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1.
Circ Heart Fail ; 14(2): e007761, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33535771

RESUMO

Targeted prevention of heart failure (HF) remains a critical need given the high prevalence of HF morbidity and mortality. Similar to risk-based prevention of atherosclerotic cardiovascular disease, optimal HF prevention strategies should include quantification of risk in the individual patient. In this review, we discuss incorporation of a quantitative risk-based approach into the existing HF staging landscape and the clinical opportunity that exists to translate available data on risk estimation to help guide personalized decision making. We first summarize the recent development of key HF risk prediction tools that can be applied broadly at a population level to estimate risk of incident HF. Next, we provide an in-depth description of the clinical utility of biomarkers to personalize risk estimation in select patients at the highest risk of developing HF. We also discuss integration of genomics-enhanced approaches (eg, Titin [TTN]) and other risk-enhancing features to reclassify risk with a precision medicine approach to HF prevention. Although sequential testing is very likely to identify low and high-risk individuals with excellent accuracy, whether or not interventions based on these risk models prevent HF in clinical practice requires prompt attention including randomized placebo-controlled trials of candidate therapies in risk-enriched populations. We conclude with a summary of unanswered questions and gaps in evidence that must be addressed to move the field of HF risk assessment forward.

3.
J Am Geriatr Soc ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33401338

RESUMO

BACKGROUND/OBJECTIVES: Obesity increases with age, is disproportionately prevalent in black populations, and is associated with heart failure with preserved ejection fraction (HFpEF). An "obesity paradox," or improved survival with obesity, has been reported in patients with HFpEF. The aim of this study was to examine whether racial differences exist in the temporal trends and outcomes associated with obesity among older patients with HFpEF. DESIGN: Community surveillance of acute decompensated heart failure (ADHF) hospitalizations, sampled by stratified design from 2005 to 2014. SETTING: Atherosclerosis Risk in Communities Study (NC, MS, MD, MN). PARTICIPANTS: A total of 10,147 weighted hospitalizations for ADHF (64% female, 74% white, mean age 77 years), with ejection fraction ≥50%. MEASUREMENTS: ADHF classified by physician review, HFpEF defined by ejection fraction ≥50%. Body mass index (BMI) calculated from weight at hospital discharge. Obesity defined by BMI ≥30 kg/m2 , class III obesity by BMI ≥40 kg/m2 . RESULTS: When aggregated across 2005-2014, the mean BMI was higher for black compared to white patients (34 vs 30 kg/m2 ; P < .0001), as was prevalence of obesity (56% vs 43%; P < .0001) and class III obesity (24% vs 13%; P < .0001). Over time, the annual mean BMI and prevalence of class III obesity remained stable for black patients, but steadily increased for white patients, with annual rates statistically differing by race (P-interaction = .04 and P = .03, respectively). For both races, a U-shaped adjusted mortality risk was observed across BMI categories, with the highest risk among patients with a BMI ≥40 kg/m2 . CONCLUSION: Black patients were disproportionately burdened by obesity in this decade-long community surveillance of older hospitalized patients with HFpEF. However, temporal increases in mean BMI and class III obesity prevalence among white patients narrowed the racial difference in recent years. For both races, the worst survival was observed with class III obesity. Effective strategies are needed to manage obesity in patients with HFpEF.

6.
Circ Cardiovasc Qual Outcomes ; : CIRCOUTCOMES120007094, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33280436

RESUMO

BACKGROUND: Randomized clinical trials have demonstrated that catheter ablation for atrial fibrillation in patients with heart failure with reduced ejection fraction may improve survival and other cardiovascular outcomes. METHODS: We constructed a decision-analytic Markov model to estimate the costs and benefits of catheter ablation and medical management in patients with symptomatic heart failure with reduced ejection fraction (left ventricular ejection fraction ≤35%) and atrial fibrillation over a lifetime horizon. Evidence from the published literature informed the model inputs, including clinical effectiveness data from meta-analyses. Probabilistic and deterministic sensitivity analyses were performed. A 3% discount rate was applied to both future costs and benefits. The primary outcome was the incremental cost-effectiveness ratio assessed from the US health care sector perspective. RESULTS: Catheter ablation was associated with 6.47 (95% CI, 5.89-6.93) quality-adjusted life years (QALYs) and a total cost of $105 657 (95% CI, $55 311-$191 934; 2018 US dollars), compared with 5.30 (95% CI, 5.20-5.39) QALYs and $63 040 (95% CI, $37 624-$102 260) for medical management. The incremental cost-effectiveness ratio for catheter ablation compared with medical management was $38 496 (95% CI, $5583-$117 510) per QALY gained. Model inputs with the greatest variation on incremental cost-effectiveness ratio estimates were the cost of ablation and the effect of catheter ablation on mortality reduction. When assuming a more conservative estimate of the treatment effect of catheter ablation on mortality (hazard ratio of 0.86), the estimated incremental cost-effectiveness ratio was $74 403 per QALY gained. At a willingness-to-pay threshold of $100 000 per QALY gained, atrial fibrillation ablation was found to be economically favorable compared with medical management in 95% of simulations. CONCLUSIONS: Catheter ablation in patients with heart failure with reduced ejection fraction patients and atrial fibrillation may be considered economically attractive at current benchmarks for societal willingness-to-pay in the United States.

7.
Am Heart J ; 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33264607

RESUMO

BACKGROUND: Post-discharge mortality following hospitalization for heart failure with reduced ejection fraction (HFrEF) has remained high and unchanged over the past two decades, despite effective therapies for HFrEF. We aimed to explore whether these patterns could in part be explained by changes in longitudinal risk profile and HF severity over time. METHODS: Among patients hospitalized for HF in the GWTG-HF registry from 1/2005 to 12/2018 with available data, we evaluated GWTG-HF and ADHERE risk scores, observing in-hospital mortality per-year. The risk profiles and outcomes were described overall and by subgroups based on ejection fraction (EF), diabetes mellitus (DM), sex, and age. RESULTS: Overall, 335,735 patients were included (50% HFrEF, 46% DM, 48% female, mean age 74 years). In-hospital mortality increased by 2.0% per year from 2005-2018. There was no significant change in mean GWTG-HF risk score overall or when stratified by EF groups (p=0.46 HFrEF, p=0.26 HF mid-range EF [HFmrEF], and p=0.72 HF preserved EF [HFpEF]), age, sex, or presence of DM. The observed/expected ratio based on the GWTG-HF risk score was 0.93 (0.91-0.96), 0.83 (0.77-0.90), 0.92 (0.89-95) for HFrEF, HFmrEF, and HFpEF, respectively. Similar findings were seen when risk was assessed using ADHERE risk score. CONCLUSIONS: There were no significant changes in average risk profiles among hospitalized HF patients over the study duration. These data do not support the notion that worsening risk profile explains the lack of improved outcomes despite therapeutic advances, underscoring the importance of aggressive implementation of guideline-recommended therapies and investigation of novel treatments.

8.
JAMA Cardiol ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33355618

RESUMO

Importance: The variant V122I is commonly enriched in the transthyretin (TTR) gene in individuals of African ancestry and associated with greater risk of heart failure (HF) in older adulthood, after age 65 years. Prevention of HF may be most effective earlier in life, but whether screening with echocardiography can identify subclinical cardiac abnormalities during middle age to risk-stratify individuals appears to be unknown. Objective: To examine the association between the V122I TTR variant and cardiac structure and function during middle age in those without prevalent HF. Design, Setting, and Participants: This serial cross-sectional study of 875 Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort was conducted at 4 urban sites across the US. Recruiting was completed in 1985-1986, and follow-up examinations occurred 25 and 30 years later. A subset of Black adults from the CARDIA cohort who underwent TTR genotyping was included. Data analysis was completed from January 2020 to October 2020. Exposures: The V122I TTR genotype. Main Outcomes and Measures: Echocardiographic left ventricular (LV) circumferential and longitudinal systolic strain and LV structure, measured at years 25 and 30 of follow-up. The analyses were adjusted for age, sex, echocardiography quality, genetic ancestry, and field center. Results: Among the 875 Black adults (mean [SD] age, 49.4 [3.8] years at year 25; 543 women [62.1%]), there were 31 individuals who were heterozygous and 1 who was homozygous for the V122I TTR variant. Of the adults who had an echocardiogram at year 25, rates of hypertension (312 [46%]), diabetes (102 [15%]), and current smoking (128 [19%]) were not significantly different between those who did and did not carry V122I TTR. At year 25, there was no difference in LV circumferential strain, longitudinal strain, or LV structure between those who did vs did not carry V122I TTR. At year 30, those who carried V122I TTR had significantly lower absolute LV circumferential strain (mean [SD], 12.4 [4.2] percentage units) compared with those who did not carry the variant (mean [SD], 14.5 [3.7] percentage units). Those who carried V122I TTR also had significantly higher LV mass index values (mean [SD], 97.5 [34.1] g/m2) compared with those who did not (mean [SD], 83.7 [22.6] g/m2) at year 30. Conclusions and Relevance: Carrier status for the V122I TTR variant is associated with subclinical cardiac abnormalities in middle age (worse LV systolic function and higher LV mass) that have been associated with increased risk of incident HF. Midlife screening of individuals who carry V122I TTR with echocardiography may prognosticate risk of symptomatic HF and inform prevention strategies.

10.
JAMA Cardiol ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185662

RESUMO

Importance: In May 2020, dapagliflozin was approved by the US Food and Drug Administration (FDA) as the first sodium-glucose cotransporter 2 inhibitor for heart failure with reduced ejection fraction (HFrEF), based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. Limited data are available characterizing the generalizability of dapagliflozin to US clinical practice. Objective: To evaluate candidacy for initiation of dapagliflozin based on the FDA label among contemporary patients with HFrEF in the US. Design, Setting, and Participants: This cohort study included 154 714 patients with HFrEF (left ventricular ejection fraction ≤40%) hospitalized at 406 sites in the Get With the Guidelines-Heart Failure (GWTG-HF) registry admitted between January 1, 2014, and September 30, 2019. Patients who left against medical advice, transferred to an acute care facility or to hospice, or had missing data were excluded. The FDA label (which excluded patients with an estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2, those undergoing dialysis, and those with type 1 diabetes) was applied to the GWTG-HF registry sample. Data analyses were conducted from April 1 to June 30, 2020. Main Outcomes and Measures: The proportion of patients hospitalized with HFrEF who would be candidates for dapagliflozin under the FDA label. Results: Among 154 714 patients hospitalized with HFrEF, 125 497 (81.1%; 83 481 men [66.5%]; mean [SD] age, 68 [15] years) would be candidates for dapagliflozin according to the FDA label. Across 355 sites with patients with 10 or more hospitalizations, the median proportion of candidates for dapagliflozin according to the FDA label was 81.1% (interquartile range, 77.8%-84.6%) at each site. This proportion was similar across all study years (interquartile range, 80.4%-81.7%) and was higher among those without type 2 diabetes than with type 2 diabetes (85.5% vs 75.6%). Among GWTG-HF participants, the most frequent reason for not meeting the FDA label criteria was eGFR less than 30 mL/min/1.73 m2 at discharge (18.5%). Among 75 654 patients with available paired admission and discharge data, 14.2% had an eGFR less than 30 mL/min/1.73 m2 at both time points, while 3.8% developed an eGFR less than 30 mL/min/1.73 m2 by discharge. Although there were more older adults, women, and Black patients in the GWTG-HF registry than in the DAPA-HF trial, most clinical characteristics were qualitatively similar between the 2 groups. Compared with the DAPA-HF trial cohort, there was lower use of evidence-based HF therapies among patients in GWTG-HF. Conclusions and Relevance: These data from a large, contemporary US registry of patients hospitalized with heart failure suggest that 4 of 5 patients with HFrEF (with or without type 2 diabetes) would be candidates for initiation of dapagliflozin, supporting its broad generalizability to US clinical practice.

11.
Circulation ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200953

RESUMO

Background: The COVID-19 pandemic has exposed longstanding racial/ethnic inequities in health risks and outcomes in the U.S.. We sought to identify racial/ethnic differences in presentation and outcomes for patients hospitalized with COVID-19. Methods: The American Heart Association COVID-19 Cardiovascular Disease Registry is a retrospective observational registry capturing consecutive patients hospitalized with COVID-19. We present data on the first 7,868 patients by race/ethnicity treated at 88 hospitals across the US between 01/17/2020 and 7/22/2020. The primary outcome was in-hospital mortality; secondary outcomes included major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, heart failure) and COVID-19 cardiorespiratory ordinal severity score (worst to best: death, cardiac arrest, mechanical ventilation with mechanical circulatory support, mechanical ventilation with vasopressors/inotrope support, mechanical ventilation without hemodynamic support, and hospitalization without any of the above). Multivariable logistic regression analyses were performed to assess the relationship between race/ethnicity and each outcome adjusting for differences in sociodemographic, clinical, and presentation features, and accounting for clustering by hospital. Results: Among 7,868 patients hospitalized with COVID-19, 33.0% were Hispanic, 25.5% were non-Hispanic Black, 6.3% were Asian, and 35.2% were non-Hispanic White. Hispanic and Black patients were younger than non-Hispanic White and Asian patients and were more likely to be uninsured. Black patients had the highest prevalence of obesity, hypertension, and diabetes. Black patients also had the highest rates of mechanical ventilation (23.2%) and renal replacement therapy (6.6%) but the lowest rates of remdesivir use (6.1%). Overall mortality was 18.4% with 53% of all deaths occurring in Black and Hispanic patients. The adjusted odds ratios (ORs) for mortality were 0.93 (95% confidence interval [CI] 0.76-1.14) for Black patients, 0.90 (95% CI 0.73-1.11) for Hispanic patients, and 1.31 (95% CI 0.96-1.80) for Asian patients compared with non-Hispanic White patients. The median OR across hospitals was 1.99 (95% CI 1.74-2.48). Results were similar for MACE. Asian patients had the highest COVID-19 cardiorespiratory severity at presentation (adjusted OR 1.48, 95% CI 1.16-1.90). Conclusions: Although in-hospital mortality and MACE did not differ by race/ethnicity after adjustment, Black and Hispanic patients bore a greater burden of mortality and morbidity due to their disproportionate representation among COVID-19 hospitalizations.

14.
PLoS One ; 15(11): e0240567, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33141828

RESUMO

Identification of individuals at risk for heart failure is needed to deliver targeted preventive strategies and maximize net benefit of interventions. To examine the clinical utility of the recently published heart failure-specific risk prediction model, the Pooled Cohort Equations to Prevent Heart Failure, we sought to demonstrate the range of risk values associated with diverse risk factor combinations in White and Black men and women. We varied individual risk factors while holding the other risk factors constant at age-adjusted national mean values for risk factors in each race-sex and age group. We also examined multiple combinations of risk factor levels and examined the range of predicted 10-year heart failure risk using the Pooled Cohort Equations to Prevent Heart Failure risk tool. Ten-year predicted heart failure risk varied widely for each race-sex group across a range of ages and risk factor scenarios. For example, predicted 10-year heart failure risk in a hypothetical 40 year old varied from 0.1% to 9.7% in a White man, 0.5% to 12.3% in a Black man, <0.1% to 9.3% in a White woman, and 0.2% to 28.0% in a Black woman. Higher risk factor burden (e.g. diabetes and hypertension requiring treatment) consistently drove higher risk estimates in all race-sex groups and across all ages. Our analysis highlights the importance of a race and sex-specific multivariable risk prediction model for heart failure to personalize the clinician-patient discussion, inform future practice guidelines, and provide a framework for future risk-based prevention trials for heart failure.

17.
Circ Heart Fail ; 13(11): e007462, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33092406

RESUMO

BACKGROUND: Guidelines recommend identification of individuals at risk for heart failure (HF). However, implementation of risk-based prevention strategies requires validation of HF-specific risk scores in diverse, real-world cohorts. Therefore, our objective was to assess the predictive accuracy of the Pooled Cohort Equations to Prevent HF within a primary prevention cohort derived from the electronic health record. METHODS: We retrospectively identified patients between the ages of 30 to 79 years in a multi-center integrated healthcare system, free of cardiovascular disease, with available data on HF risk factors, and at least 5 years of follow-up. We applied the Pooled Cohort Equations to Prevent HF tool to calculate sex and race-specific 5-year HF risk estimates. Incident HF was defined by the International Classification of Diseases codes. We assessed model discrimination and calibration, comparing predicted and observed rates for incident HF. RESULTS: Among 31 256 eligible adults, mean age was 51.4 years, 57% were women and 11% Black. Incident HF occurred in 568 patients (1.8%) over 5-year follow-up. The modified Pooled Cohort Equations to Prevent HF model for 5-year risk prediction of HF had excellent discrimination in White men (C-statistic 0.82 [95% CI, 0.79-0.86]) and women (0.82 [0.78-0.87]) and adequate discrimination in Black men (0.69 [0.60-0.78]) and women (0.69 [0.52-0.76]). Calibration was fair in all race-sex subgroups (χ2<20). CONCLUSIONS: A novel sex- and race-specific risk score predicts incident HF in a real-world, electronic health record-based cohort. Integration of HF risk into the electronic health record may allow for risk-based discussion, enhanced surveillance, and targeted preventive interventions to reduce the public health burden of HF.

18.
Eur J Heart Fail ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118664

RESUMO

AIMS: To evaluate temporal trends in the enrolment of females in randomized controlled trials (RCTs) of heart failure with reduced ejection fraction (HFrEF) published in high-impact journals, and assess RCT characteristics associated with under-enrolment. METHODS AND RESULTS: We searched MEDLINE, EMBASE and CINAHL for studies published from January 2000 to May 2019 in journals with impact factor ≥10. We included RCTs that recruited adults with HFrEF. We used a 20% threshold below the sex distribution of HFrEF to define under-enrolment. We used multivariable logistic regression to assess trial characteristics independently associated with under-enrolment. We included 317 RCTs. Among the 183 097 participants, mean (standard deviation) age was 63.0 (7.0) years and 25.5% were female. Females were under-enrolled in 71.6% [95% confidence interval (CI) 66.6-76.6%] of the RCTs; enrolment did not increase significantly between 2000-2019. Sex-related eligibility criteria [odds ratio (OR) 2.05, 95% CI 1.01-4.16; P = 0.046]; recruitment in ambulatory settings (OR 2.56, 95% CI 1.37-4.81; P = 0.003); trial coordination in North America (OR 4.44, 95% CI 1.09-18.07; P = 0.037), Europe (OR 6.79, 95% CI 1.63-27.39; P = 0.018) and Asia (OR 9.33, 95% CI 1.40-12.40; P = 0.033); drug (OR 1.76, 95% CI 1.96-7.36; P < 0.001) and device/surgical interventions (OR 1.69, 95% CI 1.16-9.43; P = 0.002); and men in first and last authorship position (OR 1.32, 95% CI 1.12-3.54; P = 0.047) were associated with under-enrolment of females. CONCLUSIONS: Females were under-enrolled relative to disease distribution in a majority of high-impact HFrEF RCTs, with no change in temporal trends between 2000 and 2019. Trial characteristics and gender of trial leaders were associated with under-enrolment.

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