RESUMEN
AIMS: Amyloid cardiomyopathy is an underappreciated cause of morbidity and mortality. Recent evidence suggests that ATTR wild-type cardiomyopathy (ATTRwt-CM) is probably much more common than widely appreciated. So far, no data are available on comparison of mortality from ATTRwt-CM and other heart failure aetiologies. METHODS AND RESULTS: This was a retrospective, observational, cohort study of 2251 patients and their data collected prospectively from May 2000 to June 2018. Long-term mortality was the main outcome measure. Underlying cardiomyopathies were classified as amyloid CM (6.1%) [ATTRwt 3.0%; light-chain amyloidosis (AL) 3.1%], dilated CM (dCMP) (46.4%), ischaemic heart disease (IHD) (24.4%), hypertensive heart disease (HHD) (14.6%), hypertrophic CM (HCM) (5.1%), and valvular heart disease (VHD) (3.4%). Median duration of follow-up was 7.1 years (interquartile range 3.4-11.3). Five-year overall survival in the whole cohort was 80.1%. In multivariate analysis, individuals with amyloid CM were 3.74 times [95% confidence interval (CI) 2.72-5.14; P < 0.001] more likely to die of any reason than were individuals with dCMP. Mortality was higher in AL-CM compared with ATTRwt-CM [hazard ratio (HR) 2.88; 95% CI 1.48-5.58; P = 0.002]. Mortality rates in patients with ATTRwt-CM were higher than in patients with dCMP (HR 1.96; 95% CI 1.24-3.22; P = 0.007), HCM (HR 2.94; 95% CI 1.28-6.67; P = 0.011), HHD (HR 2.08; 95% CI 1.27-3.45; P = 0.004), VHD (HR 2.38; 95% CI 1.30-4.35; P = 0.005), or left ventricular ejection fraction ≥ 40% (HR 1.99; 95% CI 1.12-3.52; P = 0.018). CONCLUSIONS: Our study demonstrates that amyloid CM is independently associated with poor survival among patients with various causes of heart failure. ATTRwt-CM had a better long-term prognosis than did AL-CM, but was associated with higher mortality than were dCMP, HCM, HHD, VHD, and heart failure with preserved or mid-range ejection fraction.
RESUMEN
BACKGROUND: Although abnormal liver morphology and function have long been recognized, characterization and importance of liver dysfunction in heart failure are poorly defined. This study sought to investigate the relevance of circulating liver function tests (LFTs) in an unselected chronic heart failure (CHF) cohort. MATERIALS AND METHODS: A total of 1032 consecutive ambulatory patients with CHF were enrolled from 2000 to 2008. Clinical and laboratory variables including LFTs were collected at study entry. Follow-up (median 36 months) was available in 1002 (97·1%) patients. The endpoint was defined as death from any cause or heart transplantation. Hazard ratios (HR) for transplant-free survival were estimated per log unit using Cox proportional hazard regression models for sex-stratified data. RESULTS: Sex-specific prevalence of cholestatic enzyme elevation was 19·2% as opposed to elevated transaminases in 8·3%. Cholestatic enzymes, but not transaminases, were significantly associated with severity of heart failure syndrome and backward failure. The endpoint was recorded in 339 patients (33·8%). T-Bil, γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) were associated with adverse outcome in bivariate models. Of these, GGT [HR 1·22 (1·06, 1·41); P = 0·006] and ALP [HR 1·52 (1·09, 2·12); P = 0·014] were independently associated with the endpoint after adjustment for a wide array of clinical and laboratory predictors. CONCLUSIONS: Liver dysfunction is frequent in CHF and characterized by a predominantly cholestatic enzyme profile that is associated with disease severity and prognosis. Thus, we propose a cardio-hepatic syndrome in CHF. Future studies are needed to clarify the exact mechanisms of organ interaction.
Asunto(s)
Insuficiencia Cardíaca/fisiopatología , Hepatopatías/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Hígado/enzimología , Hepatopatías/enzimología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores Sexuales , Población Blanca , Adulto JovenRESUMEN
BACKGROUND: Gamma-glutamyltransferase (GGT) and total bilirubin (T-Bil) are elevated and of prognostic significance in chronic heart failure (CHF). This study sought to compare these novel cardiovascular risk markers in CHF. METHODS AND RESULTS: We evaluated 1,087 ambulatory patients from our heart failure program. Long-term follow-up was available in 1,056 patients. The combined end point was defined as death of any cause or heart transplantation. Prevalence of elevated GGT was 43% in men and 48% in women, that of T-Bil 17% and 8%, respectively. Both variables were significantly correlated with severity of heart failure. GGT and T-Bil were associated with transplant-free survival in bivariate analysis (P values <.001 and .006, respectively). However, GGT (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.13-1.44; P < .001), but not T-Bil, remained an independent predictor of prognosis in the multivariate model. Also, categorized GGT levels beyond the gender-specific normal ranges were predictive of the combined end point (HR 1.55, 95% CI 1.23-1.95). Elevation of both GGT and T-Bil further increased the risk of reaching the end point (HR 2.57, 95% CI 1.74-3.18). CONCLUSIONS: GGT and T-Bil are associated with disease severity in CHF. However, only GGT is independently associated with adverse outcome. Our findings further highlight the clinical importance of GGT in cardiovascular disease.