Publications

The electrocardiogram (ECG) can capture obesity-related cardiac changes. Artificial intelligence-enhanced ECG (AI-ECG) can identify subclinical disease. We trained an AI-ECG model to predict body mass index (BMI) from the ECG alone. Developed from 512,950 12-lead ECGs from the Beth Israel Deaconess Medical Center (BIDMC), a secondary care cohort, and validated on UK Biobank (UKB) (n = 42,386), the model achieved a Pearson correlation coefficient (r) of 0.65 and 0.62, and an R2 of 0.43 and 0.39 in the BIDMC cohort and UK Biobank, respectively for AI-ECG BMI vs. measured BMI. We found delta-BMI, the difference between measured BMI and AI-ECG-predicted BMI (AI-ECG-BMI), to be a biomarker of cardiometabolic health. The top tertile of delta-BMI showed increased risk of future cardiometabolic disease (BIDMC: HR 1.15, p < 0.001; UKB: HR 1.58, p < 0.001) and diabetes mellitus (BIDMC: HR 1.25, p < 0.001; UKB: HR 2.28, p < 0.001) after adjusting for covariates including measured BMI. Significant enhancements in model fit, reclassification and improvements in discriminatory power were observed with the inclusion of delta-BMI in both cohorts. Phenotypic profiling highlighted associations between delta-BMI and cardiometabolic diseases, anthropometric measures of truncal obesity, and pericardial fat mass. Metabolic and proteomic profiling associates delta-BMI positively with valine, lipids in small HDL, syntaxin-3, and carnosine dipeptidase 1, and inversely with glutamine, glycine, colipase, and adiponectin. A genome-wide association study revealed associations with regulators of cardiovascular/metabolic traits, including SCN10A, SCN5A, EXOG and RXRG. In summary, our AI-ECG-BMI model accurately predicts BMI and introduces delta-BMI as a non-invasive biomarker for cardiometabolic risk stratification.

BACKGROUND: Myocardial electrical heterogeneity is critical for normal cardiac electromechanical function, but abnormal or excessive electrical heterogeneity is proarrhythmic. The spatial ventricular gradient (SVG), a vectorcardiographic measure of electrical heterogeneity, has been associated with arrhythmic events during long-term follow-up, but its relationship with short-term inducibility of ventricular arrhythmias (VAs) is unclear.

OBJECTIVE: This study was designed to determine associations between SVG and inducible VAs during electrophysiology study.

METHODS: A retrospective study was conducted of adults without prior sustained VA, cardiac arrest, or implantable cardioverter-defibrillator who underwent ventricular stimulation for evaluation of syncope and nonsustained ventricular tachycardia or for risk stratification before primary prevention implantable cardioverter-defibrillator implantation. The 12-lead electrocardiograms were converted into vectorcardiograms, and SVG magnitude (SVGmag) and direction (azimuth and elevation) were calculated. Odds of inducible VA were regressed by logistic models.

RESULTS: Of 143 patients (median age, 69 years; 80% male; median left ventricular ejection fraction [LVEF], 47%; 52% myocardial infarction), 34 (23.8%) had inducible VAs. Inducible patients had lower median LVEF (38% vs 50%; P < .0001), smaller SVGmag (29.5 vs 39.4 mV·ms; P = .0099), and smaller cosine SVG azimuth (cosSVGaz; 0.64 vs 0.89; P = .0007). When LVEF, SVGmag, and cosSVGaz were dichotomized at their medians, there was a 39-fold increase in adjusted odds (P = .002) between patients with all low LVEF, SVGmag, and cosSVGaz (65% inducible) compared with patients with all high LVEF, SVGmag, and cosSVGaz (4% [n = 1] inducible). After multivariable adjustment, SVGmag, cosSVGaz, and sex but not LVEF or other characteristics remained associated with inducible VAs.

CONCLUSION: Assessment of electrical heterogeneity by SVG, which reflects abnormal electrophysiologic substrate, adds to LVEF and identifies patients at high and low risk of inducible VA at electrophysiology study.

BACKGROUND: Multiple studies continue to evaluate the use of intracardiac echocardiography (ICE) and transesophageal echocardiography (TEE) for guiding left atrial appendage occlusion (LAAO).

OBJECTIVE: To conduct an updated meta-analysis comparing the effectiveness and safety outcomes of both imaging modalities.

METHODS: PubMed, Cochrane, and Embase were searched for studies comparing ICE vs TEE to guide LAAO. Odds ratios (OR) with 95% confidence intervals (CI) were pooled using a random-effects model. The primary effectiveness endpoint was procedural success. The primary safety endpoint included the overall complications rate. Additional safety outcomes were assessed as secondary endpoints. Subgroup analysis of primary endpoints was conducted according to device type (Amulet, LAmbre, Watchman, Watchman FLX) and study region (American, Asia, Europe). We used R version 4.3.1 for all statistical analyses.

RESULTS: Our meta-analysis included 19 observational studies encompassing 42,474 patients, of whom 4,415 (10.4%) underwent ICE-guided LAAO. Compared with TEE, ICE was associated with a marginally higher procedural success (OR 1.33; 95% CI: 1.01-1.76; p=0.04; I2=0%). There was no significant difference in the overall complications rate (OR 1.02; 95% CI: 0.77-1.36; p=0.89; I2=5%). However, ICE showed higher rates of pericardial effusion (OR 2.11; 95% CI: 1.47-3.03; p<0.001; I2=0%) and residual iatrogenic atrial septal defect (iASD) (OR 1.52; 95% CI: 1.15-2.03; p<0.004; I2=0%). Subgroup analysis revealed variations in procedural success within the ICE group across study regions (p=0.02).

CONCLUSION: In this updated meta-analysis, the increasing adoption of ICE-guided LAAO demonstrated higher procedural success rates compared to TEE, although with limited statistical significance. Overall complication rates were similar; however, ICE showed higher rates of pericardial effusion and residual iASD.

BACKGROUND: The current standard of practice for cremating patients with cardiac implantable electronic devices (CIEDs) is surgical explantation prior to 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.

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

METHODS: Seven CIED 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 hydrogren fluoride were produced but at quantities within acceptable occupational exposure limits in a cremation chamber.

CONCLUSIONS: All tested CIEDs experienced explosion at temperatures below crematorium standards. The smallest devices produced minimal risk of damage or injury suggesting they may safely remain in situ during cremation, while 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.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) intervention is an established prophylactic measure. Identifying high-benefit patients poses challenges.

PURPOSE: To assess the prognostic value of cardiac magnetic resonance imaging (MRI) parameters including myocardial deformation for risk stratification of ICD intervention in non-ischemic cardiomyopathy (NICM) while accounting for competing mortality risk.

STUDY TYPE: Retrospective and prospective.

POPULATION: One hundred and fifty-nine NICM patients eligible for primary ICD (117 male, 54 ± 13 years) and 49 control subjects (38 male, 53 ± 5 years).

FIELD STRENGTH/SEQUENCE: Balanced steady state free precession (bSSFP) and three-dimensional phase-sensitive inversion-recovery late gadolinium enhancement (LGE) sequences at 1.5 T or 3 T.

ASSESSMENT: Patients underwent MRI before ICD implantation and were followed up. Functional parameters, left ventricular global radial, circumferential and longitudinal strain, right ventricular free wall longitudinal strain (RV FWLS) and left atrial strain were measured (Circle, cvi42). LGE presence was assessed visually. The primary endpoint was appropriate ICD intervention. Models were developed to determine outcome, with and without accounting for competing risk (non-sudden cardiac death), and compared to a baseline model including LGE and clinical features.

STATISTICAL TESTS: Wilcoxon non-parametric test, Cox's proportional hazards regression, Fine-Gray competing risk model, and cumulative incidence functions. Harrell's c statistic was used for model selection. A P value <0.05 was considered statistically significant.

RESULTS: Follow-up duration was 1176 ± 960 days (median: 896). Twenty-six patients (16%) met the primary endpoint. RV FWLS demonstrated a significant difference between patients with and without events (-12.5% ± 5 vs. -16.4% ± 5.5). Univariable analyses showed LGE and RV FWLS were significantly associated with outcome (LGE: hazard ratio [HR] = 3.69, 95% CI = 1.28-10.62; RV FWLS: HR = 2.04, 95% CI = 1.30-3.22). RV FWLS significantly improved the prognostic value of baseline model and remained significant in multivariable analysis, accounting for competing risk (HR = 1.73, 95% CI = 1.12-2.66).

DATA CONCLUSIONS: In NICM, RV FWLS may provide additional predictive value for predicting appropriate ICD intervention.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 5.

BACKGROUND: Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression on cardiovascular outcomes remains uncertain.

METHODS: To determine whether frailty progression is associated with adverse cardiovascular outcomes, independent of baseline frailty and age, we evaluated all Medicare Fee-for-Service beneficiaries ≥65 years at cohort inception with continuous enrollment from 2003 to 2015. Linear mixed effects models, adjusted for baseline frailty and age, were used to estimate change in a validated claims-based frailty index (CFI) over a 5-year period. Survival analysis was used to examine frailty progression and risk of adverse health outcomes.

RESULTS: There were 8.9 million unique patients identified, mean age 77.3 ± 7.2 years, 58.7% female, 10.9% non-White race. In total, 60% had frailty progression and 40% frailty regression over median follow-up of 2.4 years. Compared to those with frailty regression, when adjusting for age and baseline CFI, those with frailty progression had a significantly greater risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.31-1.31), all-cause mortality (HR 1.34, 95% CI 1.34-1.34), acute myocardial infarction (HR 1.08, 95% CI 1.07-1.09), heart failure exacerbation (HR 1.30, 95% CI 1.29-1.30), ischemic stroke (HR 1.14, 95% CI 1.14-1.15). There was also a graded increase in risk of each outcome with more rapid progression, as well as significantly fewer days alive at home (DAH) with more rapid progression compared to the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001).

CONCLUSIONS: In this large, nationwide sample of older Medicare beneficiaries, frailty progression, independent of age and baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and ischemic stroke compared to those with frailty regression.

IMPORTANCE: Climate change may increase the risk of adverse cardiovascular outcomes by causing direct physiologic changes, psychological distress, and disruption of health-related infrastructure. Yet, the association between numerous climate change-related environmental stressors and the incidence of adverse cardiovascular events has not been systematically reviewed.

OBJECTIVE: To review the current evidence on the association between climate change-related environmental stressors and adverse cardiovascular outcomes.

EVIDENCE REVIEW: PubMed, Embase, Web of Science, and Cochrane Library were searched to identify peer-reviewed publications from January 1, 1970, through November 15, 2023, that evaluated associations between environmental exposures and cardiovascular mortality, acute cardiovascular events, and related health care utilization. Studies that examined only nonwildfire-sourced particulate air pollution were excluded. Two investigators independently screened 20 798 articles and selected 2564 for full-text review. Study quality was assessed using the Navigation Guide framework. Findings were qualitatively synthesized as substantial differences in study design precluded quantitative meta-analysis.

FINDINGS: Of 492 observational studies that met inclusion criteria, 182 examined extreme temperature, 210 ground-level ozone, 45 wildfire smoke, and 63 extreme weather events, such as hurricanes, dust storms, and droughts. These studies presented findings from 30 high-income countries, 17 middle-income countries, and 1 low-income country. The strength of evidence was rated as sufficient for extreme temperature; ground-level ozone; tropical storms, hurricanes, and cyclones; and dust storms. Evidence was limited for wildfire smoke and inadequate for drought and mudslides. Exposure to extreme temperature was associated with increased cardiovascular mortality and morbidity, but the magnitude varied with temperature and duration of exposure. Ground-level ozone amplified the risk associated with higher temperatures and vice versa. Extreme weather events, such as hurricanes, were associated with increased cardiovascular risk that persisted for many months after the initial event. Some studies noted a small increase in cardiovascular mortality, out-of-hospital cardiac arrests, and hospitalizations for ischemic heart disease after exposure to wildfire smoke, while others found no association. Older adults, racial and ethnic minoritized populations, and lower-wealth communities were disproportionately affected.

CONCLUSIONS AND RELEVANCE: Several environmental stressors that are predicted to increase in frequency and intensity with climate change are associated with increased cardiovascular risk, but data on outcomes in low-income countries are lacking. Urgent action is needed to mitigate climate change-associated cardiovascular risk, particularly in vulnerable populations.