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Atrial fibrillation/flutter (AF) is the most common dysrhythmia in patients with hypertrophic cardiomyopathy (HCM). Unexplained left ventricular hypertrophy and left ventricular outflow tract obstruction are integral components of HCM pathology which can cause increased left atrial pressure and atrial myopathy contributing to the substrate for AF. We aimed to determine the impact of AF on hospital readmissions in patients with HCM. We conducted a retrospective analysis using the 2015 to 2019 Nationwide Readmission Database to analyze the effect of AF on 30-day readmission and causes of 30-day readmission in patients with HCM. We also determined the hospital, patient, and procedure-specific independent predictors of readmission in patients with HCM and AF. Of 191,235 index HCM hospitalizations, 81,390 (42.6%) had a secondary diagnosis of AF. A total of 16.9% of patients with HCM and AF were readmitted within 30 days as compared with 14% of HCM patients without AF. The presence of AF was independently associated with a higher risk of all-cause 30-day readmission (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.17 to 1.25, p <0.001). The foremost etiology of 30-day readmission in HCM patients with AF was hypertensive heart and chronic kidney disease with heart failure, whereas the foremost etiology of 30-day readmission in HCM patients without AF was sepsis. Interventions aimed toward AF management (electrical cardioversion: adjusted HR 0.91, 95% CI 0.82 to 1.01. p = 0.074, AF ablation: HR 0.92, 95% CI 0.74 to 1.13, p = 0.409, Watchman procedure: HR 1.50, 95% CI 0.16 to 14.6, p = 0.725) during index admission did not significantly impact the 30-day readmission in HCM patients with AF. Myectomy during index hospitalization (adjusted HR 0.54, 95% CI 0.34 to 0.86, p = 0.010) was most strongly associated with a lower risk of 30-day readmission in HCM patients with AF. In conclusion, in patients hospitalized for HCM, presence of AF was associated with excess risk of 30-day all-cause readmission. Interventions aimed toward HCM management, that is, myectomy rather than interventions aimed toward AF management predicted lower readmission rate in this patient population., Competing Interests: Declaration of competing interest Dr. Fudim has received support from National Heart, Lung, and Blood Institute grant K23HL151744, American Heart Association grant 20IPA35310955, the Mario Family Award, the Duke Chair's Award, the Translating Duke Health Award, Bayer, and BTG Specialty Pharmaceuticals; and has received consulting fees from AstraZeneca, Axon Therapies, CVRx, Daxor, Edwards Lifesciences, Galvani, and NXT Biomedical. Dr. Krasuski is serving as a consultant to Actelion/Janssen Pharmaceuticals, Bayer Pharmaceuticals, Gore Medical, and Medtronic. He receives research funding from the Adult Congenital Heart Association and Actelion. Dr. Khan has taken fees from Bayer. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest Dr. Greene has received research support from the Duke University Department of Medicine Chair's Research Award, American Heart Association (number 929502), National Heart Lung and Blood Institute, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards for Amgen, AstraZeneca, Boehringer Ingelheim/ Lilly, Bristol Myers Squibb, Cytokinetics, Roche Diagnostics, Sanofi, and scPharmaceuticals; serves as a consultant for Amgen, Bayer, Bristol Myers Squibb, Corteria Pharmaceuticals, CSL Vifor, Merck, PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim, cytokinetics, and Roche Diagnostics. The remaining authors have no competing interests to declare.

Chronic kidney disease (CKD) is a major co-morbidity in patients with heart failure (HF). There are limited contemporary data characterizing the clinical profile, inhospital outcomes, and resource use in patients hospitalized for HF with co-morbid CKD. We utilized a nationally representative population to address the knowledge gap. We examined the National Inpatient Sample 2004 to 2018 database to study the co-morbid profile, in-hospital mortality, clinical resource utilization, healthcare cost, and length of stay (LOS) in primary adult HF hospitalizations stratified by presence versus absence of a diagnosis codes of CKD. There were a total of 16,050,301 adult hospitalizations with a primary HF diagnosis from January 1, 2004, to December 31, 2018. Of these, 428,175 (33.81%) had CKD; 1,110,778 (6.92%) had end-stage kidney disease (ESKD); and 9,511,348 (59.25%) had no diagnosis of CKD. Patients with hospitalizations for HF with ESKD were younger (mean age 65.4 years) compared with those without ESKD. In multivariable analysis, those with CKD had higher odds of inhospital mortality (2.82% vs 3.57%, adjusted odds ratio [aOR] 1.30, confidence interval [CI] 1.28 to 1.26, p <0.001), cardiogenic shock (1.01% vs 1.79% aOR 2.00, CI 1.95 to 2.05, p <0.001), and the need for mechanical circulatory support (0.4% vs 0.5%, aOR 1.51, 1.44 to 1.57, p <0.001) compared with those without CKD. In multivariable analysis, those with ESKD had higher odds of inhospital mortality (2.82% vs 3.84%, aOR 2.07, CI 2.01 to 2.12, p <0.001), need for invasive mechanical ventilation use (2.04% vs 3.94%, aOR 1.79, CI 1.75 to 1.84, p <0.001), cardiac arrest (0.72% vs 1.54%, aOR 2.09, CI 2.00 to 2.17, p <0.001), longer LOS (Adjusted mean difference 1.48, 1.44 to 1.53, p <0.001) and higher inflation-adjusted cost (Adjusted mean difference 3,411.63, CI 3,238.35 to 3,584.91, p <0.001) compared with those without CKD. CKD and ESKD affected about 40.7% of all primary HF hospitalizations from 2004 to 2018. The inhospital mortality, clinical complications, LOS, and inflation-adjusted cost were higher in hospitalized patients with ESKD compared with patients with and without CKD. In addition, compared with those without CKD, hospitalized patients with CKD had higher inhospital mortality, clinical complications, LOS, and inflation-adjusted cost compared with patients with no diagnosis of CKD., Competing Interests: Declaration of Competing Interest Dr. Greene has received research support from the Duke University Department of Medicine Chair's Research Award, American Heart Association, National Heart Lung and Blood Institute, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck & Co., Inc., Novartis, Pfizer, and Sanofi; has served on advisory boards for Amgen, AstraZeneca, Boehringer Ingelheim/ Lilly, Bristol Myers Squibb, Cytokinetics, Roche Diagnostics, and Sanofi; serves as a consultant for Amgen, Bayer, Bristol Myers Squibb, Merck & Co., Inc., PhamaIN, Roche Diagnostics, Sanofi, Tricog Health, Urovant Pharmaceuticals, and Vifor; and has received speaker fees from Boehringer Ingelheim. Dr. Fudim was supported by the National Heart, Lung, and Blood Institute (NHLBI) (K23HL151744), the American Heart Association (20IPA35310955), Bayer, Bodyport, BTG Specialty Pharmaceuticals, and Verily. He receives consulting fees from Abbott, Alleviant, Audicor, AxonTherapies, Bayer, Bodyguide, Bodyport, Boston Scientific, Coridea, CVRx, Daxor, Deerfield Catalyst, Edwards Lifesciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, Medtronic, NXT Biomedical, Pharmacosmos, PreHealth, Shifamed, Splendo, Vironix, Viscardia, Zoll. Dr. Virani has received research support from the Department of Veterans Affairs, the National Institutes of Health, the World Heart Federation, Tahir, and the Jooma Family; and an honorarium from the American College of Cardiology (Associate Editor for Innovations, acc.org). The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Data are limited regarding the impact of ischemic cardiomyopathy (ICM) or non-ICM (NICM) on the trajectory of in-hospital decongestion among patients with acute decompensated heart failure (ADHF). Therefore, we aimed to assess the course of decongestion among patients admitted for ADHF by history of ICM and NICM. Patients included in the DOSE (Diuretic strategies in patients with acute decompensated heart failure), ROSE (ROSE acute heart failure randomized trial), and Ultrafiltration in decompensated heart failure with cardiorenal syndrome (CARRESS-HF) trials of patients with ADHF were categorized into ICM and NICM based on history. Among 762 patients included in our meta-analysis, 433 (56.8%) had a history of ICM. Patients with ICM were older (70.8 vs 63.9 years; p ≤0.001) and had higher rates of co-morbidities. After covariate adjustment, there was no significant differences between NICM and ICM regarding net fluid loss (4,952 vs 4,384 ml, p = 0.81) or mean change in serum N-terminal pro-brain natriuretic peptide (-2,162 vs -1,809 pg/ml, p = 0.092). Mean change in weight showed modest improvement in favor of patients with NICM, but this did not meet statistical significance (-8.24 vs -7.70 pounds, p = 0.068). After adjustment, there was no significant difference in the risk of 60-day composite all-cause mortality or hospitalization for HF among those with ICM versus NICM. Among patients with left ventricular ejection fraction <40%, NICM was associated with higher scoring on global sense of well-being (global visual analog scale; +25.5 vs +19.1, p = 0.023) and improvement in serum creatinine (-0.031 mg/100 ml vs +0.042 mg/100 ml, p = 0.009) at 72 hours. Among patients with left ventricular ejection fraction >40%, NICM was associated with decreased scoring on global visual analog scale at 72 hours (+15.7 vs +21.2, p = 0.049). In conclusion, more than half of the patients admitted for ADHF had ICM. History of ICM was not independently associated with a difference in course of decongestion, self-assessment of well-being and dyspnea, or short-term clinical outcomes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The purpose of this research was to study the contemporary trends in cardiovascular disease (CVD) and diabetes mellitus (DM)-related mortality., Methods: We used the Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database to identify adults ≥25 years old where both CVD and DM were listed as an underlying or contributing cause of death between 1999 and 2019. Crude and age-adjusted mortality rates per 100,000 population were determined., Results: The overall age-adjusted mortality rate was 99.18 in 1999 and 91.43 in 2019, with a recent increase from 2014-2019 (annual percent change 1.0; 95% confidence interval [CI], 0.3-1.6). Age-adjusted mortality rate was higher for males compared with females, with increasing mortality in males between 2014 and 2019 (annual percent change 1.5; 95% CI, 0.9-2.0). Age-adjusted mortality rate was highest for non-Hispanic Black adults and was ∼2-fold higher compared with non-Hispanic White adults. Young and middle-aged adults (25-69 years) had increasing age-adjusted mortality rates in recent years. There were significant urban-rural disparities, and age-adjusted mortality rates in rural counties increased from 2014 to 2019 (annual percent change 2.2; 95% CI, 1.5-2.9); states in the 90 th percentile of mortality had age-adjusted mortality rates that were ∼2-fold higher than those in the bottom 10 th percentile of mortality., Conclusion: After an initial decrease in DM + CVD-related mortality for a decade, this trend has reversed, with increasing mortality from 2014 to 2019. Significant geographic and demographic disparities persist, requiring targeted health policy interventions to prevent the loss of years of progress., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although obesity is associated with increased phenotypic expression in patients with hypertrophic cardiomyopathy (HC), the effect of body mass index (BMI) on in-hospital mortality in hospitalized patients with HC has not been established. We evaluated the National Inpatient Sample in the United States to identify all adults with HC hospitalized for cardiac illnesses between 2008 and 2017. Using International Classification of Diseases codes, the study cohort was stratified into underweight (BMI ≤19.9 kg/m 2 ), normal weight (BMI 20.0 to 24.9 kg/m 2 ), overweight (BMI 25.0 to 29.9 kg/m 2 ), class I (BMI 30.0 to 34.9 kg/m 2 ), class II (BMI 35.0 to 39.9 kg/m 2 ), and class III (BMI ≥40.0 kg/m 2 ) obesity. Multiple logistic regression analysis was used to analyze the independent association of various BMI categories and mortality. The study included a total of 2,392,325 hospitalizations (mean age-66.1 ± 12.2 years; 42.0% female). The patients with class III obesity (adjusted mortality rate [AMR] 3.3%, adjusted odds ratio [AOR] 1.53, 95% confidence interval [CI] 1.29 to 1.82, p <0.001) and underweight patients (AMR 4.4%, AOR 2.07, 95% CI 1.74-2.46, p <0.001) had higher in-hospital mortality whereas overweight patients (AMR 1.6%, AOR 0.26, 95% CI 0.19 to 0.34, p <0.001), patients with class I obesity (AMR 0.8%, AOR 0.35, 95% CI 0.27 to 0.45, p <0.001) and patients with class II obesity (AMR 0.8%, AOR 0.34, 95% CI 0.26 to 0.45, p <0.001) had lower mortality compared with patients with normal BMI (AMR 2.9%). In conclusion, BMI has a nonlinear U-shaped relation with in-hospital mortality in patients with HC. The patients who were underweight and morbidly obese had significantly higher mortality, whereas those patients with overweight, class I, and class II obesity had lower mortality than normal BMI., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Data are limited on contemporary temporal trends in maternal characteristics and outcomes in hospitalized patients with peripartum cardiomyopathy (PC). We used the National Inpatient Sample database from January 1, 2004, to December 31, 2018, to identify PC hospitalizations in women aged 15 to 54 years. Weighted survey data were used to derive national estimates for the United States population and examine trends. Between 2004 and 2018, there was a total of 23,420 weighted hospitalizations for PC in women aged 15 to 54 years. The mean (standard error) age of this hospitalized PC population was 30.3 (0.1) years, with 44.6% White, 39.3% Black, 9.0% Hispanics, and 7.1% "Other" racial/ethnic groups. There was a nonsignificant increase in the PC hospitalization per 100,000 live births from 33.6 in 2004 to 42.4 in 2018 (p-trend = 0.06) over the study period, driven by a statistically significant increase in the younger women age group 15 to 35 years (p-trend = 0.04). The PC hospitalizations per 100,000 live births for women aged 36 to 54 years were more than double that observed in women aged 15 to 35 years (77.6 vs 33.5). PC hospitalizations were more than threefold greater in Black versus White women (103.5 vs 32.0 per 100,000 live births). Overall, inpatient mortality was 0.8%; the adjusted inpatient mortality showed a nonsignificant overall decrease from 1.1% in 2004 to 0.5% in 2018 (p-trend = 0.15). The overall mean length of stay was 4.6 days; the adjusted mean length of stay decreased from 5.8 days in 2004 to 4.6 days in 2018 (p-trend <0.01). In conclusion, there has been a nonsignificant increase in hospitalizations for PC, driven by an increasing rate of hospitalizations in younger women. The older maternal age group and Black patients had a higher proportional hospitalization as compared with the younger age group and White patients. There was a nonsignificant decrease in inpatient mortality., Competing Interests: Disclosures Outside of this work, Dr. Michos reports Advisory Boards with Novartis, Esperion, Amarin, and AstraZeneca. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Acute pericarditis is a frequent cause of hospitalization in the United States. Although recurrence of this condition is common, few studies have investigated hospital readmissions in this patient population., Methods: We queried the National Readmission Database for the years 2016 and 2017 to identify adult admissions for acute pericarditis, and analyzed the data for 30-day readmission. Using multivariate Cox regression analysis, we identified clinical characteristics that were independently predictive of hospital readmission within 30 days., Results: A total of 21,335 patients (mean age 52.5 ± 0.2 years; 38.3% women) who were discharged following hospitalization for acute pericarditis were included. The rate of 30-day readmission was 12.9% (n = 2740). Increasing age (adjusted hazard ratio [HR] 1.05 per 5-year increase; 95% confidence interval [CI], 1.02-1.09; P < 0.001), female sex (adjusted HR 1.33; 95% CI, 1.18-1.49; P < 0.001), dialysis dependence (adjusted HR 1.70; 95% CI, 1.30-2.22; P < 0.001), chronic obstructive pulmonary disease (adjusted HR 1.27; 95% CI, 1.11-1.45; P < 0.001), and presence of pericardial effusion (adjusted HR 1.24; 95% CI, 1.04-1.49; P = 0.02) were independently associated with a higher risk of readmission. In-hospital mortality was significantly higher after readmission than for the index hospitalization (3.4% vs 1.0%, P < 0.001)., Conclusion: After hospitalization for acute pericarditis, readmission within 30 days is common and is associated with increased mortality. Identification of characteristics associated with a higher risk of readmission may lead to focused interventions to improve outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The impact of body mass index (BMI) on cardiovascular outcomes in patients receiving intensive low-density lipoprotein cholesterol (LDL-C) lowering therapy is uncertain. We performed meta-analysis of 29 randomized controlled trials using PubMed, Embase, and CENTRAL through April 2019. Therapies were grouped as more intensive LDL-C lowering therapy (statins, ezetimibe + statin or PCSK9 inhibitors) and less intensive LDL-C lowering therapy (less potent active control or placebo). Random effects meta-regressions and meta-analyses were performed to evaluate association of BMI with cardiovascular endpoints. In 265,766 patients, for every 1 kg/m 2 increase in BMI, more intensive therapy compared with less intensive therapy was associated with hazard ratio (HR) of 1.07 for cardiovascular mortality (95% confidence interval 1.02 to 1.13); HR of 1.03 for all-cause mortality (0.99 to 1.06) HR of 1.06 for myocardial infarction (1.02 to 1.09), HR of 1.08 (1.03 to 1.12) for revascularization and HR of 1.04 for MACE (1.01 to 1.07). Meta-analysis showed that patients with BMI <25 kg/m 2 had the highest risk reduction in mortality and cardiovascular outcomes compared with patients with BMI ≥30 kg/m 2 (p-interaction ≤0.05). In conclusion, patients with normal BMI treated with intensive LDL-C lowering regimens may derive a larger clinical benefit compared with patients with larger BMI. The results could be due to the higher mortality rate of obese patients that may artificially lower the efficacy of therapy, or due to a true therapeutic limitation in these patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Mineralocorticoid receptor antagonists (MRA) improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and reduce risk of heart failure (HF) hospitalization in patients with heart failure with preserved ejection fraction (HFpEF). However, the benefit and risks of MRA use are not clear in HF patients and chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 . We conducted a systematic review evaluating the efficacy and safety of MRA in patients with HF and CKD. PubMed, Embase, and Cochrane Central databases were searched for relevant studies on patients with HF and reduced renal function (defined as eGFR <60 mL/min/1.73 m 2 ). Seven studies with 5,522 patients were included. We found 3 studies in patients with HFrEF, 1 study with HFpEF, and 2 in acute HF and 1 with mixed patient population of HF. Post hoc analyses from randomized controlled trials demonstrated reduction of risk in the primary end point (adverse cardiovascular outcomes and/or all-cause mortality and/or HF hospitalization) with MRA use in the CKD subgroup (eGFR 30 to 60 mL/min/1.73 m 2 ) despite a greater risk of hyperkalemia and higher rates of drug discontinuation. In 3 observational studies, propensity score matching was performed to compare patients treated with and without MRA and did not identify benefits, but conclusions from these studies were limited due to residual confounding and concern for bias. In conclusion, benefits of MRA use in HF appear to be consistent in patients with reduced renal function (eGFR 30 to 60 mL/min/1.73 m)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Restricting dietary sodium is a common recommendation given by clinicians to patients with heart failure and is one supported by current guidelines. However, the quality of evidence for this recommendation is suboptimal, and there is no consensus on the optimal level of sodium intake. Though excessive sodium intake is associated with left ventricular hypertrophy and hypertension, recent data have suggested that very low sodium intake is paradoxically associated with worse outcomes for patients with heart failure. This is possibly explained by the association between low sodium intake and activation of the sympathetic and renin-angiotensin-aldosterone systems. Nevertheless, sodium restriction is routinely recommended and remains a cornerstone of heart failure and blood pressure therapy. In this review we discuss the pros and cons of sodium restriction for patients with heart failure from the current literature., (Copyright © 2019. Published by Elsevier Inc.)

Globalization of clinical trials has prompted significant interest in assessing regional variation in patient characteristics and treatment effects. Although the placebo effect overall has been well described, it is not known whether differences in placebo effect exist in countries. The objective of this study was to assess the country-level differences in placebo effect. We undertook an exploratory post-hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial. The main outcomes were changes in the overall summary score (OSS) and clinical summary score (CSS) of the Kansas City Cardiomyopathy Questionnaire at 4, 12, 24, 36, 48, and 60 months. Of 1,723 subjects who were randomized to the placebo arm, 33.6% were enrolled from United States, 9.3% from Canada, 31.2% from Russia, 4.7% from Brazil, 3.5% from Argentina, and 17.7% from Georgia. Although patients from Georgia had the lowest (p <0.001) OSS and CSS at baseline, they had the highest improvement (>10 points) in CSS at all time points compared with other countries (p <0.001). Patients enrolled in Georgia had more than 3 times the improvement in OSS compared with patients in United States and Canada. Patients enrolled in Argentina had significantly (p <0.001) higher improvement in OSS and CSS at all time points compared with other countries, except Georgia. Greater than 10 points improvement in OSS was observed in patients from Argentina at all time points, which was more than 2-fold improvement seen in patients from United States and Canada. In conclusion, there were significant variations in longitudinal changes in Kansas City Cardiomyopathy Questionnaire scores in countries in patients receiving placebo., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Patients with diabetes mellitus (DM) are known to have reduced life expectancy and be at increased risk for multiple morbidities including serious infection. However, published data on DM outcomes after left ventricular assist device (LVAD) implantation are sparse, inconsistent and individual studies are small with limited power. We conducted a systematic review and meta-analysis to compare survival and adverse events post-LVAD in DM versus non-DM (NDM) patients. Medline, Scopus, and Cochrane Central databases were searched for studies comparing outcomes in DM and NDM patients who underwent LVAD implantation for advanced heart failure. Results were reported as random effect risk ratios (RR) with 95% confidence intervals. We identified 5 retrospective cohort studies, at low risk of bias, reporting on 1,351 patients (n = 488 DM). There was increased 30-day mortality (RR 1.57 [1.00, 2.47]; p = 0.05; I 2  = 0%) among DM versus NDM. The DM and NDM groups did not differ significantly in terms of 1-year mortality (RR 1.15 [0.98, 1.35]; p = 0.08; I 2  = 39%), device-related infection (RR 1.05 [0.92, 1.19]; p = 0.88; I 2  = 0%), ischemic stroke (RR 1.29 [0.91, 1.83]; p = 0.69; I 2  = 0%), hemorrhagic stroke (RR 1.10 [0.42, 2.83]; p = 0.85; I 2  = 69%), or bleeding (RR 1.06 [0.80, 1.40]; p = 0.70; I 2  = 27%). After LVAD implantation, patients with DM, versus patients without, have a modestly elevated 30-day mortality rate. However, 1-year mortality and morbidity did not differ., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Patients having transcatheter aortic valve implantation (TAVI) routinely undergo coronary angiography before the procedure to define the coronary anatomy and to evaluate the extend of coronary artery disease (CAD). Whether percutaneous coronary intervention (PCI) prior/concomitant with TAVI confers any additional clinical benefit in patients with CAD remains unclear. Literature search was performed using Medline, Embase, Google Scholar, and Scopus from inception of these databases till April 2019. Included outcomes were 30-day all-cause mortality, stroke, myocardial infarction (MI), acute kidney injury, and 1-year mortality. The main summary estimate was random effects odds ratio (OR) with 95% confidence intervals (CIs). Eleven cohort studies enrolling 5,580 patients (mean age 82.4 years and 52.6% females) were included. Our study found no difference in effect estimates for 30-day all-cause mortality (OR 1.30 [0.85 to 1.98], p = 0.22, I 2  = 37.5%), stroke (OR 0.7 (0.36 to 1.45), p = 0.36, I 2  = 32.8%), MI (OR 2.71 [0.55 to 12.23], p = 0.22, I 2  = 41.3%), acute kidney injury (OR 0.7 [0.46 to 1.06], p = 0.08, I 2  = 14.4%) and 1-year all-cause mortality (OR 1.19 [0.92 to 1.52], p = 0.18, I 2  = 0.0%) in patients who underwent TAVI with and without PCI. In conclusion, our analysis indicates that PCI with TAVI in patients with severe aortic stenosis and concomitant CAD grants no additional clinical advantage in terms of patient important clinical outcomes. Further randomized studies are needed to better delineate the clinical practice for myocardial revascularization in patients receiving transcatheter therapy for aortic valve disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Temporal and surgical risk dependent associations with clinical outcomes in patients receiving transcatheter versus surgical aortic valve implantation (TAVI vs SAVI) are uncertain. In this meta-analysis, 7 randomized controlled trials (7,771 patients) were included to investigate trends in outcomes in TAVI versus SAVI up to 5 years, and variation in outcomes with respect to low-, intermediate-, and high-surgical risk of the patients up to 1 year. Estimates were calculated as random effects hazard ratios (HRs) with 95% confidence intervals (CI). All-cause mortality was similar in TAVI and SAVI at 30 days (HR 0.81, 95% CI 0.55 to 1.21, p = 0.31), 1 year (HR 0.97, 95% CI 0.89 to 1.06, p = 0.49), 2 years (HR 0.96, 95 CI 0.85 to 1.09, p = 0.54), and 5 years (HR 1.04, 95% CI 0.89 to 1.21, p = 0.62). Cardiac mortality, myocardial infarction and stroke were similar in both interventions up to 5 years. TAVI was associated with lower risk of atrial fibrillation, but higher risk of vascular complications, pacemaker implantation, and paravalvular leak up to 5 years. The lower risks of major bleeding and acute kidney injury with TAVI versus SAVI were limited to 1 and 2 years, respectively. Compared with SAVI, TAVI was superior in reducing all-cause mortality in low surgical risk patients at 30 days only, whereas TAVI was noninferior to SAVI in intermediate- and high-risk patients at 30 days and across all risks at 1 year. In conclusion, TAVI was noninferior to SAVI in terms of mortality, myocardial infarction, and stroke up to 5 years. TAVI improved survival versus SAVI in low-risk patients at 30 days., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The effect of preoperative atrial fibrillation (AF) on clinical outcomes after left ventricular assist device (LVAD) implantation remains uncertain. We sought to conduct a meta-analysis to assess the safety and efficacy of LVAD implantation in AF patients. Medline and Scopus were searched for studies that assessed the effect of preoperative AF on clinical outcomes in patients who underwent LVAD implantation. Outcomes of interest included all-cause mortality, thromboembolic events, and bleeding. Estimates were combined using random effects model to calculate risk ratios (RRs) with 95% confidence intervals. In this meta-analysis of 7 studies including 5,658 patients, preoperative AF was not associated with increased risk of all-cause mortality at 30 days (RR = 0.84 [0.51, 1.37]; p = 0.49; I 2  = 0%), 6 months (RR = 1.17 [0.96, 1.14]; p = 0.11; I 2  = 21%), 1 year (RR = 1.16 [0.84, 1.60]; p = 0.37; I 2  = 53%) and 2 years (RR = 1.14 [0.96, 1.36]; p = 0.12; I 2  = 23%). Preoperative AF did not increase the risk of thromboembolism (RR = 0.86 [0.38, 1.92]; p = 0.71; I 2  = 26%), pump thrombosis (RR = 1.22 [0.88, 1.68]; p = 0.23; I 2  = 49%), stroke (RR = 1.02 [0.87, 1.19]; p = 0.79; I 2  = 11%), or major bleeding (RR = 0.86 [0.38, 1.92]; p = 0.71; I 2  = 26%) after LVAD implantation. However, AF was associated with significantly increased risk of gastro-intestinal bleeding in patients receiving LVADs (RR = 1.27 [1.05, 1.55]; p = 0.014; I 2  = 0%). In conclusion, this meta-analysis reports a significantly increased risk of gastrointestinal (GI) bleeding in LVADs recipients having concomitant AF. However, AF had no significant effect on all-cause mortality, stroke, or thromboembolic events in these patients. Further well-conducted studies are needed to validate these results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cardiogenic shock (CS) after a myocardial infarction continues to be associated with high mortality. Whether percutaneous coronary intervention (PCI) of noninfarct coronary arteries (multivessel intervention [MVI]) improves outcomes in CS after acute myocardial infarction (AMI) remains controversial. MEDLINE, Cochrane CENTRAL, and Scopus databases were searched for original studies comparing MVI with culprit-vessel intervention (CVI) in AMI patients with multivessel disease and CS. Risk ratios (RRs) and 95% confidence intervals were calculated and pooled using a random effects model. Thirteen studies, consisting of 7,906 patients (n MVI  = 1,937; n CVI  = 5,969), were included in this meta-analysis. Overall, the MVI and CVI groups did not differ significantly in the risk of short-term mortality (RR: 1.06 [0.91, 1.23]; p = 0.45; I 2  = 75.82%), long-term mortality (RR: 0.93 [0.78, 1.11]; p = 0.37; I 2  = 67.92%), reinfarction (RR: 1.16 [0.75, 1.79]; p = 0.50; I 2  = 0%), revascularization (RR: 0.84 [0.48, 1.47]; p = 0.54; I 2  = 83.01%), bleeding (RR: 1.15 [0.96, 1.38]; p = 0.09, I 2  = 0%), or stroke (RR: 1.29 [0.86, 1.94]; p = 0.80, I 2  = 0%). However, significantly increased risk of renal failure was seen in the MVI group (RR: 1.35 [1.10, 1.66]; p = 0.004; I 2  = 0%). On subgroup analysis, it was seen that results from retrospective studies showed higher short-term mortality in the MVI group in comparison with prospective studies (p = 0.003). The certainty in estimates is low due to the largely observational nature of the evidence. In conclusion, MVI provides no additional reduction in short- or long-term mortality in AMI patients with multivessel disease and CS. Additionally, the risk of renal failure may be higher with the use of MVI., (Copyright © 2018. Published by Elsevier Inc.)

Prognostic significance of coronary circulation dominance remains controversial. The primary objective of this meta-analysis was to pool all the available evidence to assess the influence of left coronary dominance (LD) on outcomes in patients who underwent percutaneous coronary intervention (PCI). MEDLINE, Cochrane CENTRAL, and Scopus databases were searched for all observational studies and randomized controlled trials that investigated the association between coronary dominance and outcomes in patients who underwent PCI. Odds ratios (OR) and 95% confidence intervals from individual studies were pooled using a random effects model. A total of nine studies including 266,119 patients were included. On pooled analysis, it was noted that LD was associated with significantly increased odds of in-hospital (OR: 1.54 [1.12, 2.11]; p = 0.007), 30-day (OR: 2.16 [1.22, 3.84]; p = 0.008), and long-term mortality (OR: 1.83 [1.33 to 2.50]; p < 0.001). LD patients also experienced a significantly higher incidence of major adverse cardiac events (OR: 1.27 [1.03, 1.58]; p = 0.03) and failed PCI (OR: 1.30 [1.03, 1.65]; p = 0.03). In contrast, no significant difference was noted between LD and non-LD patients in the incidence of stent thrombosis (OR: 1.28 [0.55, 3.01]; p = 0.57; I 2  = 0%) or reinfarction (OR: 1.73 [0.90, 3.35]; p = 0.10; I 2  = 63%). In conclusion, this meta-analysis suggests that patients with LD coronary anatomy are at significantly increased risk for mortality after PCI compared with patients with a non-LD anatomy., (Copyright © 2018. Published by Elsevier Inc.)

Contrast-induced acute kidney injury (CI-AKI) following coronary angiography is associated with increased mortality. The association between severity of anemia and CI-AKI following coronary angiography is not well-established. In this retrospective study, we aimed at assessing the association of anemia of various severity with the risk of CI-AKI in patients who underwent coronary angiography. We included all patients who underwent coronary angiography with or without percutaneous coronary intervention from January 2012 to December 2016 at a single tertiary care hospital. CI-AKI was defined as ≥0.3 mg/dL increase in creatinine from baseline and anemia was defined as baseline hemoglobin ≤13 g/dL. Patients were stratified into three subgroups-mild (11.1 to 13.0 g/dL), moderate (9.1 to 11.0 g/dL) and severe anemia (7.0 to 9.0 g/dL). Crude and adjusted odds ratios (AOR) were calculated using univariate multiple logistic regression analysis. Of 2,055 patients (females = 30.7%, mean age 58.0 ± 12.5 years) who underwent coronary angiography, 293 (14.3%) developed CI-AKI. Presence of anemia was associated with increased risk of developing CI-AKI (AOR = 5.3, 95% confidence interval [CI] = 3.8 to 7.3, p < 0.001). Risk of CI-AKI was increasingly higher with increasing severity of the anemia; mild (AOR = 3.4, 95% CI = 2.5 to 4.7, p < 0.001), moderate (AOR = 9.8, 95% CI = 6.9 to 14.2, p < 0.001) and severe (AOR = 13.7, 95% CI = 8.2 to 23.1, p < 0.001). In conclusion, severity of anemia is a strong predictor of CI-AKI following coronary angiography., (Copyright © 2018. Published by Elsevier Inc.)

ST-elevation myocardial infarction patients presenting at non-percutaneous coronary intervention (PCI)-capable hospitals often need to be transferred for primary percutaneous coronary intervention (PPCI). This increases time to revascularization, leading to increased risk of in-hospital mortality. With recent focus on total ischemic time rather than door-to-balloon time as the principal determinant of outcomes in ST-elevation myocardial infarction patients, pharmacoinvasive therapy (PIT) has gained attention as a possible improvement over PPCI in patients requiring transfer. Our objective was to observe how PIT stands against PPCI in terms of safety and efficacy. Electronic databases were searched for randomized controlled trials and observational studies comparing PPCI to PIT. PIT was defined as administration of thrombolytic drugs followed by immediate PCI only in case of failed thrombolysis. Results from studies were pooled using a random-effects model. We identified 17 relevant studies (6 randomized controlled trials, 11 observational studies) including 13,037 patients. Overall, there was no significant difference in short-term mortality (odds ratio [OR] = 1.20 [0.97 to 1.49]; I 2  = 14.2%; p = 0.099); however, PIT significantly decreased short-term mortality (OR = 1.46 [1.08 to 1.96]; I 2  = 0%; p = 0.01) in those studies with a symptom-onset-to-device time ≥200 minutes. There was a significantly lower risk reinfarction (OR = 0.69 [0.49 to 0.97]; I 2  = 0%; p = 0.033) in the PPCI group, while the risk of cardiogenic shock was significantly higher (OR = 1.48 [1.13 to 1.94]; I 2  = 0%; p = 0.005). In conclusion, PIT versus PPCI decisions should preferably be customized in patients presenting to non-PCI capable hospitals. Factors that need to be considered include symptom-onset to first medical contact time, expected time of transfer to a PCI-capable hospital, and patients risk factors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The categorization and characterization of pharmaceutical and device manufacturers or group purchasing organization payments to clinicians is an important step toward assessing conflicts of interest and the potential impact of these payments on practice patterns. Payments have not previously been compared among the subspecialties of cardiology. This is a retrospective analysis of the Open Payments database, including all installments and payments made to doctors in the calendar year 2015 by pharmaceutical and device manufacturers or group purchasing organization. Total payments to individual physicians were then aggregated based on specialty, geographic region, and payment type. The Gini Index was further employed to calculate within each specialty to measure income disparity. In 2015, a total of $166,089,335 was paid in 943,744 payments (average $175.00 per payment) to cardiologists, including 23,372 general cardiologists, 7,530 interventional cardiologists, and 2,293 cardiac electro-physiologists. Payments were mal-distributed across the 3 subspecialties of cardiology (p <0.01), with general cardiology receiving the largest number (73.5%) and total payments (62.6%) and cardiac electrophysiologists receiving significantly higher median payments ($1,662 vs $361 for all cardiologists; p <0.01). The Medtronic Company was the largest single payer for all 3 subspecialties. In conclusion, pharmaceutical and device manufacturers or group purchasing organizations continue to make substantial payments to cardiac practitioners with a significant variation in payments made to different cardiology subspecialists. The largest number and total payments are to general cardiologists, whereas the highest median payments are made to cardiac electrophysiologists. The impact of these payments on practice patterns remains to be examined., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Citation classics have been published in many fields of medicine; however, none have focused on interventional cardiology. The goal of this study was to identify the top 100 articles in the field of interventional cardiology and highlight their important trends and characteristics. The Scopus database was used by 2 independent reviewers to extract the top 100 articles using a variety of keywords. We found articles published between 1953 and 2012. Majority (n = 78) of the top 100 articles were published between 1996 and 2010, and the United States was affiliated with the highest number of articles in our list (n = 68). Over half (n = 54) the articles were funded. Private funding was correlated with higher citations (p = 0.036). A third (n = 33) of the papers had authors with conflicts of interest; however, conflict of interest had no effect on citations (p = 0.837). Majority (n = 57) of the articles studied coronary angioplasty and stenting; followed by coronary angiography (n = 14). Women were underrepresented, with only 11 female first authors in the top 100 papers, and only 1 female in the list of top authors who had 5 or more publications. In conclusion, the following features define the typical highly cited article in interventional cardiology-a clinical trial conducted in the United States, which studies angioplasty, and has been published relatively recently in a high-impact journal by a male first author., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Bibliometric analyses can help researchers and research funding agencies determine which areas of medicine need appropriate research attention. Citation classics of several specialties and subspecialties have been published; however, a literature search did not turn up any in the field of valvular heart disease (VHD). The main objective of this analysis was to overcome this paucity by identifying the top 100 cited articles in VHD and to assess their characteristics. We chose Scopus as our database, from where relevant articles were extracted after a thorough search by 2 independent researchers. A list of the top 100 cited articles was prepared, after which a detailed analysis of the list was conducted. The top-cited articles were published in the 63-year era starting from 1951, with the most articles published in the 10-year interval of 2001 to 2010. The citations of the articles ranged from 438 to 2,717 with a median of 609.5. Manuscripts from our top-cited list originated from 25 different countries. Most of the articles in the top 100 list were published in high-impact journals, with about a third of the articles published in Circulation (n = 27). Our study also reveals that the current focus of researchers in the field is on transcatheter aortic valve replacement, and therefore, funding in this area is likely to result in impactful studies. In conclusion, our study highlights the characteristics of high-impact articles in the field of VHD, and this information may be useful for investigators planning to conduct studies in this area of medicine in the future., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The prevalence of intolerance varies widely. Stopping statin therapy is associated with worse outcomes in patients with cardiovascular disease. Despite extensive studies, the benefits and risks of statins continue to be debated by clinicians and the lay public. We searched the PubMed, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials of statins compared with placebo. Studies were included if they had ≥1,000 participants, had patients who were followed up for ≥1 year, and reported rates of drug discontinuation. Studies were pooled as per the random effects model. A total of 22 studies (statins = 66,024, placebo = 63,656) met the inclusion criteria. The pooled analysis showed that, over a mean follow-up of 4.1 years, the rates of discontinuation were 13.3% (8,872 patients) for statin-treated patients and 13.9% (8,898 patients) for placebo-treated patients. The random effects model showed no significant difference between the placebo and statin arms (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.93 to 1.06). The results were similar for both primary prevention (OR = 0.98, 95% CI = 0.92 to 1.05, p = 0.39) and secondary prevention (OR = 0.92, 95% CI = 0.83 to 1.05, p = 0.43) studies. The pooled analysis suggested that the rates of myopathy were also similar between the statins and placebos (OR = 1.2, 95% CI = 0.88 to 1.62, p = 0.25). In conclusion, this meta-analysis of >125,000 patients suggests that the rate of drug discontinuation and myopathy does not significantly differ between statin- and placebo-treated patients in randomized controlled trials. These findings are limited by the heterogeneity of results, the variable duration of follow-up, and the lower doses of statins compared with contemporary clinical practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Conflicts of interests have long been recognized as potential sources of influence in the conduct and reporting of clinical trials. This controversy was again rekindled after the publication of the latest statin guidelines and a series of studies regarding competing interests in leading medical journals. We investigate the association between declared author conflicts and the outcomes of large cardiovascular trials. We searched the Medline (PubMed) database to identify "phase 2" and "phase 3" clinical trials using the search term "cardiovascular" over the past decade using "10 years" as the filter. We perceived the competing interest as present regardless of the nature such as consulting fees, honoraria, travel imbursements, stock holding, and employment. Of the 699 titles retrieved, 114 studies met the inclusion criteria. Nearly 80% of studies had at least a single author with competing interests. The 114 studies had a total of 1,433 investigators, of which 725 had declared conflicts of interests (50.6%). A total of 66 studies (58%) had half or >50 percent of investigators who had some conflicts of interests. Of these studies, 54 studies had favorable outcomes and only 12 had unfavorable outcomes (p <0.001). Among the type of competing interests, consulting or personal fees was the most common present in 58 investigators (51%). This was followed by research grants present in 55 the researchers (48%). Among 25 (22%) studies, at least one investigator reported stakes in the industry, of which only 2 studies had unfavorable outcomes for the intervention being investigated. Just 1 of the 25 clinical trials with a sample size of >1,000 had no investigators with competing interests. In conclusion, authors conflicts are associated with favorable outcomes in cardiovascular outcome trials., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The number of meta-analyses published annually has increased more than 20-fold between 1994 (n = 386) and 2014 (n = 8203). In examining how much of this increase in meta-analysis publication has genuinely represented novel contributions to clinical medicine and public health, it became clear that there was an abundance of redundant and disorganized meta-analyses, creating confusion and generating considerable debate. Ironically, meta-analyses, which should prevent redundant research, have become a victim of it. Recently, 17 meta-analyses were published based on the results of only 3 randomized controlled trials that studied the role of transcatheter closure of patent foramen ovale for prevention of cryptogenic stroke. In our search of the published literature, we identified at least 10 topics that were the subject of 10 meta-analyses. In the context of overlapping meta-analyses, one questions what needs to be done to put this "runaway train" back on track. In this review we examine the practice of redundant meta-analyses and the reasons for its disturbing "popularity." The registration of systematic reviews should be mandatory in prospective registries, such as PROSPERO, and the PRISMA checklist should be updated to incorporate new evidence and mandate the reference of previously published reviews and rationale for any new study., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Previous authors have suggested a higher likelihood for industry-sponsored (IS) studies to have positive outcomes than non-IS studies, though the influence of publication bias was believed to be a likely confounder. We attempted to control for the latter using a prepublication database to compare the primary outcome of recent trials based on sponsorship. We used the "advanced search" feature in the clinicaltrials.gov website to identify recently completed phase III studies involving the implementation of a pharmaceutical agent or device for which primary data were available. Studies were categorized as either National Institutes of Health (NIH) sponsored or IS. Results were labeled "favorable" if the results favored the intervention under investigation or "unfavorable" if the intervention fared worse than standard medical treatment. We also performed an independent literature search to identify the cardiovascular trials as a case example and again categorized them into IS versus NIH sponsored. A total of 226 studies sponsored by NIH were found. When these were compared with the latest 226 IS studies, it was found that IS studies were almost 4 times more likely to report a positive outcome (odds ratio [OR] 3.90, 95% confidence interval [CI] 2.6087 to 5.9680, p <0.0001). As a case example of a specialty, we also identified 25 NIH-sponsored and 215 IS cardiovascular trials, with most focusing on hypertension therapy (31.6%) and anticoagulation (17.9%). IS studies were 7 times more likely to report favorable outcomes (OR 7.54, 95% CI 2.19 to 25.94, p = 0.0014). They were also considerably less likely to report unfavorable outcomes (OR 0.11, 95% CI 0.04 to 0.26, p <0.0001). In conclusion, the outcomes of large clinical studies especially cardiovascular differ considerably on the basis of their funding source, and publication bias appears to have limited influence on these findings., (Copyright © 2015 Elsevier Inc. All rights reserved.)