Hypothalamic dysfunction in heart failure: pathogenetic mechanisms and therapeutic implications.

Neurohumoral activation is an important feature of heart failure. Recent advances in molecular biology and imaging techniques permitted a better understanding of the central role that hypothalamus plays in the modulation of dysfunctional mechanisms, as well as the occurrence of comorbidities, such as depression, in heart failure patients. This review summarizes the commonly reported neural reflexes and molecular signaling pathways at the level of the hypothalamus along with the dysfunctional mechanisms within the paraventricular nucleus and other areas of the hypothalamus in heart failure and describes some relevant therapeutic implications.

Safety and efficacy of salt substitution with a low sodium-potassium enriched dietary salt in patients with heart failure with reduced ejection fraction: A pilot study.

BACKGROUND AND AIMS: Increased sodium intake is associated with increased risk of decompensation in patients with heart failure. This non-randomized, open-label, controlled study aimed to examine the feasibility, preliminary safety and efficacy of a low sodium-potassium enriched salt substitute compared to regular table salt in patients with heart failure with reduced ejection fraction (HFREF). METHODS: Fifty patients (68% male, NYHA I/II/III 6%/68%/26%, mean age 70 ± 9 years, LVEF 31 ± 5%, median BNP 112 pg/ml) were included. Of these, 30 patients received the salt substitute (maximum consumption of 2 g daily), who were prospectively compared to a control group of 20 age/sex/NYHA class-matched HFREF patients who consumed regular salt (maximum consumption of 2 g daily). Consumption of regular salt was prohibited in the salt substitution group. All patients were followed for 12 weeks. RESULTS: Patient groups did not differ by sex, age, LVEF, NYHA class, 6MWD, and BNP at baseline. In primary safety analysis, no significant differences were detected between groups regarding SBP (p = 0.052), DBP (p = 0.159), HR (p = 0.246), serum potassium (p = 0.579), serum sodium (p = 0.125), and eGFR (p = 0.710) throughout the 12 weeks. Secondary efficacy analysis revealed a statistically significant difference in 6MWD at 12 weeks between the salt substitute and regular salt groups after adjustment for baseline 6MWD (mean difference±SEM, 4.7 ± 2.1 m, F = 4.92, p = 0.031). CONCLUSIONS: In this pilot study, a low sodium-potassium enriched salt substitute was found to be safe compared to regular salt in HFREF patients, while it resulted in a small albeit significant improvement in exercise capacity, possibly justifying further investigation with randomized clinical studies.

Association of mineralocorticoid receptor antagonist use and in-hospital outcomes in patients with acute heart failure.

Mineralocorticoid receptor antagonists (MRAs) constitute a beneficial therapy in chronic heart failure, but their use in the acute heart failure (AHF) setting remains rather unexplored. To assess the effect of MRAs administered during hospitalization on in-hospital outcomes of patients with AHF, we performed a post-hoc analysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF). Patients of the original study cohort (n = 4953) were categorized according to in-hospital MRA treatment status as MRA-treated (n = 1439) and untreated (n = 3514) subjects. Nearest-neighbor propensity score with 1:1 matching yielded a subsample of pairs of MRA-treated and MRA-untreated patients (n = 1003 in each treatment group) that were balanced in an extensive list of baseline characteristics. In-hospital mortality between MRA-treated and untreated patients were assessed by Cox regression analysis before and after adjustment for known prognostic factors and other concomitantly administered intravenous and oral HF specific therapies. In the matched cohort, in-hospital mortality was 4.2 vs 10.8% in MRA-treated vs untreated patients. Treatment with MRAs was associated with a reduction of in-hospital mortality [HR 0.372 (95% CI, 0.261-0.532), p < 0.001]. This association remained significant after adjustment for known prognostic factors and co-administered intravenous and oral HF therapies [HR: 0.618 (95% CI, 0.383-0.995), p = 0.048]. In conclusion, MRA therapy administered during hospitalization for AHF was associated with reduced in-hospital mortality. The role of MRAs in AHF deserves further examination in adequately powered randomized controlled studies.