Daily Cardiology Research Analysis

IMPORTANCE: Papillary muscle scarring (papSCAR) can occur without epicardial coronary artery disease, likely due to microvascular dysfunction. Dilated cardiomyopathy (DCM) has been associated with microvascular dysfunction; the prevalence and prognostic significance of papSCAR in patients with DCM are unclear. OBJECTIVE: To determine the prevalence of papSCAR in patients with DCM and to evaluate if papSCAR is associated with adverse outcomes. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among consecutive patients with known or suspected DCM prospectively enrolled at an academic hospital in North Carolina from January 2011 to December 2020. Patients were referred for cardiovascular magnetic resonance (CMR) imaging, and the study protocol included flow-independent dark blood delayed-enhancement (FIDDLE) imaging, which improves the detection of papSCAR. Data were analyzed from January 2022 to December 2022. MAIN OUTCOMES AND MEASURES: The primary end point was cardiac mortality. Secondary end points included a composite of heart failure events (heart failure death or cardiac transplant) and a composite of arrhythmia events (sudden cardiac death [SCD] or aborted SCD). RESULTS: This cohort study included 470 patients (mean [SD] age, 55.3 [14.3] years; 205 female patients [43.6%]). During up to 8 years of follow-up (2082 patient-years), there were 53 cardiac deaths, 49 heart failure events, and 24 arrhythmia events. PapSCAR was present in 137 patients (29.1%), and mean (SD) left ventricular ejection fraction (LVEF) was similar between those with and without papSCAR (30.7% [11.0%] vs 31.4% [10.3%]; P = .52). Patients with papSCAR had a higher rate of cardiac death than those without (19.0% vs 8.1%; hazard ratio [HR], 2.30; 95% CI, 1.34-3.95; P = .002). After adjustment for prespecified variables known to have prognostic value in DCM (age, systolic blood pressure, heart rate, LVEF, and midwall myocardial scar), papSCAR was independently associated with cardiac death (HR, 1.86; 95% CI, 1.07-3.24; P = .03) and provided incremental prognostic value (incremental χ2, 4.68; P = .03). PapSCAR was also independently associated with heart failure events (HR, 2.05; 95% CI, 1.16-3.61; P = .01) and arrhythmia events (HR, 3.41; 95% CI, 1.46-7.94; P = .005). CONCLUSIONS AND RELEVANCE: In this single-center cohort study, papSCAR as detected by dark blood delayed-enhancement CMR was present in approximately one-third of patients with DCM and was independently associated with cardiac death.

IMPORTANCE: Major adverse cardiovascular events (MACEs) are primary causes of morbidity and mortality in adults with type 2 diabetes (T2D), yet few head-to-head randomized trials have compared the effects of glucose-lowering medications on MACEs, and most observational analyses are limited by inadequate bias adjustment methods. OBJECTIVE: To compare the effectiveness of sustained exposure to 4 classes of glucose-lowering medications (sulfonylureas, dipeptidyl peptidase-4 inhibitors [DPP4is], sodium-glucose cotransporter-2 inhibitors [SGLT2is], and glucagon-like peptide-1 receptor agonists [GLP-1RAs]) on MACEs in US adults with T2D using modern causal methods combined with machine learning. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study included adults with T2D who were members of 6 large US health care delivery systems and initiated treatment with 1 of 4 medication classes (sulfonylureas, DPP4is, SGLT2is, and GLP-1RAs) between January 1, 2014, and December 31, 2021. Data analysis was conducted from May 1 to December 31, 2024. EXPOSURE: New use of a sulfonylurea, DPP4i, SGLT2i, or GLP-1RA based on filled prescriptions. MAIN OUTCOMES AND MEASURES: The primary outcome was MACEs defined as nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Analyses were conducted using targeted learning within a trial emulation framework. Heterogeneity of treatment effects was assessed for prespecified subgroups. RESULTS: This study included 296 676 adults. The cohort for emulating a 4-arm trial included a subset of 241 981 adults (mean [SD] age, 57.2 [12.9] years; 54.3% male) with T2D. In adjusted analyses, 2.5-year MACE risk was lowest in patients with sustained exposure to GLP-1RAs, followed by SGLT2is , sulfonylureas, and DPP4is. Comparing DPP4is with sulfonylureas and SGLT2is with GLP-1RAs, the 2.5-year cumulative risk difference was 1.9% (95% CI, 1.1%-2.7%) and 1.5% (1.1%-1.9%), respectively. Risk differences in patients with vs without atherosclerotic cardiovascular disease (ASCVD) were similar in direction but typically much smaller for patients without ASCVD. Evidence of a benefit of GLP-1RAs over SGLT2is was most pronounced in patients with baseline ASCVD or heart failure (HF), age 65 years or older, or low to moderate kidney impairment but was not found in patients younger than 50 years. CONCLUSIONS AND RELEVANCE: In this study, MACE risk varied significantly by medication class, with most protection achieved with sustained treatment with GLP-1RAs followed by SGLT2is, sulfonylureas, and DPP4is. The magnitude of benefit of GLP-1RAs over SGLT2is depended on baseline age, ASCVD, HF, and kidney impairment. These results, along with consideration of cost, availability, and collateral clinical benefits, may inform treatment decisions for adults with T2D.

BACKGROUND AND AIMS: Atrial cardiomyopathy (AtCM) is increasingly recognized as an important substrate for atrial fibrillation (AF). This study aimed to examine potential markers and risk factors of AtCM, and associations with incident AF, heart failure (HF), and stroke. METHODS: Individuals from the UK Biobank with cardiac magnetic resonance imaging and electrocardiographic information were included. Atrial cardiomyopathy markers included left atrial dilation, left atrial mechanical dysfunction, P-wave prolongation, and abnormal P-wave terminal force. Risk factors for AtCM were assessed using logistic regressions. Incident AF, HF, and stroke according to AtCM markers were assessed in multivariable Cox-regression and cumulative incidence models. AF risk according to AtCM markers, clinical and genetic risk factors was evaluated by integrating the HARMS2-AF score and a polygenic risk score for AF. We used net reclassification improvement (NRI) to evaluate reclassification of risk when considering AtCM markers. RESULTS: Among 26 467 individuals, 4145 (15.7%) had ≥1 marker and 619 (2.3%) had ≥2 markers of AtCM. Age, coronary artery disease, and hypertension were consistently associated with AtCM. Having one AtCM marker conferred a hazard ratio (HR) for AF of 1.88 [95% confidence interval (CI): 1.54-2.31; P < .001], with higher rates observed in individuals with ≥2 markers (HR: 4.59; 95% CI: 3.52-5.99; P < .001). Addition of AtCM markers was associated with an NRI of 13.7% (95% CI: 9.2%-18.3%). Integration of clinical and genetic risk factors indicated an additive effect on AF rates. Having ≥2 markers associated with HF (HR: 3.08, 95% CI: 2.03-4.66, P < .001), and stroke (HR: 3.07, 95% CI: 1.78-5.28, P < .001). CONCLUSIONS: One in seven individuals had at least one marker of AtCM. Atrial cardiomyopathy markers were associated with AF, HF, and stroke, supporting AtCM as a common substrate for all three outcomes.