Cardio-Oncology Drug Interactions: A Scientific Statement From the American Heart Association.

In the cardio-oncology population, drug interactions are of particular importance given the complex pharmacological profile, narrow therapeutic index, and inherent risk of therapies used to manage cardiovascular disease and cancer. Drug interactions may be beneficial or detrimental to the desired therapeutic effect. Clinicians in both cardiology and oncology should be cognizant of these potential drug-drug interactions that may reduce the efficacy or safety of either cardiovascular or cancer therapies. These risks can be mitigated through increased recognition of potential drug-drug interaction, use of alternative medications when possible, and careful monitoring. This scientific statement provides clinicians with an overview of pharmacodynamic and pharmacokinetic drug-drug interactions in patients with cancer exposed to common cardiovascular and cancer medications.

The Heart Team for Coronary Revascularization Decisions: 2 Illustrative Cases.

The 2021 ACC/AHA/SCAI coronary artery disease revascularization guideline highlights the importance of the multidisciplinary heart team in making patient-centered, evidence-based clinical decisions for patients considered for coronary revascularization. We present 2 cases highlighting aspects of heart team decision making for complex patients with coronary artery disease. (Level of Difficulty: Intermediate.).

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. Structure: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The guideline for coronary artery revascularization replaces the 2011 coronary artery bypass graft surgery and the 2011 and 2015 percutaneous coronary intervention guidelines, providing a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization as well as the supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. STRUCTURE: Coronary artery disease remains a leading cause of morbidity and mortality globally. Coronary revascularization is an important therapeutic option when managing patients with coronary artery disease. The 2021 coronary artery revascularization guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with coronary artery disease who are being considered for coronary revascularization, with the intent to improve quality of care and align with patients' interests.

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. STRUCTURE: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.

Future Perspectives of Cardiovascular Biomarker Utilization in Cancer Survivors: A Scientific Statement From the American Heart Association.

Improving cancer survival represents the most significant effect of precision medicine and personalized molecular and immunologic therapeutics. Cardiovascular health becomes henceforth a key determinant for the direction of overall outcomes after cancer. Comprehensive tissue diagnostic studies undoubtedly have been and continue to be at the core of the fight against cancer. Will a systemic approach integrating circulating blood-derived biomarkers, multimodality imaging technologies, strategic panomics, and real-time streams of digitized physiological data overcome the elusive cardiovascular tissue diagnosis in cardio-oncology? How can such a systemic approach be personalized for application in day-to-day clinical work, with diverse patient populations, cancer diagnoses, and therapies? To address such questions, this scientific statement approaches a broad definition of the biomarker concept. It summarizes the current literature on the utilization of a multitude of established cardiovascular biomarkers at the intersection with cancer. It identifies limitations and gaps of knowledge in the application of biomarkers to stratify the cardiovascular risk before cancer treatment, monitor cardiovascular health during cancer therapy, and detect latent cardiovascular damage in cancer survivors. Last, it highlights areas in biomarker discovery, validation, and clinical application for concerted efforts from funding agencies, scientists, and clinicians at the cardio-oncology nexus.

Recognition, Prevention, and Management of Arrhythmias and Autonomic Disorders in Cardio-Oncology: A Scientific Statement From the American Heart Association.

With the advent of novel cancer therapeutics and improved screening, more patients are surviving a cancer diagnosis or living longer with advanced disease. Many of these treatments have associated cardiovascular toxicities that can manifest in both an acute and a delayed fashion. Arrhythmias are an increasingly identified complication with unique management challenges in the cancer population. The purpose of this scientific statement is to summarize the current state of knowledge regarding arrhythmia identification and treatment in patients with cancer. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. Despite increased recognition, dedicated prospective studies evaluating true incidence are lacking. Moreover, few studies have addressed appropriate prevention and treatment strategies. As such, this scientific statement serves to mobilize the cardio-oncology, electrophysiology, and oncology communities to develop clinical and scientific collaborations that will improve the care of patients with cancer who have arrhythmias.

Patient reported physical and mental health changes associated with a comprehensive cardiovascular risk reduction program for women with breast cancer receiving potentially cardiotoxic chemotherapy.

OBJECTIVE: Women with breast cancer (BCA) and cardiovascular disease (CVD) risk factors are at increased risk of developing cardiovascular complications when exposed to potentially cardiotoxic cancer therapy. The benefit of aggressive CVD risk factor modification to reduce adverse treatment-related psychologic and biologic effects is not well established. METHODS: Using a single group pre-test, post-test design, 33 women with BCA receiving anthracycline and/or trastuzumab therapy participated in a 6-month comprehensive CVD risk reduction program involving formal cardio-oncology evaluation along with regular motivational counseling for improved nutrition and physical activity. Study parameters were assessed at baseline and 6 months with paired t-tests used to evaluate changes after the intervention. RESULTS: The mental component summary score assessed by SF-36V2 improved significantly after program completion (45.0 to 48.8, effect size 0.37, p = 0.017), however the physical component summary score declined (46.2 to 40.9, effect size - 0.53, p = 0.004). Despite this decline in perceived physical health, markers of health-related fitness and nutritional status were maintained or improved. Systolic and diastolic blood pressure also improved after the intervention (136.7 to 124.1 mmHg, p = 0.001 and 84.0 to 78.7 mmHg, p = 0.031, respectively). No significant change in resting heart rate, body mass index, lipids, hemoglobin A1C, or left ventricular ejection fraction was observed. CONCLUSIONS: Patient-reported mental health improved significantly in women with BCA enrolled in a comprehensive CVD risk reduction program despite exposure to potentially cardiotoxic therapies. This study provides preliminary data for future randomized controlled trials evaluating the effects CVD risk reduction program in high-risk breast cancer cohorts.

Home-Based Cardiac Rehabilitation: A Scientific Statement From the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Heart Association, and the American College of Cardiology.

Cardiac rehabilitation (CR) is an evidence-based intervention that uses patient education, health behavior modification, and exercise training to improve secondary prevention outcomes in patients with cardiovascular disease. CR programs reduce morbidity and mortality rates in adults with ischemic heart disease, heart failure, or cardiac surgery but are significantly underused, with only a minority of eligible patients participating in CR in the United States. New delivery strategies are urgently needed to improve participation. One potential strategy is home-based CR (HBCR). In contrast to center-based CR services, which are provided in a medically supervised facility, HBCR relies on remote coaching with indirect exercise supervision and is provided mostly or entirely outside of the traditional center-based setting. Although HBCR has been successfully deployed in the United Kingdom, Canada, and other countries, most US healthcare organizations have little to no experience with such programs. The purpose of this scientific statement is to identify the core components, efficacy, strengths, limitations, evidence gaps, and research necessary to guide the future delivery of HBCR in the United States. Previous randomized trials have generated low- to moderate-strength evidence that HBCR and center-based CR can achieve similar improvements in 3- to 12-month clinical outcomes. Although HBCR appears to hold promise in expanding the use of CR to eligible patients, additional research and demonstration projects are needed to clarify, strengthen, and extend the HBCR evidence base for key subgroups, including older adults, women, underrepresented minority groups, and other higher-risk and understudied groups. In the interim, we conclude that HBCR may be a reasonable option for selected clinically stable low- to moderate-risk patients who are eligible for CR but cannot attend a traditional center-based CR program.

Home-Based Cardiac Rehabilitation: A Scientific Statement From the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Heart Association, and the American College of Cardiology.

Cardiac rehabilitation (CR) is an evidence-based intervention that uses patient education, health behavior modification, and exercise training to improve secondary prevention outcomes in patients with cardiovascular disease. CR programs reduce morbidity and mortality rates in adults with ischemic heart disease, heart failure, or cardiac surgery but are significantly underused, with only a minority of eligible patients participating in CR in the United States. New delivery strategies are urgently needed to improve participation. One potential strategy is home-based CR (HBCR). In contrast to center-based CR services, which are provided in a medically supervised facility, HBCR relies on remote coaching with indirect exercise supervision and is provided mostly or entirely outside of the traditional center-based setting. Although HBCR has been successfully deployed in the United Kingdom, Canada, and other countries, most US healthcare organizations have little to no experience with such programs. The purpose of this scientific statement is to identify the core components, efficacy, strengths, limitations, evidence gaps, and research necessary to guide the future delivery of HBCR in the United States. Previous randomized trials have generated low- to moderate-strength evidence that HBCR and center-based CR can achieve similar improvements in 3- to 12-month clinical outcomes. Although HBCR appears to hold promise in expanding the use of CR to eligible patients, additional research and demonstration projects are needed to clarify, strengthen, and extend the HBCR evidence base for key subgroups, including older adults, women, underrepresented minority groups, and other higher-risk and understudied groups. In the interim, we conclude that HBCR may be a reasonable option for selected clinically stable low- to moderate-risk patients who are eligible for CR but cannot attend a traditional center-based CR program.

Home-Based Cardiac Rehabilitation: A SCIENTIFIC STATEMENT FROM THE AMERICAN ASSOCIATION OF CARDIOVASCULAR AND PULMONARY REHABILITATION, THE AMERICAN HEART ASSOCIATION, AND THE AMERICAN COLLEGE OF CARDIOLOGY.

Cardiac rehabilitation (CR) is an evidence-based intervention that uses patient education, health behavior modification, and exercise training to improve secondary prevention outcomes in patients with cardiovascular disease. CR programs reduce morbidity and mortality rates in adults with ischemic heart disease, heart failure, or cardiac surgery but are significantly underused, with only a minority of eligible patients participating in CR in the United States. New delivery strategies are urgently needed to improve participation. One potential strategy is home-based CR (HBCR). In contrast to center-based CR services, which are provided in a medically supervised facility, HBCR relies on remote coaching with indirect exercise supervision and is provided mostly or entirely outside of the traditional center-based setting. Although HBCR has been successfully deployed in the United Kingdom, Canada, and other countries, most US healthcare organizations have little to no experience with such programs. The purpose of this scientific statement is to identify the core components, efficacy, strengths, limitations, evidence gaps, and research necessary to guide the future delivery of HBCR in the United States. Previous randomized trials have generated low- to moderate-strength evidence that HBCR and center-based CR can achieve similar improvements in 3- to 12-month clinical outcomes. Although HBCR appears to hold promise in expanding the use of CR to eligible patients, additional research and demonstration projects are needed to clarify, strengthen, and extend the HBCR evidence base for key subgroups, including older adults, women, underrepresented minority groups, and other higher-risk and understudied groups. In the interim, we conclude that HBCR may be a reasonable option for selected clinically stable low- to moderate-risk patients who are eligible for CR but cannot attend a traditional center-based CR program.

Cardiovascular Disease and Breast Cancer: Where These Entities Intersect: A Scientific Statement From the American Heart Association.

Cardiovascular disease (CVD) remains the leading cause of mortality in women, yet many people perceive breast cancer to be the number one threat to women's health. CVD and breast cancer have several overlapping risk factors, such as obesity and smoking. Additionally, current breast cancer treatments can have a negative impact on cardiovascular health (eg, left ventricular dysfunction, accelerated CVD), and for women with pre-existing CVD, this might influence cancer treatment decisions by both the patient and the provider. Improvements in early detection and treatment of breast cancer have led to an increasing number of breast cancer survivors who are at risk of long-term cardiac complications from cancer treatments. For older women, CVD poses a greater mortality threat than breast cancer itself. This is the first scientific statement from the American Heart Association on CVD and breast cancer. This document will provide a comprehensive overview of the prevalence of these diseases, shared risk factors, the cardiotoxic effects of therapy, and the prevention and treatment of CVD in breast cancer patients.

Physicians' tacit and stated policies for determining patient benefit and referral to cardiac rehabilitation.

BACKGROUND / PURPOSE: The benefits of prescribing cardiac rehabilitation (CR) for patients following heart surgery is well documented; however, physicians continue to underuse CR programs, and disparities in the referral of women are common. Previous research into the causes of these problems has relied on self-report methods, which presume that physicians have insight into their referral behavior and can describe it accurately. In contrast, the research presented here used clinical judgment analysis (CJA) to discover the tacit judgment and referral policies of individual physicians. The specific aims were to determine 1) what these policies were, 2) the degree of self-insight that individual physicians had into their own policies, 3) the amount of agreement among physicians, and 4) the extent to which judgments were related to attitudes toward CR. METHODS: Thirty-six Canadian physicians made judgments and decisions regarding 32 hypothetical cardiac patients, each described on 5 characteristics (gender, age, type of cardiovascular procedure, presence/absence of musculoskeletal pain, and degree of motivation) and then completed the 19 items of the Attitude towards Cardiac Rehabilitation Referral scale. RESULTS: Consistent with previous studies, there was wide variation among physicians in their tacit and stated judgment policies, and self-insight was modest. On the whole, physicians showed evidence of systematic gender bias as they judged women as less likely than men to benefit from CR. Insight data suggest that 1 in 3 physicians were unaware of their own bias. There was greater agreement among physicians in how they described their judgments (stated policies) than in how they actually made them (tacit policies). Correlations between attitude statements and CJA measures were modest. CONCLUSIONS: These findings offer some explanation for the slow progress of efforts to improve CR referrals and for gender disparities in referral rates.

The relationships between FAM5C SNP (rs10920501) variability and metabolic syndrome and inflammation in women with coronary heart disease.

INTRODUCTION: The leading cause of death among women is coronary heart disease (CHD), a multifactorial disease with polygenic heritability estimated at 50%. Polymorphisms in the family with sequence similarity 5, member C' (FAM5C) gene have been associated with myocardial infarction (MI). FAM5C also corresponds directly with the inflammatory biomarker monocyte chemoattractant protein 1 (MCP-1) and metabolic syndrome. METHOD: The purpose of this descriptive gene association pilot study was to investigate the variability of FAM5C (rs10920501) in 91 women with CHD. The authors also examined the associations between the variability of FAM5C (rs10920501) and metabolic syndrome, inflammatory markers, and early onset CHD. RESULTS: No women in this study with the homozygous variant (TT) had an MI. Women with a history of MI and the heterozygous (AT) genotype had a later age of onset of CHD compared to those with the homozygous wild type (AA; F(3, 34) = 5.00, p < .01). These findings suggest a protective effect of the T allele in women with a history of MI. The genotype of FAM5C rs10920501 explained approximately 7% of the variability of age of onset of CHD in women who have had an MI, while holding body mass index (BMI) and smoking history constant. There was no significant relationship between FAM5C (rs10920501) and metabolic syndrome or any inflammatory biomarkers in this sample. CONCLUSION: FAM5C remains a gene of interest in a complex disease process.

The association between variants on chromosome 9p21 and inflammatory biomarkers in ethnically diverse women with coronary heart disease: a pilot study.

BACKGROUND: The most consistently replicated genetic variants associated with coronary heart disease (CHD) in populations of European descent have been found on chromosome 9p21. Yet there is little known about these associations in ethnic groups of African ancestry. These disease-associated variants are located in a genomic region of unknown function. The purpose of this exploratory study was to examine the allelic frequencies and haplotype structure of single nucleotide polymorphisms (SNPs) for Black and White women with CHD. The authors also sought to explore the relationship between these genetic variants and biomarkers of inflammation. METHODS: Using polymerase chain reaction amplification, the authors genotyped 8 SNPs in a 58-kilobase region of chromosome 9p21 in a cohort of women with CHD (n = 91). The authors examined the interethnic relationship between the SNPs and four inflammatory biomarkers (C-reactive protein, intercellular adhesion molecule-1, interleukin-6, and tumor necrosis factor-alpha) using analysis of variance (ANOVA). RESULTS: We found considerable interethnic allelic and haplotype diversity across the 9p21 locus, with only two SNPs in perfect linkage disequilibrium (LD) in both races. A pair of high- and low-risk haplotypes was most common in White women, while about 41% of Blacks carried the risk alleles for three of the eight SNPs the authors examined. The interethnic associations between the SNP genotypes and inflammatory markers were divergent in both direction and magnitude. CONCLUSIONS: Our results lend support for the importance of ancestry-specific allelic context when examining variants on chromosome 9p21. Additional work is needed to elucidate the genetic contribution to inflammatory biomarkers for diverse racial groups.

Predicting cardiac rehabilitation attendance in a gender-tailored randomized clinical trial.

PURPOSE: This study compared attendance of women participating in a motivationally enhanced, gender-tailored cardiac rehabilitation (CR) program with that of women attending a traditional outpatient CR program. We also sought to determine the significant baseline predictors of attendance of the exercise and education components of the interventions. METHODS: Data from 252 women with CHD in the randomized clinical trial, the Women's-Only Cardiac Rehabilitation Program, were used in this study. The experimental design used 2 treatment groups: both receiving a comprehensive, 12-week, CR program, with 1 group receiving a gender-tailored, stage-of-change matched, behavioral enhancement using individualized motivational interviewing. RESULTS: Compared with women in the traditional CR program, women in the gender-tailored program attended significantly more of the prescribed exercise (90% vs 77%) and education sessions (87% vs 56%). Group assignment accounted for about 5% of the variance in exercise attendance (F1,250 = 12.755, P < .001) and about 24% of the variance in education attendance (F1,250 = 77.942, P < .001). After controlling for group assignment, the baseline characteristics of smoking status, marital status, and anxiety accounted for about 17% of the variance in exercise attendance (F5,245 = 10.494, P < .001). Smoking status and marital status were significant baseline predictors of education attendance (F5,245 = 6.115, P < .001) after controlling for group assignment. CONCLUSIONS: The long-standing, poor attendance of women in CR continues to be an unresolved international challenge. Gender-tailored, stage-matched, CR programs hold promise for enhancing attendance to prescribed protocols. Additional research examining the efficacy of gender-sensitive, motivationally enhanced CR for women compared with generic CR programs is warranted.

The influence of cardiac rehabilitation on inflammation and metabolic syndrome in women with coronary heart disease.

BACKGROUND: Metabolic syndrome (MetS) and increased inflammatory markers, both predictors of future cardiovascular events, are more prevalent in women with coronary heart disease (CHD). The influence of cardiac rehabilitation (CR) on MetS and inflammatory biomarkers is not well characterized for women. PURPOSE: : The purpose of this article was to examine the effects of a 12-week behaviorally enhanced CR exclusively for women compared with traditional CR on components of the MetS and inflammatory markers in women with CHD. METHODS: The randomized clinical trial used 2 treatment groups, both receiving a comprehensive 12-week CR program, with 1 group receiving a motivationally enhanced intervention exclusively for women. A subset of 91 women (mean age, 61.6 years) from the parent study provided serum samples to examine the effects of CR on high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and intercellular adhesion molecule-1 (ICAM-1). RESULTS: After CR, the total sample of women demonstrated significant reductions in hsCRP (P =.002), IL-6 (P <.001), TNF-alpha (P =.010), and ICAM-1 (P =.016). Women in the gender-tailored CR program significantly improved all biomarker levels compared with baseline (P <.05 for all), whereas those in the traditional group improved only hsCRP (P <.05) and IL-6 (P <.05) levels. The combined study group demonstrated improvements in several components of MetS (triglycerides, waist circumference, and systolic blood pressure) but not in others (high-density lipoprotein cholesterol, fasting glucose, and diastolic blood pressure). CONCLUSION: Cardiac rehabilitation promotes greater improvements in inflammatory biomarkers than in components of MetS for women with CHD. Improvements in body composition or weight may not be a precondition for the benefits of exercise because of loss of abdominal fat. Examining components of MetS as continuous variables is recommended to prevent lost information inherent in dichotomization.