Chahal, C. Anwar A.

Introduction: The impact of COVID-19 was felt across cardiology as resources were redirected to critical care, delaying elective cardiology procedures. Hypothesis: To evaluate differences in outcomes of cardiac implantable electronic device (CIED) procedures in 2020 (height of COVID) vs. 2016-2019 (pre-COVID). Methods: Adults >= 18 years undergoing CIED procedures were identified from National Inpatient Sample Databases (NIS) 2016-2020. Complications and mortality were assessed based on the type of device: Permanent Pacemaker (PPM); Implantable Cardioverter Defibrillator (ICD); Cardiac Resynchronization Therapy with Pacemaker (CRT-P) or defibrillator (CRT-D): Leadless PPM; Generator explant (GE), and Lead extraction (LE). Results: A 13.8% drop in CIED admissions was recorded between 2019 and 2020 (p<0.01). Fewer procedures involving PPM, ICD, CRT-P, CRT-D, LE, and GE were observed between 2019 and 2020. Leadless PPM utilization rose consistently between 2016-2020 (47.6% increase during 2020 vs 2019)(Figure). In 2020, a higher proportion of patients were classified with a Charlson Comorbidity Index score of ≥3 (severe) (47.4% in 2020 vs. 42.9% in 2016-2019, p<0.01). The table shows significantly higher complications during CIED implants with no changes in mortality related to procedures. Conclusions: Patients admitted for CIED implants in 2020 had more severe comorbidities and expressed considerable differences in complications than pre-COVID era (2016-2019), but mortality remained unchanged. Leadless PPM use increased during pandemic, as against a decrease in the use of other CIEDs.

Introduction: While Coronavirus disease 2019 (COVID-19) primarily affects the respiratory system but can impact the cardiovascular system can triggering various complications. Hypothesis: To investigate the trend in age-adjusted mortality rates (AAMRs) in patients with atrial fibrillation(AF) among COVID-19-positive patients (CPP) by race and sex. Methods: Trends in AAMRs (per 100,000) from all-cause in patients with AF between April to December 2016-2020 were evaluated via the National Inpatient Sample and the US Census Bureau. The AAMRs among CPP with AF in 2020 was also evaluated between racial and sex cohorts. Results: A gradual rise in AAMR(all causes) in patients with AF was observed between 2016-2019, with a 49.4% overall rise between 2019(271 per 100,000) and 2020(405 per 100,000) ( Table 1a and Figure ). Around 250475 COVID-19-positive patients had AF, and 24.2% of cases did not survive their hospitalization (vs. 10.9% in those without AF, p<0.01, aOR 1.457, 95% CI 1.438-1.477). Among CPP males and females with AF that died, White females and males were the oldest, while Black males and females reported the highest mean Charlson Comorbidity Index (CCI) score ( Table 1b ).Furthermore, among the CPP with AF in 2020, Hispanics reported a higher AAMR (119.6 per 100,000) than Whites(111.1 per 100,000) and Blacks(101.9 per 100,000). AAMRs in males were higher in Hispanic males (144.8 per 100,000), followed by White males (129.7 per 100,000), and Black males (110 per 100,000). However, the AAMRs in females were highest in Black females (91.3 per 100,000), followed by White females (88.3 per 100,000) and Hispanic females (87.0 per 100,000). ( Table 1c ) Conclusions: AAMRs in patients with AF are on the rise and a sharp growth was seen during the first year of the pandemic. AAMRs among CPP patients with AF were highest among Black females and Hispanic males, while White males and females were oldest and Black males and females reported the highest CCI scores.

Abstract Cardiac disease affects the heart non-uniformly. Examples include focal septal or apical hypertrophy with reduced strain in hypertrophic cardiomyopathy, replacement fibrosis with akinesia in an infarct-related coronary artery territory, and a pattern of scarring in dilated cardiomyopathy. The detail and versatility of cardiovascular magnetic resonance (CMR) imaging mean it contains a wealth of information imperceptible to the naked eye and not captured by standard global measures. CMR-derived heterogeneity biomarkers could facilitate early diagnosis, better risk stratification, and a more comprehensive prediction of treatment response. Small cohort and case–control studies demonstrate the feasibility of proof-of-concept structural and functional heterogeneity measures. Detailed radiomic analyses of different CMR sequences using open-source software delineate unique voxel patterns as hallmarks of histopathological changes. Meanwhile, measures of dispersion applied to emerging CMR strain sequences describe variable longitudinal, circumferential, and radial function across the myocardium. Two of the most promising heterogeneity measures are the mean absolute deviation of regional standard deviations on native T1 and T2 and the standard deviation of time to maximum regional radial wall motion, termed the tissue synchronization index in a 16-segment left ventricle model. Real-world limitations include the non-standardization of CMR imaging protocols across different centres and the testing of large numbers of radiomic features in small, inadequately powered patient samples. We, therefore, propose a three-step roadmap to benchmark novel heterogeneity biomarkers, including defining normal reference ranges, statistical modelling against diagnosis and outcomes in large epidemiological studies, and finally, comprehensive internal and external validations.

AbstractBackgroundCardiac tamponade (CT) can be a complication following invasive cardiac procedures. We assessed CT following common cardiac electrophysiology (EP) procedures to facilitate risk prediction of associated morbidity and in‐hospital mortality.MethodsPatients who underwent various EP procedures in the cardiac catheterization lab (ablations and device implantations) were identified using the International Classification of Diseases, Ninth and Tenth Edition, Clinical Modification (ICD‐9‐CM and ICD‐10‐CM, respectively) from the Nationwide Inpatient Sample (NIS) database. Patient demographics, presence of comorbidities, CT‐related events, and in‐hospital death were also abstracted from the NIS database.ResultsThe frequency of CT‐related events in patients with EP intervention from 2010 to 2017 ranged from 3.4% to 7.0%. In‐hospital mortality related to CT‐related events was found to be 2.2%. Increasing age was the only predictor of higher mortality in atrial fibrillation (AF) ablation and cardiac resynchronization therapy (CRT) groups (OR [95% CI]: AF ablation = 11.15 [1.70–73.34], p = .01; CRT = 1.41 [1.05–1.90], p = .02).ConclusionsIn the real‐world setting, CT‐related events in EP procedures were found to be 3.4%–7.0% with in‐hospital mortality of 2.2%. Older patients undergoing AF ablation were found to have higher mortality.

BACKGROUND: With genetic testing advancements, the burden of incidentally identified cardiac disease-associated gene variants is rising. These variants may carry a risk of sudden cardiac death, highlighting the need for accurate diagnostic interpretation. We sought to identify pathogenic hotspots in sudden cardiac death-associated genes using amino acid-level signal-to-noise (S:N) analysis and develop a web-based precision medicine tool, DiscoVari , to improve variant evaluation. METHODS: The minor allele frequency of putatively pathogenic variants was derived from cohort-based cardiomyopathy and channelopathy studies in the literature. We normalized disease-associated minor allele frequencies to rare variants in an ostensibly healthy population (Genome Aggregation Database) to calculate amino acid-level S:N. Amino acids with S:N above the gene-specific threshold were defined as hotspots. DiscoVari was built using JavaScript ES6 and using open-source JavaScript library ReactJS, web development framework Next.js, and JavaScript runtime NodeJS. We validated the ability of DiscoVari to identify pathogenic variants using variants from ClinVar and individuals clinically evaluated at the Duke University Hospitals with cardiac genetic testing. RESULTS: We developed DiscoVari as an internet-based tool for S:N-based variant hotspots. Upon validation, a higher proportion of ClinVar likely pathogenic/pathogenic variants localized to DiscoVari hotspots (43.1%) than likely benign/benign variants (17.8%; P< 0.0001). Further, 75.3% of ClinVar variants reclassified to likely pathogenic/pathogenic were in hotspots, compared with 41.3% of those reclassified as variants of uncertain significance ( P< 0.0001) and 23.4% of those reclassified as likely benign/benign ( P <0.0001). Of the clinical cohort variants, 73.1% of likely pathogenic/pathogenic were in hotspots, compared with 0.0% of likely benign/benign ( P< 0.01). CONCLUSIONS: DiscoVari reliably identifies disease-susceptible amino acid residues to evaluate variants by searching amino acid-specific S:N ratios.

Introduction: Cardiovascular complications are the main contributors towards morbidity and mortality in hemochromatosis. Iron overload can cause arrhythmias and heart failure (HF). There is a paucity of data on haemochromatosis and the burden of HF and its sequalae. Hypothesis: To determine characteristics of HF patients with and without haemochromatosis, and in-hospital outcomes (mortality, length of stay (LOS), mechanical circulatory support, and cardiac transplantation). Methods: Patients with HF, with and without hemochromatosis, were identified from the Nationwide Inpatient Sample Database. Results: Between 2016-2019, 2,940 (0.06%) of 4,823,994 HF patients had hemochromatosis. The hemochromatosis cohort was younger (mean age, 68 vs 71 years), predominantly men (63% vs 52%), White (77% vs 64%), and had less cardiovascular comorbidity burden (coronary artery disease (41% vs 51%), atrial fibrillation (45% vs 46%), hypertension (20% vs 24%), hyperlipidaemia (44% vs 53%), diabetes (42% vs 49%) and obesity (18% vs 25%), compared with HF patients without hemochromatosis (p<0.01 for all). However, hemochromatosis patients had a higher concomitant third degree atrio-ventricular block (1.2% vs 0.7%), ventricular tachycardia (7.8% vs 5.4%), ventricular fibrillation (0.5% vs 0.3%), chronic liver disease (24% vs 6%) and anemia (51% vs 37%) [p<0.01]. The hemochromatosis patients had a higher mean LOS (6.1 vs 5.4 days, p<0.01), need for mechanical circulatory support (0.9% vs 0.6%, p<0.01) and cardiac transplantation (0.2% vs 0.1%, p<0.01). Mortality (2.0% vs 2.7%, p=0.09) was comparable between the groups. Conclusion: Despite younger age and lower burden of cardiovascular comorbidities, patients with hemochromatosis had a higher burden of arrhythmias, need for mechanical circulatory support and cardiac transplantation and a higher LOS. This warrants the need to devise early management strategies for HF patients with hemochromatosis.

Introduction: Cardiac resynchronization therapy (CRT) has known benefit for heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and dyssynchrony. However, very little is known about its benefit in infiltrative cardiomyopathies such as cardiac amyloidosis (CA) due to relative rarity of these conditions. Methods: This retrospective case series (2003-2021) comprised patients with HF due to transthyretin wild-type CA with (case) or without (control) CRT implant. Only controls with an indication for CRT or LVEF <40% were included. To further match disease severity, cases were 1:1 matched (propensity score tolerance 0.04) to controls for age, NYHA class, and CA stage (UK Staging). Primary outcome was MACE (major adverse cardiac events) which included stroke, myocardial infarction, HF hospitalization and cardiac mortality during a 3-year follow-up. Loss to follow-up was censored as per last visit date. LVEF and NYHA were noted closest to 1-year follow-up. Survival analysis for MACE was performed with Kaplan-Meier (KM) and multivariable cox regression models. Results: Study Cohort (n=160) had a mean age of 75.5 (SD 7.8) years and 97.5% were males. A majority had NYHA class 2 or 3 (92.3%) and CA stage 2 (42.2.%). Notably, median LVEF at baseline was lower in controls (33.5 vs 36.5; P = .001) and 77.5% of controls had an indication for CRT device. A total of 79 MACE events occurred, most frequent being HF hospitalization (n=45). KM curves were comparable for MACE events in the two groups (log-rank test; P = .059). Even after adjusting, as in table, CRT device was not associated with MACE events (adjusted HR 0.66; 95% CI 0.40-1.09; P = .106). Lastly, change in LVEF ( P = .84) and NYHA ( P = .86) at follow-up was similar in cases vs controls. Conclusions: The findings of this largest yet observational study to examine this question suggest that CRT in patients with transthyretin wild-type CA does not favorably impact outcomes for MACE events, improve LVEF or NYHA functional class.