Daily Cardiology Research Analysis

BACKGROUND AND AIMS: Immune checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this 'cardiomyotoxicity' are lacking. The main aim of this study was to determine predictors and construct a risk score associated with negative outcomes in patients admitted for ICI myocarditis. METHODS: A multicentre registry collected data retrospectively from 17 countries between 2014 and 2023. A multivariable Cox regression model was used to determine risk factors for the primary composite outcome: time to severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardiomuscular symptoms, diagnostics, and treatments. Time-dependent covariates were used, and missing data were imputed. A point-based prognostic risk score was derived and externally validated. RESULTS: In 748 patients (67% male, age 23-94 years), 30-day incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17%, respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7), presence of cardiomuscular symptoms (HR 2.6 [1.5-4.2]), low QRS voltage on presenting electrocardiogram (HR for ≤0.5 mV vs >1 mV 1.9 [1.1-3.1]), left ventricular ejection fraction (LVEF) < 50% (HR 1.7 [1.1-2.6]), and incremental troponin elevation (HR 1.8 [1.4-2.4], 2.9 [1.8-4.7], and 4.6 [2.3-9.3], for 20, 200, and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-day primary outcome incidence increased gradually from 4% (risk score = 0) to 81% (risk score ≥ 4). This risk score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low-risk patients who were managed with no immunosuppression resulting in no cardiomyotoxic events. CONCLUSIONS: ICI-associated myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low QRS voltage, depressed LVEF, and cardiomuscular symptoms. A risk score incorporating these features performed well. CLINICAL TRIAL REGISTRATION: NCT04294771 and NCT05454527.

BACKGROUND: The microaxial flow pump (mAFP) improves survival in selected patients with ST-segment elevation myocardial infarction-induced cardiogenic shock (STEMI-CS). Understanding the impact on cardiac output (CO), cardiac power output (CPO), and pulmonary artery pressure (PAP) provides insight into the potential unloading effect of the device, which is a reduction in total intrinsic mechanical work of the heart. OBJECTIVE: This study sought to determine the effect of mAFP on hemodynamics in STEMI-CS. METHODS: This substudy of the DanGer (Danish-German) shock trial randomized patients with STEMI-CS to mAFP or standard of care. Patients were monitored using a pulmonary artery catheter. Outcome measures were CO, CPO, and mean PAP during the first 48 hours. RESULTS: Of 324 patients admitted to the cardiac intensive care unit (CICU), 223 patients (68%) had data on hemodynamic monitoring: 98 patients (63%) in the standard of care, and 125 (74%) patients in the mAFP group. The median first measured CO after CICU admission was 3.4 L/min (Q1-Q3: 2.6-4.4 L/min) in the control vs 3.7 L/min (Q1-Q3: 3.2-4.5 L/min) in the mAFP group; P = 0.13. After 6 hours, the CO increased in and was consistently higher in the mAFP group from 12 hours until 48 hours. The first measured mean PAP in the CICU had a median value of 31 mm Hg (Q1-Q3: 29-39 mm Hg) in the standard of care group compared with 27 mm Hg (Q1-Q3: 23-33 mm Hg) in the mAFP group (P < 0.001) and remained lower at all time points in the mAFP. Also, the first measured PCWP was lower in mAFP vs standard of care (18 mm Hg [Q1-Q3: 14-22 mm Hg] vs 22 mm Hg [Q1-Q3: 20-26 mm Hg]; P < 0.001) and remained lower until 48 hours. The median first measured CPO was 0.56 W (95% CI: 0.41-0.76 W) in the control vs 0.68 W (95% CI: 0.51-0.85 W; P = 0.01), in the mAFP group, and remained higher in the mAFP group until 48 hours. CONCLUSIONS: The mAFP reduces intrinsic mechanical work of the heart in STEMI-CS patients enrolled in the DanGer shock trial by reducing native CO, pulmonary pressures, and LV filling pressures while maintaining hydraulic power output delivered to the body by the heart and mAFP (CPO). (Danish Cardiogenic Shock Trial [DanShock]; NCT01633502).

BACKGROUND: In women with severe aortic stenosis, there are limited data regarding outcome differences following transcatheter (TAVR) vs surgical aortic valve replacement (SAVR). OBJECTIVES: The authors sought to examine outcomes of TAVR vs SAVR in a patient-level pooled analysis of women in the RHEIA and PARTNER 3 trials. METHODS: Patients in both trials were randomly allocated to a balloon-expandable SAPIEN 3/Ultra valve or to surgical bioprostheses. Individual patient data of female participants in the 2 trials were pooled. The primary endpoint was all-cause mortality, all stroke, or rehospitalization at 1 year. RESULTS: A total of 376 women were randomized to TAVR and 336 to SAVR. The mean age was ∼73 years, and the mean Society of Thoracic Surgeons (STS) score was 2.1%. Kaplan-Meier estimates of event rates at 1 year with TAVR vs SAVR were 8.5% vs 16.8% for the composite of all-cause mortality, all stroke, or rehospitalization (absolute difference -8.2%; 95% CI: -13.1% to -3.3%; P < 0.001), 1.1% vs 2.1% (P = 0.27) for all-cause mortality, 2.7% vs 3.9% (P = 0.35) for all stroke, and 5.4% vs 11.9% (P = 0.002) for rehospitalization. The composite endpoint of all-cause death or stroke was similar between the 2 treatment groups: 3.5% vs 5.4% (absolute difference -1.9%; 95% CI: -5.0% to 1.1%; P = 0.21). CONCLUSIONS: Among women with symptomatic severe aortic stenosis, TAVR led to a reduction in the rate of the combined endpoint of all-cause mortality, stroke, or rehospitalization at 1-year follow-up, largely due to a significant reduction in the rate of rehospitalization.