Publications by authors named "Ambarish Pandey"

297 Publications

The Future of AI-Enhanced ECG Interpretation for Valvular Heart Disease Screening.

J Am Coll Cardiol 2022 Aug;80(6):627-630

Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, Florida, USA.

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http://dx.doi.org/10.1016/j.jacc.2022.05.034DOI Listing
August 2022

Diffusion of Percutaneous Ventricular Assist Devices in US Markets.

Circ Cardiovasc Interv 2022 Jul 29:101161CIRCINTERVENTIONS121011778. Epub 2022 Jul 29.

Division of Cardiovascular Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (A.P., S.G.).

Background: Percutaneous ventricular assist devices (PVADs) have been replacing intra-aortic balloon pumps for hemodynamic support during percutaneous coronary intervention (PCI), even though data supporting a benefit for hard clinical end points remain limited. We evaluated diffusion of PVADs across US markets and examined the association of market utilization of PVAD with mortality and cost.

Methods: Using the 2013 to 2019 Medicare data, we identified all patients aged ≥65 years who underwent PCI with either a PVAD or intra-aortic balloon pump. We used hospital referral region to define regional health care markets and categorized them in quartiles based on the proportional use of PVADs during PCI. Multilevel models were constructed to determine the association of patient, hospital, and market factors with utilization of PVADs and the association of PVAD utilization with 30-day mortality and cost.

Results: A total of 79 176 patients underwent PCI with either intra-aortic balloon pump (47 514 [60.0%]) or PVAD (31 662 [40.0%]). The proportion of PCI procedures with PVAD increased over time (17% in 2013 to 57% in 2019; for trend, <0.001), such that PVADs overtook intra-aortic balloon pump for hemodynamic support during PCI in 2018. There was a large variation in PVAD utilization across markets (range, 0%-85%), which remained unchanged after adjustment of patient characteristics (median odds ratio, 2.05 [95% CI, 1.91-2.17]). The presence of acute myocardial infarction, cardiogenic shock, and emergent status was associated with a 45% to 50% lower odds of PVAD use suggesting that PVADs were less likely to be used in the sickest patients. Greater utilization of PVAD at the market level was not associated with lower risk mortality but was associated with higher cost.

Conclusions: Although utilization of PVADs for PCI continues to increase, there is large variation in PVAD utilization across markets. Greater market utilization of PVADs was not associated with lower mortality but was associated with higher cost.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.121.011778DOI Listing
July 2022

Supranormal Left Ventricular Ejection Fraction, Stroke Volume, and Cardiovascular Risk: Findings From Population-Based Cohort Studies.

JACC Heart Fail 2022 Aug;10(8):583-594

Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA. Electronic address:

Background: Supranormal ejection fraction by echocardiography in clinically referred patient populations has been associated with an increased risk of cardiovascular disease (CVD). The prognostic implication of supranormal left ventricular ejection fraction (LVEF)-assessed by cardiac magnetic resonance (CMR)-in healthy, community-dwelling individuals is unknown.

Objectives: The purpose of this study is to investigate the prognostic implication of supranormal LVEF as assessed by CMR and its inter-relationship with stroke volume among community-dwelling adults without CVD.

Methods: Participants from the MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) cohorts free of CVD who underwent CMR with LVEF above the normal CMR cutoff (≥57%) were included. The association between cohort-specific LVEF categories and risk of clinically adjudicated major adverse cardiovascular events (MACE) was assessed using adjusted Cox models. Subgroup analysis was also performed to evaluate the association of LVEF and risk of MACE among individuals stratified by left ventricular stroke volume index.

Results: The study included 4,703 participants from MESA and 2,287 from DHS with 727 and 151 MACE events, respectively. In adjusted Cox models, the risk of MACE was highest among individuals in LVEF Q4 (vs Q1) in both cohorts after accounting for potential confounders (MESA: HR = 1.27 [95% CI: 1.01-1.60], P = 0.04; DHS: HR = 1.72 [95% CI: 1.05-2.79], P = 0.03). A significant interaction was found between the continuous measures of LVEF and left ventricular stroke volume index (P interaction = 0.02) such that higher LVEF was significantly associated with an increased risk of MACE among individuals with low but not high stroke volume.

Conclusions: Among community-dwelling adults without CVD, LVEF in the supranormal range is associated with a higher risk of adverse cardiovascular outcomes, particularly in those with lower stroke volume.
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http://dx.doi.org/10.1016/j.jchf.2022.05.007DOI Listing
August 2022

Non-Alcoholic Fatty Liver Disease, Heart Failure, and Long-Term Mortality: Insights From the National Health and Nutrition Examination Survey.

Curr Probl Cardiol 2022 Jul 25:101333. Epub 2022 Jul 25.

Division of Cardiology, Duke University School of Medicine, Durham, NC, USA. Electronic address:

Objective: To evaluate the association between non-alcoholic fatty liver disease (NAFLD), heart failure (HF), and all-cause mortality.

Background: Both NAFLD and HF are increasing in prevalence due to shared risk factors.

Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 to identify non-pregnant individuals aged ≥20 years with HF and NAFLD and linked with the cause of death data from the National Center for Health Statistics. The associations between NAFLD, HF, and all-cause mortality were assessed using logistic regression and Cox proportional hazard modeling as appropriate.

Results: There were 82,358,893 weighted eligible participants of whom 3,833,667 (4.7%) had NAFLD. The mean (SE) age was 51.5 (0.35) years, 45.1% women, 63.0% Non-Hispanic White and 11.8% Non-Hispanic Black. Cardiovascular comorbidities were more common in participants with NAFLD; they were more likely to have hypertension (81.7% vs 53.5%), diabetes (65.1% vs 17.1%), stroke (7.3% vs 4.1%), coronary artery disease (14.9% vs 8.4%), or HF (10.5% v s 3.5%) compared with participants without NAFLD. In multivariate logistic regression models adjusting for age, race/ethnicity and sex, participants with NAFLD were 3.5 times more likely to have HF [aOR, 95% CI: 3.47 (1.98-6.06)]. Older age, male sex, presence of diabetes and coronary artery disease were associated with higher odds of HF in participants with established NAFLD. At the end of the follow-up period, participants with NAFLD had higher all-cause mortality compared with participants without NAFLD [HR(95% CI): 1.93 (1.24-2.99), p<0.001].

Conclusion: In this analysis of US adults, ambulatory participants with NAFLD were ∼3.5 times more likely to have HF, and twice as likely to experience mortality compared with participants without NAFLD. Further studies are needed to identify the possible linkage between NAFLD and HF beyond the shared risk factor pathogenesis.
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http://dx.doi.org/10.1016/j.cpcardiol.2022.101333DOI Listing
July 2022

Demographic and Regional Trends of Heart Failure-Related Mortality in Young Adults in the US, 1999-2019.

JAMA Cardiol 2022 Jul 27. Epub 2022 Jul 27.

Division of Cardiology, Duke University School of Medicine, Durham, North Carolina.

Importance: There are limited data on mortality trends in young adults with heart failure (HF).

Objective: To study the trends in HF-related mortality among young adults.

Design, Setting, And Participants: This retrospective cohort analysis used mortality data of young adults aged 15 to 44 years with HF listed as a contributing or underlying cause of death in the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1999 to December 2019. Analysis took place in October 2021.

Exposures: Age 15 to 44 years with HF listed as a contributing or underlying cause of death.

Main Outcomes And Measures: HF-related age-adjusted mortality rates (AAMR) per 100 000 US population stratified by sex, race and ethnicity, and geographic areas.

Results: Between 1999 and 2019, a total of 61 729 HF-related deaths occurred in young adults. Of these, 38 629 (62.0%) were men and 23 460 (38.0%) were women, and 22 156 (35.9%) were Black, 6648 (10.8%) were Hispanic, and 30 145 (48.8%) were White. The overall AAMR per 100 000 persons for HF in young adults increased from 2.36 in 1999 to 3.16 in 2019. HF mortality increased in young men and women, with men having higher AAMRs throughout the study period. AAMR increased for all race and ethnicity groups, with Black adults having the highest AAMRs (6.41 in 1999 and 8.58 in 2019). AAMR for Hispanic adults and White adults increased from 1.62 to 2.04 and 1.83 to 2.45 over the same time period, respectively. Across most demographic and regional subgroups, HF-related mortality stayed stable or decreased between 1999 and 2012, followed by an increase between 2012 and 2019. There were significant regional differences in the burden of HF-related mortality, with states in the upper 90th percentile of HF-related mortality (Oklahoma, South Carolina, Louisiana, Arkansas, Alabama, and Mississippi) having a significantly higher mortality burden compared with those in the bottom tenth percentile.

Conclusions And Relevance: Following an initial period of stability, HF-related mortality in young adults increased from 2012 to 2019 in the United States. Black adults have a 3-fold higher AAMR compared with White adults, with significant geographic variation. Targeted health policy measures are needed to address the rising burden of HF in young adults, with a focus on prevention, early diagnosis, and reduction in disparities.
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http://dx.doi.org/10.1001/jamacardio.2022.2213DOI Listing
July 2022

Should Polypills Be Used for Heart Failure With Reduced Ejection Fraction?

Circulation 2022 Jul 25;146(4):276-278. Epub 2022 Jul 25.

Division of Cardiology, Department of Medicine, UT Southwestern Medical Center, Dallas, TX.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.122.059661DOI Listing
July 2022

Prognostic significance of obstructive coronary artery disease in patients admitted with acute decompensated heart failure: the ARIC study community surveillance.

Eur J Heart Fail 2022 Jul 18. Epub 2022 Jul 18.

Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Chapel Hill, NC, USA.

Aims: We aimed to investigate the impact of obstructive coronary artery disease (CAD) in patients with acute decompensated heart failure (ADHF), and examine potential differences in prognostic utility for heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF).

Methods And Results: The Atherosclerosis Risk in Communities study conducted hospital surveillance of ADHF from 2005 to 2014. Obstructive CAD was defined as ≥50% or ≥75% stenosis, respectively, for the left main and other major epicardial arteries. Adjusted associations between obstructive CAD and 30-, 60-, and 90-day mortality were analysed. A total of 934 (4146 weighted) patients admitted with ADHF (mean age 72 years, 46% women, 30% Black, 30% HFpEF) had available angiography (61% performed in hospital). Obstructive CAD was more prevalent with HFrEF than HFpEF, whether at the left main (15% vs. 11%), left anterior descending (LAD) (48% vs. 30%), left circumflex (37% vs. 32%), right coronary (42% vs. 32%), or multiple coronary arteries (45% vs. 33%). In-hospital revascularization was performed in 25% and 22% of patients with HFrEF and HFpEF, respectively. Obstructive CAD was associated with higher adjusted mortality, particularly with left main or LAD involvement, and had a more pronounced association with 90-day mortality in HFrEF (odds ratio [OR] 2.77; 95% confidence interval [CI] 1.53-5.02) than HFpEF (OR 0.94; 95% CI 0.36-2.41) (p-interaction = 0.05).

Conclusion: Patients hospitalized with ADHF and coexisting obstructive CAD have higher short-term mortality, warranting the need for effective interventions and secondary prevention.
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http://dx.doi.org/10.1002/ejhf.2617DOI Listing
July 2022

Machine Learning-Based Models Incorporating Social Determinants of Health vs Traditional Models for Predicting In-Hospital Mortality in Patients With Heart Failure.

JAMA Cardiol 2022 Jul 6. Epub 2022 Jul 6.

Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas.

Importance: Traditional models for predicting in-hospital mortality for patients with heart failure (HF) have used logistic regression and do not account for social determinants of health (SDOH).

Objective: To develop and validate novel machine learning (ML) models for HF mortality that incorporate SDOH.

Design, Setting, And Participants: This retrospective study used the data from the Get With The Guidelines-Heart Failure (GWTG-HF) registry to identify HF hospitalizations between January 1, 2010, and December 31, 2020. The study included patients with acute decompensated HF who were hospitalized at the GWTG-HF participating centers during the study period. Data analysis was performed January 6, 2021, to April 26, 2022. External validation was performed in the hospitalization cohort from the Atherosclerosis Risk in Communities (ARIC) study between 2005 and 2014.

Main Outcomes And Measures: Random forest-based ML approaches were used to develop race-specific and race-agnostic models for predicting in-hospital mortality. Performance was assessed using C index (discrimination), regression slopes for observed vs predicted mortality rates (calibration), and decision curves for prognostic utility.

Results: The training data set included 123 634 hospitalized patients with HF who were enrolled in the GWTG-HF registry (mean [SD] age, 71 [13] years; 58 356 [47.2%] female individuals; 65 278 [52.8%] male individuals. Patients were analyzed in 2 categories: Black (23 453 [19.0%]) and non-Black (2121 [2.1%] Asian; 91 154 [91.0%] White, and 6906 [6.9%] other race and ethnicity). The ML models demonstrated excellent performance in the internal testing subset (n = 82 420) (C statistic, 0.81 for Black patients and 0.82 for non-Black patients) and in the real-world-like cohort with less than 50% missingness on covariates (n = 553 506; C statistic, 0.74 for Black patients and 0.75 for non-Black patients). In the external validation cohort (ARIC registry; n = 1205 Black patients and 2264 non-Black patients), ML models demonstrated high discrimination and adequate calibration (C statistic, 0.79 and 0.80, respectively). Furthermore, the performance of the ML models was superior to the traditional GWTG-HF risk score model (C index, 0.69 for both race groups) and other rederived logistic regression models using race as a covariate. The performance of the ML models was identical using the race-specific and race-agnostic approaches in the GWTG-HF and external validation cohorts. In the GWTG-HF cohort, the addition of zip code-level SDOH parameters to the ML model with clinical covariates only was associated with better discrimination, prognostic utility (assessed using decision curves), and model reclassification metrics in Black patients (net reclassification improvement, 0.22 [95% CI, 0.14-0.30]; P < .001) but not in non-Black patients.

Conclusions And Relevance: ML models for HF mortality demonstrated superior performance to the traditional and rederived logistic regressions models using race as a covariate. The addition of SDOH parameters improved the prognostic utility of prediction models in Black patients but not non-Black patients in the GWTG-HF registry.
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http://dx.doi.org/10.1001/jamacardio.2022.1900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260645PMC
July 2022

Association Between Thigh Muscle Fat Infiltration and Incident Heart Failure: The Health ABC Study.

JACC Heart Fail 2022 Jul;10(7):485-493

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address:

Background: Excess adiposity is a well-known risk factor for heart failure (HF). Fat accumulation in and around the peripheral skeletal muscle may further inform risk for HF.

Objectives: The purpose of this study was to evaluate the association between intramuscular and intermuscular fat deposition and incident HF in a longitudinal cohort of community-dwelling older adults.

Methods: The associations of intramuscular and intermuscular fat with incident HF were assessed using Cox models among 2,399 participants from the Health ABC (Health, Aging and Body Composition) study (70-79 years of age, 48% male, 40.2% Black) without baseline HF. Intramuscular fat was determined by bilateral thigh muscle density on computed tomography and intermuscular fat area was determined with computed tomography.

Results: After a median follow-up of 12.2 years, there were 485 incident HF events. Higher sex-specific tertiles of intramuscular and intermuscular fat were each associated with HF risk. After multivariable adjustment for age, sex, race, education, blood pressure, fasting blood sugar, current smoking, prevalent coronary disease, and creatinine, higher intramuscular fat, but not intermuscular fat, was associated with higher risk for HF (HR: 1.34 [95% CI: 1.06-1.69]; P = 0.012, tertile 3 vs tertile 1). This association remained significant after additional adjustment for body mass index (HR: 1.32 [95% CI: 1.03-1.69]), total percent fat (HR: 1.33 [95% CI: 1.03-1.72]), visceral fat (HR: 1.30 [95% CI: 1.01-1.65]), and indexed thigh muscle strength (HR: 1.30 [95% CI: 1.03-1.64]). The association between higher intramuscular fat and HF appeared specific to higher risk of incident HF with reduced ejection fraction (HR: 1.53 [95% CI: 1.03-2.29]), but not with HF with preserved ejection fraction (HR: 1.28 [95% CI: 0.82-1.98]).

Conclusions: Intramuscular, but not intermuscular, thigh muscle fat is independently associated with HF after adjustment for cardiometabolic risk factors and other measurements of adiposity.
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http://dx.doi.org/10.1016/j.jchf.2022.04.012DOI Listing
July 2022

Post-operative atrial fibrillation and risk of heart failure hospitalization.

Eur Heart J 2022 Jun 28. Epub 2022 Jun 28.

Division of Neurocritical Care, Weill Cornell Medicine, New York, NY, USA.

Aims: Post-operative atrial fibrillation (POAF) is associated with stroke and mortality. It is unknown if POAF is associated with subsequent heart failure (HF) hospitalization. This study aims to examine the association between POAF and incident HF hospitalization among patients undergoing cardiac and non-cardiac surgeries.

Methods And Results: A retrospective cohort study was conducted using all-payer administrative claims data that included all non-federal emergency department visits and acute care hospitalizations across 11 states in the USA. The study population included adults aged at least 18 years hospitalized for surgery without a prior diagnosis of HF. Cox proportional hazards regression models were used to examine the association between POAF and incident HF hospitalization after making adjustment for socio-demographics and comorbid conditions. Among 76 536 patients who underwent cardiac surgery, 14 365 (18.8%) developed incident POAF. In an adjusted Cox model, POAF was associated with incident HF hospitalization [hazard ratio (HR) 1.33; 95% confidence interval (CI) 1.25-1.41]. In a sensitivity analysis excluding HF within 1 year of surgery, POAF remained associated with incident HF hospitalization (HR 1.15; 95% CI 1.01-1.31). Among 2 929 854 patients who underwent non-cardiac surgery, 23 763 (0.8%) developed incident POAF. In an adjusted Cox model, POAF was again associated with incident HF hospitalization (HR 2.02; 95% CI 1.94-2.10), including in a sensitivity analysis excluding HF within 1 year of surgery (HR 1.49; 95% CI 1.38-1.61).

Conclusions: Post-operative atrial fibrillation is associated with incident HF hospitalization among patients without prior history of HF undergoing both cardiac and non-cardiac surgeries. These findings reinforce the adverse prognostic impact of POAF and suggest that POAF may be a marker for identifying patients with subclinical HF and those at elevated risk for HF.
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http://dx.doi.org/10.1093/eurheartj/ehac285DOI Listing
June 2022

Longitudinal Changes in Cardiac Troponin and Risk of Heart Failure Among Black Adults.

J Card Fail 2022 Jun 8. Epub 2022 Jun 8.

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address:

Background: Among Black adults, high-sensitivity cardiac troponin I (hs-cTnI) is associated with heart failure (HF) risk. The association of longitudinal changes in hs-cTnI with risk of incident HF, HF with reduced and preserved ejection fraction (HFrEF and HFpEF, respectively), among Black adults is not well-established.

Methods And Results: This study included Black participants from the Jackson Heart Study with available hs-cTnI data at visits 1 (2000-2004) and 2 (2005-2008) and no history of cardiovascular disease. Cox models were used to evaluate associations of categories of longitudinal change in hs-cTnI with incident HF risk. Among 2423 participants, 11.6% had incident elevation in hs-cTnI at visit 2, and 16.9% had stable or improved elevation (≤50% increase in hs-cTnI), and 4.0% had worsened hs-cTnI elevation (>50% increase). Over a median follow-up of 12.0 years, there were 139 incident HF hospitalizations (64 HFrEF, 58 HFpEF). Compared with participants without an elevated hs-cTnI, those with incident, stable or improved, or worsened hs-cTnI elevation had higher HF risk (adjusted hazard ratio 3.20 [95% confidence interval, 1.92-5.33]; adjusted hazard ratio 2.40, [95% confidence interval, 1.47-3.92]; and adjusted hazard ratio 8.10, [95% confidence interval, 4.74-13.83], respectively). Similar patterns of association were observed for risk of HFrEF and HFpEF.

Conclusions: Among Black adults, an increase in hs-cTnI levels on follow-up was associated with a higher HF risk.

Lay Summary: The present study included 2423 Black adults from the Jackson Heart Study with available biomarkers of cardiac injury and no history of cardiovascular disease at visits 1 and 2. The majority of participants did not have evidence of cardiac injury at both visits (67.5%), 11.6% had evidence of cardiac injury only on follow-up, 14.5% had stable elevations, 4.0% had worsened elevations, and 2.4% had improved elevations of cardiac injury biomarkers during follow-up. Compared with participants without evidence of cardiac injury, those with new, stable, and worsened levels of cardiac injury had a higher risk of developing heart failure.

Tweet: Among Black adults, persistent or worsening subclinical myocardial injury is associated with an elevated risk of HF.
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http://dx.doi.org/10.1016/j.cardfail.2022.05.013DOI Listing
June 2022

Forecasting Heart Failure Risk in Diabetes.

J Am Coll Cardiol 2022 06;79(23):2294-2297

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1016/j.jacc.2022.04.011DOI Listing
June 2022

Validation of the WATCH-DM and TRS-HF Risk Scores to Predict the Risk of Incident Hospitalization for Heart Failure Among Adults With Type 2 Diabetes: A Multicohort Analysis.

J Am Heart Assoc 2022 06 3;11(11):e024094. Epub 2022 Jun 3.

Division of Cardiology Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX.

Background The WATCH-DM (weight [body mass index], age, hypertension, creatinine, high-density lipoprotein cholesterol, diabetes control [fasting plasma glucose], ECG QRS duration, myocardial infarction, and coronary artery bypass grafting) and TRS-HF (Thrombolysis in Myocardial Infarction [TIMI] risk score for heart failure in diabetes) risk scores were developed to predict risk of heart failure (HF) among individuals with type 2 diabetes. WATCH-DM was developed to predict incident HF, whereas TRS-HF predicts HF hospitalization among patients with and without a prior HF history. We evaluated the model performance of both scores to predict incident HF events among patients with type 2 diabetes and no history of HF hospitalization across different cohorts and clinical settings with varying baseline risk. Methods and Results Incident HF risk was estimated by the integer-based WATCH-DM and TRS-HF scores in participants with type 2 diabetes free of baseline HF from 2 randomized clinical trials (TECOS [Trial Evaluating Cardiovascular Outcomes With Sitagliptin], N=12 028; and Look AHEAD [Look Action for Health in Diabetes] trial, N=4867). The integer-based WATCH-DM score was also validated in electronic health record data from a single large health care system (N=7475). Model discrimination was assessed by the Harrell concordance index and calibration by the Greenwood-Nam-D'Agostino statistic. HF incidence rate was 7.5, 3.9, and 4.1 per 1000 person-years in the TECOS, Look AHEAD trial, and electronic health record cohorts, respectively. Integer-based WATCH-DM and TRS-HF scores had similar discrimination and calibration for predicting 5-year HF risk in the Look AHEAD trial cohort (concordance indexes=0.70; Greenwood-Nam-D'Agostino >0.30 for both). Both scores had lower discrimination and underpredicted HF risk in the TECOS cohort (concordance indexes=0.65 and 0.66, respectively; Greenwood-Nam-D'Agostino <0.001 for both). In the electronic health record cohort, the integer-based WATCH-DM score demonstrated a concordance index of 0.73 with adequate calibration (Greenwood-Nam-D'Agostino =0.96). TRS-HF score could not be validated in the electronic health record because of unavailability of data on urine albumin/creatinine ratio in most patients in the contemporary clinical practice. Conclusions The WATCH-DM and TRS-HF risk scores can discriminate risk of HF among intermediate-risk populations with type 2 diabetes.
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http://dx.doi.org/10.1161/JAHA.121.024094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238735PMC
June 2022

Frailty Status Modifies the Efficacy of Exercise Training Among Patients With Chronic Heart Failure and Reduced Ejection Fraction: An Analysis From the HF-ACTION Trial.

Circulation 2022 Jul 26;146(2):80-90. Epub 2022 May 26.

Cardiovascular Medicine and Geriatrics Sections, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC (D.K.).

Background: Supervised aerobic exercise training (ET) is recommended for stable outpatients with heart failure (HF) with reduced ejection fraction (HFrEF). Frailty, a syndrome characterized by increased vulnerability and decreased physiologic reserve, is common in patients with HFrEF and associated with a higher risk of adverse outcomes. The effect modification of baseline frailty on the efficacy of aerobic ET in HFrEF is not known.

Methods: Stable outpatients with HFrEF randomized to aerobic ET versus usual care in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial were included. Baseline frailty was estimated using the Rockwood frailty index (FI), a deficit accumulation-based model of frailty assessment; participants with FI scores >0.21 were identified as frail. Multivariable Cox proportional hazard models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether frailty modified the treatment effect of aerobic ET on the primary composite end point (all-cause hospitalization or mortality), secondary end points (composite of cardiovascular death or cardiovascular hospitalization, and cardiovascular death or HF hospitalization), and Kansas City Cardiomyopathy Questionnaire score. Separate models were constructed for continuous (FI) and categorical (frail versus not frail) measures of frailty.

Results: Among 2130 study participants (age, 59±13 years; 28% women), 1266 (59%) were characterized as frail (FI>0.21). Baseline frailty burden significantly modified the treatment effect of aerobic ET ( interaction: FI × treatment arm=0.02; frail status [frail versus nonfrail] × treatment arm=0.04) with a lower risk of primary end point in frail (hazard ratio [HR], 0.83 [95% CI, 0.72-0.95]) but not nonfrail (HR, 1.04 [95% CI, 0.87-1.25]) participants. The favorable effect of aerobic ET among frail participants was driven by a significant reduction in the risk of all-cause hospitalization (HR, 0.84 [95% CI, 0.72-0.99]). The treatment effect of aerobic ET on all-cause mortality and other secondary endpoints was not different between frail and nonfrail patients ( interaction>0.1 for each). Aerobic ET was associated with a nominally greater improvement in Kansas City Cardiomyopathy Questionnaire scores at 3 months among frail versus nonfrail participants without a significant treatment interaction by frailty status ( interaction>0.2).

Conclusions: Among patients with chronic stable HFrEF, baseline frailty modified the treatment effect of aerobic ET with a greater reduction in the risk of all-cause hospitalization but not mortality.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.122.059983DOI Listing
July 2022

Mediators of ertugliflozin effects on heart failure and kidney outcomes among patients with type 2 diabetes mellitus.

Diabetes Obes Metab 2022 Sep 15;24(9):1829-1839. Epub 2022 Jun 15.

Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Aims: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the risk of hospitalization for heart failure (HHF) and composite kidney outcomes, but the mediators underlying these benefits are unknown.

Materials And Methods: Among participants from VERTIS CV, a trial of patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease randomized to ertugliflozin versus placebo, Cox proportional hazards regression models were used to evaluate the percentage mediation of ertugliflozin efficacy on the first HHF and kidney composite outcome in 26 potential mediators. Time-dependent approaches were used to evaluate associations between early (change from baseline to the first post-baseline measurement) and average (weighted average of change from baseline using all post-baseline measurements) changes in covariates with clinical outcomes.

Results: For the HHF analyses, early changes in four biomarkers (haemoglobin, haematocrit, serum albumin and urate) and average changes in seven biomarkers (early biomarkers + weight, chloride and serum protein) were identified as fulfilling the criteria as mediators of ertugliflozin effects on the risk of HHF. Similar results were observed for the composite kidney outcome, with early changes in four biomarkers (glycated haemoglobin, haemoglobin, haematocrit and urate), and average changes in five biomarkers [early biomarkers (not glycated haemoglobin) + weight, serum albumin] mediating the effects of ertugliflozin on the kidney outcome.

Conclusions: In these analyses from the VERTIS CV trial, markers of volume status and haemoconcentration and/or haematopoiesis were the strongest mediators of the effect of ertugliflozin on reducing risk of HHF and composite kidney outcomes in the early and average change periods.

Clinicaltrials:

Gov Identifier: NCT01986881.
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http://dx.doi.org/10.1111/dom.14769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357198PMC
September 2022

The need for increased pragmatism in cardiovascular clinical trials.

Nat Rev Cardiol 2022 May 17. Epub 2022 May 17.

Division of Cardiology, Duke University School of Medicine, Durham, NC, USA.

The majority of cardiovascular randomized controlled trials (RCTs) test interventions in selected patient populations under explicitly protocol-defined settings. Although these 'explanatory' trial designs optimize conditions to test the efficacy and safety of an intervention, they limit the generalizability of trial findings in broader clinical settings. The concept of 'pragmatism' in RCTs addresses this concern by providing counterbalance to the more idealized situation underpinning explanatory RCTs and optimizing effectiveness over efficacy. The central tenets of pragmatism in RCTs are to test interventions in routine clinical settings, with patients who are representative of broad clinical practice, and to reduce the burden on investigators and participants by minimizing the number of trial visits and the intensity of trial-based testing. Pragmatic evaluation of interventions is particularly important in cardiovascular diseases, where the risk of death among patients has remained fairly stable over the past few decades despite the development of new therapeutic interventions. Pragmatic RCTs can help to reveal the 'real-world' effectiveness of therapeutic interventions and elucidate barriers to their implementation. In this Review, we discuss the attributes of pragmatism in RCT design, conduct and interpretation as well as the general need for increased pragmatism in cardiovascular RCTs. We also summarize current challenges and potential solutions to the implementation of pragmatism in RCTs and highlight selected ongoing and completed cardiovascular RCTs with pragmatic trial designs.
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http://dx.doi.org/10.1038/s41569-022-00705-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112643PMC
May 2022

Trends in HF Hospitalizations Among Young Adults in the United States From 2004 to 2018.

JACC Heart Fail 2022 05;10(5):350-362

Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA. Electronic address:

Objectives: The aim of this study was to assess trends in heart failure (HF) hospitalizations among young adults.

Background: Data are limited regarding clinical characteristics and outcomes of young adults hospitalized for HF.

Methods: The National Inpatient Sample database was analyzed to identify adults aged 18 to 45 years who were hospitalized for HF between 2004 and 2018.

Results: In total, 767,180 weighted hospitalizations for HF in young adults were identified, equivalent to 4.32 (95% CI: 4.31-4.33) per 10,000 person-years. Overall HF hospitalizations per 10,000 U.S. population of young adults decreased from 2.43 in 2004 to 1.82 in 2012, followed by an increase to 2.51 in 2018. Black adults (50.1%) had a significantly higher proportion of HF hospitalizations compared with White (31.9%) and Hispanic adults (12.2%) throughout the study period. Nearly half of patients (45.8%) lived in zip codes in the lowest quartile of national household income. Overall, in-hospital mortality was 1.3%, which decreased over time; this trend was consistent by sex and race. The overall mean LOS (5.2 days) remained stable over time, while the mean inflation-adjusted cost increased from $12,449 in 2004 to $16,786 in 2018, with significant overall differences by race and sex.

Conclusions: This longitudinal examination of U.S. clinical practice revealed that HF hospitalizations among young adults have increased since 2013. Approximately half of these patients are Black and reside in zip codes in the lowest quartile of national household income. Temporal trends showed decreased in-hospital mortality, stable adjusted lengths of stay, and increased inflation-adjusted costs, with significant racial differences in hospitalization rates.
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http://dx.doi.org/10.1016/j.jchf.2022.01.021DOI Listing
May 2022

Association of Baseline and Longitudinal Changes in Frailty Burden and Risk of Heart Failure in Type 2 Diabetes - Findings from the Look AHEAD Trial.

J Gerontol A Biol Sci Med Sci 2022 Apr 22. Epub 2022 Apr 22.

Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC.

Background: Individuals with diabetes have a high frailty burden and increased risk of heart failure (HF). In this study, we evaluated the association of baseline and longitudinal changes in frailty with risk of HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF).

Methods: Participants (age: 45-76 years) of the Look AHEAD trial without prevalent HF were included. The frailty index (FI) was used to assess frailty burden using a 35-variable deficit model. The association between baseline and longitudinal changes (1-year, 4-year follow-up) in FI with risk of overall HF, HFpEF (ejection fraction (EF)≥50%)], and HFrEF (EF<50%) independent of other risk factors and cardiorespiratory fitness was assessed using adjusted Cox models.

Results: The study included 5,100 participants, of which 257 developed HF. In adjusted analysis, higher frailty burden was significantly associated with a greater risk of overall HF. Among HF subtypes, higher baseline FI was significantly associated with risk of HFpEF (HR[95% CI] per 1-SD higher FI: 1.37[1.15-1.63]) but not HFrEF (HR[95% CI]: 1.19[0.96-1.46]) after adjustment for potential confounders, including traditional HF risk factors. Among participants with repeat measures of FI at 1-year and 4-year follow-up, an increase in frailty burden was associated with a higher risk of HFpEF (HR[95%CI] per 1-SD increase in FI at 4-year: 1.78[1.35-2.34]) but not HFrEF after adjustment for other confounders.

Conclusions: Among individuals with T2DM, higher baseline frailty and worsening frailty burden over time were independently associated with higher risk of HF, particularly HFpEF after adjustment for other confounders.
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http://dx.doi.org/10.1093/gerona/glac094DOI Listing
April 2022

Long-Term Cardiovascular Outcomes After Bariatric Surgery in the Medicare Population.

J Am Coll Cardiol 2022 04;79(15):1429-1437

Heart, Vascular and Thoracic Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Background: The long-term effect of bariatric surgery on cardiovascular outcomes in the elderly population is not well studied.

Objectives: The aim of this study was to evaluate the association between bariatric surgery and long-term cardiovascular outcomes in the Medicare population.

Methods: Medicare beneficiaries who underwent bariatric surgery from 2013 to 2019 were matched to a control group of patients with obesity with a 1:1 exact matching based on age, sex, body mass index, and propensity score matching on 87 clinical variables. The study outcomes included all-cause mortality, new-onset heart failure (HF), myocardial infarction (MI), and ischemic stroke. An instrumental variable analysis was performed as a sensitivity analysis.

Results: The study cohort included 189,770 patients (94,885 matched patients in each group). By study design, the 2 groups had similar age (mean: 62.33 ± 10.62 years), sex (70% female), and degree of obesity (mean body mass index: 44.7 ± 7.3 kg/m) and were well balanced on all clinical variables. After a median follow-up of 4.0 years (IQR: 2.4-5.7 years), bariatric surgery was associated with a lower risk of mortality (9.2 vs 14.7 per 1,000 person-years; HR: 0.63; 95% CI: 0.60-0.66), new-onset HF (HR: 0.46; 95% CI: 0.44-0.49), MI (HR: 0.63; 95% CI: 0.59-0.68), and stroke (HR: 0.71; 95%: CI: 0.65-0.79) (P < 0.001). The benefit of bariatric surgery was evident in patients who were 65 years and older. Using instrumental variable analysis, bariatric surgery was associated with a lower risk of mortality, HF, and MI.

Conclusions: Among Medicare beneficiaries with obesity, bariatric surgery is associated with lower risk of mortality, new-onset HF, and MI.
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http://dx.doi.org/10.1016/j.jacc.2022.01.047DOI Listing
April 2022

Association of Non-Alcoholic Fatty Liver Disease With in-Hospital Outcomes in Primary Heart Failure Hospitalizations With Reduced or Preserved Ejection Fraction.

Curr Probl Cardiol 2022 Apr 9:101199. Epub 2022 Apr 9.

Division of Cardiology, Department of Medicine, Duke University, Durham, NC; Department of Cardiology, Duke Clinical Research Institute, Durham, NC.

Recent studies focusing on the prevalence, characteristics, and outcomes of primary heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) in non-alcoholic fatty liver disease (NAFLD) are sparse. We sought to assess these using a nationally-representative population. We used the 2016-2018 National Inpatient Sample database to study the prevalence, characteristics, clinical risk profiles, morbidity, mortality, cost, and resource utilization among primary HFpEF and HFrEF hospitalizations with and without NAFLD. In the period from January 1, 2016, to December 31, 2018, there were 3,522,459 admissions of patients aged ≥18 years with a diagnosis of primary HF. Of these, 82,585 (2.3%) hospitalizations had secondary diagnosis of NAFLD. Admissions with NAFLD and HFrEF were associated with higher rates of in-hospital mortality (aOR 1.84, CI 1.66-2.04, P < 0.001) compared to admissions of HFrEF without NAFLD. Similarly, hospitalizations with HFpEF-NAFLD were associated with higher rates of in hospital mortality (aOR 1.65 CI 1.43-1.9, P < 0.001) compared to HFpEF admissions without NAFLD. Pressors use, cardiogenic shock, AKI with or without dialysis use, cardiac arrest, LOS and hospitalization cost were higher in admissions of HFrEF and HFpEF with NAFLD compared to those without NAFLD. In-hospital mortality, was higher in primary HFrEF and HFpEF admissions with NAFLD compared to without NAFLD. Physicians must be aware of the worse clinical outcomes of HFrEF and HFpEF in patients with NAFLD. Further clinical research is needed to address the knowledge gap and treatment options available for the patients with HF and NAFLD.
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http://dx.doi.org/10.1016/j.cpcardiol.2022.101199DOI Listing
April 2022

Frailty, Guideline-Directed Medical Therapy, and Outcomes in HFrEF: From the GUIDE-IT Trial.

JACC Heart Fail 2022 04 9;10(4):266-275. Epub 2022 Mar 9.

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address:

Objectives: In this study, we sought to evaluate the association of frailty with the use of optimal guideline-directed medical therapy (GDMT) and outcomes in heart failure with reduced ejection fraction (HFrEF).

Background: The burden of frailty in HFrEF is high, and the patterns of GDMT use according to frailty status have not been studied previously.

Methods: A post hoc analysis of patients with HFrEF enrolled in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial was conducted. Frailty was assessed with the use of a frailty index (FI) using a 38-variable deficit model, and participants were categorized into 3 groups: class 1: nonfrail, FI <0.21); class 2: intermediate frailty, FI 0.21-0.31), and class 3: high frailty, FI >0.31). Multivariate-adjusted Cox models were used to study the association of frailty status with clinical outcomes. Use of optimal GDMT over time (beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists) across frailty strata was assessed with the use of adjusted linear and logistic mixed-effect models.

Results: The study included 879 participants, of which 56.3% had high frailty burden (class 3 FI). A higher frailty burden was associated with a significantly higher risk of HF hospitalization or death in adjusted Cox models: high frailty vs nonfrail HR: 1.76, 95% CI: 1.20-2.58. On follow-up, participants with high frailty burden also had a significantly lower likelihood of achieving optimal GDMT: high frailty vs non-frail GDMT triple therapy use at study end: 17.7% vs 28.4%; P interaction, frailty class × time <0.001.

Conclusions: Patients with HFrEF with a high burden of frailty have a significantly higher risk for adverse clinical outcomes and are less likely to be initiated and up-titrated on an optimal GDMT regimen.
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http://dx.doi.org/10.1016/j.jchf.2021.12.004DOI Listing
April 2022

Neighborhood-level Social Vulnerability and Prevalence of Cardiovascular Risk Factors and Coronary Heart Disease.

Curr Probl Cardiol 2022 Mar 27:101182. Epub 2022 Mar 27.

Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH; School of Medicine, Case Western Reserve University, Cleveland, OH; Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH. Electronic address:

Social determinants of health are implicated in the geographic variation in cardiovascular diseases (CVDs). The social vulnerability index (SVI) is an estimate of a neighborhood's potential for deleterious outcomes when faced with natural disasters or disease outbreaks. We sought to investigate the association of the SVI with cardiovascular risk factors and the prevalence of coronary heart disease (CHD) in the United States at the census tract level. We linked census tract SVI with prevalence of census tract CVD risk factors (smoking, high cholesterol, diabetes, high blood pressure, low physical activity and obesity), and prevalence of CHD obtained from the behavioral risk factor surveillance system. We evaluated the association between SVI, its sub-scales, CVD risk factors and CHD prevalence using linear regression. Among 72,173 census tracts, prevalence of all cardiovascular risk factors increased linearly with SVI. A higher SVI was associated with a higher CHD prevalence (R = 0.17, P < 0.0001). The relationship between SVI and CHD was stronger when accounting for census-tract median age (R = 0.57, P < 0.0001). A multivariable linear regression model including 4 SVI themes separately explained considerably more variation in CHD prevalence than the composite SVI alone (50.0% vs 17.3%). Socioeconomic status and household composition and disability were the SVI themes most closely associated with cardiovascular risk factors and CHD prevalence. In the United States, social vulnerability can explain significant portion of geographic variation in CHD, and its risk factors. Neighborhoods with high social vulnerability are at disproportionately increased risk of CHD and its risk factors. Social determinants of health are implicated in the geographic variation in cardiovascular diseases (CVDs). We investigated the association of social vulnerability index (SVI) with cardiovascular risk factors and the prevalence of coronary heart disease (CHD) in the United States at the census tract level. We show that cardiovascular risk factors and CHD were more common with higher SVI. A multivariable linear regression model including 4 SVI themes separately explained considerably more variation in CHD prevalence than the composite SVI alone (50.0% vs 17.3%). Socioeconomic status and household composition and/or disability were the SVI themes most closely associated with cardiovascular risk factors and CHD prevalence.
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http://dx.doi.org/10.1016/j.cpcardiol.2022.101182DOI Listing
March 2022

Meta-Analysis of Nonalcoholic Fatty Liver Disease and Incident Heart Failure.

Am J Cardiol 2022 05 16;171:180-181. Epub 2022 Mar 16.

Division of Cardiology, Department of Medicine, School of Medicine, Duke University, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina. Electronic address:

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http://dx.doi.org/10.1016/j.amjcard.2022.02.012DOI Listing
May 2022

Exerkines in health, resilience and disease.

Nat Rev Endocrinol 2022 05 18;18(5):273-289. Epub 2022 Mar 18.

Department of Genetics, Stanford School of Medicine, Stanford, CA, USA.

The health benefits of exercise are well-recognized and are observed across multiple organ systems. These beneficial effects enhance overall resilience, healthspan and longevity. The molecular mechanisms that underlie the beneficial effects of exercise, however, remain poorly understood. Since the discovery in 2000 that muscle contraction releases IL-6, the number of exercise-associated signalling molecules that have been identified has multiplied. Exerkines are defined as signalling moieties released in response to acute and/or chronic exercise, which exert their effects through endocrine, paracrine and/or autocrine pathways. A multitude of organs, cells and tissues release these factors, including skeletal muscle (myokines), the heart (cardiokines), liver (hepatokines), white adipose tissue (adipokines), brown adipose tissue (baptokines) and neurons (neurokines). Exerkines have potential roles in improving cardiovascular, metabolic, immune and neurological health. As such, exerkines have potential for the treatment of cardiovascular disease, type 2 diabetes mellitus and obesity, and possibly in the facilitation of healthy ageing. This Review summarizes the importance and current state of exerkine research, prevailing challenges and future directions.
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http://dx.doi.org/10.1038/s41574-022-00641-2DOI Listing
May 2022

Heart failure quality of care and in-hospital outcomes during the COVID-19 pandemic: findings from the Get With The Guidelines-Heart Failure registry.

Eur J Heart Fail 2022 Jun 6;24(6):1117-1128. Epub 2022 Apr 6.

Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.

Aims: To assess heart failure (HF) in-hospital quality of care and outcomes before and during the COVID-19 pandemic.

Methods And Results: Patients hospitalized for HF with ejection fraction (EF) <40% in the American Heart Association Get With The Guidelines©-HF (GWTG-HF) registry during the COVID-19 pandemic (3/1/2020-4/1/2021) and pre-pandemic (2/1/2019-2/29/2020) periods were included. Adherence to HF process of care measures, in-hospital mortality, and length of stay (LOS) were compared in pre-pandemic vs. pandemic periods and in patients with vs. without COVID-19. Overall, 42 004 pre-pandemic and 37 027 pandemic period patients (median age 68, 33% women, 58% White) were included without observed differences across clinical characteristics, comorbidities, vital signs, or EF. Utilization of guideline-directed medical therapy at discharge was comparable across both periods, with rates of implantable cardioverter defibrillator (ICD) placement or prescription lower during the pandemic (vs. pre-pandemic period). In-hospital mortality (3.0% vs. 2.5%, p <0.0001) and LOS (mean 5.7 vs. 5.4 days, p <0.0004) were higher during the pandemic vs. pre-pandemic. The highest in-hospital mortality during the pandemic was observed among patients hospitalized in the Northeast region (3.4%). Among patients concurrently diagnosed with COVID-19 (n = 549; 1.5%), adherence to ICD placement or prescription, prescription of aldosterone antagonist or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor at discharge were lower, and in-hospital mortality (8.2% vs. 3.0%, p <0.0001) and LOS (mean 7.7 vs. 5.7 days, p <0.0001) were higher than those without COVID-19.

Conclusion: Among GWTG-HF participating hospitals, patients hospitalized for HF with reduced EF during the pandemic received similar care quality but experienced higher in-hospital mortality than the pre-pandemic period.
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http://dx.doi.org/10.1002/ejhf.2484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087396PMC
June 2022

Genetic variation in sodium glucose co-transporter 1 and cardiac structure and function at middle age.

ESC Heart Fail 2022 04 15;9(2):1496-1501. Epub 2022 Feb 15.

Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, 676 N. St Clair St, Suite 600, Chicago, IL, 60611, USA.

Aims: The effects of inhibition of sodium glucose cotransporter (SGLT)-1, as opposed to SGLT2, on cardiovascular structure and function are not well known. We assessed the associations of a missense genetic variant of SGLT1 with cardiac structure and function.

Methods And Results: We evaluated associations of a functionally modifying variant of SLC5A1 (rs17683011 [p.Asn51Ser]), the gene that encodes SGLT1, with cardiac structure and function on echocardiography among middle-aged adults in the Coronary Artery Risk Development in Young Adults Study. Of 1904 participants (55.3 ± 3.5 years, 57% female, 34% Black), 166 (13%) White participants and 18 (3%) Black participants had at least one copy of rs17683011. There were no significant differences in age, sex, body mass index, glucose, or diabetes status by the presence of the rs17683011 variant. In Black participants, the presence of at least one copy of the rs17683011 variant was significantly associated with better GLS compared with those without a copy of the variant after covariate adjustment (-15.8 ± 0.7% vs. -14.0 ± 0.1%, P = 0.02). Although the direction of effect was consistent, the association between the presence of at least one copy of rs17683011 and GLS was not statistically significant in White participants (-15.1 ± 0.2% vs. -14.8 ± 0.1%, P = 0.16). There were no significant associations between rs17683011 and other measures of LV structure, systolic function, or diastolic function.

Conclusions: The rs17683011 variant, a functionally modifying variant of the SGLT1 gene, was associated with higher GLS among middle-age adults. These exploratory findings require further validation and suggest that SGLT1 inhibition may have beneficial effects upon LV systolic function.
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http://dx.doi.org/10.1002/ehf2.13841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934939PMC
April 2022

Transthyretin V142I Genetic Variant and Cardiac Remodeling, Injury, and Heart Failure Risk in Black Adults.

JACC Heart Fail 2022 02 8;10(2):129-138. Epub 2021 Dec 8.

Department of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address:

Objectives: This study evaluated the association of transthyretin (TTR) gene variant, in which isoleucine substitutes for valine at position 122 (V142I), with cardiac structure, function, and heart failure (HF) risk among middle-aged Black adults.

Background: The valine-to-isoleucine substitution in the TTR protein is prevalent in Black individuals and causes cardiac amyloidosis.

Methods: Jackson Heart Study participants without HF at baseline who had available data on the TTR V142I variant were included. The association of the TTR V142I variant with baseline echocardiographic parameters and repeated measures of high-sensitivity cardiac troponin-I (hs-cTnI) was assessed using adjusted linear regression models and linear mixed models, respectively. Adjusted Cox models, restricted mean survival time analysis, and Anderson-Gill models were constructed to determine the association of TTR V142I variant with the risk of incident HF, survival free of HF, and total HF hospitalizations.

Results: A total of 119 of 2,960 participants (4%) were heterozygous carriers of the TTR V142I variant. The TTR V142I variant was not associated with measures of cardiac parameters at baseline but was associated with a greater increase in high-sensitivity troponin I (hs-TnI) levels over time. In adjusted Cox models, TTR V142I variant carriers had significantly higher risk of incident HF (HR: 1.80; 95% CI: 1.07-3.05; P = 0.03), lower survival free of HF (mean difference: 4.0 year; 95% CI: 0.6-6.2 years); P = 0.02), and higher risk of overall HF hospitalizations (HR: 2.12; 95% CI: 1.23-3.63; P = 0.007).

Conclusions: The TTR V142I variant in middle-aged Black adults is not associated with adverse cardiac remodeling but was associated with a significantly higher burden of chronic myocardial injury, and greater risk of incident HF and overall HF hospitalizations.
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http://dx.doi.org/10.1016/j.jchf.2021.09.006DOI Listing
February 2022

Glycemic Markers and Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA).

J Card Fail 2022 Jan 31. Epub 2022 Jan 31.

Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.

Background: Although diabetes increases heart failure (HF) risk, it is unclear how various dysglycemia markers (hemoglobin A [HbA], fasting plasma glucose [FPG], homeostasis model assessment of insulin resistance, and fasting insulin) are associated with HF subtypes (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction [HFrEF]). We assessed the relation of markers of dysglycemia and risks of HFpEF and HFrEF.

Methods And Results: We included 6688 adults without prevalent cardiovascular disease who attended the first MESA visit (2000-2002) and were followed for incident hospitalized HF (HFpEF or HFrEF). Association of glycemic markers and status (normoglycemia, prediabetes, diabetes) with HFpEF and HFrEF were evaluated using adjusted Cox models. Over a median follow-up of 14.9 years, there were 356 HF events (145 HFpEF, 173 HFrEF, and 38 indeterminate HF events). Diabetes status conferred higher risks of HFpEF (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.57-2.68) and HFrEF (HR 2.02, 95% CI 1.38-2.97) compared with normoglycemia. Higher levels of FPG (≥126 mg/dL) and HbA (≥6.5%) were associated with similarly higher risks of HFpEF (HR for FPG 1.96, 95% CI 1.21-3.17; HR for HbA 2.00, 95% CI 1.20-3.31) and HFrEF (HR for FPG 1.84, 95% CI 1.18-2.88; HR for HbA 1.99, 95% CI 1.28-3.09) compared with reference values. Prediabetic range HbA (5.7%-6.4%) or FPG (100%-125 mg/dL), homeostasis model assessment of insulin resistance, and fasting insulin were not significantly associated with HFpEF or HFrEF.

Conclusions: Among community-dwelling individuals, HbA and FPG in the diabetes range were each associated with higher risks of HFpEF and HFrEF, with similar magnitudes of their associations.

Lay Abstract: Heart failure (HF) has 2 major subtypes (the heart's inability to pump or to fill up). Diabetes is known to increase HF risk, but its effects and that of markers of high glucose levels (fasting blood glucose and hemoglobin A) on the occurrence of HF subtypes remains unknown. Among 6688 adults without known cardiovascular disease followed for nearly 15 years, diabetes conferred significantly higher risks of both HF types, compared with those with normal blood glucose levels. Higher levels of fasting blood glucose and hemoglobin A were similarly associated with higher risks of both types of HF.
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http://dx.doi.org/10.1016/j.cardfail.2022.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339035PMC
January 2022

Association of polypill therapy with cardiovascular outcomes, mortality, and adherence: A systematic review and meta-analysis of randomized controlled trials.

Prog Cardiovasc Dis 2022 Feb 1. Epub 2022 Feb 1.

Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States of America. Electronic address:

Prior studies have reported improvements in population-level risk factor burden and cardiovascular disease (CVD) outcomes using polypills for CVD risk reduction. However, a comprehensive assessment of the impact of polypills on CVD outcomes, mortality, adherence, and side effects across different settings has not previously been reported. We performed a systematic review and meta-analysis of randomized controlled trials examining the association between polypill therapy and CVD outcomes published before February 2021. The primary outcome of interest was the risk of major adverse CVD events (MACE). Risk ratios for dichotomous outcomes were converted to log RR and pooled using a generic inverse variance weighted random-effects model. Data for continuous outcomes were pooled using random-effects modeling and presented as mean differences with 95% CIs. Eight studies representing 25,584 patients were included for analysis. In the overall pooled analysis, the use of polypills was associated with a non-significant reduction in the risk of MACE (RR: 0.85; 95% CI: 0.70-1.02) and significant reductions in the risk of all-cause mortality (RR: 0.90; 95% CI: 0.81-1.00). The reductions in the risk of MACE with polypill use varied by baseline risk and nature of the study population (primary prevention vs. secondary prevention), with the most significant risk reduction among lower-risk cohorts, including within primary prevention populations [RR 0.70 (0.62, 0.79)]. Among measures of CVD risk factors, modest but significant reductions were observed for systolic and diastolic blood pressure [systolic: mean difference 1.99 mmHg (95% CI: -3.07 to -0.91); diastolic: mean difference 1.30 mmHg (95% CI: -2.42 to -0.19), but not for levels of total or low-density lipoprotein-cholesterol. Use of the polypill strategy significantly improved drug adherence (RR: 1.31; 95% CI: 1.11-1.55) with no association between polypill use and rates of adverse events or drug discontinuation. The use of polypill formulations is associated with significant reductions in CVD risk factors and the risk of all-cause mortality and MACE, particularly in the low-risk and primary prevention population.
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http://dx.doi.org/10.1016/j.pcad.2022.01.005DOI Listing
February 2022
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