Deshmukh, Abhishek

Background: Different arrhythmias have been reported in patients with COVID-19 due to the complication of the disease, and medications used in the management of COVID-19. Remdesivir was approved by FDA for the management of COVID-19 patients in October 2020. There are several case reports suggesting remdesivir causing bradyarrhythmia in COVID-19 patients. Objective: To increase the knowledge and awareness among healthcare professions (HCPs) about the risk of arrhythmias associated with the use of remdesivir. Methods: We used the FDA Adverse Events Reporting System (FAERS) database to find bradyarrhythmia as a reported adverse event (AE) due to remdesivir until October,2021. Total 6,504 events were reported, out of which 5,996 (92.2%) were reported by HCPs. These AEs were included and further analyzed. Results: Out of 5,996 AEs reported with remdesivir, total 537 (9.0%) events were bradyarrhythmia. There were 74 (1.27%) events reported for atrial fibrillation, and 24 (0.04%) for ventricular tachycardia attributed to the use of remdesivir. Reported events of bradyarrhythmia were further divided and analyzed into men vs women, and different age groups of years 18-64, 65-85, >85. Total events of bradyarrhythmia among men (238, 6.5%) vs women (141, 6.4%) were not significantly different. Among all the age groups, more events were reported in younger women in the age group of 18-64 (12.3%) vs 65-85 (7.9%) vs >85 (6.9%). Conclusion: Multiple studies have shown COVID-19 associated tachyarrhythmias, likely secondary to the myocardial damage due to hypoxia. Few studies have also suggested bradyarrhythmias in these patients. Our analysis of the FAERS database also showed many reported AEs of bradyarrhythmia attributed to the use of remdesivir. Postulated mechanisms include; medication side effects, damage to the SA node as a complication of the COVID-19 disease process, and electrolyte imbalance due to the renal failure. Close surveillance of these patients with early diagnosis can lead to prompt discontinuation of the medication, which can further decrease the mortality related to bradyarrhythmias. Further studies are required to identify the at-risk population and to better understand the risk of bradyarrhythmia associated with remdesivir.

Background: Sacubitril-valsartan is a combination of a neprilysin inhibitor and an angiotensin II receptor blocker respectively. Sacubitril-valsartan has become a standard of care in the treatment of patients with Congestive Heart Failure (CHF) with reduced EF. During its clinical trials and upon review of U.S. Food and Drug Administration (FDA) approval, sacubitril-valsartan exhibited a side effect profile including hyperkalemia, hypotension, renal dysfunction, and angioedema. Recently, sacubitril-valsartan was also approved for the treatment of CHF patients with preserved EF. Objective: In view of new indications and increased usage, it is important to establish the updated safety profile of sacubitril-valsartan in the general population since the PARADIGM-HF trial. Methods: We explored reported Adverse Events (AEs) of sacubitril-valsartan using the FDA Adverse Event Reporting System. A total of 57,958 AEs were reported until August 2021. Total of 16,658 (28.7%) AEs were reported by HCPs, which were further analyzed. AEs were analyzed in men (56.7%) vs women (25.3%), and also in 3 age groups of 18-64, 65-85, >85. Results: Out of 16,658 AEs, the most frequently reported AE was hypotension (17.2%). Other commonly reported AEs were renal dysfunction (14.3%), allergic reactions including angioedema (10.8%), GI distress (8.8%), tachyarrhythmias (5.8%), hyperkalemia (4.5%), and cough (3.0%). Out of 16,658 AEs, 11,631 (69%) were deemed serious and 4,422 (26.5%) resulted in hospitalization. Deaths were attributed to 3,909 serious AEs (23.5%). In the age group of 18-64, events of atrial fibrillation were less among women compared to men (1% vs 3%), while total events of ventricular tachycardia were noted more among men compared to women (2% vs 0.5%). Conclusion: Most of the reported AEs were consistent with the observed AEs from PARADIGM-HF except for tachyarrhythmia. There are few reports documenting arrhythmias followed by the use of sacubitril-valsartan, however, the clear mechanism is unknown. Despite the wide use of sacubitril-valsartan, there is currently limited data on the safety profile. In future with the increasing use, further randomized controlled trials (RCTs) are needed to better understand the safety profile of the medication.

Introduction: In the last two decades, risk factors, prevalence, and mortality due to coronary artery disease in young adults is on the rise. Hypothesis: Assess the prevalence, trends, and economic burden of ventricular tachycardia (VT) in young adults (18-44 years). Methods: The Nationwide Inpatient Sample was explored for hospitalizations with VT in patients (Age 19-44) between 2005-2018 and divided among 3 groups of the quadrennial period using validated ICD-9 and ICD-10 CM codes. The Pearson chi-square test and Student’s t-test were used for categorical and continuous variables, respectively. We assessed the temporal trends of mortality in VT as well as trends of VT stratified by age, sex, and race by the linear-by-linear association test (Figure 1). Results: Out of 5,156,326 patients were admitted with VT between 2005-2018, 309,636 were in young adults. Among them, 102,433 were admitted between 2005-2009 (mean age 36.1±6.99; 61% male, 58.5% white), 109,591 between 2010-2014 (mean age 35.5±7.16; 59% male, 54.2% white), and 97,495 between 2015-2018 (mean age 35.4±7.00; 60% male, 52.3% white) (p<0.0001). In the young adults with VT, all-cause mortality was 7.37% from 2005-2009, 7.85% from 2010-2014 (6.5% relative increase from 2005-2009), and 8.98% from 2015-2018 (relative increase of 14.4% from 2010-2014) (p<0.0001). Inflation adjusted cost increased over the years [$12,177 in 2005-2009; $13,249 in 2010-2014; $15,807 in 2015-2018; p<0.0001)]. Conclusions: The prevalence of VT in young individuals is rising. VT-related mortality and healthcare utilization costs are on the rise in the study period. VT burden and poor outcomes were notable for Black males. Further studies are required for targeted screening and preventative measures in young adults.

Introduction: Real-world data on the significance of adding a defibrillator to cardiac resynchronization therapy (CRT-D) in patients with nonischemic cardiomyopathy (NICM) are limited. Hypothesis: CRT-D is associated with a lower risk of mortality and heart failure (HF) readmissions compared to CRT-P in NICM. Methods: We identified patients with NICM who underwent CRT-D and CRT without an ICD (CRT-P) by analyzing the nationwide readmission database from October 2015- December 2018 and using appropriate ICD-10 CM codes. Propensity score matching was performed to adjust for the confounders. Kaplan Meier curves were utilized for time to event analysis. Cox proportional hazard regression was used to generate hazard ratios. All-cause mortality at 6 months was the primary outcome whereas readmission due to HF and any other cause at 6 months were defined as secondary outcomes. Results: Post-PSM, 3054 patients with NICM underwent CRT-P, and 2863 patients underwent CRT-D placement. CRT-D did not show any benefit over CRT-P in reducing all-cause mortality at 6 months (2.92% vs. 2.79%, HR: 0.84, 95% CI: 0.61-1.16, p=0.29). Similarly, there was no difference in terms of readmissions due to other causes among both groups of patients (36.25% vs. 31.85%, HR: 0.98, 95% CI: 0.89-1.08, p=0.77). However, patients with CRT-P implantations had a lower risk of HF readmissions compared to the CRT-D group (10.05% vs. 14.25%, HR: 0.67, 95% CI: 0.58-0.79, p<0.0001). Conclusions: The addition of a defibrillator to CRT failed to show a survival benefit in patients with NICM. Moreover, HF readmissions were higher in CRT-D patients compared to CRT-P.

Introduction: Cardiac Sarcoidosis (CS) is a non-ischemic cardiomyopathy (NICM) characterized by infiltration of non-caseating granulomas involving in the heart with highly variable clinical manifestations. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its effectiveness in patients with CS. Hypothesis: We sought to determine if CRT improved cardiac remodeling and reduced hospitalizations in patients with CS. Methods: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at a Mayo Clinic site from 2000-2021. Baseline characteristics, echocardiographic parameters, heart failure hospitalization, and major adverse cardiac events (MACE) were assessed. Results: Our cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. At baseline, 38 (69.1%) patients had isolated CS, while 17 (30.9%) had evidence of CS with extra-cardiac sarcoidosis. The overwhelming majority underwent CRT-D implantation (n=52, 94.5%) with 67.3% of implanted devices upgrades from prior pacemaker or implantable cardioverter defibrillator. At 6 months post-implantation there was no significant different in ejection fraction (34.8 ± 10.9 % vs. 37.7 ± 14.2 %, p = 0.237), left ventricular end systolic diameter (49.1 ± 9.9 mm vs. 45.7 ± 9.9 mm, p = 0.077) or left ventricular end-diastolic diameter (58.5 ± 10.2 mm vs. 57.5 ± 8.1 mm, p = 0.574). Within the first 6 months post-implantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow up of 4.1 ± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent LVAD implantation and 7 (12.7%) patients died. Conclusions: Our findings suggest a poor response to CRT in patients with CS with no significant evidence of reverse remodeling within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

Background: Bariatric surgery (BS) has been shown to be beneficial in improving co-morbid conditions in morbidly obese patients. Long-term cardiovascular complications remain undefined and warrant further investigation. We examined the prevalence and risk of atrial fibrillation (AF) in obese patients who underwent BS. Methods: PUBMED/Medline, SCOPUS, EMBASE databases were systematically reviewed using relevant keywords to search prospective and retrospective studies reporting AF with long-term (at least >1-year follow-up) follow-up in patients who had undergone BS. Random effects models were used for meta-analysis and subgroup analysis. I 2 statistics was used to identify substantial (>75%) heterogeneity. Results: Nine studies (3 USA, 2 UK, 4 Sweden) including 24,164 patients who had undergone BS (mean BMI cut off: 35, mean age 42 years) with 29,330 controls were included in the analysis with a median follow-up of 8 years. Pooled prevalence of AF was lower in BS arm (3.0%, 95%CI: 1.4%-5%) as compared to non-BS arm (3.8%, 95% CI: 1.8%-5.0%). The Forest Plot (Fig. 1) depicts significantly reduced odds of having AF in patients who have undergone BS vs controls (OR: 0.74, 95%CI: 0.60-0.91, I 2 =70.2%, p<0.01). Sensitivity analysis using the leave-one-out method did confirm equivalent results. On subgroup analysis, AF prevalence in the BS group was slightly higher in studies with a mean age of ≥50 years (4.8%, 0-12%) as compared to cohorts with mean age <50 (2.0%, 1.4-5.0%). The pooled rate of AF was low on short-term follow-up compared to long-term follow-up after BS: 1.5% (0.9-2.5%) in 1-5 years, 1.9% (0.2-4.5%) in 6-10 years, 5.4% (0-13.9%) ≥10 years of BS. Conclusions: Obese patients undergoing BS had nearly 25% lower risk and lower pooled rate of AF when compared to controls over 8 years of follow-up. The protective effect of BS on reduced risk of AF was seen to gradually wane over longer follow-up which warrants continued efforts to effectively control CVD risk factors.

Introduction: Takotsubo cardiomyopathy (TTC) is diagnosed in 1-2% of the patients presenting with troponin positive suspected acute coronary syndromes(ACS). Rising trends of adverse events in patients with TTC, makes it imperative to explore causes and predictors of readmission in this patient population. Methods: National Readmission Data (NRD) 2013-14 was utilized to select study cohort. International Classification of Diseases, 9th Revision (ICD-9-CM) diagnostic code 429.83 was used to identify takotsubo cardiomyopathy. Admissions within 90 day of index admission were considered as early readmissions. Readmission etiologies were identified by ICD-9-CM code in primary diagnosis field of readmissions. Hierarchical multivariate models were used to evaluate predictors of early readmission. Results: A total of 12255 patients were identified during study period out of which 23.92% (n=2932 with 4224 readmissions) patients were readmitted within 90 days of discharge following index admission. Most common etiologies for readmission were cardiac (18.56%), respiratory (17.20%), GI renal (9.10%), infections (13.12%) and neurological complications (5.88%). Among cardiac complications acute heart failure was the most common etiology (7.48%). Highest number of readmissions happened on first day after discharge (n=125) and within 33 days after discharge, >50% of readmissions took place (n=2136). Conclusions: Patients with TTC are highly likely to be readmitted with first month after discharge, most likely secondary to cardiac or respiratory complications. These findings warrant close post discharge transition to reduce morbidity and improve health care outcomes.

Introduction: Catheter ablation is widely accepted intervention for atrial fibrillation (AF), but data is limited on contemporary trends in major complications and mortality due to the procedure. Methods: HCUP’s Nationwide inpatient sample (NIS) database was utilized from 2011-14 to identify the AF patients treated with Catheter Ablation using ICD-9- CM codes. χ 2 test was utilized to compare categorical variables, the student’s t-test for continuous variables and hierarchical mixed-effects logistic regression models for multivariate predictors of post-procedural complications. Results: In total 50,969 patients were identified undergoing AF ablation during the study period (37.6% female, 51.4 age ≥ 65). Overall complication rate was 5.5% with relative increase over study period (+56.4%, p < 0.001). In subgroup analysis of complication trends significant relative increase seen in respiratory (+352.7%, p < 0.001), neurological (+43.9%, p = 0.003) and vascular (+38.7%, p = 0.003) complications. While cardiac complications (+9.1%, p = 0.323) and In-hospital mortality (+ 60%, p = 0.173) showed insignificant change. On multivariate analysis of mortality and complication significant increased risk was associated with female gender (OR, 95% CI, p-value) (1.40, 1.17-1.68, p < 0.001), as well as higher comorbidity burden (CCI ≥ 1). While higher hospital volume (≥ 50 procedures) was associated with significantly decreased complication rates. Conclusions: Patients undergoing AF ablation showed an insignificant change in mortality, with increase trends of complication. Which was likely related to higher comorbidity burden over study period.

Background: There is lack of data regarding impact of atherectomy on the length of stay (LOS) and cost of hospitalization in lower extremity arterial revascularization. Methods: HCUP’s Nationwide Inpatient Sample (NIS) 2012 was queried using the ICD-9- CM code for peripheral vascular disease and procedural codes 39.90 (bare metal stent - BMS), 00.55 (drug eluting stent - DES), 17.56 (peripheral atherectomy) and 39.50 for angioplasty. Only procedures performed in patients ≥18 years of age were included. Hierarchical mixed effects linear regression models were generated to evaluate multivariate predictors of LOS and hospitalization costs. Results: A total of 13,206 (weighted: 66,030) lower extremity arterial revascularizations were identified (43.8% female & 65.5% white). Out of these, atherectomy was utilized in 23.2%. Atherectomy utilization was associated with significant reduction in LOS (4.96 ± 0.11 days vs. 5.78 ± 0.07 days, p <0.001) but higher hospitalization cost ($ 25196 ± 359 vs. $ 23408 ± 185, p < 0.001). Multivariate analysis showed similar results with decrease in LOS (-0.71 days, -1.00 - - 0.43; p < 0.001) but higher hospitalization cost (+1875 $, +811 - +2940; p = 0.001) with atherectomy, which was matched by propensity score analysis. Additionally, emergent/urgent & weekend admissions and Charlson score ≥2 were further associated with increased LOS and hospitalization costs. (Figure) Conclusion: Our study demonstrates that atherectomy utilization is associated with significant reduction in length of stay, which was counterbalanced by a slight increase in hospitalization costs following lower extremity arterial revascularization.

Introduction: Use of transcatheter endovascular stenting has been increasing in the treatment of Coarctation of Aorta (CoA). The present study was undertaken on adults with CoA undergoing stent placement from the period of 2000 to 2011 to analyze the relationship of hospital volume to the outcomes of stenting in adults with CoA. Methods: We queried Healthcare Cost and Utilization Project (HCUP)’s Nationwide Inpatient Sample (NIS) database from 2000 to 2011. Patients with CoA were identified using ICD-9-CM diagnosis code of 747.10. Patients≥18 years of age undergoing endovascular stenting were identified using ICD-9-CM procedure code of 39.90. Hospital volume was divided into two groups with ≥3 and <3 procedures annually. The outcomes studied were procedure-related complications, length of stay (LOS), and cost in relation to the hospital volume. Complications were coded using specific patient safety indicator codes released by HCUP. Length of stay (≤1 and >1 days) and cost (≤ $13,830 and > $13,830) were divided at median and included in regression analysis. Results: No in-hospital death was reported in either group. Hospitals with ≥3 procedures annually had significantly lower incidence of complications (9.50% vs. 23.01%) compared to the hospitals with <3 procedures annually (p=0.002). After multivariate regression analysis, compared to hospitals with <3 procedures annually, the hospitals with ≥3 procedures annually had odds ratio (OR) of 0.40 (95% CI: 0.19-0.82, p=0.013) for having any complications, OR of 0.67 (95% CI: 0.39-1.17, p=0.15) for having LOS>1 day, and OR of 0.72 (95% CI: 0.45-1.13, p=0.15) for having cost>$13,830. Conclusion: Stenting in adults for aortic coarctation is remarkably safe and the outcomes of the procedure have improved in centers with annual hospital volume of ≥3 procedures, and there is also decreasing trend of procedure-related complications, shorter hospital stay, and lower costs compared to centers with annual volume <3 procedures.