Combining loop and thiazide diuretics for acute heart failure across the estimated glomerular filtration rate spectrum: A post-hoc analysis of the CLOROTIC trial.

AIMS: In patients with acute heart failure (AHF), the addition of hydrochlorothiazide (HCTZ) to furosemide improved diuretic response in the CLOROTIC trial. This work aimed to evaluate if these effects differ across the estimated glomerular filtration rate (eGFR) spectrum. METHODS AND RESULTS: This post-hoc analysis of the CLOROTIC trial analysed 230 patients with AHF and explored the influence of eGFR on primary and secondary endpoints. The median eGFR was 43 ml/min/1.73 m2 (range 14-109) and 23% had eGFR ≥60 ml/min/1.73 m2 (group 1), 24% from 45 to 59 ml/min/1.73 m2 (group 2), and 53% <45 ml/min/1.73 m2 (group 3). Patients treated with HCTZ had greatest weight loss at 72 h in all three groups, but patients in group 1 had a significantly greater response (-2.1 kg [-3.0 to 0.5]), compared to patients in groups 2 (-1.3 kg [-2.3 to 0.2]) and 3 (-0.1 kg [-1.3 to 0.4]) (p-value for interaction = 0.246). At 96 h, the differences in weight were -1.8 kg (-3.0 to -0.3), -1.4 kg (-2.6 to 0.3), and -0.5 kg (-1.3 to -0.1) in groups 1, 2, and 3, respectively (p-value for interaction = 0.256). There were no significant differences observed with the addition of HCTZ in terms of diuretic response, mortality or rehospitalizations, or safety endpoints (impaired renal function, hyponatraemia, and hypokalaemia) among the three eGFR groups (all p-values for interaction were no significant). CONCLUSION: The addition of eGFR-adjusted doses of oral HCTZ to loop diuretics in patients with AHF improved diuretic response across the eGFR spectrum. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT01647932; EudraCT number: 2013-001852-36.

Review of the prognostic value of galectin-3 in heart failure focusing on clinical utility of repeated testing.

Galectin-3 is a soluble ß-galactoside-binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. A number of recent studies suggest that galectin-3 may provide relevant information regarding the pathophysiologic process of heart failure. We analyzed the most recent and comprehensive studies which are focused on the association between galectin-3 and heart failure. Galectin-3 has also been associated with acute and chronic heart failure. Although most of the studies involved patients with heart failure and systolic dysfunction, galectin-3 seems to have more accurate role in heart failure with preserved left ventricular ejection fraction. However, the mechanism of this relationship and its clinical implications remain uncertain. Some studies have not been able to prove the association between galectin-3 and heart failure, so there are many questions to answer. Galectin-3 has also been involved to renal dysfunction, so it could be a mediator of worsening renal function. Serial measurement of galectin-3 could provide further prognostic information in heart failure patients.

Heart failure with preserved and reduced ejection fraction: different phenotypes in old-elderly patients?

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFPEF) represent an important group of patients presenting in clinical practice. However, whether it is an earlier stage of heart failure with reduced ejection fraction (HFREF) remains uncertain. We evaluated the potential progression of HFPEF to HFREF. METHODS AND RESULTS: We evaluated retrospectively 178 patients (mean age 80.5±5.8 years; 75.3% females) with heart failure with preserved ejection fraction from a specialized Internal Medicine unit, offering an integrated usual care. Diagnosis of heart failure with preserved ejection fraction was made according to European guidelines. The main objective was to evaluate the progression to systolic dysfunction, defined by left ventricular ejection fraction less than 45%. Mean baseline left ventricular ejection fraction was 64.6±7.2. After a mean follow-up of 24-months, mean baseline ejection fraction was 67.1±9.3%. Only five patients (2.8%) progressed to HFREF. Brain natriuretic peptide values were significantly higher in those patients who progressed. CONCLUSIONS: These results strongly suggest that heart failure with preserved and reduced ejection fraction could be distinct pathophysiological entities, at least in elderly patients.

[Predictive variables for mortality in elderly patients hospitalized due to heart failure with preserved ejection fraction]. / Variables predictoras de mortalidad en pacientes ancianos hospitalizados por insuficiencia cardiaca con fracción de eyección preservada.

BACKGROUND AND OBJECTIVES: The prevalence of heart failure (HF) increases with age. Even though the mortality of patients ≥ 80 years of age with HF and preserved left ventricle ejection fraction (LVEF) is very high, the predictor variables are not well-known. The main goal of this study was to evaluate the mortality predictor factors in this subgroup of the elderly population. PATIENTS AND METHODS: An observational and prospective study of patients hospitalized due to HF with preserved LVEF has been conducted. The demographic, clinical, functional and analytic factors were evaluated when the patients were admitted with special attention to the co-morbidities. The primary endpoint was the total mortality in the subgroup of patients ≥ 80 years of age after a year of follow-up. The predictor variables were studied by means of a multivariate Cox regression model. RESULTS: From a total of 218 patients with an average age of 75.6 (±8.7) years of age, 75 patients (34.4%) were ≥ 80 years. The mortality rate of patients ≥ 80 years of age totaled 42.7%, in relation to 26.6% for the lower age group (log-rank<.001). After a multivariate analysis using the Cox regression model in patients ≥ 80, the serum urea levels above the average (hazard ratio [HR] 3.93; 95% confidence interval [95% CI] 1.58-9.75; P = .003), the age (HR 1.17; 95% CI 1.07-1.28; P<.001), the hyponatremia (HR 3.19; 95% CI 1.51-6.74; P = .002) and a lower score on the Barthel index (BI) (HR 1.016; 95% CI 1.002-1.031; P = .034) were independent mortality predictors after an one-year follow-up. CONCLUSIONS: Serum urea levels, age, hyponatremia and a low BI score could be proposed as independent mortality predictors in patients ≥ 80 of age hospitalized for HF with preserved LVEF.

Predictive value of serum galectin-3 levels in patients with acute heart failure with preserved ejection fraction.

AIMS: This study was conducted to determine whether galectin-3 (Gal3), a ß-galactoside-binding lectin, has usefulness to predict outcomes in patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We measured Gal3, urea, creatinine and natriuretic peptides on admission in 419 selected patients with HF and LVEF over 45%. The primary endpoint was all-cause mortality and/or readmission at one-year follow-up. Multivariable Cox proportional hazards models were generated for Gal3 and classical risk factors. We also evaluated the reclassification of patients on the basis of the different score category after adding Gal3 levels. A total of 219 patients had combined adverse events, and 129 patients died during the follow-up. Kaplan-Meir survival curve showed significantly increased primary endpoint and all-cause mortality according to quartiles of Gal3 (log rank, P<0.001). Serum Gal3 levels above median (13.8 ng/ml) was a significant predictor of primary endpoint risk after adjustment for age, estimated glomerular filtration rate, anemia, diabetes, serum sodium, brain natriuretic peptide levels, NYHA class and urea, respectively (hazard ratio 1.43, 95% CI 1.07-1.91 P=0.015). The reclassification index increased significantly after addition of Gal3 (9.5%, P<0.001) and the integrated discrimination index was 0.022, (P=0.001). The clinical prediction model with Gal3 increased the c-statistic from 0.711 to 0.731 (difference of 0.020, P=0.001). CONCLUSIONS: Serum Gal3 is a strong and independent predictor of unfavorable outcomes in patients with HF and preserved LVEF. We also demonstrated the improvement of adding the new biomarker to the model.