Daily Cardiology Research Analysis

IMPORTANCE: Patients with frailty are often perceived to have a less favorable benefit-risk profile for novel therapies and therefore may be less likely to receive these. OBJECTIVE: To examine the efficacy and safety of finerenone, compared with placebo, according to frailty status in patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or with HF and preserved ejection fraction (HFpEF). DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of a phase 3 randomized clinical trial, the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF), conducted across 653 sites in 37 countries. Patients with HF with New York Heart Association functional class II through IV, a left ventricular ejection fraction of 40% or higher, evidence of structural heart disease, and elevated natriuretic peptide levels were randomized between September 2020 and January 2023. Data analysis was conducted from October 1 to November 30, 2024. INTERVENTION: Addition of once-daily finerenone or placebo to usual therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular death and total worsening HF events. Frailty was measured using the Rockwood cumulative deficit approach. RESULTS: Of the 6001 patients randomized in FINEARTS-HF, a frailty index (FI) was calculable in 5952 patients (mean [SD] age, 72.0 [9.6] years; 3241 [54.4%] male). In total, 1588 patients (26.7%) had class I frailty (FI ≤0.210 [not frail]), 2141 (36.0%) had class II frailty (FI 0.211-0.310 [more frail]), and 2223 (37.3%) had class III frailty (FI ≥0.311 [most frail]). Compared with patients with class I frailty, those with class II and III frailty had a higher risk of the primary outcome (unadjusted rate ratio [RR], 1.88 [95% CI, 1.54-2.28] for class II and 3.86 [95% CI, 3.22-4.64] for class III). The effect of finerenone on the primary outcome did not vary significantly by frailty class (class I: RR, 1.07 [95% CI, 0.77-1.49]; class II: RR, 0.66 [95% CI, 0.52-0.83]; class III: RR, 0.91 [95% CI, 0.76-1.07]; P for interaction = .77). Frailty class did not modify the effects of finerenone on the components of the primary outcome, all-cause death, or improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score. The effects of finerenone, compared with placebo, on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty class. CONCLUSIONS AND RELEVANCE: In FINEARTS-HF, finerenone reduced the risk of total worsening HF events and cardiovascular death, and it improved symptoms; these effects were not modified by frailty status. In addition, the effects of finerenone on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty status. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

BACKGROUND: Abnormal ventricular depolarization, evident as a broad QRS complex on an ECG, is traditionally categorized into left bundle-branch block (LBBB) and right bundle-branch block or nonspecific intraventricular conduction delay. This categorization, although physiologically accurate, may fail to capture the nuances of diseases subtypes. METHODS: We used unsupervised machine learning to identify and characterize novel broad QRS phenogroups. First, we trained a variational autoencoder on 1.1 million ECGs and discovered 51 latent features that showed high disentanglement and ECG reconstruction accuracy. We then extracted these features from 42 538 ECGs with QRS durations >120 milliseconds and employed a reversed graph embedding method to model population heterogeneity as a tree structure with different branches representing phenogroups. RESULTS: Six phenogroups were identified, including phenogroups of right bundle-branch block and LBBB with varying risk of cardiovascular disease and mortality. The higher risk right bundle-branch block phenogroup exhibited increased risk of cardiovascular death (adjusted hazard ratio [aHR], 1.46 [1.30-1.63], CONCLUSIONS: Our findings challenge the current paradigm, highlighting the potential for these phenogroups to enhance cardiac resynchronization therapy patient selection for subjects with LBBB and guide investigation and follow-up strategies for subjects with higher risk right bundle-branch block.

IMPORTANCE: Healthy lifestyles and uptake of primary preventive therapies for cardiovascular disease remain poor. OBJECTIVE: To determine the impact of coronary computed tomography (CT) angiography on healthy lifestyle behaviors, acceptance of recommended treatments, and modification of risk factors as compared with guideline-directed cardiovascular risk scoring. DESIGN, SETTING, AND PARTICIPANTS: This was a nested substudy conducted from September 2020 to August 2024 of a randomized clinical trial where participants underwent cardiovascular risk scoring or coronary CT angiography. Primary care-based screening took place in Scotland. Included in the analysis were asymptomatic individuals aged 40 to 70 years without known cardiovascular disease and with at least 1 cardiovascular risk factor. Study data were analyzed from August to September 2024. INTERVENTIONS: All participants received lifestyle advice with additional recommendations for moderate-intensity statin therapy if the 10-year cardiovascular risk was greater than or equal to 10% or combined antiplatelet and at least moderate-intensity statin therapies if coronary atherosclerosis was identified on CT angiography. MAIN OUTCOMES AND MEASURES: The composite primary outcome was compliance with the National Institute for Health and Care Excellence recommendations for diet, body mass index, smoking, and physical exercise at 6 months. RESULTS: Between September 2020 and January 2024, 400 participants were enrolled (median [IQR] age, 62 [56-65] years; 198 female [49.5%]; median [IQR] 10-year cardiovascular risk, 14% [9%-19%]) with 195 randomized to cardiovascular risk scoring and 205 to coronary CT angiography. At 6 months, those who underwent CT angiography were more likely to meet the primary composite end point (17% [33 of 194 participants] vs 6% [10 of 177 participants]; odds ratio, 3.42; 95% CI, 1.63-6.94; P < .001). Compared with cardiovascular risk scoring, fewer participants were recommended preventive therapy after CT angiography (51% [105 of 205 participants] vs 75% [147 of 195 participants]; P < .001), but acceptance of recommendations was higher (77% [81 of 105 participants] vs 46% [68 of 147 participants]; P < .001). This resulted in similar use of lipid-lowering therapy (44% [90 of 205 participants] vs 35% [69 of 195 participants]; OR, 1.43; 95% CI, 0.96-2.15; P = .08) and greater use of antiplatelet therapy in those randomized to CT angiography (40% [83 of 205 participants] vs 0.5% [1 of 195 participants]; P < .001). Participants randomized to coronary CT angiography had small incremental improvements in risk factors and 10-year cardiovascular risk, largely driven by those with CT-defined coronary atheroma. CONCLUSIONS AND RELEVANCE: Results of this cohort study reveal that compared with cardiovascular risk scoring, coronary CT angiography was associated with modest improvements in healthier lifestyle behaviors, acceptance of recommended preventive therapy, and risk factor modification. Whether this strategy reduces coronary events remains to be established.