Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying causes. Wild-type transthyretin (TTR) amyloidosis (ATTRwt) is an underdiagnosed cause of HFpEF that might benefit from new specific treatments. ATTRwt can be diagnosed non-invasively by (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy. We sought to determine the prevalence of ATTRwt among elderly patients admitted due to HFpEF. METHODS AND RESULTS: We prospectively screened all consecutive patients ≥60 years old admitted due to HFpEF [left ventricular (LV) ejection fraction ≥50%] with LV hypertrophy (≥12 mm). All eligible patients were offered a (99m)Tc-DPD scintigraphy. The study included 120 HFpEF patients (59% women, 82 ± 8 years). A total of 16 patients (13.3%; 95% confidence interval: 7.2-19.5) showed a moderate-to-severe uptake on the (99m)Tc-DPD scintigraphy. All patients with a positive scan underwent genetic testing of the TTR gene, and no mutations were found. An endomyocardial biopsy was performed in four patients, confirming ATTRwt in all cases. There were no differences in age, gender, hypertension, diabetes, coronary artery disease, or atrial fibrillation between ATTRwt patients and patients with other HFpEF forms. Although patients with ATTRwt exhibited higher median N-terminal pro-brain natriuretic peptide (6467 vs. 3173 pg/L; P = 0.019), median troponin I (0.135 vs. 0.025 µg/L; P < 0.001), mean LV maximal wall thickness (17 ± 3.4 vs. 14 ± 2.5 mm; P = 0.001), rate of pericardial effusion (44 vs. 19%; P = 0.047), and rate of pacemakers (44 vs. 12%; P = 0.004), clinical overlap between ATTRwt and other HFpEF forms was high. CONCLUSION: ATTRwt is an underdiagnosed disease that accounts for a significant number (13%) of HFpEF cases. The effect of emerging TTR-modifying drugs should be evaluated in these patients.

Prognostic Impact and Predictors of Ejection Fraction Recovery in Patients With Alcoholic Cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Recovery of left ventricular ejection fraction (LVEF) has been described in alcoholic cardiomyopathy (ACM) after a period of alcohol withdrawal. Nevertheless, the prognostic impact of LVEF recovery in ACM and its determinants have not been studied. We sought to define the role of LVEF improvement in the long-term outcome of ACM and to identify predictors of LVEF recovery in these patients. METHODS: We evaluated 101 ACM patients during a median follow-up period of 82 months [interquartile range 36-134]. RESULTS: At latest follow-up, 42 patients (42%) showed substantial LVEF recovery defined as an absolute increase in LVEF ≥ 10% to a final value of ≥ 40%. Patients who recovered LVEF had better outcomes than patients who did not (heart transplant or cardiovascular death 1% vs 30%; P <.001). A QRS with <120ms (OR, 6.68; 95%CI, 2.30-19.41), beta-blocker therapy (OR, 3.01; 95%CI, 1.09-8.28), and the absence of diuretics (OR, 3.35; 95%CI, 1.08-10.42) predicted LVEF recovery in multivariate analysis. Although alcohol cessation did not predict LVEF recovery, none of the patients (n=6) who persisted with heavy alcohol consumption recovered LVEF. The rate of patients who recovered LVEF did not differ between abstainers and moderate drinkers (44% vs 45%; P=.9). CONCLUSIONS: The LVEF recovery is associated with an excellent prognosis in ACM. Beta-blocker treatment, QRS <120ms and absence of diuretics are independent predictors of LVEF recovery. LVEF recovery is similar in moderate drinkers and abstainers.

Genetic Etiology for Alcohol-Induced Cardiac Toxicity.

BACKGROUND: Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol. OBJECTIVES: This study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity. METHODS: The authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM. RESULTS: Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 ×10-5), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: -2.3% to -15.1%; p < 0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome, or functional recovery on treatment in ACM patients. CONCLUSIONS: TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM.

Natural history and prognostic factors in alcoholic cardiomyopathy.

OBJECTIVES: This study sought to determine the natural history of contemporary alcoholic cardiomyopathy (ACM), to compare it with that of idiopathic dilated cardiomyopathy (IDCM), and to identify risk factors for poor outcome. BACKGROUND: ACM is a common cause of dilated cardiomyopathy (DCM), but little is known about its natural history or the effect of reducing alcohol intake on disease progression. METHODS: We studied the clinical characteristics and outcomes of 94 consecutive patients with ACM and 188 with IDCM, evaluated over the period between 1993 and 2011. RESULTS: After a median follow-up of 59 months (interquartile range: 25 to 107 months), 14 ACM patients (15%) had died from cardiovascular causes (6 from heart failure and 8 from sudden cardiac death), 14 (15%) underwent heart transplantation, 35 (37%) experienced recovery in left ventricular function, and 31 (33%) remained clinically stable without improvement in systolic function. Transplantation-free survival was higher in ACM patients than in IDCM patients (p = 0.002), and ACM was associated with a favorable outcome on multiple analysis of the entire cohort (odds ratio [OR]: 0.4; 95% confidence interval [CI]: 0.2 to 0.8; p = 0.01). Independent predictors of death or heart transplantation in ACM identified by multiple logistic regression analysis were atrial fibrillation (OR: 9.7; 95% CI: 2.56 to 36.79; p = 0.001); QRS duration >120 ms (OR: 7.2; 95% CI: 2.02 to 26; p = 0.002), and lack of beta-blocker therapy (OR: 4.4; 95% CI: 1.35 to 14.49; p = 0.014). ACM patients who reduced their alcohol intake to moderate levels exhibited similar survival (p = 0.22) and cardiac function recovery (p = 0.8) as abstainers. CONCLUSIONS: ACM has a better prognosis than IDCM. Atrial fibrillation, QRS width >120 ms, and the absence of beta-blocker therapy identify patients with a poor outcome. Alcohol abstainers and those who reduce intake to a moderate degree show similar clinical outcomes.

Malignant ventricular arrhythmias in alcoholic cardiomyopathy.

BACKGROUND: Excessive alcohol consumption is a well-known aetiology of atrial arrhythmias but there is little information concerning the prevalence or incidence of malignant ventricular arrhythmias in alcoholic cardiomyopathy (ACM). This study sought to investigate incidence and predictive factors of ventricular arrhythmias in ACM. METHODS: Retrospective observational study of the clinical characteristics and long-term arrhythmic events in 282 consecutive patients with ACM (94 individuals) and idiopathic dilated cardiomyopathy (IDCM) (188 individuals) evaluated between 1993 and 2011. RESULTS: During a median follow-up of 38months (IQR:12-77), 42 patients died and 79 underwent heart transplantation [31 (33%) with ACM vs 90 (48%) with IDCM; p=0.017]. A total of 37 (13%) patients [18 (19%) ACM vs 20 (11%) IDCM; p=0.048] suffered malignant ventricular arrhythmias. On multivariate analysis, left bundle branch block (LBBB) (OR 2.4; CI95%: 1.2-5; p=0.015) and alcoholic aetiology (OR 2.3; CI95%: 1.1-4.5; p=0.026) were the only independent predictors of malignant ventricular arrhythmic events. A total of 18 (19%) ACM patients experienced 20 malignant ventricular arrhythmic events (4 aborted SCD, 8 SCD and 8 appropriate ICD therapies). At baseline evaluation, the only independent predictor of malignant ventricular arrhythmias in ACM patients was LBBB (OR 11.2; CI95%: 2.6-50; p=0.001). No malignant ventricular arrhythmias were recorded during follow-up in ACM patients if left ventricular ejection fraction (LVEF) had increased or remained ≥40%. CONCLUSIONS: Malignant ventricular arrhythmias are more frequent in ACM than in IDCM. LBBB identifies ACM patients with increased risk of SCD. No malignant ventricular arrhythmias were found during follow-up in ACM patients when LVEF was ≥40%.

Alcoholic cardiomyopathy.

Alcohol is the most frequently consumed toxic substance in the world. Low to moderate daily intake of alcohol has been shown to have beneficial effects on the cardiovascular system. In contrast, exposure to high levels of alcohol for a long period could lead to progressive cardiac dysfunction and heart failure. Cardiac dysfunction associated with chronic and excessive alcohol intake is a specific cardiac disease known as alcoholic cardiomyopathy (ACM). In spite of its clinical importance, data on ACM and how alcohol damages the heart are limited. In this review, we evaluate available evidence linking excessive alcohol consumption with heart failure and dilated cardiomyopathy. Additionally, we discuss the clinical presentation, prognosis and treatment of ACM.

Genetics in dilated cardiomyopathy.

Discoveries made during the last 20 years have revealed a genetic origin in many cases of dilated cardiomyopathy (DCM). Currently, over 40 genes have been associated with the disease. Mutations in DCM-causing genes induce the condition through a variety of different pathological pathways with complex and not completely understood mechanisms. Genes that encode for sarcomeric, cytoskeletal, nuclear membrane, dystrophin-associated glycoprotein complex and desmosomal proteins are the principal genes involved. In this review we discuss the most frequent DCM-causing genes. We propose a classification in which DCM genes are considered as being major or minor genes according to their mutation frequency and the available supporting evidence. The main phenotypic characteristics associated with each gene are discussed.

Impacto pronóstico y factores predictores de la recuperación de la fracción de eyección en pacientes con miocardiopatía dilatada alcohólica / Prognostic impact and predictors of ejection fraction recovery in patients with alcoholic cardiomyopathy

Introducción y objetivos: La recuperación de la fracción de eyección del ventrículo izquierdo (FEVI) está descrita en la miocardiopatía alcohólica (MCA) tras la abstinencia alcohólica. Sin embargo, se desconoce el impacto pronóstico de esta recuperación y los factores con que se asocia. El objetivo es definir el papel pronóstico a largo plazo de la mejoría de la FEVI en la MCA e identificar sus predictores. Métodos: Se evaluó a 101 pacientes con MCA, con una mediana de seguimiento de 82 [intervalo intercuartílico, 36-134] meses. Resultados: Al final del seguimiento, 42 pacientes (42%) mostraron una recuperación significativa de la FEVI, definida como un incremento absoluto ≥ 10% y FEVI final ≥ 40%. Estos pacientes mostraron mejor pronóstico que aquellos sin recuperación de la FEVI (trasplante cardiaco o muerte cardiovascular, el 1 frente al 30%; p < 0,001). La duración del QRS < 120 ms (OR = 6,68; IC95%, 2,30-19,41), el tratamiento bloqueador beta (OR = 3,01; IC95%, 1,09-8,28) y no necesitar diuréticos (OR = 3,35; IC95%, 1,08-10,42) predijeron la recuperación de la FEVI en el análisis multivariable. Aunque el cese del consumo de alcohol no fue predictor, ninguno de los pacientes (n = 6) que mantuvieron un consumo excesivo recuperó la FEVI. Entre los abstemios y quienes mantuvieron un consumo moderado, hubo similar número de pacientes que recuperaron la FEVI (el 44 frente al 45%; p = 0,9). Conclusiones: La recuperación de la FEVI se asocia con un excelente pronóstico en la MCA. El tratamiento con bloqueadores beta, un QRS < 120 ms y no tomar diuréticos son predictores independientes de esta recuperación. La recuperación de la FEVI es similar entre bebedores moderados y abstemios

Introduction and objectives: Recovery of left ventricular ejection fraction (LVEF) has been described in alcoholic cardiomyopathy (ACM) after a period of alcohol withdrawal. Nevertheless, the prognostic impact of LVEF recovery in ACM and its determinants have not been studied. We sought to define the role of LVEF improvement in the long-term outcome of ACM and to identify predictors of LVEF recovery in these patients. Methods: We evaluated 101 ACM patients during a median follow-up period of 82 months [interquartile range 36-134]. Results: At latest follow-up, 42 patients (42%) showed substantial LVEF recovery defined as an absolute increase in LVEF ≥ 10% to a final value of ≥ 40%. Patients who recovered LVEF had better outcomes than patients who did not (heart transplant or cardiovascular death 1% vs 30%; P < .001). A QRS with < 120 ms (OR, 6.68; 95%CI, 2.30-19.41), beta-blocker therapy (OR, 3.01; 95%CI, 1.09-8.28), and the absence of diuretics (OR, 3.35; 95%CI, 1.08-10.42) predicted LVEF recovery in multivariate analysis. Although alcohol cessation did not predict LVEF recovery, none of the patients (n = 6) who persisted with heavy alcohol consumption recovered LVEF. The rate of patients who recovered LVEF did not differ between abstainers and moderate drinkers (44% vs 45%; P = .9). Conclusions: The LVEF recovery is associated with an excellent prognosis in ACM. Beta-blocker treatment, QRS < 120 ms and absence of diuretics are independent predictors of LVEF recovery. LVEF recovery is similar in moderate drinkers and abstainers

Indicación de desfibrilador automático implantable en paciente con angina de Prinzmetal y síncopes / No disponible

No disponible