Daily Cardiology Research Analysis

BACKGROUND: Despite favorable hemodynamic and neurohormonal effects, endothelin receptor antagonists have not improved outcomes in patients with heart failure (HF), possibly because they cause fluid retention. METHODS: In this randomized, double-blind, multicenter trial (SERENADE [Macitentan in Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease]), we evaluated the effects of an endothelin receptor antagonist, macitentan, in patients with HF, left ventricular ejection fraction ≥40%, and pulmonary vascular disease. After a 4-week placebo run-in (to ensure clinical stability), followed by a 5-week single-blind macitentan run-in, patients who did not exhibit fluid retention were randomized to macitentan or placebo. The primary end point was change in NT-proBNP (N-terminal pro-B-type natriuretic peptide; baseline to 24 weeks); secondary end points included change in KCCQ (Kansas City Cardiomyopathy Questionnaire) clinical summary score (baseline to 24 weeks) and time to worsening HF by 52 weeks. RESULTS: Of 230 patients enrolled, 28 were excluded during the placebo run-in, 60 excluded during the macitentan run-in, and 142 were randomized. Macitentan had no effect on change in NT-proBNP (geometric mean ratio [macitentan/placebo], 1.02 [90% CI, 0.88-1.19]; CONCLUSIONS: Despite a novel enrichment trial design to target pulmonary vascular disease and exclude treatment-related fluid retention in patients with HF and preserved/mildly reduced left ventricular ejection fraction, macitentan neither lowered NT-proBNP nor improved HF outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03153111 and NCT03714815.

AIMS: Clonal haematopoiesis (CH) is recognized as a significant risk factor for various non-haematologic conditions, including cardiovascular diseases. However, recent studies examining its relationship with heart failure (HF) have reported conflicting findings. To address these inconsistencies, the present meta-analysis aimed to evaluate the association of CH with the incidence and clinical outcomes of HF. METHODS AND RESULTS: MEDLINE, Cochrane Library and Scopus were searched until 12 December 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using three-level mixed-effects meta-analyses. Participants (n = 57 755) with CH had significantly greater risk of new-onset HF compared to the non-CH group (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.35, p < 0.0001; I CONCLUSION: Clonal haematopoiesis is associated with an increased risk of incident HF and worse prognosis in individuals affected by HF. These findings highlight the potential of CH to contribute to a deeper understanding of HF, improve risk stratification, and support more personalized approaches to its management.

AIMS: Lipoprotein(a) [Lp(a)] is an emerging risk factor for major adverse cardiovascular events (MACE). However, evidence on MACE risk according to Lp(a) level in atherosclerotic patients is insufficient, and more data is needed about whether type 2 diabetes (T2DM) additionally contributes to this risk. We aimed to investigate the association between Lp(a) and MACE in atherosclerotic patients and compare the magnitude of Lp(a)-MACE association in the patients with and without T2DM. METHODS AND RESULTS: Using a retrospective cohort study of atherosclerotic patients with and without T2DM who were screened for Lp(a) between 1 January 2000 to 31 December 2020, we estimated the risk of MACE according to Lp(a) level stratified by quintiles and compared the difference in magnitude of Lp(a)-MACE association according to presence of T2DM with partial likelihood ratio test. The study included 25 826 patients with established atherosclerotic cardiovascular disease, of whom 7535 had T2DM (29.2%) and 18 291 did not (70.8%). During 160 174 person-years (PY) of follow-up, a total of 4836 MACE were observed. Compared to the lowest quintile (Q) of Lp(a) levels, multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for MACEs across Q2 to Q5 were 1.10 (95% CI: 0.94-1.30), 0.98 (95% CI: 0.83-1.16), and 1.25 (95% CI: 1.06-1.46), 1.29 (95% CI: 1.10-1.51) in patients with T2DM, and 0.99 (95% CI: 0.88-1.12), 1.10 (95% CI: 0.98-1.23), 1.01 (95% CI: 0.90-1.13), and 1.13 (95% CI: 1.01-1.27) for those without T2DM. The strength of Lp(a)-MACE association was stronger among the patients with T2DM (P < 0.001). CONCLUSION: Among atherosclerotic patients with and without T2DM, elevated Lp(a) level was significantly associated with a higher risk of MACE. Compared to those without T2DM, the patients with T2DM showed an excess MACE risk, suggesting the need for clinical interventions concerning both Lp(a) level and glycemic control. In a population-based study of 25 826 patients with established atherosclerotic cardiovascular disease, we found a significant association between elevated lipoprotein(a) and an increased risk of incident major adverse cardiovascular events in the patients with and without type 2 diabetes mellitus. However, patients with established atherosclerotic cardiovascular disease with type 2 diabetes mellitus exhibited excess risk of major adverse cardiovascular disease for the same unit increase in lipoprotein(a) compared to those without type 2 diabetes mellitus. This study highlights the need for additional clinical attention, personalized risk assessment, and prevention strategies for patients with established atherosclerotic cardiovascular disease, particularly among those with type 2 diabetes mellitus.