Regional variation in cause of death in patients with type 2 diabetes: Insights from EXSCEL.

AIMS: Type 2 diabetes (T2D) is a risk factor for cardiovascular and non-cardiovascular mortality. However, global distribution of cause-specific deaths in T2D is poorly understood. We characterized cause-specific deaths by geographic region among individuals with T2D at risk for cardiovascular disease (CVD). METHODS AND RESULTS: The international EXSCEL trial included 14,752 participants with T2D (73% with established CVD). We identified the proportion of deaths over 5-year follow-up attributed to cardiovascular and non-cardiovascular causes, and associated risk factors. During median 3.2-year follow-up, 1,091 (7.4%) participants died. Adjudicated causes of death were 723 cardiovascular (66.3% of deaths), including 252 unknown, and 368 non-cardiovascular (33.7%). Most deaths occurred in North America (N = 356/9.6% across region) and Eastern Europe (N = 326/8.1%), with fewest in Asia/Pacific (N = 68/4.4%). The highest proportional cause-specific deaths by region were sudden cardiac in Asia/Pacific (23/34% of regional deaths) and North America (86/24%); unknown in Eastern Europe (90/28%) and Western Europe (39/21%); and non-malignant non-cardiovascular in Latin America (48/31%). Cox proportional hazards model for adjudicated causes of death showed prognostic risk factors (hazard ratio [95% CI]) for cardiovascular and non-cardiovascular deaths, respectively: heart failure 2.04 (1.72-2.42) and 1.86 (1.46-2.39); peripheral artery disease 1.83 (1.54-2.18) and 1.78 (1.40-2.26); and current smoking status 1.61 (1.29-2.01) and 1.77 (1.31-2.40). CONCLUSIONS: In a contemporary T2D trial population, with and without established CVD, leading causes of death varied by geographic region. Underlying mechanisms leading to variability in cause of death across geographic regions and its impact on clinical trial endpoints warrant future research.

Improving Guideline-Directed Medical Therapy for Patients With Heart Failure With Reduced Ejection Fraction: A Review of Implementation Strategies.

Despite recent advances in the use of guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF), achievement of target GDMT use and up-titration to goal dosages continue to be modest. In recent years, a number of interventional approaches to improve the usage of GDMT have been published, but many are limited by single-center experiences with small sample sizes. However, strategies including the use of multidisciplinary teams, dedicated GDMT titration algorithms and clinician audits with feedback have shown promise. There remains a critical need for large, rigorous trials to assess the utility of differing interventions to improve the use and titration of GDMT in HFrEF. Here, we review existing literature in GDMT implementation for those with HFrEF and discuss future directions and considerations in the field.

Long-term outcomes of phenoclusters in severe tricuspid regurgitation.

AIMS: Severe tricuspid regurgitation (TR) exhibits high 1-year morbidity and mortality, yet long-term cardiovascular risk overall and by subgroups remains unknown. This study characterizes 5-year outcomes and identifies distinct clinical risk profiles of severe TR. METHODS AND RESULTS: Patients were included from a large US tertiary referral center with new severe TR by echocardiography based on four-category American Society of Echocardiography grading scale between 2007 and 2018. Patients were categorized by TR etiology (with lead present, primary, and secondary) and by supervised recursive partitioning (survival trees) for outcomes of death and the composite of death or heart failure hospitalization. The Kaplan-Meier estimates and Cox regression models were used to evaluate any association by (i) TR etiology and (ii) groups identified by survival trees and outcomes over 5 years. Among 2379 consecutive patients with new severe TR, median age was 70 years, 61% were female, and 40% were black. Event rates (95% confidence interval) were 30.9 (29.0-32.8) events/100 patient-years for death and 49.0 (45.9-52.2) events/100 patient-years for the composite endpoint, with no significant difference by TR etiology. After applying supervised survival tree modeling, two separate groups of four phenoclusters with distinct clinical prognoses were separately identified for death and the composite endpoint. Variables discriminating both outcomes were age, albumin, blood urea nitrogen, right ventricular function, and systolic blood pressure (all P < 0.05). CONCLUSION: Patients with newly identified severe TR have high 5-year risk for death and death or heart failure hospitalization. Partitioning patients using supervised survival tree models, but not TR etiology, discriminated clinical risk. These data aid in identifying relevant subgroups in clinical trials of TR and clinical risk/benefit analysis for TR therapies.

Electronic health record characterization and outcomes of heart failure with preserved ejection fraction.

BACKGROUND: Electronic health record (EHR)-based identification of heart failure with preserved ejection fraction (HFpEF) in the clinical setting may facilitate screening for clinical trials by improving the understanding of its epidemiology and outcomes; yet, previous data have yielded variable results. We sought to characterize groups identified with HFpEF by different EHR screening strategies and their associated long-term outcomes across a large and diverse population. METHODS: We retrospectively analyzed 116,499 consecutive patients from an academic referral center who underwent echocardiography, and 9,263 patients who underwent echocardiography within 6 months of right heart catheterization (RHC), between 2008 and 2018. EHR-based screening strategies identified patients with HFpEF using 1) International Classification of Diseases (ICD)-9/10 codes, 2) H2FpEF score ≥6 and ejection fraction (EF) ≥50%, or 3) RHC wedge pressure ≥15 mmHg and EF ≥50%, when available. Primary outcomes were 1) cumulative incident heart failure hospitalization (HFH), and 2) death, over 10 years. RESULTS: There were 33,461 (29%) patients who met either ICD or H2FpEF-HFpEF definition, of whom 5,310 (16%) met both criteria. Compared to ICD-HFpEF, patients with H2FpEF-HFpEF were more likely older (median age 72 vs 67), White (78% vs 64%), and had atrial fibrillation (97% vs 41%). Among those also with RHC, 6,353 (69%) patients met any HFpEF criteria, of whom only 783 (12%) satisfied all three criteria. Female sex was more common among RHC-HFpEF (55%) compared to other methods (H2FpEF-HFpEF, 47%; ICD-HFpEF, 43%). Atrial fibrillation was substantially higher among HFpEF identified by the H2FpEF score (97%) compared to other methods (49% for ICD and 47% for RHC). Across HFpEF screening methods, 10-year cumulative incidence rates for HFH was 32% to 45% for echocardiography only and 43% to 52% for echocardiography and RHC populations; 10-year risk of death was 54% to 56% for echocardiography only and 52% to 57% for echocardiography and RHC populations. CONCLUSIONS: Different EHR-based HFpEF definitions identified cohorts with modest overlap and varying baseline characteristics. Yet, long-term risk for HFH and death were similarly high for cohorts identified among both populations undergoing echocardiography only or echocardiography and RHC. These data aid in identifying relevant subgroups in clinical trials of HFpEF.

Practical Patient Care Considerations With Use of Vericiguat After Worsening Heart Failure Events.

Vericiguat is a soluble guanylate cyclase stimulator approved by multiple global regulatory bodies and recommended in recently updated clinical practice guidelines to reduce morbidity and mortality in patients with worsening chronic heart failure (HF) with reduced ejection fraction (HFrEF). Despite the growing armaments of evidence-based medical therapy for HFrEF that have demonstrated clinical outcome benefits, there is a need to address residual risk following worsening HF events. When considering therapies aimed to mitigate postevent cardiovascular risk, potential barriers preventing the prescription of vericiguat in eligible patients may include providers' lack of familiarity with it, clinical inertia, limited knowledge about monitoring response to therapy, and concerns about potential adverse effects as well as integration of its routine use during an era of in-person and telehealth hybrid ambulatory care. This review provides an overview of vericiguat therapy and proposes an evidence-based and practical guidance strategy toward implementing its use in various clinical settings. This review additionally summarizes patient counseling points for its initiation and maintenance.

Machine learning to define phenotypes and outcomes of patients hospitalized for heart failure with preserved ejection fraction: Findings from ASCEND-HF.

BACKGROUND: Heart Failure with Preserved Ejection Fraction (HFpEF) is a heterogenous disease with few therapies proven to provide clinical benefit. Machine learning can characterize distinct phenotypes and compare outcomes among patients with HFpEF who are hospitalized for acute HF. METHODS: We applied hierarchical clustering using demographics, comorbidities, and clinical data on admission to identify distinct clusters in hospitalized HFpEF (ejection fraction >40%) in the ASCEND-HF trial. We separately applied a previously developed latent class analysis (LCA) clustering method and compared in-hospital and long-term outcomes across cluster groups. RESULTS: Of 7141 patients enrolled in the ASCEND-HF trial, 812 (11.4%) were hospitalized for HFpEF and met the criteria for complete case analysis. Hierarchical Cluster 1 included older women with atrial fibrillation (AF). Cluster 2 had elevated resting blood pressure. Cluster 3 had young men with obesity and diabetes. Cluster 4 had low resting blood pressure. Mortality at 180 days was lowest among Cluster 3 (KM event-rate 6.2 [95% CI: 3.5, 10.9]) and highest among Cluster 4 (18.8 [14.6, 24.0], P < .001). Twenty four-hour urine output was higher in Cluster 3 (2700 mL [1800, 3975]) than Cluster 4 (2100 mL [1400, 3055], P < .001). LCA also identified four clusters: A) older White or Asian women, B) younger men with few comorbidities, C) older individuals with AF and renal impairment, and D) patients with obesity and diabetes. Mortality at 180 days was lowest among LCA Cluster B (KM event-rate 5.5 [2.0, 10.3]) and highest among LCA Cluster C (26.3 [19.2, 35.4], P < .001). CONCLUSIONS: In patients hospitalized for HFpEF, cluster analysis demonstrated distinct phenotypes with differing clinical profiles and outcomes.

Pericardial Adipose Tissue Volume and Left Ventricular Assist Device-Associated Outcomes.

BACKGROUND: Pericardial adipose tissue (PAT) is associated with adverse cardiovascular outcomes in those with and without established heart failure (HF). However, it is not known whether PAT is associated with adverse outcomes in patients with end-stage HF undergoing left ventricular assist device (LVAD) implantation. This study aimed to evaluate the associations between PAT and LVAD-associated outcomes. METHODS AND RESULTS: We retrospectively measured computed tomography-derived PAT volumes in 77 consecutive adults who had available chest CT imaging prior to HeartMate 3 LVAD surgery between October 2015 and March 2019 at Duke University Hospital. Study groups were divided into above-median (≥219 cm3) and below-median (<219 cm3) PAT volume. Those with above-median PAT had a higher proportion of atrial fibrillation, chronic kidney disease and ischemic cardiomyopathy. Groups with above-median vs below-median PAT had similar Kaplan-Meier incidence rates over 2 years for (1) composite all-cause mortality, redo-LVAD surgery and cardiac transplantation (35.9 vs 32.2%; log-rank P = 0.65) and (2) composite incident hospitalizations for HF, gastrointestinal bleeding, LVAD-related infection, and stroke (61.5 vs 60.5%; log-rank P = 0.67). CONCLUSIONS: In patients with end-stage HF undergoing LVAD therapy, PAT is not associated with worse 2-year LVAD-related outcomes. The significance of regional adiposity vs obesity in LVAD patients warrants further investigation.

Emergency Department Visits Versus Hospital Readmissions Among Patients Hospitalized for Heart Failure.

BACKGROUND: Worsening heart failure (HF) often requires hospitalization but in some cases may be managed in the outpatient or emergency department (ED) settings. The predictors and clinical significance of ED visits without admission vs hospitalization are unclear. METHODS: The ASCEND-HF trial included 2661 US patients hospitalized for HF with reduced or preserved ejection fraction. Clinical characteristics were compared between patients with a subsequent all-cause ED visit (with ED discharge) within 30 days vs all-cause readmission within 30 days. Factors associated with each type of care were assessed in multivariable models. Multivariable models landmarked at 30 days evaluated associations between each type of care and subsequent 150-day mortality. RESULTS: Through 30-day follow-up, 193 patients (7%) had ED discharge, 459 (17%) had readmission, and 2009 (76%) had neither urgent visit. Patients with ED discharge vs readmission were similar with respect to age, sex, systolic blood pressure, ejection fraction, and coronary artery disease, whereas ED discharge patients had a modestly lower creatinine (P < .01). Among patients with either event within 30 days, a higher creatinine and prior HF hospitalization were associated with a higher likelihood of readmission, as compared with ED discharge (P < .02). Landmarked at 30 days, rates of death during the subsequent 150 days were 21.0% for patients who were readmitted and 11.4% for patients discharged from the ED. Compared with patients who were readmitted, ED discharge was independently associated with lower 150-day mortality (adjusted hazard ratio 0.58, 95% confidence interval 0.36-0.92, P = .02). CONCLUSIONS: In this cohort of US patients hospitalized for HF, worse renal function and prior HF hospitalization were associated with a higher likelihood of early postdischarge readmission, as compared with ED discharge. Although subsequent mortality was high after discharge from the ED, this risk of mortality was significantly lower than patients who were readmitted to the hospital.

Quantitative Blood Volume Analysis and Hemodynamic Measures of Vascular Compliance in Patients With Worsening Heart Failure.

BACKGROUND: The role of blood volume (BV) expansion vs a change in vascular compliance in worsening heart failure (HF) remains under debate. We aimed to assess the relationship between BV and resting and stress hemodynamics in worsening HF and to further elucidate the significance of BV in cardiac decompensation. METHODS AND RESULTS: Patients with worsening HF underwent radiolabeled indicator-dilution BV analysis and cardiac catheterization. Intravascular volumes and resting/stress hemodynamics were recorded. Provocative stress maneuvers included change in systolic blood pressure (ΔSBP) from lying to standing and Valsalva and intracardiac pressure changes with leg raise. Correlation between BV and invasive hemodynamics were assessed by linear regression. Of 27 patients with worsening HF, patients' characteristics included mean age 61 ± 12 years, 70% male, 19% Black, and mean ejection fraction 29% ± 15%. Of the patients, 13 (48%) had hypervolemia as measured by total BV, which weakly correlated with ΔSBP by position (R2 = 0.009) and Valsalva (R2 = 0.003) and with right atrial (R2 = 0.049) and pulmonary capillary wedge (R2 = 0.047) pressure changes during leg raise. CONCLUSIONS: In patients with worsening HF, BV mildly correlated with intracardiac pressures at rest. Provocative maneuvers intended to test vascular compliance did not correlate with BV, indicating that compliance may serve as a stand-alone metric in HF.

The Association of Digital Health Application Use With Heart Failure Care and Outcomes: Insights From CONNECT-HF.

BACKGROUND: It is unknown whether digital applications can improve guideline-directed medical therapy (GDMT) and outcomes in heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Care Optimization Through Patient and Hospital Engagement Clinical Trial for Heart Failure trial (CONNECT-HF) included an optional, prospective ancillary study of a mobile health application among patients hospitalized due to HFrEF. Digital users were matched to nonusers from the usual-care group. Coprimary outcomes included change in opportunity-based composite HF quality scores and HF rehospitalization or all-cause mortality. Among 2431 patients offered digital applications across the United States, 1526 (63%) had limited digital access or insufficient data, 425 (17%) were digital users, and 480 (20%) declined use. Digital users were similar in age to those who declined use (mean 58 vs 60 years; P = 0.031). Digital users (n = 368) vs matched nonusers (n = 368) had improved composite HF quality scores (48.0% vs 43.6%; + 4.76% [3.27-6.24]; P = 0.001) and composite clinical outcomes (33.0% vs 39.6%; HR 0.76 [0.59-0.97]; P = 0.027). CONCLUSIONS: Among participants in the CONNECT-HF trial, use of digital applications was modest but was associated with higher HF quality-of-care scores, including use of GDMT and better clinical outcomes. Although cause and effect cannot be determined from this study, the application of technology to guide GDMT use and dosing among patients with HFrEF warrants further investigation.

AMBULATORY BLOOD PRESSURE PATTERNS IN PATIENTS WITH RETINAL VEIN OCCLUSION.

PURPOSE: Failure of blood pressure (BP) to dip during sleep (nondipper pattern) is associated with cardiovascular disease and stroke. The prevalence and degree of nondipping and masked hypertension in patients with retinal vein occlusion (RVO), which is associated with stroke, has not been previously examined. METHODS: We measured clinic and 24-hour ambulatory BPs in 22 patients with RVO and 20 control participants without known eye disease matched by age and sex. Mean BP dipping, defined as the ratio of difference in mean awake and sleep systolic BPs to mean awake systolic BP, and masked and nocturnal hypertension were compared between groups. RESULTS: Mean 24-hour ambulatory BP was 144/79 mmHg among those with RVO and 136/77 mmHg among controls. Patients with RVO had an almost 2-fold higher prevalence of nondipping pattern (80.8% [95% confidence interval, 52.8-94.1] vs. 50.4% [95% confidence interval, 26.1-74.5]; P = 0.008). Average sleep systolic BP dip in patients with RVO was 6.1% versus 11.9% in controls (P = 0.004). More patients with RVO had masked hypertension by ambulatory BPs than controls (71% vs. 50%), but this difference was not statistically significant. CONCLUSION: Our data suggest an association between RVO and nondipper BP pattern. Ambulatory BP monitoring may be useful in the evaluation of patients with RVO by identifying those who may benefit from more aggressive BP control.

Pressure-Volume Profiles in Heart Failure Across Sexes and Phenotypes.

Studies have shown poor correlation between intra-cardiac pressures and blood volume (BV) measurements including HF. The impact of sex and left ventricular ejection fraction (LVEF) on this relationship has not been studied. We obtained pressure (pulmonary artery diastolic pressure (PADP)) and volume (total blood volume (TBV) and estimated stress blood volume (eSBV)) measurements from HF patients at the time of CardioMEMS implantation. A total of 20 patients were included. There was no significant difference between PADP, TBV, and eSBV between sexes. There was only a moderate correlation between PADP and eSBV in men but not in women or with TBV in both sexes. HFrEF had higher PADP and eSBV than HFpEF. There was a consistent lack of correlation between PADP and both TBV and eSBV. Further studies evaluating mid- to long-term implications of pressure-volume profiles as well as changes following decongestion therapy are warranted to better understand the pressure-volume interplay and determine appropriate decongestion strategy for each pressure-volume phenotype.

In-Hospital Virtual Peer-to-Peer Consultation to Increase Guideline-Directed Medical Therapy for Heart Failure: A Pilot Randomized Trial.

BACKGROUND: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) improves clinical outcomes and quality of life. Optimizing GDMT in the hospital is associated with greater long-term use in HFrEF. This study aimed to describe the efficacy of a multidisciplinary virtual HF intervention on GDMT optimization among patients with HFrEF admitted for any cause. METHODS: In this pilot randomized, controlled study, consecutive patients with HFrEF admitted to noncardiology medicine services for any cause were identified at a large academic tertiary care hospital between May to September 2021. Major exclusions were end-stage renal disease, hemodynamic instability, concurrent COVID-19 infection, and current enrollment in hospice care. Patients were randomized to a clinician-level virtual peer-to-peer consult intervention providing GDMT recommendations and information on medication costs versus usual care. Primary end points included (1) proportion of patients with new GDMT initiation or use and (2) changes to HF optimal medical therapy scores which included target dosing (range, 0-9). RESULTS: Of 242 patients identified, 91 (38%) were eligible and randomized to intervention (N=52) or usual care (N=39). Baseline characteristics were similar between intervention and usual care (mean age 63 versus 67 years, 23% versus 26% female, 46% versus 49% Black, mean ejection fraction 33% versus 31%). GDMT use on admission was also similar. There were greater proportions of patients with GDMT initiation or continuation with the intervention compared with usual care. After adjusting for optimal medical therapy score on admission, changes to optimal medical therapy score at discharge were higher for the intervention group compared with usual care (+0.44 versus -0.31, absolute difference +0.75, adjusted estimate 0.86±0.42; P=0.041). CONCLUSIONS: Among eligible patients with HFrEF hospitalized for any cause on noncardiology services, a multidisciplinary pilot virtual HF consultation increased new GDMT initiation and dose optimization at discharge.

Neighborhood Socioeconomic Disadvantage and Hospitalized Heart Failure Outcomes in the American Heart Association Get With The Guidelines-Heart Failure Registry.

BACKGROUND: Neighborhood socioeconomic status (SES) is associated with worse health outcomes, yet its relationship with in-hospital heart failure (HF) outcomes and quality metrics are underexplored. We examined the association between socioeconomic neighborhood disadvantage and in-hospital HF outcomes for patients from diverse neighborhoods in the Get With The Guidelines-Heart Failure registry. METHODS: SES-disadvantage scores were derived from geocoded US census data using a validated algorithm, which incorporated household income, home value, rent, education, and employment. We examined the association between SES-disadvantage quintiles with all-cause in-hospital mortality, adjusting for demographics and comorbidities. RESULTS: Of 593 053 patients hospitalized for HF between 2017 and 2020, 321 314 (54%) had residential ZIP Codes recorded. Patients from the most compared with least disadvantaged neighborhoods were younger (mean age 67 versus 76 years), more often Black (42% versus 9%) or Hispanic (14% versus 5%), and had higher comorbidity burden. Demographic-adjusted length of stay increased by ≈1.5 hours with each increment in worsening SES-disadvantage quintiles. Adjusted-mortality odds ratios increased with worsening SES-disadvantage quintiles (Ptrend=0.003), and was 28% higher (adjusted OR=1.28 [1.12-1.48]) for the most compared with least disadvantaged neighborhood groups. CONCLUSIONS: Patients hospitalized for HF from disadvantaged neighborhoods were younger and more often Black or Hispanic. SES disadvantage was independently associated with higher in-hospital mortality. Further research is needed to characterize care delivery patterns in disadvantaged neighborhoods and to address social determinants of health among patients hospitalized for HF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02693509.

Acute cardiovascular hospitalizations and illness severity before and during the COVID-19 pandemic.

BACKGROUND: Cardiovascular disease (CVD) hospitalizations declined worldwide during the COVID-19 pandemic. It is unclear how shelter-in-place orders affected acute CVD hospitalizations, illness severity, and outcomes. HYPOTHESIS: COVID-19 pandemic was associated with reduced acute CVD hospitalizations (heart failure [HF], acute coronary syndrome [ACS], and stroke [CVA]), and worse HF illness severity. METHODS: We compared acute CVD hospitalizations at Duke University Health System before and after North Carolina's shelter-in-place order (January 1-March 29 vs. March 30-August 31), and used parallel comparison cohorts from 2019. We explored illness severity among admitted HF patients using ADHERE ("high risk": >2 points) and GWTG-HF (">10%": >57 points) in-hospital mortality risk scores, as well as echocardiography-derived parameters. RESULTS: Comparing hospitalizations during January 1-March 29 (N = 1618) vs. March 30-August 31 (N = 2501) in 2020, mean daily CVD hospitalizations decreased (18.2 vs. 16.1 per day, p = .0036), with decreased length of stay (8.4 vs. 7.5 days, p = .0081) and no change in in-hospital mortality (4.7 vs. 5.3%, p = .41). HF hospitalizations decreased (9.0 vs. 7.7 per day, p = .0019), with higher ADHERE ("high risk": 2.5 vs. 4.5%; p = .030), but unchanged GWTG-HF (">10%": 5.3 vs. 4.6%; p = .45), risk groups. Mean LVEF was lower (39.0 vs. 37.2%, p = .034), with higher mean LV mass (262.4 vs. 276.6 g, p = .014). CONCLUSIONS: CVD hospitalizations, HF illness severity, and echocardiography measures did not change between admission periods in 2019. Evaluating short-term data, the COVID-19 shelter-in-place order was associated with reductions in acute CVD hospitalizations, particularly HF, with no significant increase in in-hospital mortality and only minor differences in HF illness severity.

Regional Adiposity and Risk of Heart Failure and Mortality: The Jackson Heart Study.

Background Visceral adipose tissue (VAT) is associated with incident heart failure (HF) and HF with preserved ejection fraction, yet it is unknown how pericardial and abdominal adiposity affect HF and mortality risks in Black individuals. We examined the associations of pericardial adipose tissue (PAT), VAT, and subcutaneous adipose tissue (SAT) with incident HF hospitalization and all-cause mortality in a large community cohort of Black participants. Methods and Results Among the 2882 Jackson Heart Study Exam 2 participants without prevalent HF who underwent body computed tomography, we used Cox proportional hazards models to examine associations between computed tomography-derived regional adiposity and incident HF hospitalization and all-cause mortality. Fully adjusted models included demographics and cardiovascular disease risk factors. Median follow-up was 10.6 years among participants with available VAT (n=2844), SAT (n=2843), and PAT (n=1386). Fully adjusted hazard ratios (95% CIs) of distinct computed tomography-derived adiposity measures (PAT per 10 cm3, VAT or SAT per 100 cm3) were as follows: for incident HF, PAT 1.08 (95% CI, 1.02-1.14) and VAT 1.04 (95% CI, 1.01-1.08); for HF with preserved ejection fraction, PAT 1.13 (95% CI, 1.04-1.21) and VAT 1.07 (95% CI, 1.01-1.13); for mortality, PAT 1.07 (95% CI, 1.03-1.12) and VAT 1.01 (95% CI, 0.98-1.04). SAT was not associated with either outcome. Conclusions High PAT and VAT, but not SAT, were associated with incident HF and HF with preserved ejection fraction, and only PAT was associated with mortality in the fully adjusted models in a longitudinal community cohort of Black participants. Future studies may help understand whether changes in regional adiposity improves HF, particularly HF with preserved ejection fraction, risk predictions. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005485.

Relationship of Nonalcoholic Fatty Liver Disease and Heart Failure With Preserved Ejection Fraction.

Although there is an established bidirectional relationship between heart failure with reduced ejection fraction and liver disease, the association between heart failure with preserved ejection fraction (HFpEF) and liver diseases, such as nonalcoholic fatty liver disease (NAFLD), has not been well explored. In this paper, the authors provide an in-depth review of the relationship between HFpEF and NAFLD and propose 3 NAFLD-related HFpEF phenotypes (obstructive HFpEF, metabolic HFpEF, and advanced liver fibrosis HFpEF). The authors also discuss diagnostic challenges related to the concurrent presence of NAFLD and HFpEF and offer several treatment options for NAFLD-related HFpEF phenotypes. The authors propose that NAFLD-related HFpEF should be recognized as a distinct HFpEF phenotype.

Nonalcoholic Fatty Liver Disease and Risk of Heart Failure Among Medicare Beneficiaries.

Background Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are increasing in prevalence. The independent association between NAFLD and downstream risk of HF and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction) is not well established. Methods and Results This was a retrospective, cohort study among Medicare beneficiaries. We selected Medicare beneficiaries without known prior diagnosis of HF. NAFLD was defined using presence of 1 inpatient or 2 outpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), claims codes. Incident HF was defined using at least 1 inpatient or at least 2 outpatient HF claims during the follow-up period (October 2015-December 2016). Among 870 535 Medicare patients, 3.2% (N=27 919) had a clinical diagnosis of NAFLD. Patients with NAFLD were more commonly women, were less commonly Black patients, and had a higher burden of comorbidities, such as diabetes, obesity, and kidney disease. Over a mean 14.3 months of follow-up, patients with (versus without) baseline NAFLD had a significantly higher risk of new-onset HF in unadjusted (6.4% versus 5.0%; P<0.001) and adjusted (adjusted hazard ratio [HR] [95% CI], 1.23 [1.18-1.29]) analyses. Among HF subtypes, the association of NAFLD with downstream risk of HF was stronger for HF with preserved ejection fraction (adjusted HR [95% CI], 1.24 [1.14-1.34]) compared with HF with reduced ejection fraction (adjusted HR [95% CI], 1.09 [0.98-1.2]). Conclusions Patients with NAFLD are at an increased risk of incident HF, with a higher risk of developing HF with preserved ejection fraction versus HF with reduced ejection fraction. The persistence of an increased risk after adjustment for clinical and demographic factors suggests an epidemiological link between NAFLD and HF beyond the basis of shared risk factors that requires further investigation.