Sudden Cardiac Death in Heart Failure: A 20-Year Perspective From a Mediterranean Cohort.

BACKGROUND: The prediction of sudden cardiac death (SCD) in heart failure (HF) remains an unmet need. The aim of our study was to assess the prevalence of SCD over 20 years in outpatients with HF managed in a Mediterranean multidisciplinary HF Clinic, and to compare the proportion of SCD (SCD/all-cause death) to the expected proportional occurrence based on the validated Seattle Proportional Risk Model (SPRM) score. METHODS AND RESULTS: This prospective observational registry study included 2772 outpatients with HF admitted between August 2001 and May 2021. Patients were included when the cause of death was known and SPRM score was available. Over the 20-year study period, 1351 patients (48.7%) died during a median follow-up period of 3.8 years (interquartile range 1.6-7.6). Among these patients, the proportion of SCD out of the total of deaths was 13.6%, whereas the predicted by SPRM was 39.6%. This lower proportion of SCD was observed independently of left ventricular ejection fraction, ischemic etiology, and the presence of an implantable cardiac defibrillator. CONCLUSIONS: In a Mediterranean cohort of outpatients with HF, the proportion of SCD was lower than expected based on the SPRM score. Future studies should investigate to what extend epidemiological and guideline-directed medical therapy patterns influence SCD.

Right Heart Dysfunction and Readmission Risk Across Left Ventricular Ejection Fraction Status in Patients With Acute Heart Failure.

BACKGROUND: Right heart dysfunction (RHD) parameters are increasingly important in heart failure (HF). This study aimed to evaluate the association of advanced RHD with the risk of recurrent admissions across the spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We included 3383 consecutive patients discharged for acute HF. Of them, in 1435 patients (42.4%), the pulmonary artery systolic pressure could not be measured accurately, leaving a final sample size of 1948 patients. Advanced RHD was defined as the combination of a ratio of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure of less than 0.36 and significant tricuspid regurgitation (n = 196, 10.2%). Negative binomial regression analyses were used to evaluate the risk of recurrent admissions. At a median follow-up of 2.2 years (interquartile range 0.63-4.71), 3782 readmissions were registered in 1296 patients (66.5%). Patients with advanced RHD showed higher readmission rates, but only if the LVEF was 40% or greater (P < .001). In multivariable analyses, this differential association persisted for cardiovascular and HF recurrent admissions (P value for interaction = .015 and P = .016; respectively). Advanced RHD was independently associated with the risk of recurrent cardiovascular and HF admissions if HF with an LVEF of 40% or greater (incidence rate ratio 1.64, 95% confidence interval 1.18-2.26, P = .003; and incidence rate ratio 1.73; 95% confidence interval 1.25-2.41, P = .001;respectively). In contrast, it was not associated with readmission risks if the LVEF was less than 40%. CONCLUSIONS: After an admission for acute HF, advanced RHD was strongly associated with a higher risk of recurrent cardiovascular and HF admissions, but only in patients with an LVEF of 40% or greater.

Soluble ST2 and Diuretic Efficiency in Acute Heart Failure and Concomitant Renal Dysfunction.

BACKGROUND: Identifying patients at risk of poor diuretic response in acute heart failure (AHF) is critical to make prompt adjustments in therapy. The objective of this study was to investigate whether the circulating levels of soluble ST2 predict the cumulative diuretic efficiency (DE) at 24 and 72 hours in patients with AHF and concomitant renal dysfunction. METHODS AND RESULTS: This is a post hoc analysis of the IMPROVE-HF trial, in which we enrolled 160 patients with AHF and renal dysfunction (estimated glomerular filtrate rate of <60 mL/min/1.73 m2). DE was calculated as the net fluid output produced per 40 mg of furosemide equivalents. The association between sST2 and DE was evaluated by using multivariate linear regression analysis. The median cumulative DE at 24 and 72 hour was 747 mL (interquartile range 490-1167 mL) and 1844 mL (interquartile range 1142-2625 mL), respectively. The median sST2 and mean estimated glomerular filtrate rate were 72 ng/mL (interquartile range 47-117 ng/mL), and 34.0 ± 8.5 mL/min/1.73 m2, respectively. In a multivariable setting, higher sST2 were significant and nonlinearly related to lower DE both at 24 and 72 hours (P = .002 and P = .019, respectively). CONCLUSIONS: In patients with AHF and renal dysfunction at presentation, circulating levels of sST2 were independently and negatively associated with a poor diuretic response, both at 24 and 72 hours.

Role of spot urinary sodium in outpatients with heart failure.

INTRODUCTION AND OBJECTIVES: Spot determination of urinary sodium (UNa+) has emerged as a useful tool for monitoring diuretic response in patients with acute heart failure (AHF). However, the evidence in outpatients is scarce. We aimed to examine the relationship between spot UNa+ levels and the risk of mortality and worsening heart failure (WHF) events in individuals with chronic HF. METHODS: This observational and ambispective study included 1145 outpatients with chronic HF followed in a single center specialized HF clinic. UNa+ assessment was carried out 1-5 days before each visit. The endpoints of the study were the association between UNa+ and risk of a) long-term death and b) AHF-hospitalization and total WHF events (including AHF-hospitalization, emergency department visits or parenteral loop-diuretic administration in HF clinic), assessed by multivariate Cox and negative binomial regressions. RESULTS: The mean ± standard deviation of age was 73 ± 11 years, 670 (58.5%) were men, 902 (78.8%) were on stable NYHA class II, and 595 (52%) had LFEF ≥ 50%. The median (interquartile range) UNa+ was 72 (51-94) mmol/L. Over a median follow-up of 2.63 (1.70-3.36) years, there were 293 (25.6%) deaths and 382 WHF events (244 AHF-admissions) in 233 (20.3%) patients. After multivariate adjustment, baseline UNa+ was inverse and linearly associated with the risk of total WHF (IRR, 1.07; 95%CI, 1.02-1.12; P = .007) and AHF-admissions (IRR, 1.08; 95%CI, 1.02-1.14; P = .012) and borderline associated with all-cause mortality (HR, 1.04; 95%CI, 0.99-1.09; P = .068). CONCLUSIONS: In outpatients with chronic HF, lower UNa+ was associated with a higher risk of recurrent WHF events.

Short-Term Changes in Peak VO2 After Initiation of Dapagliflozin in Heart Failure Across Iron Status.

BACKGROUND: Some studies have indicated that sodium-glucose cotransporter-2 (SGLT2) inhibitors promote an increase in cell iron use. OBJECTIVES: The aim of this study was to examine, in patients with stable heart failure with reduced left ventricular ejection fraction (HFrEF), the effect of dapagliflozin on ferrokinetic parameters and whether short-term changes in peak oxygen consumption (Vo2) after dapagliflozin treatment are influenced by baseline and serial ferrokinetic status. METHODS: This was an exploratory analysis of a randomized, double-blind clinical trial that evaluated the effect of dapagliflozin vs placebo on peak Vo2 in patients with HFrEF (NCT04197635) and included 76 of the 90 patients initially enrolled in the trial. Changes in peak Vo2 at 1 and 3 months were explored according to baseline and longitudinal ferrokinetic parameters (natural logarithm [ln] ferritin, transferrin saturation index [TSAT], soluble transferrin receptor, and hepcidin). Linear mixed-effect regression was used for the analyses. RESULTS: Compared with placebo, dapagliflozin led to a significant decrease in 3-month ln ferritin (P = 0.040) and an increase in 1-month ln soluble transferrin receptor (P = 0.023). Between-treatment comparisons revealed a stepwise increase in peak Vo2 in the dapagliflozin group at 1 and 3 months, which was especially apparent at lower baseline values of TSAT and ferritin (P < 0.05). Lower time-varying values of TSAT (1 and 3 months) also identified patients with greater improvements in peak Vo2. CONCLUSIONS: In patients with stable HFrEF, treatment with dapagliflozin resulted in short-term increases in peak Vo2, which were most marked in patients with surrogates of greater iron deficiency at baseline and during treatment. (Short-Term Effects of Dapagliflozin on Peak Vo2 in HFrEF [DAPA-VO2]; NCT04197635).