeling contributed to this sustained effect. Patients with larger mitral valve tenting areas are less amenable to benefit from CRT.

The mortality rate of patients with cardiogenic shock complicating acute myocardial infarction remains exceedingly high despite early mechanical revascularization. Early risk stratification is of great importance to identify patients who could benefit from ventricular assist devices and urgent heart transplantation (UHT). All consecutive patients with cardiogenic shock complicating acute myocardial infarction admitted from June 2001 to December 2007 were prospectively included. Clinical, hemodynamic, and echocardiographic variables were registered on admission and patients were followed for a median of 297 days. A total of 74 patients were included. One-year mortality was 55% and 7 patients (9%) underwent UHT. One-year mortality or need for UHT for patients with postprocedural Thrombolysis In Myocardial Infarction (TIMI) grade 3, 2, and 0 or 1 flows were 38%, 92%, and 90%, respectively (p0.001). After adjustment by multivariate analysis, the most important predictors of mortality or need for UHT were age75 years (hazard ratio [HR] 3.56, 95% confidence interval [CI] 1.07 to 11.80), left main coronary artery occlusion (HR 3.75, 95% CI 1.09 to 12.84), left ventricular ejection fraction25% (HR 2.70, 95% CI 1.17 to 6.22), and postprocedural TIMI grade3 flow (HR 3.37, 95% CI 1.48 to 7.72). A simple risk score constructed with these 4 variables effectively predicted 1-year survival without the need for UHT (83% for score 0, 19% for score 1, and 6% for score 2, p0.001). In conclusion, age75 years, left main coronary artery occlusion, left ventricular ejection fraction25%, and postprocedural TIMI grade3 flow were significantly associated with worse prognosis. A simple risk score rapidly available in the catheterization laboratory can efficiently estimate prognosis.

This study assessed the role of heart transplantation (HTx) in the management of patients with acute myocardial infarction (MI) complicated by refractory cardiogenic shock despite percutaneous coronary intervention (PCI). The primary end-point of the study was mortality at the 1-year follow-up.Between January 2001 and December 2005, 74 consecutive patients with acute MI complicated with cardiogenic shock were retrospectively analyzed. Thirty-nine patients did not have a contraindication for HTx and qualified for the study (age65 years, no comorbidities).Urgent HTx was performed in 10 patients. The remaining 29 patients served as controls. The HTx vs no HTx groups were well balanced in age (50 vs 53 years), proportion of multivessel disease (30% vs 10%), cardiac index (2.2 vs 2.4 liters/min/m(2)), and left ventricular ejection fraction (23% vs 25%). Mortality rates were significantly lower in the HTx group, both in the hospital (10% vs 45%, p0.03) and at 1 year (10% vs 52%, p0.03). Survival at 1 year among patients alive at hospital discharge was 100% in the HTx group vs 94% in the no HTx group.Urgent HTx dramatically improves survival of acute MI patients presenting with refractory cardiogenic shock despite early PCI. Therefore, this approach--wherever feasible--needs to be considered in the management of this particular subset of patients.

Pulmonary hypertension (PH) and subsequent right ventricular (RV) failure are increasingly recognized as global health problems, affecting patients with highly prevalent diseases such as chronic heart failure, chronic obstructive pulmonary disease, collagen vascular disease, or chronic pulmonary

This work is supported by National Institutes of Health RO1 HL083156, HL093183, HL119046, P20HL100396 and a NHLBI Program of Excellence in Nanotechnology Award, Contract # HHSN268201000045C (RJH) and NIH R01 105301 (JAL). Part of the work was funded by a Leducq Foundation grant (RJH). JA was supported by the Fundacion Alfonso Martin-Escudero. Pulmonary hypertension (PH) is associated with aberrant vascular remodeling and right ventricular (RV) dysfunction that contribute to early mortality. Large animal models that recapitulate human PH are essential for mechanistic studies and evaluating novel therapies; however, these models are not readily accessible to the field owing to the need for advanced surgical techniques or hypoxia. In this study, we present a novel swine model that develops cardiopulmonary hemodynamics and structural changes characteristic of chronic PH. This percutaneous model was created in swine (n=6) by combining distal embolization of dextran beads with selective coiling of the lobar pulmonary arteries (2 procedures per lung over 4 weeks). As controls, findings from this model were compared with those from a standard weekly distal embolization model (n=6) and sham animals (n=4). Survival with the combined embolization model was 100%. At 8 weeks after the index procedure, combined embolization procedure animals had increased mean pulmonary artery pressure (mPA) and pulmonary vascular resistance (PVR) compared to the controls with no effect on left heart or systemic pressures. RV remodeling and RV dysfunction were also present with a decrease in the RV ejection fraction, increase in the myocardial performance index, impaired longitudinal function, as well as cardiomyocyte hypertrophy, and interstitial fibrosis, which were not present in the controls. Pulmonary vascular remodeling occurred in both embolization models, although only the combination embolization model had a decrease in pulmonary capacitance. Taken together, these cardiopulmonary hemodynamic and structural findings identify the novel combination embolization swine model as a valuable tool for future studies of chronic PH. Sí

Background Biomarkers are frequently used to estimate infarct size ( IS ) as an endpoint in experimental and clinical studies. Here, we prospectively studied the impact of left ventricular (LV) hypertrophy ( LVH ) on biomarker release in clinical and experimental myocardial infarction (MI). Methods and Results ST ‐segment elevation myocardial infarction ( STEMI ) patients (n=140) were monitored for total creatine kinase ( CK ) and cardiac troponin I ( cTnI ) over 72 hours postinfarction and were examined by cardiac magnetic resonance ( CMR ) at 1 week and 6 months postinfarction. MI was generated in pigs with induced LVH (n=10) and in sham‐operated pigs (n=8), and serial total CK and cTnI measurements were performed and CMR scans conducted at 7 days postinfarction. Regression analysis was used to study the influence of LVH on total CK and cTnI release and IS estimated by CMR (gold standard). Receiver operating characteristic ( ROC ) curve analysis was performed to study the discriminatory capacity of the area under the curve ( AUC) of cTnI and total CK in predicting LV dysfunction. Cardiomyocyte cTnI expression was quantified in myocardial sections from LVH and sham‐operated pigs. In both the clinical and experimental studies, LVH was associated with significantly higher peak and AUC of cTnI , but not with differences in total CK . ROC curves showed that the discriminatory capacity of AUC of cTnI to predict LV dysfunction was significantly worse for patients with LVH . LVH did not affect the capacity of total CK to estimate IS or LV dysfunction. Immunofluorescence analysis revealed significantly higher cTnI content in hypertrophic cardiomyocytes. Conclusions Peak and AUC of cTnI both significantly overestimate IS in the presence of LVH , owing to the higher troponin content per cardiomyocyte. In the setting of LVH , cTnI release during STEMI poorly predicts postinfarction LV dysfunction. LV mass should be taken into consideration when IS or LV function are estimated by troponin release.

We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)–administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference –11.4; 95% confidence interval [CI] –18.6 to –4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference –11.1; 95% CI –21.5 to –0.6). Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours. Sin financiación 5.008 JCR (2015) Q1, 2/24 Emergency medicine UEM

participation and the influence of having CVD on income poverty of older workers. Int J Cardiol Mar 24 2012;156(1):80–3. [3] Saunders P, Bradbury B. Monitoring trends in poverty and income distribution: data, methodology and measurement. Econ Rec 2006;82(258):341-36. [4] Saunders P, Hill T, Bradbury B. Poverty in Australia: sensitivity analysis and recent trends. Sydney: Social Policy Research Centre, University of New South Wales; 2007. [5] Mejer L, Siermann C. Income poverty in the European Union: children, gender and poverty gaps. Eurostat 2000. [6] Dewey Helen M, Thrift Amanda G, Mihalopoulos Cathy, et al. Cost of stroke in Australia from a societal perspective: results from the North East Melbourne Stroke Incidence Study (NEMESIS). Stroke 2001;32:2409–16.

We appreciate the interest of and comments by Drs Argulian and Messerli on our recently published study.1 Defining inclusion and exclusion criteria, along with dose selection of the administered pharmacological therapy, is critical in the early stages of a clinical trial design. The scientific method strongly recommends performing a profound bibliographic research in this regard, and for this purpose, we carefully reviewed previously conducted trials on the use of β-blockers in the setting of ST-segment–elevation acute myocardial infarction, taking note of the strengths and weaknesses of each of them. Thus, for the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial, we randomized anterior myocardial infarctions revascularized by primary angioplasty in

Few studies have addressed the additional value of B-type natriuretic peptide (BNP) on risk stratification in non-ST-elevation acute coronary syndrome (NSTE-ACS). We aimed to evaluate whether BNP levels provide additional improvement on discrimination and reclassification of patients at risk of mortality during admission and follow up after a NSTE-ACS.BNP levels were measured 24-96 hours post admission in 600 patients with a NSTE-ACS. The incremental predictive value of including BNP into the multivariate models with the highest predictive accuracy for mortality during admission (logistic regression) and follow up (Cox regression) and over the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores was assessed using calibration, discrimination (area under the ROC curve (AUC) and Harrell's C statistic), and reclassification measures (net reclassification improvement (NRI) and index discrimination improvement (IDI)).A total of 19 (3.2%) patients died during admission and 29 (4.1%) during follow up (median 13.4 months). BNP was independently associated with mortality during admission (OR 3.56, 95% CI 1.75-7.23) and improved discrimination (AUC 0.95 vs. 0.92, p=0.01) and reclassification (NRI 72% and IDI 8%, p0.05 for both). Similarly, BNP was an independent predictor of mortality during follow up (HR 2.46, 95% CI 1.94-3.12) and provided additional discriminative value (Harrell's C 0.86 vs. 0.84, p=0.04). Similarly, BNP demonstrated additional value above the TIMI and GRACE scores.Determination of BNP 24-96 hours after a NSTE-ACS improved discrimination of patients at risk for mortality during admission and follow up.

Pulmonary embolism (PE) is a common cardiovascular emergency which can lead to pulmonary hypertension (PH) and right ventricular failure as a consequence of pulmonary arterial bed occlusion. The diagnosis of PE is challenging due to nonspecific clinical presentation, which results in relatively high mortality. Moreover, the pathological factors associated with PE are poorly understood. Metabolomics can provide new highlights which can help in the understanding of the processes and even propose biomarkers for its diagnosis. In order to obtain more information about PE and PH, acute PE was induced in large white pigs and plasma was obtained before and after induction of PE. Metabolic fingerprints from plasma were obtained with LC-QTOF-MS (positive and negative ionization) and GC-Q-MS. Data pretreatment and statistical analysis (uni- and multivariate) were performed in order to compare metabolic fingerprints and to select the metabolites that showed higher loading for the classification (28 from LC and 19 from GC). The metabolites found differentially distributed among groups are mainly related to energy imbalance in hypoxic conditions, such as glycolysis-derived metabolites, ketone bodies, and TCA cycle intermediates, as well as a group of lipidic mediators that could be involved in the transduction of the signals to the cells such as sphingolipids and lysophospholipids, among others. Results presented in this report reveal that combination of LC-MS- and GC-MS-based metabolomics could be a powerful tool for diagnosis and understanding pathophysiological processes due to acute PE.

Objectives: To evaluate the occurrence of ventricular systolic dysfunction in human immunodeficiency virus (HIV)-related pulmonary arterial hypertension (PAH). Background: Patients with HIV-related PAH may develop ventricular systolic dysfunction both as a consequence of PAH progression or of the myocardial involvement from the HIV infection itself. Methods: Cardiac magnetic resonance imaging was applied to measure ejection fraction for the left ventricle and the right ventricle in patients with HIV-related PAH (n ¼ 27) and in patients with PAH from other aetiologies (n ¼ 115). Results: In HIV-related PAH, ejection fraction values were lower and a higher proportion of patients presented with an advanced stage of ventricular dysfunction (55% vs. 25%; p ¼ 0.009). In a multivariate model, PAH related to HIV infection remained independently associated with advanced ventricular dysfunction (p ¼ 0.011). Conclusions: Patients with HIV-related PAH have more prevalent and severe ventricular systolic dysfunction compared to patients with PAH from other aetiologies.

Background Assessment of myocardial deformation in Chagas disease may help us to better understand the disease pathophysiology and to detect early myocardial involvement. We aimed to characterize myocardial deformation in patients in different forms of Chagas disease and, specifically, assess differences between patients in the indeterminate form and controls. Methods and Results Speckle tracking echocardiography was performed in 98 subjects (22 with Chagas cardiomyopathy, 32 in the indeterminate form, and 44 control subjects) to quantify global and segmental left ventricular (LV) radial strain (RS), circumferential strain (CS), and longitudinal strain (LS). In a subset of patients from the indeterminate and control groups (n = 25), LV peak systolic twist and untwisting velocities were additionally assessed. Global RS, CS, and LS showed a significant decreasing trend across groups. Patients in the indeterminate form had significantly lower global RS and RS in the midinferior segment (median 39.8% vs 49.3% [ P = .046] and 44.0% vs 56.0% [ P = .038], respectively) and lower twist and untwisting velocity ( P Conclusion Evaluation of myocardial deformation, particularly of RS, appears to be a sensitive technique for detection of myocardial involvement in patients in the indeterminate form and provides insights into the still unrevealed pathophysiology of Chagas heart involvement.

To investigate comorbid conditions with prognostic influence in non-ST-segment elevation acute coronary syndrome (NSTEACS).The study group consisted of a derivation cohort of 1017 patients (admitted from October 1, 2002, through October 1, 2008) and an external validation cohort of 652 patients (admitted from February 1, 2006, through September 30, 2009). Comorbid conditions, including risk factors and components of the Charlson comorbidity index (ChCI) and coronary artery disease-specific index, were recorded. The main outcome was one-year mortality.During follow-up, 103 patients died. After adjusting for variables associated with NSTEACS characteristics (base model), 5 comorbid conditions predicted mortality: severe or mild renal failure (hazard ratio [HR], 2.9 and HR, 1.6, respectively), dementia (HR, 3.1), peripheral artery disease (HR, 2.0), previous heart failure (HR, 2.6), and previous myocardial infarction (HR, 1.4). A simple comorbidity index (SCI) was developed using these variables, (per point: HR, 1.6; 95% confidence interval, 1.4-1.8; P = .0001). Adding the SCI, Charlson comorbidity index, or coronary artery disease-specific index to the base model resulted in a gain of 6.58%, 5.00%, and 4.04%, respectively, in discriminative ability (P = .001), without significant differences among the 3 indices. In patients with comorbid conditions, the highest risk period was in the first weeks after NSTEACS. The strength of the association between SCI and mortality rate was similar in the external validation cohort (HR, 1.3; 95% confidence interval, 1.1-1.6; P = .001).Renal dysfunction, dementia, peripheral artery disease, previous heart failure, and previous myocardial infarction are the comorbid conditions that predict mortality in NSTEACS. A simple index using these variables proved to be as accurate as the more complex comorbidity indices for risk stratification. In-hospital management of patients with comorbid conditions merits further investigation.

Background Chagas' disease is becoming a public health problem in Europe because of migratory movements. Cardiac magnetic resonance (CMR) has emerged as a non-invasive tool to assess cardiac tissue characteristics. There is scarce data available on CMR in patients with Chagas' disease. Objective To describe CMR findings in patients with Chagas' disease living in a non-endemic area focusing on differentiation from other cardiomyopathies and relation with clinical status. Methods and results Sixty-seven Chagas' disease patients divided into 3 groups—group 1 (indeterminate form: positive serology without ECG or 2D-echocardiographic abnormalities; N =27), group 2 (ECG abnormalities of Chagas' disease but normal 2D-echocardiography; N =19), and group 3 (regional wall motion abnormalities, LV end-diastolic diameter >55mm or LV ejection fraction N =21)—were studied. The presence of wall motion abnormalities and delayed enhancement (DE) by CMR was more frequent in the inferolateral and apical segments. DE distribution in the myocardial wall was heterogeneous (subendocardial 26.8%, midwall 14.0%, subepicardial 22.6%, and transmural 36.0% of total segments with DE) and related to larger cardiac chambers and worse systolic function. Conclusion Pattern of DE in Chagas' disease may mimic that of both ischemic and nonischemic cardiomyopathies, with especial predilection for the apical and inferolateral segments of the left ventricle. These findings support that myocardial involvement in chronic Chagas' cardiomyopathy (CCC) may be due to both microvascular disturbances and chronic myocarditis and may favor CCC in the differential diagnosis of patients with compatible epidemiological history and heart failure of uncertain etiology.

The number of patients with Chagas disease in Spain has increased significantly. Chronic inflammation and endothelial dysfunction have been considered among the physiopathological mechanisms of Chagas heart disease. However, there have been conflicting data from clinical studies. Our purpose was to assess endothelial function and systemic levels of nitric oxide and high-sensitivity C-reactive protein in patients with the indeterminate form and with chronic Chagas cardiomyopathy living in a nonendemic area.Flow-mediated endothelium-dependent vasodilatation and nitroglycerin-mediated vasodilatation were assessed with high-resolution ultrasound of the brachial artery in 98 subjects (32 with the indeterminate form, 22 with chronic Chagas cardiomyopathy and 44 controls). Nitric oxide and high-sensitivity C-reactive protein levels were measured in peripheral venous blood.Mean age was 37.6 ± 10.2 years and 60% were female. Nitroglycerin-mediated vasodilatation was significantly reduced in chronic Chagas cardiomyopathy compared to controls (median 16.8% vs 22.5%; P=.03). No significant differences were observed in flow-mediated vasodilatation and nitric oxide levels, although a trend towards lower flow-mediated vasodilatation after correction by baseline brachial artery diameter was observed in chronic Chagas cardiomyopathy. Levels of C-reactive protein were significantly higher in patients with the indeterminate form and with Chagas cardiomyopathy compared with controls (P.05).Reduced nitroglycerin-mediated vasodilatation suggesting dysfunction of vascular smooth muscle cells was found in patients with chronic Chagas cardiomyopathy living in a nonendemic area. Higher C-reactive protein levels were observed in the indeterminate form and early stages of chronic Chagas cardiomyopathy, which could be related to the inflammatory response to the infection or early cardiovascular involvement.

Right ventricular (RV) failure is a major contributor to morbidity and mortality after left ventricular assist device (LVAD) implantation. Accurate evaluation of RV function in patients with LVAD remains challenging. We hypothesized that, after LVAD implantation, electrocardiographic-gated cardiac computed tomography (CCT) allows RV evaluation with higher feasibility and reproducibility compared with echocardiography.Thirty-six patients with an implanted LVAD who had 2-dimensional echocardiography and CCT evaluation were studied. RV end-diastolic and end-systolic volumes and ejection fraction were quantified using CCT. RV fractional area change, tricuspid annular plane systolic excursion and RV end-diastolic short-to-long axis ratio were calculated by echocardiography. Intraclass correlation coefficients (ICCs) and Bland-Altman analysis were used to assess intra- and interobserver reproducibility for all measurements.The quality of CCT studies was good in all cases except for one. Intra- and interobserver reproducibility for all CCT measurements was high (interobserver ICC for RV ejection fraction = 0.89, 95% confidence interval 0.74 to 0.95). Echocardiographic indices of RV function and geometry had lower reproducibility. The echocardiographic index that best correlated with the CCT-determined RV ejection fraction was RV fractional area change (r = 0.80, p0.001). In addition, CCT detected relevant post-operative findings in 50% of the patients.CCT is highly effective and reproducible compared with echocardiography for the evaluation of RV function in patients with LVAD support and provides relevant information on post-operative findings. Our results suggest that CCT should be considered as a useful imaging modality in this clinical setting.

Introduction Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP) in the early identification of cardiac involvement in Chagas disease. Methodology/Principal Findings Fifty-four patients divided into 3 groups—group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32), group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14), and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction 37 pg/ml) were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27±26 vs. 11±8 pg/ml, p = 0.03). Conclusion/Significance In conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease., Author Summary Chagas disease remains a major cause of morbidity and mortality in several countries of Latin America and has become a potential public health problem in countries where the disease is not endemic as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac damage is desirable, since early treatment may improve prognosis. Diastolic dysfunction and elevated brain natriuretic peptide levels are present in different cardiomyopathies and in advanced phases of Chagas disease. However, there are scarce data about the role of these parameters in earlier forms of the disease. We conducted a study to assess the diastolic function, regional systolic abnormalities and brain natriuretic peptide levels in the different forms of Chagas disease. The main finding of our investigation is that diastolic dysfunction occurs before any cardiac dilatation or motion abnormality. In addition, BNP levels identify patients with diastolic dysfunction and Chagas disease with high specificity. The results reported in this study could help to early diagnose myocardial involvement and better stratify patients with Chagas disease.

Background In patients with severe aortic regurgitation and reduced left ventricular ejection fraction (LVEF), uncertainty remains whether to recommend aortic valve replacement (AVR) over heart transplantation, especially when mitral regurgitation and/or coronary heart disease coexist. Methods We assessed outcomes in 26 consecutive AVR patients aged ≤70 years with severe aortic regurgitation and reduced LVEF, comparing the group undergoing isolated AVR with the group requiring combined surgery. Results The difference in mortality and morbidity between the groups was 10% vs 6%, which was not significant ( p = 0.6 in both cases). Also observed was a significant improvement in functional class and a reduction in LV end-diastolic diameter from a median value of 69 to 64 mm in the isolated AVR group and to 66 mm in the combined group ( p Conclusions AVR in patients with symptomatic severe aortic regurgitation and reduced LVEF is feasible, even in the presence of concomitant mitral regurgitation and/or coronary heart disease requiring a combined surgical procedure.

The development of the so-called "targeted therapies", particularly those drugs that inhibit the activity of tyrosine kinases, has become a remarkable progress in the treatment of neoplastic diseases. The small molecule tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of chronic myeloid leukemia, and trastuzumab, the humanized monoclonal antibody against the ERBB2 receptor tyrosine kinase, has proved to have a high efficacy in 25% of breast cancers. On the basis of treatment success it is expected that targeted therapies will spread its use in the future. Recent data has shown that some of these therapies are associated with certain cardiotoxicity ranging from asymptomatic mild left ventricular dysfunction to congestive heart failure through different mechanisms. However, rates of cardiotoxicity associated with TKI are not well known mainly because clinical trials usually do not include predefined cardiac endpoints or the assessment of left ventricular function before and during treatment. In addition, it is especially difficult to diagnose heart failure in patients with some kinds of cancer who have many reasons to develop dyspnoea. Here we summarize what is known up to date about the cardiotoxicity of drugs targeting the tyrosine kinases. Being aware of the risk of using these drugs is particularly important to early detect and institute the appropriate treatment to prevent irreversible myocardial injury, especially when some neoplastic diseases, as haematological or breast cancers, can affect to young people with an estimated long-term survival.