Vallabhajosyula, Saraschandra

Introduction: The management of asymptomatic severe aortic stenosis (AS) is controversial and guidelines for the management of the same is not updated based on recently available evidence. Hypothesis: The main objective is to determine the optimal strategy for the management of asymptomatic severe AS between early intervention versus conservative management. Methods: We performed a systematic electronic search of the PubMed and Cochrane databases from the inception of the database to May 31 st , 2020. We used the Mantel Haenszel method with the Paule-Mandel estimator of Tau 2 and Hartung-Knapp adjustment to calculate relative risk (RR) with a 95% confidence interval (CI) and 95% prediction interval (PI). We used P curve analysis to assess publication bias and estimate the true effect of an intervention. All analysis was carried out using R version 3.6.2. Results: A total of seven studies were included in the final analysis, consisting of 1213 patients with early intervention and 2601 patients with conservative management. Early intervention as compared to conservative management was associated with reduced risk of all-cause mortality (RR: 0.32, 95% CI: 0.21-0.48) (Panel A) , cardiac mortality (RR: 0.36, 95% CI: 0.27-0.48) (Panel B) and non-cardiac mortality (RR: 0.40, 95% CI: 0.28-0.56) (Panel C) . There was no difference in the risk of sudden cardiac death (RR: 0.46, 95% CI: 0.15-1.40), stroke (RR: 0.79, 95% CI: 0.17-3.64), myocardial infarction (RR: 0.44, 95% CI: 0.01-16.82) or heart failure hospitalization (RR: 0.18, 95% CI: 0.01-5.29) between the groups. The pooled estimate for all the outcomes was associated with low-moderate heterogeneity. Conclusions: Among asymptomatic severe AS patients, early intervention is associated with reduced mortality without increasing any procedure-related clinical outcomes. Hence, this meta-analysis supports early intervention as opposed to watchful waiting for the management of asymptomatic severe AS.

Introduction: Atrial Fibrillation (AF) has been associated with various behavioral risk factors such as tobacco, alcohol, and/or substance abuse. Hypothesis: The main objective is to describe the national trends and burden of tobacco and substance abuse in AF hospitalizations. Methods: The National Inpatient Sample database from 2007 to 2015 was utilized and the hospitalizations with AF were identified using the international classification of disease, Ninth Revision, Clinical Modification (ICD-9-CM) code 427.31 in the primary diagnosis column. They were stratified into without abuse, tobacco use disorder (TUD), substance use disorder (SUD), alcohol use disorder (AUD), and drug use disorder (DUD). We used the Jonckheere-Terpstra trend test to analyze the trend in this study. Results: Out of 3,631,507 AF hospitalizations, 852,110 (23.46%) had TUD, 1851,170 (5.1%) had SUD, 155,681 (4.29%) had AUD and 42,667 (1.17%) had DUD. The trends of all increased substantially during the study period (Figure) . The prevalence of TUD, SUD, AUD, and DUD was substantially increased across all age groups, races, and gender during the study period. Female sex was associated with lower odds TUD (0.57 (0.56-0.57), P-value <0.001), SUD (0.27 (0.26-0.27), P-value <0.001), AUD (0.22 (0.22-0.22), P-value <0.001), and DUD (0.51 (0.5-0.52), P-value <0.001). Among AF hospitalizations, the black race was associated with higher odds of SUD (1.12 (1.1-1.14), P-value <0.001), and DUD(1.42 (1.38-1.47), P-value <0.001). The younger age group (18-35 years), male, Medicare/Medicaid as primary insurance, and lower socioeconomic status were associated with increased risk of both TUD and SUDs. Conclusions: Tobacco and substance use disorder among hospitalized AF patients in the US mainly affects males, younger individuals, white more than black, and those of lower socioeconomic status which demands the development of preventive strategies to address multilevel influences.

Introduction: Cardiovascular disease risks are significantly higher in patients with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS). There are limited data on the management and outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in patients with HIV/AIDS> Methods: A retrospective cohort of AMI-CS during 2000-2017 from the National Inpatient Sample was evaluated for concomitant HIV and AIDS. Outcomes of interest included in-hospital mortality, use of cardiac procedures, hospital length of stay, hospitalization costs, use of do-not-resuscitate (DNR) status, and palliative care use. A sub-group analysis was performed for those with and without AIDS within the HIV cohort. Results: A total 557,974 AMI-CS admissions were included, with HIV and AIDS in 1,321 (0.2%) and 985 (0.2%), respectively. The HIV cohort was younger (54.1 vs. 69.0 years), more often male, of non-white race, uninsured, from a lower socioeconomic status, and with higher comorbidity (all p <0.001). The HIV cohort had comparable multiorgan failure (37.8% vs. 39.0%) and cardiac arrest (28.7% vs. 27.4%) ( p >0.05). The cohorts with and without HIV had comparable rates of coronary angiography (70.2% vs. 69.0%; p =0.37), but less frequent early coronary angiography (hospital day zero) (39.1% vs. 42.5%; p <0.001). The cohort with HIV had comparable in-hospital mortality compared to those without (26.9% vs. 37.4%; adjusted odds ratio 1.04 [95% confidence interval 0.90-1.21]; p =0.61). The cohort with HIV had longer duration of hospitalization (10.8±10.1 vs 9.9±11.4 days), higher hospitalization costs (158±155 vs. 143±182 x1000 USD) and was discharged home (48.6% vs 41.8%) more often as compared to those without HIV (all p <0.005). In the HIV cohort, AIDS was associated with higher in-hospital mortality (28.8% vs. 21.1%; adjusted odds ratio 4.12 [95% confidence interval 1.89-9.00]; p <0.001). Secondary outcomes were relatively comparable between those with and without AIDS. Conclusions: The cohort with HIV had longer hospital stay and higher hospitalization costs; however these were comparable between those with and without AIDS.

Introduction: There is a paucity of contemporary data on the burden of intracranial hemorrhage (ICH) complicating acute myocardial infarction (AMI). Methods: The National Inpatient Sample database (2000 to 2017) was used to evaluate in-hospital burden of ICH in adult (>18 years) AMI admissions. In-hospital mortality, hospitalization costs, length of stay, and measure of functional ability were the outcomes of interest. The discharge destination along with use of tracheostomy and percutaneous endoscopic gastrostomy (PEG) were used to estimate functional burden. Results: Of a total 11,622,528 AMI admissions, 23,422 (0.2%) had concomitant ICH. Compared to those without, admissions with ICH were on average older, female, of non-White race, with greater comorbidities, and higher rates of arrhythmias (all p<0.001). Female sex, non-White race, ST-segment-elevation AMI presentation, use of fibrinolytics, mechanical circulatory support and invasive mechanical ventilation were identified as individual predictors of ICH. The AMI admissions with ICH received less frequent coronary angiography (46.9% vs. 63.8%), percutaneous coronary intervention (22.7% vs. 41.8%), and coronary artery bypass grafting (5.4% vs. 9.2%) as compared to those without (all p<0.001). ICH was associated with a significantly higher in-hospital mortality (41.4% vs. 6.1%; adjusted OR 5.65 [95% CI 5.47-5.84]; p<0.001), and adjusted temporal trends showed a steady decrease in in-hospital mortality over the 18-year period (Figure 1A). AMI-ICH admissions also had longer hospital length of stay, higher hospitalization costs, and greater use of PEG (all p<0.001). In AMI-ICH survivors (N=13, 689), 81.3% had a poor functional outcome indicating severe morbidity and temporal trends revealed a slight increase over the study period (Figure 1B). Conclusions: ICH causes a substantial burden in AMI due to associated higher in-hospital mortality, resource utilization, and poor functional outcomes.

Introduction: There are limited contemporary data on prevalence and outcomes of acute ischemic stroke (AIS) complicating acute myocardial infarction (AMI). Methods: Adult (>18 years) AMI admissions using the National Inpatient Sample database (2000-2017) were evaluated for in-hospital AIS. Outcomes of interest included in-hospital mortality, hospitalization costs, length of stay, and use of tracheostomy and percutaneous endoscopic gastrostomy (PEG). The discharge destination was used to classify AIS survivors into good and poor functional outcomes with poor (moderate to severe disability) defined as discharge to extended care facility including short-term hospital/rehabilitation facility, intermediate care or long-term care facilities. Results: Of a total 11,622,528 AMI admissions, 183,896 (1.6%) had concomitant AIS. Over the 18-year period, AIS rates were stable in STEMI admissions and decreased in NSTEMI (p<0.001). Compared to those without, the AIS cohort was on average older, female, of non-White race, with greater comorbidities, and higher rates of arrhythmias. The AMI-AIS admissions received less frequent coronary angiography (46.9% vs. 63.8%) and percutaneous coronary angiography (22.7% vs 41.8%) (p<0.001). Female sex, non-White race, higher comorbidity, ST-segment-elevation AMI presentation, atrial fibrillation/flutter, use of mechanical circulatory support and invasive mechanical ventilation were identified as individual predictors of AIS after AMI. The AIS cohort had higher in-hospital mortality (16.4% vs. 6.0%; adjusted OR 1.75 [95% CI 1.72-1.78]; p<0.001) with a steady decrease in the adjusted in-hospital mortality in over the 18-year period (21% in 2000 vs 17% in 2017). The AIS cohort had longer hospital length of stay, higher hospitalization costs, greater use of tracheostomy and PEG, and less frequent discharges to home (all p<0.001). In AMI-AIS survivors (N=153,318), 57.3% had a poor functional outcome with temporal trends showing a slight increase in recent years (57% in 2000 vs 62% in 2017). Conclusions: AIS is associated with significantly higher in-hospital mortality and poor functional outcomes in AMI admissions. Despite improvement in in-hospital mortality, poor functional outcomes remain high.

Background: Sex disparities exist in acute cardiovascular care. Despite sex-specific cardiac arrest (CA) research being identified as a priority by professional societies, there are limited studies on this topic. Objectives: To assess sex disparities in management and outcomes of CA complicating acute myocardial infarction (AMI) in a contemporary United States population. Methods: Adult admissions with a primary diagnosis of AMI and concomitant diagnosis of CA were identified using the National Inpatient Sample. Outcomes of interest included sex disparities in in-hospital mortality, coronary angiography (CAG), percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS) use. Results: Between January 1, 2000 and December 31, 2017, 11,622,528 admissions for AMI were identified, of which 584,216 (5.0%) were complicated by CA. Men had higher prevalence of CA compared to women (5.4% vs 4.4%, p< 0.001) in both STEMI and NSTEMI (2017 vs 2000, STEMI-men: 12.3% vs 7.8%, STEMI-women: 10.4% vs 7.5%, NSTEMI-men: 3.1% vs 2.7%, NSTEMI-women: 2.4% vs 2.5%). Women with AMI-CA were on average older (70.4 vs 65.0, p<0.001), of black race (12.6% vs 7.9%, p<0.001) and had higher comorbidity. Women were more likely to present with NSTEMI (36.4% vs 32.3%, p<0.001) and a non-shockable rhythm (47.6% vs 33.3%, p<0.001). Women less frequently received CAG (56.0% vs 66.2 %), early CAG (32.0% vs 40.2%), PCI (40.4% vs 49.7%), MCS (17.6% vs 22.0%), and CABG (all p<0.001). Women had significantly higher unadjusted in-hospital mortality (52.6% vs 40.6%, p < 0.001). In a multivariable logistic regression analysis, female sex was associated with higher in-hospital mortality (OR 1.13 [95% CI 1.11-1.14]; p< 0.001). When stratified by type of rhythm, type of AMI, presence of cardiogenic shock and location of CA, women consistently received less frequent CAG and experienced higher in-hospital mortality. Conclusion: In the largest 18-year study evaluating management and outcomes of CA in AMI, we identified the presence of significant sex disparities. Women with AMI-CA were older, with higher rates of non-shockable rhythm, were less likely to undergo therapeutic procedures including CAG, PCI, and MCS. Women had higher unadjusted and adjusted in-hospital mortality.

Background: Antidepressants are one of the most prescribed medications, particularly for patients with mental disorders. Nevertheless, there are still limited data regarding the risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) associated with these medications. Thus, we performed systemic review and meta-analysis to characterize the risks of VA and SCD among patients who used common antidepressants. Methods: A literature search for studies that reported risk of ventricular arrhythmias and sudden cardiac death in antidepressant use from MEDLINE, EMBASE, and Cochrane Database from inception through September 2020. A random-effects model network meta-analysis model was used to analyze the relation between antidepressants and VA/SCD. Surface Under Cumulative Ranking Curve (SUCRA) was used to rank the treatment for each outcome. Results: The mean study sample size was 355,158 subjects. Tricyclic antidepressant (TCA) patients were the least likely to develop ventricular arrhythmia events/sudden cardiac deaths at OR 0.24, 0.028–1.2, OR 0.32 (95% CI 0.038–1.6) for serotonin and norepinephrine reuptake inhibitors (SNRI), and OR 0.36 (95% CI 0.043, 1.8) for selective serotonin reuptake inhibitors (SSRI), respectively. According to SUCRA analysis, TCA was on a higher rank compared to SNRI and SSRI considering the risk of VA/SCD. Conclusion: Our network meta-analysis demonstrated the low risk of VA/SCD among patients using antidepressants for SNRI, SSRI and especially, TCA. Despite the relatively lowest VA/SCD in TCA, drug efficacy and other adverse effects should be taken into account in patients with mental disorders.

Background: Ranolazine has the potential to prevent atrial fibrillation (AF) and plays a role in rhythm control strategy for atrial fibrillation in various clinical settings. However, data on the use of ranolazine in patients with left ventricular (LV) systolic dysfunction are limited. The aims of this meta-analysis of randomized clinical trials are to investigate the efficacy and safety of ranolazine in AF patients with LV systolic dysfunction. PubMed and the Cochrane Database of Systematic Reviews were searched until July 2020. The efficacy outcomes included the incidence of new-onset AF, the rate of sinus rhythm restoration, and the time until sinus rhythm restoration. Safety endpoints were at death, and any adverse events were reported in the enrolled studies. We initially identified 204 studies and finally retrieved 5 RCTs. Three studies were analyzed in the meta-analysis. Among AF patients with LV systolic dysfunction, our meta-analysis showed that the combination of ranolazine to amiodarone significantly increased the sinus rhythm restoration rate compared to amiodarone alone (risk ratio (RR) 2.87, 95% confidence interval (CI) 2.48–3.32). Moreover, the time to sinus rhythm restoration was 2.46 h shorter in the ranolazine added to amiodarone group (95% CI: 2.27–2.64). No significant adverse events and proarrhythmias in the ranolazine group were identified. In conclusion, in AF patients with LV systolic dysfunction, ranolazine as an add-on therapy to amiodarone potentiates and accelerates the conversion of AF to sinus rhythm. Moreover, ranolazine shows good safety profiles. Further studies to investigate the effectiveness of ranolazine in the prevention of new-onset AF among patients with LV systolic dysfunction are needed.

Abstract Aims This study aims to evaluate the impact of the combination of cardiogenic shock (CS) and cardiac arrest (CA) complicating non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results Adult (&gt;18 years) NSTEMI admissions using the National Inpatient Sample database (2000 to 2017) were stratified by the presence of CA and/or CS. Outcomes of interest included in-hospital mortality, early coronary angiography, hospitalization costs, and length of stay. Of the 7 302 447 hospitalizations due to NSTEMI, 147 795 (2.0%) had CS only, 155 522 (2.1%) had CA only, and 41 360 (0.6%) had both CS and CA. Compared with 2000, the adjusted odds ratios (ORs) and 95% confidence interval (CIs) for CS, CA, and both CS and CA in 2017 were 3.75 (3.58–3.92), 1.46 (1.42–1.50), and 4.52 (4.16–4.87), respectively (all P &lt; 0.001). The CS + CA (61.2%) cohort had higher multiorgan failure than CS (42.3%) and CA only (32.0%) cohorts, P &lt; 0.001. The CA only cohort had lower rates of overall (52% vs. 59–60%) and early (17% vs. 18–27%) angiography compared with the other groups (all P &lt; 0.001). CS + CA admissions had higher in-hospital mortality compared with those with CS alone (aOR 4.12 [95% CI 4.00–4.24]), CA alone (aOR 1.69 [95% CI 1.65–1.74]), or without CS/CA (aOR 22.66 [95% CI 22.06–23.27]). The presence of CS, either alone or with CA, was associated with higher hospitalization costs and longer hospital length of stay. Conclusions The combination of CS and CA is associated with higher rates of acute non-cardiac organ failure and in-hospital mortality in NSTEMI admissions as compared with those with either CS or CA alone.

Racial disparities in utilization and outcomes of mechanical circulatory support (MCS) in patients with acute myocardial infarction-cardiogenic shock (AMI-CS) are infrequently studied. This study sought to evaluate racial disparities in the outcomes of MCS in AMI-CS. The National Inpatient Sample (2012–2017) was used to identify adult AMI-CS admissions receiving MCS support. MCS devices were classified as intra-aortic balloon pump (IABP), percutaneous left ventricular assist device (pLVAD) or extracorporeal membrane oxygenation (ECMO). Self-reported race was classified as white, black and others. Outcomes included in-hospital mortality, hospital length of stay and discharge disposition. During this period, 90,071 admissions were included with white, black and other races constituting 73.6%, 8.3% and 18.1%, respectively. Compared to white and other races, black race admissions were on average younger, female, with greater comorbidities, and non-cardiac organ failure (all p < 0.001). Compared to the white race (31.3%), in-hospital mortality was comparable in black (31.4%; adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.93–1.05); p = 0.60) and other (30.2%; aOR 0.96 (95% CI 0.92–1.01); p = 0.10). Higher in-hospital mortality was noted in non-white races with concomitant cardiac arrest, and those receiving ECMO support. Black admissions had longer lengths of hospital stay (12.1 ± 14.2, 10.3 ± 11.2, 10.9 ± 1.2 days) and transferred less often (12.6%, 14.2%, 13.9%) compared to white and other races (both p < 0.001). In conclusion, this study of AMI-CS admissions receiving MCS devices did not identify racial disparities in in-hospital mortality. Black admissions had longer hospital stay and were transferred less often. Further evaluation with granular data including angiographic and hemodynamic parameters is essential to rule out racial differences.