Equity in Cardio-Oncology Care and Research: A Scientific Statement From the American Heart Association.

Advances in cancer therapeutics have revolutionized survival outcomes in patients with cancer. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Recent studies have uncovered excess risks of these cardiotoxic events, especially in traditionally underrepresented populations. Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations. Previously decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigation, and potential optimal strategies to address disparate cardiotoxicity in contemporary cancer care (eg, with immunotherapy, biologic, or cytotoxic therapies) settings. This scientific statement aims to define the current state of evidence for disparate cardiotoxicity while proposing uniform and novel methodological approaches to inform the identification and mitigation of disparate cardio-oncology outcomes in future clinical trials, registries, and daily clinical care settings. We also propose an evidence-based integrated approach to identify and mitigate disparities in the routine clinical setting. This consensus scientific statement summarizes and clarifies available evidence while providing guidance on addressing inequities in the era of emerging anticancer therapies.

Change in Caregiver Health-Related Quality of Life From Before to Early After Surgery: SUSTAIN-IT Study.

BACKGROUND: Information about health-related quality of life (HRQOL) among caregivers of older patients with heart failure who receive heart transplantation (HT) and mechanical circulatory support (MCS) is sparse. We describe differences and factors associated with change in HRQOL before and early post-surgery among caregivers of older heart failure patients who underwent 3 surgical therapies: HT with pretransplant MCS (HT MCS), HT without pretransplant MCS (HT non-MCS), and long-term MCS. METHODS: Caregivers of older patients (60-80 years) from 13 US sites completed the EQ-5D-3 L visual analog scale (0 [worst]-100 [best] imaginable health state) and dimensions before and 3 and 6 months post-surgery. Analyses included linear regression, t tests, and nonparametric tests. RESULTS: Among 227 caregivers (HT MCS=54, HT non-MCS=76, long-term MCS=97; median age 62.7 years, 30% male, 84% White, 83% spouse/partner), EQ-5D visual analog scale scores were high before (84.8±14.1) and at 3 (84.7±13.0) and 6 (83.9±14.7) months post-surgery, without significant differences among groups or changes over time. Patient pulmonary hypertension presurgery (ß=-13.72 [95% CI, -21.07 to -6.36]; P<0.001) and arrhythmia from 3 to 6 months post-operatively (ß=-14.22 [95% CI, -27.41 to -1.02]; P=0.035) were associated with the largest decrements in caregiver HRQOL; patient marital/partner status (ß=6.21 [95% CI, 1.34-11.08]; P=0.013) and presurgery coronary disease (ß=8.98 [95% CI, 4.07-13.89]; P<0.001) were associated with the largest improvements. CONCLUSIONS: Caregivers of older patients undergoing heart failure surgeries reported overall high HRQOL before and early post-surgery. Understanding factors associated with caregiver HRQOL may inform decision-making and support needs. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02568930.

Misconceptions and Facts about Heart Failure with Reduced Ejection Fraction.

Heart failure with reduced ejection fraction is a significant driver of morbidity and mortality. There are common misconceptions regarding the disease processes underlying heart failure and best practices for therapy. The terms heart failure with reduced ejection fraction and left ventricular systolic dysfunction are not interchangeable terms. Key therapies for heart failure with reduced ejection fraction target the underlying disease processes, not the left ventricular ejection fraction alone. The absence of congestion does not rule out heart failure. Patients with cardiac amyloidosis can also present with heart failure with reduced ejection fraction. A rise in serum creatinine in acute heart failure exacerbation is not associated with tubular injury. Guideline directed medical therapy should be continued during acute exacerbations of heart failure with reduced ejection fraction and should be started in the same hospitalization in new diagnoses. Marginal blood pressure is not a relative contraindication to optimal guideline directed medical therapy. Guideline directed medical therapy should be continued even if ejection fraction improves. There are other therapies that provide significant benefit besides the four key medications in guideline directed medical therapy.

Applicability of Vericiguat to Patients Hospitalized for Heart Failure in the United States.

BACKGROUND: In January 2021, vericiguat, a soluble guanylate cyclase stimulator, was approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of cardiovascular death and heart failure (HF) hospitalization among patients with a recent worsening HF event based on the VICTORIA (VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial. OBJECTIVES: This study sought to leverage a contemporary U.S. registry of patients hospitalized for heart failure (HF) to characterize patients who may be candidates for vericiguat based on FDA label and the VICTORIA trial eligibility criteria. METHODS: The authors studied patients hospitalized for HF with ejection fraction (EF) <45% across 525 sites in the GWTG-HF (Get With The Guidelines-Heart Failure) registry between January 2014 and December 2020. Approximate FDA label criteria (excluding estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2, dialysis, or patients with heart transplantation or durable mechanical circulatory support) and eligibility criteria for the VICTORIA trial were applied to the GWTG-HF cohort. RESULTS: Among 241,057 patients with EF <45% in the GWTG-HF registry, 221,730 (92%) could be candidates for vericiguat under the FDA label and 92,249 (38%) would have been eligible for the VICTORIA trial. The most frequent reasons for ineligibility for the FDA label were eGFR <15 mL/min/1.73 m2 (5.7%) and dialysis (1.6%). Although there were greater proportions of women and Black patients in the GWTG-HF registry, most clinical characteristics were qualitatively similar with patients enrolled in the VICTORIA trial. Among Medicare beneficiaries in the GWTG-HF registry eligible for vericiguat by either FDA label or VICTORIA trial criteria, 12-month postdischarge rates of mortality (36%-37%), HF hospitalization (33%-35%), all-cause hospitalization (64%-66%), and mean health care expenditure (U.S. $25,106-$25,428) were high. CONCLUSIONS: Data from a large, contemporary U.S. registry of patients actively hospitalized for HF with EF <45% suggest that approximately 4 in 10 patients meet the criteria of the VICTORIA trial and that more than 9 in 10 patients are potential candidates for vericiguat based on the FDA label. Contemporary Medicare beneficiaries hospitalized for HF with EF <45% and eligible for vericiguat face high rates of postdischarge mortality and readmission and accrue substantial health care costs.

Interconnected Clinical and Social Risk Factors in Breast Cancer and Heart Failure.

Breast cancer and heart failure share several known clinical cardiovascular risk factors, including age, obesity, glucose dysregulation, cholesterol dysregulation, hypertension, atrial fibrillation and inflammation. However, to fully comprehend the complex interplay between risk of breast cancer and heart failure, factors attributed to both biological and social determinants of health must be explored in risk-assessment. There are several social factors that impede implementation of prevention strategies and treatment for breast cancer and heart failure prevention, including socioeconomic status, neighborhood disadvantage, food insecurity, access to healthcare, and social isolation. A comprehensive approach to prevention of both breast cancer and heart failure must include assessment for both traditional clinical risk factors and social determinants of health in patients to address root causes of lifestyle and modifiable risk factors. In this review, we examine clinical and social determinants of health in breast cancer and heart failure that are necessary to consider in the design and implementation of effective prevention strategies that altogether reduce the risk of both chronic diseases.

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. STRUCTURE: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. STRUCTURE: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

Propensity Score-Matched Comparison of Right Ventricular Strain in Women and Men Before and After Left Ventricular Assist Device Implantation.

Objective: Adverse events following left ventricular assist device (LVAD) implantation are more common in women than in men, but the impact of gender differences on right ventricular (RV) failure is not well defined. Therefore, we calculated RV strain before and after LVAD implantation in matched groups of men and women to determine if gender differences in RV failure after LVAD might account for the gender differences in overall outcomes. Methods: RV free wall longitudinal strain (FWS) and fractional area change were calculated preoperatively and 3 months postoperatively using speckle-tracking echocardiography analysis. A total of 172 patients (86 women, 86 men) were then propensity score matched (1:1) for comparison. Results: Although women had higher preoperative CHA2DS2-VASc scores and more frequent moderate mitral regurgitation than men (P = 0.018), the preoperative hemodynamic parameters were similar. Preoperative RV-FWS was -6.7% in women and -6.0% in men (P = 0.65). Postoperatively, women had more progression to severe tricuspid regurgitation (TR) than men (15% vs 7%, P = 0.06). At 3 months the RV-FWS was -7.7% in women and -7.0% in men (P = 0.59). Postoperative TR was moderate-severe in 20% of women and in 9% of men (P = 0.001). Women had a higher incidence of venous thromboembolism, cardiac arrhythmias, and bleeding compared with men. Women also had higher mortality rates at discharge and 30 days after surgery, but the survival rates at 5 years were similar. Conclusions: RV strain measurements track standard hemodynamic and echocardiographic parameters and confirm that gender differences in outcomes following LVAD implantation are not related to gender differences in RV failure rates.

Development and Validation of a Long-Term Incident Heart Failure Risk Model.

BACKGROUND: Average lifetime risk for heart failure (HF) is high but differs significantly across and within sex-race groups. No models for estimating long-term risk for HF exist, which would allow for earlier identification and interventions in high-risk subsets. The authors aim to derive 30-year HF risk equations. METHODS: Adults between the ages of 20 to 59 years and free of cardiovascular disease at baseline from 5 population-based cohorts were included. Among 24 838 participants (55% women, 25% Black based on self-report), follow-up consisted of 599 551 person-years. Sex- and race-specific 30-year HF risk equations were derived and validated accounting for competing risk of non-HF death. HF was based on a clinical diagnosis. Model discrimination and calibration were assessed using 10-fold cross-validation. Finally, the model was applied to varying risk factor patterns for systematic examination. RESULTS: The rate of incident HF was 4.0 per 1000 person-years. Harrell C statistics were 0.82 (0.80-0.83) and 0.84 (0.82-0.85) in White and Black men and 0.84 (0.82-0.85) and 0.85 (0.83-0.87) in White and Black women, respectively. Hosmer-Lemeshow calibration was acceptable, with χ2 <30 in all subgroups. Risk estimation varied across sex-race groups: for example, in an average 40-year-old nonsmoker with an untreated systolic blood pressure of 140 mm Hg and body mass index of 30 kg/m2, risk was estimated to be 22.8% in a Black man, 13.7% in a White man, 13.0% in a Black woman, and 12.1% in a White woman. CONCLUSIONS: Sex- and race-specific equations for prediction of long-term risk of HF demonstrated high discrimination and adequate calibration.

Clinical Effectiveness of Sacubitril/Valsartan Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction.

Background Sacubitril/Valsartan has been highly efficacious in randomized trials of heart failure with reduced ejection fraction (HFrEF). However, the effectiveness of sacubitril/valsartan in older patients hospitalized for HFrEF in real-world US practice is unclear. Methods and Results This study included Medicare beneficiaries age ≥65 years who were hospitalized for HFrEF ≤40% in the Get With The Guidelines-Heart Failure registry between October 2015 and December 2018, and eligible for sacubitril/valsartan. Associations between discharge prescription of sacubitril/valsartan and clinical outcomes were assessed after inverse probability of treatment weighting and adjustment for other HFrEF medications. Overall, 1551 (10.9%) patients were discharged on sacubitril/valsartan. Of those not prescribed sacubitril/valsartan, 7857 (62.0%) were prescribed an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. Over 12-month follow-up, compared with a discharge prescription of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, sacubitril/valsartan was independently associated with lower all-cause mortality (adjusted hazard ratio [HR], 0.82; 95% CI, 0.72-0.94; P=0.004) but not all-cause hospitalization (adjusted HR, 0.97; 95% CI, 0.89-1.07; P=0.55) or heart failure hospitalization (adjusted HR, 1.04; 95% CI, 0.91-1.18; P=0.59). Patients prescribed sacubitril/valsartan versus those without a prescription had lower risk of all-cause mortality (adjusted HR, 0.69; 95% CI, 0.60-0.79; P<0.001), all-cause hospitalization (adjusted HR, 0.90; 95% CI, 0.82-0.98; P=0.02), but not heart failure hospitalization (adjusted HR, 0.94; 95% CI, 0.82-1.08; P=0.40). Conclusions Among patients hospitalized for HFrEF, prescription of sacubitril/valsartan at discharge was independently associated with reduced postdischarge mortality compared with angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, and reduced mortality and all-cause hospitalization compared with no sacubitril/valsartan. These findings support the use of sacubitril/valsartan to improve postdischarge outcomes among older patients hospitalized for HFrEF in routine US clinical practice.

Kidney Function and Outcomes in Patients Hospitalized With Heart Failure.

BACKGROUND: Few contemporary data exist evaluating care patterns and outcomes in heart failure (HF) across the spectrum of kidney function. OBJECTIVES: This study sought to characterize differences in quality of care and outcomes in patients hospitalized for HF by degree of kidney dysfunction. METHODS: Guideline-directed medical therapies were evaluated among patients hospitalized with HF at 418 sites in the GWTG-HF (Get With The Guidelines-Heart Failure) registry from 2014 to 2019 by discharge CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)-derived estimated glomerular filtration rate (eGFR). We additionally evaluated the risk-adjusted association of admission eGFR with in-hospital mortality. RESULTS: Among 365,494 hospitalizations (age 72 ± 15 years, left ventricular ejection fraction [EF]: 43 ± 17%), median discharge eGFR was 51 ml/min/1.73 m2 (interquartile range: 34 to 72 ml/min/1.73 m2), 234,332 (64%) had eGFR <60 ml/min/1.73 m2, and 18,869 (5%) were on dialysis. eGFR distribution remained stable from 2014 to 2019. Among 157,439 patients with HF with reduced EF (≤40%), discharge guideline-directed medical therapies, including beta-blockers, were lowest in discharge eGFR <30 mL/min/1.73 m2 or dialysis (p < 0.001). "Triple therapy" with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor + beta-blocker + mineralocorticoid receptor antagonist was used in 38%, 33%, 25%, 15%, 5%, and 3% for eGFR ≥90, 60 to 89, 45 to 59, 30 to 44, <30 ml/min/1.73 m2, and dialysis, respectively; p < 0.001. Mortality was higher in a graded fashion at lower admission eGFR groups (1.1%, 1.5%, 2.0%, 3.0%, 5.0%, and 4.2%, respectively; p < 0.001). Steep covariate-adjusted associations between admission eGFR and mortality were observed across EF subgroups, but was slightly stronger for HF with reduced EF compared with HF with mid-range or preserved EF (pinteraction = 0.045). CONCLUSIONS: Despite facing elevated risks of mortality, patients with comorbid HF with reduced EF and kidney disease are not optimally treated with evidence-based medical therapies, even at levels of eGFR where such therapies would not be contraindicated by kidney dysfunction. Further efforts are required to mitigate risk in comorbid HF and kidney disease.

Risk-Based Approach for the Prediction and Prevention of Heart Failure.

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.

Cardiac transplantation outcomes in patients with amyloid cardiomyopathy.

OBJECTIVE: Amyloid cardiomyopathy (ACM) is a progressive and life-threatening disease caused by abnormal protein deposits within cardiac tissue. The most common forms of ACM are caused by immunoglobulin derived light chains (AL) and transthyretin (TTR). Orthotopic heart transplantation (OHT) remains the definitive treatment for patients with end stage heart failure. In this study, we perform a contemporary multicenter analysis evaluating post OHT survival in patients with ACM. METHODS: We conducted a multicenter analysis of 40,044 adult OHT recipients captured in the United Network for Organ Sharing (UNOS) registry from 1987-2018. Patients were characterized as ACM or non-ACM. Baseline characteristics were obtained, and summary characteristics were calculated. Outcomes of interest included post-transplant survival, infection, treated rejection, and the ability to return to work. Racial differences in OHT survival were also analyzed. Unadjusted associations between ACM and non-ACM survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. RESULTS: Three hundred ninety-eight patients with a diagnosis of ACM were identified of which 313 underwent heart only OHT. ACM patients were older (61 vs 53; P < .0001) and had a higher proportion of African Americans (30.7% vs 17.6%; P < .0001). Median survival for ACM was 10.2 years vs 12.5 years in non-ACM (P = .01). After adjusting for confounding, ACM patients had a higher likelihood of death post-OHT (HR 1.39 CI: 1.14, 1.70; P = .001). African American ACM patients had a higher likelihood of survival compared to White ACM patients (HR 0.51 CI 0.31-0.85; P = .01). No difference was observed in episodes of treated rejection (OR 0.63 CI 0.23, 1.78; P = .39), hospitalizations for infections (OR 1.24 CI: 0.85, 1.81; P = .26), or likelihood of returning to work for income (OR 1.23 CI: 0.84, 1.80; P = .30). CONCLUSIONS: In this analysis of OHT in ACM, ACM was associated with a higher likelihood of post-OHT mortality. Racial differences in post-OHT were observed with African American patients with ACM having higher likelihood of survival compared to White patients with ACM. No differences were observed in episodes of treated rejection, hospitalization for infection, or likelihood to return to work for income.