Paloma Gastelurrutia

Statins in Heart Failure: The Paradox Between Large Randomized Clinical Trials and Real Life

OBJECTIVE To assess the relationship between statins and prognosis in ischemic and nonischemic patients with heart failure (HF) in a real-life cohort followed up for a long period. PATIENTS AND METHODS This prospective study included 960 patients with HF with preserved or depressed left ventricular ejection fraction (LVEF), irrespective of HF etiology, who were referred to the HF clinic of a university hospital between August 1, 2001, and December 31, 2008. The patients were followed up for a maximum of 9.1 years (median, 3.7 years), and survival in ischemic and nonischemic patients was determined. RESULTS Median age was 69 years, and median LVEF was 31%. Of the 960 patients, 532 (55.4%) had ischemic HF etiology, and most received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (846; 88.1%) and β-blockers (776; 80.8%). Patients with HF of ischemic origin were more often treated with statins (P<.001). During follow-up, 440 patients (45.8%) died. Statin therapy was associated with significantly improved survival (hazard ratio, 0.45 [95% confidence interval, 0.37-0.54]; P<.001). After adjustment for HF prognostic factors (age, sex, cholesterol level, New York Heart Association class, HF etiology, LVEF, body mass index, HF duration, atrial fibrillation, implantable cardioverter-defibrillator therapy, and medicines), statins remained significantly associated with lower mortality risk in both ischemic (P=.007) and nonischemic (P=.002) patients. CONCLUSION In contrast to results of large randomized trials, statins were independently and significantly associated with lower mortality risk in our real-life HF cohort, including patients with nonischemic HF etiology.

Usefulness of Body Mass Index to Characterize Nutritional Status in Patients With Heart Failure

The obesity paradox in heart failure (HF) is criticized because of the limitations of body mass index (BMI) in correctly characterizing overweight and obese patients, necessitating a better evaluation of nutritional status. The aim of this study was to assess nutritional status, BMI, and significance in terms of HF survival. Anthropometry and biochemical nutritional markers were assessed in 55 HF patients. Undernourishment was defined as the presence of ≥2 of the following indexes below the normal range: triceps skinfold, subscapular skinfold, arm muscle circumference, albumin, and total lymphocyte count. Patients were also stratified by BMI and followed for a median of 26.7 months. Across BMI strata, no patient was underweight, 31% were normal weight, 42% were overweight, and 27% were obese. Undernourishment was present in 53% of normal-weight patients, 22% of overweight patients, and none of the obese patients (p = 0.001). Undernourished patients had significantly higher mortality (p = 0.009) compared to well-nourished patients. In multivariate analysis, only undernutrition (hazard ratio 3.149, 95% confidence interval 1.367 to 7.253), New York Heart Association functional class (hazard ratio 3.374, 95% confidence interval 1.486 to 7.659), and age (hazard ratio 1.115, 95% confidence interval 1.045 to 1.189) remained in the model. Among nutritional indicators, subscapular skinfold was the best predictor of mortality; patients with subscapular skinfold in the fifth percentile had higher mortality (p = 0.0001). In conclusion, BMI does not indicate true nutritional status in HF. Classifying patients as well nourished or undernourished may improve risk stratification.

Quality of life monitoring in ambulatory heart failure patients: temporal changes and prognostic value

Heart failure (HF) is a chronic condition that typically affects a patients quality of life (QoL). Little is known about long‐term QoL monitoring in HF. This study aimed to evaluate the temporal changes and prognostic value of QoL assessment in a real‐life cohort of HF patients.

Obesity paradox and risk of sudden death in heart failure: Results from the MUerte Subita en Insuficiencia Cardiaca (MUSIC) Study

BACKGROUND among patients with heart failure (HF), body mass index (BMI) has been inversely associated with mortality, giving rise to the so-called obesity paradox. The aim of this study was to examine the relationship between BMI and two modes of cardiac death: pump failure death and sudden death. METHODS nine hundred seventy-nine patients with mild to moderate chronic symptomatic HF from the MUSIC (MUerte Subita en Insuficiencia Cardiaca) Study, a prospective, multicenter, and longitudinal study designed to assess risk predictors of cardiac mortality, were followed up during a median of 44 months. Independent predictors of death were identified by a multivariable Cox proportional hazards model. RESULTS higher BMI emerged as an independent predictor of all-cause mortality (hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.91-0.97, P = .0003) and pump failure death (HR = 0.93, 95% CI = 0.88-0.98, P = .004). Sudden death accounted for 45% of deaths in obese patients, 53% in overweight patients, and 37% in lean patients. No significant relationship between BMI and sudden death was observed (HR = 0.97, 95% CI = 0.92-1.02, P = .28). The only independent predictors of sudden death were prior history of myocardial infarction (HR = 1.89, 95% CI = 1.23-2.90, P = .004), hypertension (HR = 1.66, 95% CI = 1.05-2.63, P = .03), left ventricular ejection fraction (HR = 0.88, 95% CI = 0.79-0.96, P = .006), and N-terminal pro-B-type natriuretic peptide (HR = 1.01, 95% CI = 1.00-1.02, P = .048). CONCLUSIONS the obesity paradox in HF affects all-cause mortality and pump failure death but not sudden death. The risk of dying suddenly was similar across BMI categories in this cohort of ambulatory patients with HF.

Fragility is a key determinant of survival in heart failure patients

BACKGROUND Heart failure (HF) is a chronic condition with poor prognosis, and has a high prevalence among older adults. Due to older age, fragility is often present among HF patients. However, even young HF patients show a high degree of fragility. The effect of fragility on long-term prognosis in HF patients, irrespective of age, remains unexplored. The aim of this study was to assess the influence of fragility on long-term prognosis in outpatients with HF. METHODS AND RESULTS At least one abnormal evaluation among four standardized geriatric scales was used to identify fragility. Predefined criteria for such scales were: Barthel Index, <90; OARS scale, <10 in women and <6 in men; Pfeiffer Test, >3 (± 1, depending on educational grade); and ≥ 1 positive response for depression on the abbreviated Geriatric Depression Scale (GDS). We assessed 1314 consecutive HF outpatients (27.8% women, mean age years 66.7 ± 12.4 years with different etiologies. Fragility was detected in 581 (44.2%) patients. 626 deaths occurred during follow-up; the median follow-up was 3.6 years [P25-P75: 1.8-6.7] for the total cohort, and 4.9 years [P25-P75: 2.5-8.4] for living patients. Fragility and its components were significantly associated with decreased survival by univariate analysis. In a comprehensive multivariable Cox regression analysis, fragility remained independently associated with survival in the entire cohort, and in age and left ventricular ejection fraction subgroups. CONCLUSION Fragility is a key determinant of survival in ambulatory patients with HF across all age strata.

Body mass index, body fat, and nutritional status of patients with heart failure: The PLICA study

BACKGROUND & AIMS Nutritional assessment may help to explain the incompletely understood obesity paradox in patients with heart failure (HF). Currently, obesity is usually identified by body mass index (BMI). Our objective was to assess the prognostic influence of undernourishment in HF outpatients. METHODS Two published definitions of undernourishment were used to assess 214 ambulatory HF patients. Definition 1 included albumin, total lymphocyte count, tricipital skinfold (TS), subscapular skinfold, and arm muscle circumference (AMC) measurements (≥2 below normal considered undernourishment). Definition 2 included TS, AMC, and albumin (≥1 below normal considered undernourishment). Patients were also stratified by BMI and body fat percentage and followed for 2 years. All-cause death or HF hospitalization was the primary endpoint. RESULTS Based on BMI strata, among underweight patients, 60% and 100% were undernourished by Definitions 1 and 2, respectively (31% and 44% among normal-weight, 4% and 11% among overweight, and 0% and 3% among obese patients, respectively, according to the two definitions). The most prevalent undernourishment type was marasmus-like (18% of the total cohort). Undernourishment by both definitions was significantly associated with lower event-free survival. Following multivariable analysis, age, NYHA functional class, NTproBNP, and undernourishment (hazard ratio [HR] 2.25 [1.11-4.56] and 2.24 [1.19-4.21] for Definitions 1 and 2, respectively) remained in the model. In this cohort, BMI and percentage of body fat did not independently predict 2-year event-free survival. CONCLUSIONS Nutritional status is a key prognostic factor in HF above and beyond BMI and percentage of body fat. Patients in normal BMI range and even in overweight and obese groups showed undernourishment. The high mortality observed in undernourishment, infrequent in high BMI patients, may help to partly explain the obesity paradox. Proper undernourishment assessment should become routine in patients with HF.

Multimarker Strategy for Heart Failure Prognostication. Value of Neurohormonal Biomarkers: Neprilysin vs NT-proBNP

INTRODUCTION AND OBJECTIVES Neprilysin breaks down numerous vasoactive peptides. The soluble form of neprilysin, which was recently identified in heart failure, is associated with cardiovascular outcomes. Within a multibiomarker strategy, we directly compared soluble neprilysin and N-terminal pro-B-type natriuretic peptide as risk stratifiers in a real-life cohort of heart failure patients. METHODS Soluble neprilysin, N-terminal pro-B-type natriuretic peptide, ST2, and high-sensitivity troponin T levels were measured in 797 consecutive ambulatory heart failure patients followed up for 4.7 years. Comprehensive multivariable analyses and soluble neprilysin vs N-terminal pro-B-type natriuretic peptide head-to-head assessments of performance were performed. A primary composite endpoint included cardiovascular death or heart failure hospitalization. A secondary endpoint explored cardiovascular death alone. RESULTS Median soluble neprilysin and N-terminal pro-B-type natriuretic peptide concentrations were 0.64ng/mL and 1187 ng/L, respectively. Both biomarkers significantly correlated with age (P<.001) and ST2 (P<.001), but only N-terminal pro-B-type natriuretic peptide significantly correlated with estimated glomerular filtration rate (P<.001), body mass index (P<.001), left ventricular ejection fraction (P=.02) and high-sensitivity troponin T (P<.001). In multivariable Cox regression analyses, soluble neprilysin remained independently associated with the composite endpoint (hazard ratio=1.14; 95% confidence interval, 1.02-1.27; P=.03) and cardiovascular death (hazard ratio=1.15; 95% confidence interval, 1.01-1.31; P=.04), but N-terminal pro-B-type natriuretic peptide did not. The head-to-head soluble neprilysin vs N-terminal pro-B-type natriuretic peptide comparison showed good calibration and similar discrimination and reclassification for both neurohormonal biomarkers, but only soluble neprilysin improved overall goodness-of-fit. CONCLUSIONS When added to a multimarker strategy, soluble neprilysin remained an independent prognosticator, while N-terminal pro-B-type natriuretic peptide lost significance as a risk stratifier in ambulatory patients with heart failure. Both biomarkers performed similarly in head-to-head analyses.

Limited Value of Cystatin-C over Estimated Glomerular Filtration Rate for Heart Failure Risk Stratification

Background To compare the prognostic value of estimated glomerular filtration rate, cystatin-C, an alternative renal biomarker, and their combination, in an outpatient population with heart failure.Estimated glomerular filtration rate is routinely used to assess renal function in heart failure patients. We recently demonstrated that the Cockroft-Gault formula is the best among the most commonly used estimated glomerular filtration rate formulas for predicting heart failure prognosis. Methodology/Principal Findings A total of 879 consecutive patients (72% men, age 70.4 years [P25–75 60.5–77.2]) were studied. The etiology of heart failure was mainly ischemic heart disease (52.7%). The left ventricular ejection fraction was 34% (P25–75 26–43%). Most patients were New York Heart Association class II (65.8%) or III (25.9%). During a median follow-up of 3.46 years (P25–75 1.85–5.05), 312 deaths were recorded. In an adjusted model, estimated glomerular filtration rate and cystatin-C showed similar prognostic value according to the area under the curve (0.763 and 0.765, respectively). In Cox regression, the multivariable analysis hazard ratios were 0.99 (95% CI: 0.98–1, P = 0.006) and 1.14 (95% CI: 1.02–1.28, P = 0.02) for estimated glomerular filtration rate and cystatin-C, respectively. Reclassification, assessed by the integration discrimination improvement and the net reclassification improvement indices, was poorer with cystatin-C (−0.5 [−1.0;−0.1], P = 0.024 and −4.9 [−8.8;−1.0], P = 0.013, respectively). The value of cystatin-C over estimated glomerular filtration rate for risk-stratification only emerged in patients with moderate renal dysfunction (eGFR 30–60 ml/min/1.73 m2, chi-square 12.9, P<0.001). Conclusions/Significance Taken together, the results indicate that estimated glomerular filtration rate and cystatin-C have similar long-term predictive values in a real-life ambulatory heart failure population. Cystatin-C seems to offer improved prognostication in heart failure patients with moderate renal dysfunction.

Aging and Heart Rate in Heart Failure: Clinical Implications for Long-term Mortality.

OBJECTIVE To assess the relationship between resting heart rate and long-term all-cause mortality in ambulatory patients with heart failure (HF) relative to age, considering that although heart rate has been strongly associated with mortality in HF, the influence of age on target heart rate is incompletely characterized. PATIENTS AND METHODS Consecutive patients in sinus rhythm referred to an ambulatory HF clinic of a university hospital between August 1, 2001, and March 31, 2012, were included. Unadjusted and adjusted Cox regression analyses were performed to assess heart rate as a prognostic marker, both as a continuous variable and after categorization into quintiles. Smooth spline estimates and hazard ratios (HRs) were plotted for 2 age strata (<75 years vs ≥75 years) for each individual heart rate. RESULTS A total of 1033 patients were included (766 men [74.2%]; mean age, 65.1±12.6 years). During a mean follow-up of 4.6±3.3 years (median, 3.8 years [25th-75th percentile, 1.9-6.9]), 476 patients (46.1%) died. Mortality was associated with a statistically greater heart rate in the total cohort (HR, 1.18; 95% CI, 1.11-1.26; P<.001). From a clinical viewpoint, this means an 18% increased risk for every 10-beats/min elevation in heart rate. The same characteristics were present in the relationship between heart rate assessed after 6 months and long-term mortality (HR, 1.30; 95% CI, 1.20-1.42; P<.001). Overall, the prognostic importance of heart rate in ambulatory patients with HF was largely influenced by patient age. Remarkably, in the elderly population (≥75 years), heart rate below 68 beats/min conferred an increased risk of death, whereas in younger patients, mortality exhibited a declining slope at even the lowest heart rates. CONCLUSION Our research, if applicable to the prospective management of patients with ambulatory HF, suggests that patients aged 75 years or older have the best outcomes with target heart rates of 68 beats/min; however, younger patients may benefit from lower heart rates, even below 55 beats/min.

First-in-man Safety and Efficacy of the Adipose Graft Transposition Procedure (AGTP) in Patients With a Myocardial Scar.

Background The present study evaluates the safety and efficacy of the Adipose Graft Transposition Procedure (AGTP) as a biological regenerative innovation for patients with a chronic myocardial scar. Methods This prospective, randomized single-center controlled study included 10 patients with established chronic transmural myocardial scars. Candidates for myocardial revascularization were randomly allocated into two treatment groups. In the control arm (n = 5), the revascularizable area was treated with CABG and the non-revascularizable area was left untouched. Patients in the AGTP-treated arm (n = 5) were treated with CABG and the non-revascularizable area was covered by a biological adipose graft. The primary endpoint was the appearance of adverse effects derived from the procedure including hospital admissions and death, and 24-hour Holter monitoring arrhythmias at baseline, 1 week, and 3 and 12 months. Secondary endpoints of efficacy were assessed by cardiac MRI. Findings No differences in safety were observed between groups in terms of clinical or arrhythmic events. On follow-up MRI testing, participants in the AGTP-treated arm showed a borderline smaller left ventricular end systolic volume (LVESV; p = 0.09) and necrosis ratio (p = 0.06) at 3 months but not at 12 months. The AGTP-treated patient with the largest necrotic area and most dilated chambers experienced a noted improvement in necrotic mass size (− 10.8%), and ventricular volumes (LVEDV: − 55.2 mL and LVESV: − 37.8 mL at one year follow-up) after inferior AGTP. Interpretation Our results indicate that AGTP is safe and may be efficacious in selected patients. Further studies are needed to assess its clinical value. (ClinicalTrials.org NCT01473433, AdiFlap Trial).