Publications

KEY POINTS: This Myocardial Ischemia and Transfusion (MINT) trial analysis evaluated the optimal transfusion strategy for patients with CKD and anemia experiencing acute myocardial infarction. In patients with CKD, a liberal transfusion strategy overall did not demonstrate benefit over a restrictive strategy.

BACKGROUND: CKD is associated with higher risk of myocardial infarction and anemia. Among patients with anemia and CKD who experience myocardial infarction, it remains uncertain whether a liberal red blood cell transfusion threshold strategy (hemoglobin cutoff <10 g/dl) is superior to a restrictive transfusion threshold (hemoglobin, 7–8 g/dl) strategy.

METHODS: Among the 3504 patients enrolled in the Myocardial Ischemia and Transfusion (MINT) trial with nonmissing serum creatinine, we compared baseline characteristics and 30-day and 6-month outcomes of patients without CKD (N=1279), CKD with eGFR 30–60 ml/min per 1.73 m2 (N=999), CKD with eGFR <30 ml/min per 1.73 m2 (N=802), and CKD requiring dialysis (N=415) by assigned transfusion strategy.

RESULTS: No statistically significant interactions were observed between CKD stage and assigned transfusion strategy. Among non–dialysis-dependent patients with an eGFR <30 ml/min per 1.73 m2, a restrictive transfusion strategy was associated with a higher risk of 30-day death or recurrent myocardial infarction (risk difference [RD], 5.8%; 95% confidence interval [CI], 0.4% to 11.2%) compared with a liberal transfusion strategy. Among patients with an eGFR 30–60 ml/min per 1.73 m2, a restrictive strategy was associated with a similar risk of 30-day death or recurrent myocardial infarction (RD, 3.7%; 95% CI, −0.9% to 8.2%) compared with a liberal transfusion strategy. Among patients with CKD requiring dialysis, a restrictive strategy was also associated with a similar risk of 30-day death or recurrent myocardial infarction (RD, −2.6%; 95% CI, −10.0% to 4.8%) compared with a liberal transfusion strategy.

CONCLUSIONS: In patients with CKD included in this MINT subgroup analysis, a liberal transfusion strategy was not worse than a restrictive transfusion strategy and was associated with less harm in subgroups not receiving dialysis.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:: Myocardial Ischemia and Transfusion (MINT), NCT02981407.

BACKGROUND: Patients with cardiovascular (CV) diseases are increasingly frail but rarely represented in trials. Understanding effect modification by frailty on CV trials is critical as it could help define treatment strategies in frail patients.

OBJECTIVES: This meta-analysis aims to assess the implications of frailty on CV outcomes in clinical trials.

METHODS: Randomized controlled trials examining the effects of frailty in the context of CV trials were included (CRD42024528279). Outcomes included a composite of major adverse cardiac events (MACE), all-cause mortality, CV mortality, hospitalizations, and frailty-specific outcomes (physical, quality of life, and frailty scores). HRs and 95% CIs were pooled for clinical endpoints, and standardized mean differences (SMDs) were calculated for frailty-specific outcomes.

RESULTS: Thirty unique randomized controlled trials were included with a pooled total of 87,711 participants. Frail patients had a significantly increased risk of MACE (HR: 2.33 [95% CI: 1.87-2.91], P < 0.001, I2 = 83%), all-cause mortality (HR: 2.34 [95% CI: 1.80-3.05], P < 0.01, I2 = 75%), CV mortality (HR: 1.76 [95% CI: 1.60-1.93], P < 0.001, I2 = 0%), and hospitalizations (HR: 2.38 [95% CI: 1.65-3.43], P < 0.001, I2 = 92%) compared to nonfrail patients. In the frailest group, trial interventions decreased MACE (HR: 0.81 [95% CI: 0.74-0.88], P < 0.001, I2 = 0%) and hospitalization (HR: 0.81 [95% CI: 0.72-0.90], P < 0.001, I2 = 0%) risks with no significant difference in mortality risk (P > 0.05) compared with the control group. Trial interventions significantly improved physical (SMD: 0.15, 0.04-0.26) and quality of life (SMD: 0.15, 0.09-0.21) but not frailty scores (P > 0.05).

CONCLUSIONS: While frailty prognosticated a higher risk of CV events and mortality, frailty did not reduce treatment efficacy. CV trial interventions appear beneficial even in the frailest group.

BACKGROUND: Aortic valve calcium (AVC) is associated with increased risk of mortality, cardiovascular disease (CVD), non-CVD such as dementia. Traditional atherosclerotic CVD risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown.

OBJECTIVES: To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of CVD.

METHODS: We examined 6346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m2. AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR < 60 mL/min/1.73 m2 accompanied with an at least 40 % decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable adjusted Cox proportional hazard regression models to examine the association between AVC (categorical and log-transformed) and incident CKD.

RESULTS: Participants had a mean age 62.2 ± 10.1 years, 53 % were women, and AVC >0 was present in 795 (12 %) participants. During a median follow-up time of 16.9 years, 982 (15 %) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95 % CI: 1.02-1.10]; p = 0.005). Kaplan-Meier models showed a higher cumulative incidence for CKD with higher AVC levels. In the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95 % CI: 1.15-1.89]; p = 0.002). The observed associations remained after further adjusting for CAC score (p = 0.024), Lp(a) (p = 0.004), and the APOE-ε4 genotype (p = 0.004).

CONCLUSIONS: In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD. Further work is needed to understand the multidirectional relationship between AVC, CKD, and atherosclerosis.

BACKGROUND: Risk stratification in patients with nonischemic dilated cardiomyopathy (DCM) remains challenging. Although late gadolinium enhancement (LGE) cardiovascular magnetic resonance is recognized as a major risk factor for ventricular tachycardia/ventricular fibrillation (VT/VF), the prognostic value of LGE radiomics is unknown.

OBJECTIVES: The purpose of this study was to investigate if radiomic analysis of LGE images can improve arrhythmia risk stratification in patients with DCM beyond current clinical and imaging markers.

METHODS: In a 2-center retrospective study, patients with DCM were identified among those who received primary prevention implantable cardioverter-defibrillators (ICDs) according to the clinical guidelines and had a cardiovascular magnetic resonance before ICD implantation. The study included patients with DCM from the Cleveland Clinic Foundation for model development and patients with DCM from Beth Israel Deaconess Medical Center for external validation. Left ventricular myocardial radiomic features were extracted from LGE images. The primary outcome was appropriate ICD intervention defined as shock or antitachycardia pacing for VT/VF. Consensus clustering and pairwise correlation were used to identify the radiomic signature. To assess the prognostic value of LGE radiomics, we built 2 logistic regression models using the development data: 1) model 1, including clinical risk factors and scar presence and 2) model 2, which combines model 1 and LGE radiomics.

RESULTS: In total, 270 patients with DCM (61% male, age 58 ± 13 years) in development data and 113 patients with DCM (71% male, age 55 ± 14 years) in external validation were included. VT/VF occurred in 40 (15%) patients in development and 16 (15%) in external validation cohorts over a median follow-up period of 4.0 (IQR: 2.5-6.1) and 2.6 (IQR: 1.2-4.1) years, respectively. Consensus clustering and pairwise correlation revealed 3 distinct radiomic features. Model 2 showed a higher C-statistic than model 1 (0.71 [95% CI: 0.62-0.80] vs 0.61 [95% CI: 0.53-0.71]; P = 0.028 in development and 0.70 [95% CI: 0.59-0.85] vs 0.61 [95% CI: 0.46-0.77]; P = 0.025 in external validation). This also significantly improved risk stratification with a continuous net reclassification index of 0.60 [95% CI: 0.29-0.91; P < 0.001] in development and of 0.29 [95% CI: 0.26-0.56; P = 0.03] in external validation. Additionally, 1 radiomic feature, namely the gray level co-occurrence matrix autocorrelation, was an independent predictor of VT/VF in both development (HR: 1.45 [95% CI: 1.10-1.91]; P = 0.01) and in external validation (HR: 2.38 [95% CI: 1.28-4.42]; P = 0.01).

CONCLUSIONS: In this proof-of-concept study, radiomic analysis of LGE images provides additional prognostic value beyond LGE presence in predicting arrhythmia in patients with DCM.

BACKGROUND: The current standard of practice for cremating patients with cardiac implantable electronic devices (CIEDs) is surgical explantation before cremation to mitigate the risk of device explosion. This surgery may conflict with patient or family beliefs, whereas cremation of CIEDs may create occupational hazards.

OBJECTIVE: This study sought to establish an ex vivo model for screening CIED behavior during cremation.

METHODS: Seven CIEDs underwent testing including projectile/sound testing, impact testing, and gas analysis. In the projectile test, devices were heated until thermal failure (explosion) and filmed with a high-speed camera and microphone. For impact testing, brick structures were built to assess damage after explosion. Gas chromatography-mass spectrometry identified released gases. Findings were compared with occupational health standards, where available.

RESULTS: The implantable loop recorder and leadless pacemaker produced minimal kinetic energy and impact risk with thermal failure. The remaining devices demonstrated explosive disintegration at thermal temperatures <500°C. The pacemakers and implantable cardiac defibrillators produced sound levels >120 dB and resulted in damage to brick structures. Small quantities of benzene and hydrogen fluoride were produced but at quantities within acceptable occupational exposure limits in a cremation chamber.

CONCLUSION: All tested CIEDs experienced explosion at temperatures below crematorium standards. The smallest devices produced minimal risk of damage or injury, suggesting that they may safely remain in situ during cremation, whereas the larger devices produced more kinetic energy, testing chamber damage, and louder explosions, suggesting potential risk with cremation. Cadaveric testing in full-sized cremation chambers is required to determine real-world risk.

INTRODUCTION: Early detection of cardiovascular disease in primary care is a public health priority, for which the clinical and cost-effectiveness of an artificial intelligence-enabled stethoscope that detects left ventricular systolic dysfunction, atrial fibrillation and cardiac murmurs is unproven but potentially transformative.

METHODS AND ANALYSIS: TRICORDER is a pragmatic, two-arm, multi-centre (decentralised), cluster-randomised controlled trial and implementation study. Up to 200 primary care practices in urban North West London and rural North Wales, UK, will be randomised to usual care or to have artificial intelligence-enabled stethoscopes available for use. Primary care clinicians will use the artificial intelligence-enabled stethoscopes at their own discretion, without patient-level inclusion or exclusion criteria. They will be supported to do so by a clinical guideline developed and approved by the regional health system executive board. Patient and outcome data will be captured from pooled primary and secondary care records, supplemented by qualitative and quantitative clinician surveys. The coprimary endpoints are (i) difference in the coded incidence (detection) of heart failure and (ii) difference in the ratio of coded incidence of heart failure via hospital admission versus community-based diagnostic pathways. Secondary endpoints include difference in the incidence of atrial fibrillation and valvular heart disease, cost-consequence differential, and prescription of guideline-directed medical therapy.

ETHICS AND DISSEMINATION: This trial has ethical approval from the UK Health Research Authority (23/LO/0051). Findings from this trial will be disseminated through publication of peer-reviewed manuscripts, presentations at scientific meetings and conferences with local and national stakeholders.

TRIAL REGISTRATION NUMBER: NCT05987670.