Daily Cardiology Research Analysis

IMPORTANCE: Sodium-glucose cotransporter-2 inhibitors have emerged as important therapeutic options for heart failure (HF). However, their comparative clinical effectiveness remains uncertain. OBJECTIVE: To compare the outcomes associated with dapagliflozin and empagliflozin use in patients diagnosed with HF. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a clinical data warehouse platform shared by 8 medical centers affiliated with The Catholic University of Korea to screen all patients who were diagnosed with HF between January 2021 and November 2023 at these 8 medical centers. Patients were taking either dapagliflozin or empagliflozin and underwent transthoracic echocardiography. One-to-one propensity score matching was performed to ensure comparable baseline characteristics between groups. The propensity score-matched cohort was stratified by left ventricular ejection fraction (LVEF) into subgroups: HF with reduced ejection fraction group had an LVEF of 40% or lower, HF with mildly reduced ejection fraction group had an LVEF of 41% to 49%, and HF with preserved ejection fraction group had an LVEF of 50% or higher. Statistical analyses were performed from December 2023 to July 2025. EXPOSURE: All patients received either dapagliflozin or empagliflozin. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. Secondary outcomes included the individual primary outcome components, all-cause death, and cardiovascular hospitalization. RESULTS: After propensity score matching, the balanced cohort included 4930 patients (2465 each in the dapagliflozin and empagliflozin group; mean [SD] age, 68.8 [13.4] years; 2944 males [59.7%]). The median (IQR) follow-up duration was 16.0 (8.0-27.0) months. In the propensity score-matched cohort, dapagliflozin and empagliflozin showed no significant difference in the primary outcome: a composite of cardiovascular death or HF hospitalization occurred in 9.8% of patients (241 of 2465) taking dapagliflozin vs 9.3% of patients (229 of 2465) taking empagliflozin (adjusted hazard ratio [AHR], 0.99; 95% CI, 0.83-1.19; P = .95). The results did not change after stratifying the cohort by LVEF 40% or lower (14.9% [126 of 844] vs 15.4% [132 of 855]; AHR, 1.06 [95% CI, 0.83-1.35; P = .64]), LVEF 41% to 49% (5.0% [17 of 343] vs 6.3% [22 of 350]; AHR, 1.28 [95% CI, 0.68-2.42; P = .45]), and LVEF 50% or higher (7.7% [98 of 1278] vs 6.0% [75 of 1260]; AHR, 0.80 [95% CI, 0.60-1.09; P = .32]), without between-group heterogeneity (P for interaction = .32). For the secondary outcomes, there were also no significant differences between the dapagliflozin and empagliflozin groups. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with HF, dapagliflozin and empagliflozin had similar clinical outcomes in HF management. Further research and clinical trials are necessary to validate these findings and inform clinical decision-making.

BACKGROUND AND AIMS: Tissular gene expression profiling applicable to formalin-fixed, paraffin-embedded (FFPE) endomyocardial biopsies (EMBs) may refine the diagnosis of cardiac rejection while being easily implemented in clinical practice. This study aimed to develop and validate the first FFPE-based molecular diagnostic system dedicated to heart transplant rejection. METHODS: An international study was conducted (NCT06436027), establishing a deeply phenotyped cohort of heart transplant recipients. EMBs were graded according to international classifications, and gene expression was analysed on FFPE-EMBs using the Banff Human Organ Transplant Panel. Molecular classifiers for antibody-mediated rejection (AMR) and acute cellular rejection (ACR) were developed, with discrimination and calibration assessed in internal and external validation cohorts. RESULTS: A total of 671 biopsies were included, with 591 in the main cohort (AMR: n = 188, ACR: n = 289, matched non-rejection: n = 114); this was split into a derivation set (n = 475) and an internal validation set (n = 116). The external validation cohort comprised 80 biopsies (AMR: n = 20, ACR: n = 32, non-rejection: n = 28). AMR was associated with significant transcripts related to the interferon-gamma pathway, endothelial activation, and monocyte-macrophage recruitment, while ACR was characterized by transcripts related to T-cell receptor signalling, CD3 receptor activation, and CD28 signalling. Molecular ACR and AMR models accurately identified rejection in the validation cohorts (internal: ROC-AUC: AMR = 0.812, ACR = 0.849; external: ROC-AUC: AMR = 0.822, ACR = 0.815) and were strongly associated with pathologic severity. Calibration was adequate. An automated report was developed to enhance the clinical applicability of these classifiers. CONCLUSIONS: A novel FFPE-based molecular diagnostic system accurately identified cardiac allograft rejection. This tool is readily applicable in clinical practice as a companion to pathology and has the potential to refine the diagnosis of rejection.

BACKGROUND: The clinical performance of a novel nanosecond pulsed field ablation (nsPFA) system (Insight Medtech) for pulmonary vein isolation in patients with paroxysmal atrial fibrillation remains unclear. OBJECTIVES: This trial sought to evaluate the efficacy and safety of nsPFA vs ablation index (AI)-guided radiofrequency ablation (RFA) for symptomatic atrial fibrillation. METHODS: The InsightPFA trial was a prospective, multicenter, randomized controlled trial. Patients were randomly allocated in a 1:1 ratio to receive either nsPFA or ablation index (AI)-guided RFA for pulmonary vein isolation. Participants completed a standardized 12-month follow-up protocol. The primary efficacy endpoint was defined as freedom from documented atrial tachyarrhythmia recurrence without the use of class I or III antiarrhythmic drugs. The safety assessment evaluated death, stroke, transient ischemic attack, procedure- and device-related events, and other adverse outcomes in both groups. Secondary efficacy endpoints included acute procedural success and procedural evaluations. RESULTS: Among 287 patients from 13 centers in China, 141 nsPFA patients and 142 AI-guided RFA patients completed follow-up. The proportions of conscious sedation use were 89.4% in the nsPFA group and 92.4% in the AI-guided RFA group. The primary efficacy endpoint was achieved in 93 (65.5%) patients in the nsPFA group and 93 (64.1%) in the AI-guided RFA group in the full analysis set population (adjusted rate difference: 2.0%; 95% CI: -8.7% to 12.8%; P = 0.0019 for noninferiority), demonstrating that the noninferiority was met. The 12-month Kaplan-Meier treatment success rates were 66.7% and 67.4% in the nsPFA and AI-guided RFA groups, respectively (HR in the PFA group: 0.99; 95% CI: 0.66 to 1.48; P = 0.0020 for noninferiority). There was no significant difference in the incidence of procedure-related adverse events between the 2 groups. Acute procedural success rates were 100% in both groups. The nsPFA group demonstrated significantly shorter total procedure time, left atrial dwell time, and ablation time but experienced longer fluoroscopy times and higher radiation exposure doses. CONCLUSIONS: The nsPFA exhibited noninferior efficacy and comparable safety to AI-guided RFA while obviating the need for general anesthesia. Furthermore, the study revealed that this ablation technique significantly reduced both total procedure time and left atrial dwelling time. (InsightPFA Trial of the LotosPFA Catheter [InsightPFA]; NCT06014996).