Cost-Effectiveness of Coronary Artery Bypass Surgery Versus Medicine in Ischemic Cardiomyopathy: The STICH Randomized Clinical Trial.

BACKGROUND: The STICH Randomized Clinical Trial (Surgical Treatment for Ischemic Heart Failure) demonstrated that coronary artery bypass grafting (CABG) reduced all-cause mortality rates out to 10 years compared with medical therapy alone (MED) in patients with ischemic cardiomyopathy and reduced left ventricular function (ejection fraction ≤35%). We examined the economic implications of these results. METHODS: We used a decision-analytic patient-level simulation model to estimate the lifetime costs and benefits of CABG and MED using patient-level resource use and clinical data collected in the STICH trial. Patient-level costs were calculated by applying externally derived US cost weights to resource use counts during trial follow-up. 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: For the CABG arm, we estimated 6.53 quality-adjusted life-years (95% CI, 5.70-7.53) and a lifetime cost of $140 059 (95% CI, $106 401 to $180 992). For the MED arm, the corresponding estimates were 5.52 (95% CI, 5.06-6.09) quality-adjusted life-years and $74 894 lifetime cost (95% CI, $58 372 to $93 541). The incremental cost-effectiveness ratio for CABG compared with MED was $63 989 per quality-adjusted life-year gained. At a societal willingness-to-pay threshold of $100 000 per quality-adjusted life-year gained, CABG was found to be economically favorable compared with MED in 87% of microsimulations. CONCLUSIONS: In the STICH trial, in patients with ischemic cardiomyopathy and reduced left ventricular function, CABG was economically attractive relative to MED at current benchmarks for value in the United States. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00023595.

Policy and Payment Challenges in the Postpandemic Treatment of Heart Failure: Value-Based Care and Telehealth.

Increasing patient and therapeutic complexity have created both challenges and opportunities for heart failure care. Within this background, the coronavirus disease-2019 pandemic has disrupted care as usual, accelerating the need for transition from volume-based to value-based care, and demanding a rapid expansion of telehealth and remote care for heart failure. Patients, clinicians, health systems, and payors have by necessity become more invested in these issues. Herein we review recent changes in health care policy related to the movement from volume to value-based payment and from in-person to remote care delivery.

Race and Ethnicity in Heart Failure: JACC Focus Seminar 8/9.

Heart failure (HF) affects >6 million Americans, with variations in incidence, prevalence, and clinical outcomes by race/ethnicity. Black adults have the highest risk for HF, with earlier age of onset and the highest risk of death and hospitalizations. The risk of hospitalizations for Hispanic patients is higher than White patients. Data on HF in Asian individuals are more limited. However, the higher burden of traditional cardiovascular risk factors, particularly among South Asian adults, is associated with increased risk of HF. The role of environmental, socioeconomic, and other social determinants of health, more likely for Black and Hispanic patients, are increasingly recognized as independent risk factors for HF and worse outcomes. Structural racism and implicit bias are drivers of health care disparities in the United States. This paper will review the clinical, physiological, and social determinants of HF risk, unique for race/ethnic minorities, and offer solutions to address systems of inequality that need to be recognized and dismantled/eradicated.

Managing the economic challenges in the treatment of heart failure.

BACKGROUND: Treatment of heart failure is complex and inherently challenging. Patients traverse multiple practice settings as inpatients and outpatients, often resulting in fragmented care. The Center for Medicare and Medicaid Services is implementing payment programs that reward delivery of high-quality, cost-effective care, and one of the newer programs, the Bundled Payment for Care Improvement Advanced program, attempts to improve the coordination of care across practices for a hospitalization episode and post-acute care. The quality and cost of care contribute to its value, but value may be defined in different ways by different entities. CONCLUSIONS: The rapidly changing world of digital health may contribute to or detract from the quality and cost of care. Health systems, payers, and patients are all grappling with these issues, which were reviewed at a symposium at the Heart Failure Society of America conference in Philadelphia, Pennsylvania on September 14, 2019. This article constitutes the proceedings from that symposium.

Research Priorities in the Secondary Prevention of Atrial Fibrillation: A National Heart, Lung, and Blood Institute Virtual Workshop Report.

There has been sustained focus on the secondary prevention of coronary heart disease and heart failure; yet, apart from stroke prevention, the evidence base for the secondary prevention of atrial fibrillation (AF) recurrence, AF progression, and AF-related complications is modest. Although there are multiple observational studies, there are few large, robust, randomized trials providing definitive effective approaches for the secondary prevention of AF. Given the increasing incidence and prevalence of AF nationally and internationally, the AF field needs transformative research and a commitment to evidenced-based secondary prevention strategies. We report on a National Heart, Lung, and Blood Institute virtual workshop directed at identifying knowledge gaps and research opportunities in the secondary prevention of AF. Once AF has been detected, lifestyle changes and novel models of care delivery may contribute to the prevention of AF recurrence, AF progression, and AF-related complications. Although benefits seen in small subgroups, cohort studies, and selected randomized trials are impressive, the widespread effectiveness of AF secondary prevention strategies remains unknown, calling for development of scalable interventions suitable for diverse populations and for identification of subpopulations who may particularly benefit from intensive management. We identified critical research questions for 6 topics relevant to the secondary prevention of AF: (1) weight loss; (2) alcohol intake, smoking cessation, and diet; (3) cardiac rehabilitation; (4) approaches to sleep disorders; (5) integrated, team-based care; and (6) nonanticoagulant pharmacotherapy. Our goal is to stimulate innovative research that will accelerate the generation of the evidence to effectively pursue the secondary prevention of AF.

Temporal Trends and Factors Associated With Cardiac Rehabilitation Participation Among Medicare Beneficiaries With Heart Failure.

OBJECTIVES: The purpose of this study was to assess temporal trends and factors associated with cardiac rehabilitation (CR) enrollment and participation among Medicare beneficiaries after the 2014 Medicare coverage expansion. BACKGROUND: CR improves exercise capacity, quality of life, and clinical outcomes in heart failure (HF) with reduced ejection fraction (HFrEF). In 2014, Medicare coverage for CR was expanded to include chronic HFrEF. METHODS: Among Medicare beneficiaries from quarter (Q) 1 2014 to Q2 2016, 11,696 patients from 14,258 hospitalizations with primary discharge diagnosis of HF were identified. Patients with HF with preserved ejection fraction were excluded. Quarterly CR participation rates among hospitalized HF patients within 6 months of discharge were identified through outpatient administrative claims. The predictors of CR participation were assessed with the use of a multivariable logistic regression model that included patient- and hospital-level characteristics. A secondary analysis to assess participation rates of CR after outpatient encounters for HF was performed. RESULTS: Overall, only 611 (4.3%) and 349 (2.2%) eligible patients participated CR after primary hospitalization or outpatient visit for HF, respectively. There was a modest, statistically significant increase in CR participation after HF admissions (2.8% in Q1 2014; 5.0% in Q2 2016; p < 0.001) without significant increase after outpatient visits for HF (2.6% to 3.8%; p = 0.21). Younger age, male sex, nonblack race, previous cardiovascular procedures, and hospitalization at hospitals with available CR facilities were all independently associated with CR participation. CONCLUSIONS: CR participation among eligible Medicare beneficiaries with HFrEF was low with minimal increase since 2014 Medicare coverage decision. Sex, race, and institution-dependent variables were independent predictors of CR participation.

Racial and Ethnic Differences in Biomarkers, Health Status, and Cardiac Remodeling in Patients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan.

BACKGROUND: Among patients with heart failure and reduced ejection fraction (left ventricular (LV) ejection fraction ≤40%), sacubitril/valsartan (S/V) treatment is associated with improved health status and reverse cardiac remodeling. Data regarding racial and ethnic differences in response to S/V are lacking. METHODS: This was an analysis from the PROVE-HF study (Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure). Longitudinal changes in NT-proBNP (N-terminal pro-B-type natriuretic peptide), cardiac reverse remodeling, and health status scores were compared between groups using multivariate latent growth curve modeling. RESULTS: Among the 782 patients included in this study, 22.7% were non-Hispanic Black (from here referred to as Black), 14.9% were Hispanic, and 62.4% were non-Hispanic White (from here referred to as White). At baseline, compared with White patients, Black and Hispanic patients had lower NT-proBNP (g=0.34) and differences between groups in baseline values for LV end-diastolic volume index and LV end-systolic volume index were negligible (g<0.10). Following S/V initiation, NT-proBNP decreased in all 3 groups (P<0.0001) associated with improvements in LV ejection fraction, LV end-diastolic volume index, and LV end-systolic volume index. Although total improvement in LV measures was similar between groups, Black patients averaged larger gains in the first half of the trial while White patients averaged larger gains in the second half. Improvements in Kansas City Cardiomyopathy Questionnaire-23 Total Symptom scores were seen in all 3 groups. Treatment with S/V was well-tolerated. CONCLUSIONS: Among Black, Hispanic, and White patients with heart failure and reduced ejection fraction, treatment with S/V was associated with similar reduction in NT-proBNP, improvement in health status, and reverse remodeling. More data regarding racial and ethnic responses to heart failure and reduced ejection fraction treatment are needed. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.

Assessment of Limitations to Optimization of Guideline-Directed Medical Therapy in Heart Failure From the GUIDE-IT Trial: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Despite evidence that guideline-directed medical therapy (GDMT) improves outcomes in patients with heart failure (HF) and reduced ejection fraction, many patients are undertreated. The Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) trial tested whether a strategy of using target concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) to guide optimization of GDMT could improve outcomes. Objective: To examine medical therapy for HF in GUIDE-IT and potential reasons why the intervention did not produce improvements in medical therapy. Design, Setting, and Participants: GUIDE-IT, a randomized clinical trial performed at 45 sites in the United States and Canada, was conducted from January 16, 2013, to September 20, 2016. A total of 894 patients with HF and reduced ejection fraction (≤40%) were randomized to NT-proBNP-guided treatment with a goal to suppress NT-proBNP concentrations to less than 1000 pg/mL vs usual care. This secondary analysis examined the medical therapy titration and reasons why the intervention did not produce improvements in care and outcomes. Data were analyzed March 27 to June 28, 2019. Main Outcomes and Measures: For each encounter, medication titrations were captured. A reason was requested if a modification was not made. A Cox proportional hazards regression model was used to assess the independent association of drug class with outcomes. Results: Among the 838 patients available for analysis (566 men [67.5%]; median age, 62.0 years), 6223 visits occurred during 24 months. Adjustments of HF medication were made during 2847 of 5218 qualified visits (54.6%) (all usual care visits and all guided care visits with NT-proBNP level ≥1000 pg/mL) in 862 patients (96.4%). Most adjustments occurred within the first 6 months, primarily within the first 6 weeks. The most common reasons for not adjusting were "clinically stable" and "already at maximally tolerated therapy." Only 130 patients (15.5%) achieved optimal GDMT (≥50% of the target dose of ß-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or any dose of mineralocorticoid antagonists) at 6 months, an increase from the baseline (79 of 891 [8.9%]) but not different by treatment arm. Higher doses of ß-blockers were associated with reduced risk of the composite outcome of HF hospitalization and cardiovascular death (hazard ratio [HR], 0.98; 95% CI, 0.97-1.00; P = .008) and of all-cause death (HR, 0.97; 95% CI, 0.95-0.99; P = .01). Higher doses of angiotensin-converting enzyme inhibitors (HR, 0.84; 95% CI, 0.75-0.93; P < .001) and angiotensin receptor blockers (HR, 0.84; 95% CI, 0.71-0.99; P = .04) were associated with reduced risk of all-cause death. Increasing doses of mineralocorticoid antagonists did not appear to be associated with improved outcomes. Conclusions and Relevance: Despite a protocol-driven approach, many patients in GUIDE-IT did not receive medication adjustments and did not achieve optimal GDMT, including those with known elevated NT-proBNP concentrations. These results suggest that opportunities exist to titrate medications for maximal benefit in HF. GUIDE-IT may have failed to achieve treatment benefit because of therapeutic inertia in clinical practice, or current GDMT goals may be unrealistic. Trial Registration: ClinicalTrials.gov Identifier: NCT01685840.

Burden of medical co-morbidities and benefit from surgical revascularization in patients with ischaemic cardiomyopathy.

AIMS: The landmark STICH trial found that surgical revascularization compared to medical therapy alone improved survival in patients with heart failure (HF) of ischaemic aetiology and an ejection fraction (EF) ≤ 35%. However, the interaction between the burden of medical co-morbidities and the benefit from surgical revascularization has not been previously described in patients with ischaemic cardiomyopathy. METHODS AND RESULTS: The STICH trial (ClinicalTrials.gov Identifier: NCT00023595) enrolled patients ≥ 18 years of age with coronary artery disease amenable to coronary artery bypass grafting (CABG) and an EF ≤ 35%. Eligible participants were randomly assigned 1:1 to receive medical therapy (MED) (n = 602) or MED/CABG (n = 610). A modified Charlson co-morbidity index (CCI) based on the availability of data and study definitions was calculated by summing the weighted points for all co-morbid conditions. Patients were divided into mild/moderate (CCI 1-4) and severe (CCI ≥ 5) co-morbidity. Cox proportional hazards models were used to evaluate the association between CCI and outcomes and the interaction between severity of co-morbidity and treatment effect. The study population included 349 patients (29%) with a mild/moderate CCI score and 863 patients (71%) with a severe CCI score. Patients with a severe CCI score had greater functional limitations based on 6-min walk test and impairments in health-related quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire. A total of 161 patients (Kaplan-Meier rate = 50%) with a mild/moderate CCI score and 579 patients (Kaplan-Meier rate = 69%) with a severe CCI score died over a median follow-up of 9.8 years. After adjusting for baseline confounders, patients with a severe CCI score were at higher risk for all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.19-1.74; P < 0.001). There was no interaction between CCI score and treatment effect on survival (P = 0.756). CONCLUSIONS: More than 70% of patients had a severe burden of medical co-morbidities at baseline, which was independently associated with increased risk of death. There was not a differential benefit of surgical revascularization with respect to survival based on severity of co-morbidity.

Increasing Diversity in Clinical Trials: Overcoming Critical Barriers.

Clinical trial results provide the critical evidence base for evaluating the safety and efficacy of new medicines and medical products. Efficacy and safety may differ among population subgroups depending on intrinsic/extrinsic factors, including sex, age, race, ethnicity, lifestyle, and genetic background. Racial and ethnic minorities continue to be underrepresented in cardiovascular and other clinical trials. Although barriers to diversity in trials are well recognized, sustainable solutions for overcoming them have proved elusive. We investigated barriers impacting minority patients' willingness to participate in trials and-based on literature review and evaluation, and input from key stakeholders, including minority patients, referring physicians, investigators who were minority-serving physicians, and trial coordinators-formulated potential solutions and tested them across stakeholder groups. We identified key themes from solutions that resonated with stakeholders using a transtheoretical model of behavior change and created a communications message map to support a multistakeholder approach for overcoming critical participant barriers.

Managing the Economic Challenges in the Treatment of Heart Failure.

The economics of heart failure (HF) touches all patients with HF, their families, and the physicians and health systems that care for them. HF is specifically targeted by cost-reduction and care quality initiatives from the Centers for Medicare and Medicaid Services (CMS). The changing quality assessment and payment landscape is, and will continue to be, challenging for hospitals and HF specialists as they provide care for patients with this debilitating disease. Quality-based payment systems with evolving performance metrics are replacing traditional volume-based fee-for-service models. A critical objective of quality-based models is to improve care and reduce cost, but there are few data to support decision-making on how to improve. CMS payment programs and their implications for health systems treating HF were reviewed at a symposium at the Heart Failure Society of America conference in Nashville, Tennessee on September 15, 2018. This article constitutes the proceedings from that symposium.

Economic and Quality-of-Life Outcomes of Natriuretic Peptide-Guided Therapy for Heart Failure.

BACKGROUND: The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial prospectively compared the efficacy of an N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided heart failure treatment strategy (target NT-proBNP level <1,000 pg/ml) with optimal medical therapy alone in high-risk patients with heart failure and reduced ejection fraction. When the study was stopped for futility, 894 patients had been enrolled. OBJECTIVES: The purpose of this study was to assess treatment-related quality-of-life (QOL) and economic outcomes in the GUIDE-IT trial. METHODS: The authors prospectively collected a battery of QOL instruments at baseline and 3, 6, 12, and 24 months post-randomization (collection rates 90% to 99% of those eligible). The principal pre-specified QOL measures were the Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and the Duke Activity Status Index (DASI). Cost data were collected for 735 (97%) U.S. RESULTS: Baseline variables were well balanced in the 446 patients randomized to the NT-proBNP-guided therapy and 448 to usual care. Both the KCCQ and the DASI improved over the first 6 months, but no evidence was found for a strategy-related difference (mean difference [biomarker-guided - usual care] at 24 months of follow-up 2.0 for DASI [95% confidence interval (CI): -1.3 to 5.3] and 1.1 for KCCQ [95% CI: -3.7 to 5.9]). Total winsorized costs averaged $5,919 higher in the biomarker-guided strategy (95% CI: -$1,795, +$13,602) over 15-month median follow-up. CONCLUSIONS: A strategy of NT-proBNP-guided HF therapy had higher total costs and was not more effective than usual care in improving QOL outcomes in patients with heart failure and a reduced ejection fraction. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

Personalized medicine and Hispanic health: improving health outcomes and reducing health disparities - a National Heart, Lung, and Blood Institute workshop report.

Persons of Hispanic/Latino descent may represent different ancestries, ethnic and cultural groups and countries of birth. In the U.S., the Hispanic/Latino population is projected to constitute 29% of the population by 2060. A personalized approach focusing on individual variability in genetics, environment, lifestyle and socioeconomic determinants of health may advance the understanding of some of the major factors contributing to the health disparities experienced by Hispanics/Latinos and other groups in the U.S., thus leading to new strategies that improve health care outcomes. However, there are major gaps in our current knowledge about how personalized medicine can shape health outcomes among Hispanics/Latinos and address the potential factors that may explain the observed differences within this heterogeneous group, and between this group and other U.S. demographic groups. For that purpose, the National Heart, Lung, and Blood Institute (NHLBI), in collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the Food and Drug Administration (FDA), held a workshop in which experts discussed (1) potential approaches to study medical treatments and health outcomes among Hispanics/Latinos and garner the necessary evidence to fill gaps of efficacy, effectiveness and safety of therapies for heart, lung, blood and sleep (HLBS) disorders and conditions--and their risk factors; (2) research opportunities related to personalized medicine to improve knowledge and develop effective interventions to reduce health disparities among Hispanics/Latinos in the U.S.; and (3) the incorporation of expanded sociocultural and socioeconomic data collection and genetic/genomic/epigenetic information of Hispanic/Latino patients into their clinical assessments, to account for individual variability in ancestry; physiology or disease risk; culture; environment; lifestyle; and socioeconomic determinants of health. The experts also provided recommendations on: sources of Hispanic/Latino health data and strategies to enhance its collection; policy; genetics, genomics and epigenetics research; and integrating Hispanic/Latino health research within clinical settings.

American Heart Association's Call to Action for Payment and Delivery System Reform.

The healthcare system is undergoing a transition from paying for volume to paying for value. Clinicians, as well as public and private payers, are beginning to implement alternative delivery and payment models, such as the patient-centered medical home, accountable care organizations, and bundled payment arrangements. Implementation of these new models will necessitate delivery system transformation and will actively involve all fields of medical care, in particular medicine and surgery. This call to action, on behalf of the American Heart Association's Expert Panel on Payment and Delivery System Reform, serves to offer support and direction for further involvement by the American Heart Association. In doing so, it (1) provides baseline review and definition of the present models and some of the early results of these delivery models, including outcomes; (2) initiates a conversation within the American Heart Association on the impact of payment and delivery system reform, as well as how the American Heart Association should engage in the interest of patients; (3) issues a call to action to our organization and to cardiovascular and stroke health professionals across the country to become educated about these models so to as to understand their impact on patient care; and (4) asks the government and other funding agencies, including the American Heart Association, to begin supporting and prioritizing meaningful research endeavors to further evaluate these models.

Predictors of Cardiac Rehabilitation Initiation and Adherence in a Multiracial Urban Population.

BACKGROUND: Lack of initiation and adherence to cardiac rehabilitation (CR) remains a persistent problem. We sought to examine predictors of initiation, adherence, and completion of CR in a unique, minority predominant, urban population. METHODS: We included all patients who were first-time referred to the outpatient CR program at Montefiore Medical Center between 1997 and 2010. The indications for referral included acute myocardial infarction, coronary artery disease, heart failure, stable angina, and valvular heart disease. Adherence was defined as attendance of at least 18 sessions of CR, and completion was defined as attendance of 36 sessions. Multivariable logistic regression was utilized to examine the predictors of initiation, adherence, and completion of CR. RESULTS: A total of 590 patients were included (43.9% white and 56.1% nonwhite patients). Among 400 patients who initiated CR, 229 patients (57.3%) attended at least 18 sessions and 140 patients (35.0%) completed all sessions. Initiation of CR was less likely in patients who were nonwhite (OR = 0.66; 95% CI: 0.44-0.97; P = .04) and those who lacked insurance (OR = 0.54; 95% CI: 0.29-0.83; P = .04). Older age was associated with better adherence (OR = 1.04; 95% CI: 1.02-1.07; P < .001). Requirement of a copayment (OR = 0.57; 95% CI: 0.37-0.87; P = .01) was associated with poor adherence. CONCLUSION: In a multiracial population, nonwhite patients and those who did not have insurance were less likely to initiate CR. Younger age and requirement of copayment were independent predictors for poor adherence. Increasing medical insurance coverage and eliminating copayment may improve the participation and adherence of CR.

Non-invasive assessment of low risk acute chest pain in the emergency department: A comparative meta-analysis of prospective studies.

BACKGROUND: The aim of this meta-analysis was to compare the diagnostic accuracy of cardiac computed tomographic angiography (CCTA), stress echocardiography (SE) and radionuclide single photon emission computed tomography (SPECT) for the assessment of chest pain in emergency department (ED) setting. METHODS: A systematic review of Medline, Cochrane and Embase was undertaken for prospective clinical studies assessing the diagnostic efficacy of CCTA, SE or SPECT, as compared to intracoronary angiography (ICA) or the later presence of major adverse clinical outcomes (MACE), in patients presenting to the ED with chest pain. Standard approach and bivariate analysis were performed. RESULTS: Thirty-seven studies (15 CCTA, 9 SE, 13 SPECT) comprising a total of 7800 patients fulfilled inclusion criteria. The respective weighted mean sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and total diagnostic accuracy for CCTA were: 95%, 99%, 84%, 100% and 99%, for SE were: 84%, 94%, 73%, 96% and 96%, and for SPECT were: 85%, 86%, 57%, 95% and 88%. There was no significant difference between modalities in terms of NPV. Bivariate analysis revealed that CCTA had statistically greater sensitivity, specificity, PPV and overall diagnostic accuracy when compared to SE and SPECT. CONCLUSIONS: All three modalities, when employed by an experienced clinician, are highly accurate. Each has its own strengths and limitations making each well suited for different patient groups. CCTA has higher accuracy than SE and SPECT, but it has many drawbacks, most importantly its lack of physiologic data.