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.

Cardiovascular Imaging in Contemporary Cardio-Oncology: A Scientific Statement From the American Heart Association.

Advances in cancer therapeutics have led to dramatic improvements in survival, now inclusive of nearly 20 million patients and rising. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Advances in cardiovascular imaging have solidified the critical role for robust methods for detecting, monitoring, and prognosticating cardiac risk among patients with cancer. However, decentralized evaluations have led to a lack of consensus on the optimal uses of imaging in contemporary cancer treatment (eg, immunotherapy, targeted, or biological therapy) settings. Similarly, available isolated preclinical and clinical studies have provided incomplete insights into the effectiveness of multiple modalities for cardiovascular imaging in cancer care. The aims of this scientific statement are to define the current state of evidence for cardiovascular imaging in the cancer treatment and survivorship settings and to propose novel methodological approaches to inform the optimal application of cardiovascular imaging in future clinical trials and registries. We also propose an evidence-based integrated approach to the use of cardiovascular imaging in routine clinical settings. This scientific statement summarizes and clarifies available evidence while providing guidance on the optimal uses of multimodality cardiovascular imaging in the era of emerging anticancer therapies.

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.

Cardiovascular disease in cancer survivors.

Certain cancer therapies, including radiation therapy and some types of chemotherapies, are associated with increased risk of cardiovascular disease (CVD) and events. Some of these effects such as those presented by anthracyclines, radiation therapy, cisplatin, as well as those presented by hormone therapy for breast cancer-usually taken for many years for some breast and prostate cancers-are long-lasting and associated with cardiovascular events risk more than 20 years after cancer treatment. Cardiovascular testing, diagnostic assessment of suspected cardiovascular symptomatology, as well as laboratory tests for CVD risk factors are imperative. The early recognition and treatment of CVD processes that arise in survivorship years is pivotal, with specific attention to some CVD processes with specific suggested treatment modalities. Preventive measures include adequate screening, the use of medications such as ACE inhibitors/angiotensin receptor blockers and/or beta blockers, statin therapy and aspirin in persons who warrant these medications, as well as therapeutic lifestyle modifications such as exercise/physical activity, weight loss and appropriate diet for a healthy lifestyle. Periodic follow-up with a good primary care physician who understands the risks associated with cancer therapy is important, and referral to onco-cardiology for further management of cardiovascular risk in these survivors is based on a patient's cardiovascular risk level and the type, amount and duration of cancer therapies received during the patient's lifetime.

Left ventricular hypertrophy and cardiovascular disease risk prediction and reclassification in blacks and whites: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Left ventricular hypertrophy (LVH) is a major independent predictor of cardiovascular disease (CVD) survival and is more prevalent in blacks than whites. In a large biracial population, we evaluated the ability of electrocardiography (ECG)-determined LVH (ECG-LVH) to reclassify CVD/coronary heart disease (CHD) events beyond traditional risk factors in blacks and whites. METHODS: The analysis included 14,489 participants (mean age 54 ± 5.7 years; 43.5% men; 26% black) from the ARIC cohort, with baseline (1987-1989) ECG, followed up for 10 years. Predicted risk for incident CVD and CHD were estimated using the 10-year Pooled Cohort and Framingham risk equations (base models 1A/1B), respectively. Models 2A and 2B included respective base model plus LVH by "any" of 10 traditional ECG-LVH criteria. Net reclassification improvement (NRI) was calculated, and the distribution of risk was compared using models 2A and 2B versus models 1A and 1B, respectively. RESULTS: There were 792 (5.5%) 10-year Pooled Cohort CVD events and 690 (4.8%) 10-year Framingham CHD events. Left ventricular hypertrophy defined by any criteria was associated with CVD and CHD events (hazard ratio [95% CI] 1.62 [1.38-1.90] and 1.56 [1.32-1.86], respectively]. Left ventricular hypertrophy did not significantly reclassify or improve C statistic in models 2A/B (C statistics 0.767/0.719; NRI = 0.001 [P = not significant]), compared with the base models 1A/B (C statistics 0.770/0.718), respectively. No racial interactions were observed. CONCLUSIONS: In this large cohort of black and white participants, ECG-LVH was associated with CVD/CHD risk but did not significantly improve CVD and CHD events risk prediction beyond the new Pooled Cohort and most used Framingham risk equations in blacks or whites.

Baseline Electrocardiographic Abnormalities in Pre-Treatment Cancer Compared With Non-Cancer Patients: A Propensity Score Analysis.

Background: Most studies have compared post-treatment electrocardiogram (ECG) abnormalities in cancer patients to the general population. To assess baseline cardiovascular (CV) risk, we compared pre-treatment ECG abnormalities in cancer patients with a non-cancer surgical population. Methods: We conducted a combined prospective (n = 30) and retrospective (n = 229) cohort study of patients aged 18 - 80 years with diagnosis of hematologic or solid malignancy, compared with 267 pre-surgical, non-cancer, age- and sex-matched controls. Computerized ECG interpretations were obtained, and one-third of the ECGs underwent blinded interpretation by a board-certified cardiologist (agreement r = 0.94). We performed contingency table analyses using likelihood ratio Chi-square statistics, with calculated odds ratios. Data were analyzed after propensity score matching. Results: The mean age of cases was 60.97 ± 13.86; and 59.44 ± 11.83 years for controls. Pre-treatment cancer patients had higher likelihood of abnormal ECG (odds ratio (OR): 1.55; 95% confidence interval (CI): 1.05 to 2.30), and more ECG abnormalities (χ2 = 4.0502; P = 0.04) compared with non-cancer patients. ECG abnormalities were higher in black compared to non-black patients (P = 0.001). In addition, baseline ECGs among cancer patients prior to cancer therapy demonstrated less QT prolongation and intra-ventricular conduction defect (P = 0.04); but showed more arrhythmias (P < 0.01) and atrial fibrillation (AF) (P = 0.01) compared with the general patient population. Conclusions: Based on these findings, we recommend that all cancer patients receive an ECG, a low-cost and widely available tool, as part of their CV baseline screening, prior to cancer treatment.

Exercise, cancer and cardiovascular disease: what should clinicians advise?

Cardiovascular disease is one of the leading causes of morbidity and mortality in persons with cancer. The elevated risk is thought to derive from the combination of cardiovascular risk factors and direct cardiotoxicity from cancer therapies. Exercise may be a potential strategy to counteract these toxicities and maintain cardiovascular reserve. In this article, we review the evidence for the potential cardioprotective effects of exercise training in cancer patients before, during, and following treatment. We also propose a patient-tailored approach for the development of targeted prescriptions based on individual exercise capacity and cardiovascular reserve.

Statin use and risk of prostate cancer biochemical recurrence after radical prostatectomy.

BACKGROUND: Multiple studies have investigated the role of statins in prostate cancer (CaP), the leading cause of cancer related death in men. Retrospective cohort studies investigating the correlation between statin use and biochemical recurrence free (BCRF) survival in men with CaP have been inconclusive. OBJECTIVES: In the largest reported surgical cohort to date, we investigated the effect of statin therapy on BCRF and overall survival in patients with CaP who have undergone radical prostatectomy (RP). PATIENTS AND METHODS: We performed a retrospective analysis of men (n = 3,088) participating in the NCI funded Specialized Program of Research Excellence (SPORE) in CaP at Northwestern University (NM) in Chicago, Illinois. Patients were treated with RP between 2002 and 2015. Patients in the statin users group received treatment within 2 years prior to or subsequent to RP. Wilcoxon rank-sum and Fisher's exact tests were used to compare age, race, Gleason score, clinical staging, and pathological stage between statin users and nonstatin users. RESULTS: The analysis identified 1,222 statin users and 1,865 nonusers (mean age 71 years, 92% Caucasian). After a median follow-up time of 49.0 months, the 5-year BCRF survival rate was 93.3% (95% confidence interval [CI]: 91.9-94.8%) among statin users and 88.6% (95% CI: 87.1%-90%) among nonusers (log-rank P< 0.001). After 10 years, the progression-free survival (PFS) was 91.7% (95% CI: 90.1%-93.3%) among statin users and 86.5% (95% CI: 84.4%-88.2%) among nonusers (log-rank P< 0.001). CONCLUSIONS: Extended follow-up data in this large surgical cohort show statin use improves BCRF but not overall survival in RP patients.

Impact of Hormonal Therapies for Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association.

Cardiovascular disease and cancer are the leading causes of death in the United States, and hormone-dependent cancers (breast and prostate cancer) are the most common noncutaneous malignancies in women and men, respectively. The hormonal (endocrine-related) therapies that serve as a backbone for treatment of both cancers improve survival but also increase cardiovascular morbidity and mortality among survivors. This consensus statement describes the risks associated with specific hormonal therapies used to treat breast and prostate cancer and provides an evidence-based approach to prevent and detect adverse cardiovascular outcomes. Areas of uncertainty are highlighted, including the cardiovascular effects of different durations of hormonal therapy, the cardiovascular risks associated with combinations of newer generations of more intensive hormonal treatments, and the specific cardiovascular risks that affect individuals of various races/ethnicities. Finally, there is an emphasis on the use of a multidisciplinary approach to the implementation of lifestyle and pharmacological strategies for management and risk reduction both during and after active treatment.

Left ventricular mass from gated SPECT myocardial perfusion imaging: comparison with cardiac computed tomography.

BACKGROUND: Increased left ventricular mass (LVM) has been correlated with adverse cardiac events, such as sudden cardiac death. However, LVM quantitation with widely utilized gated SPECT myocardial perfusion imaging (MPI) software, has little validation and clinical application. Thus, we compared LVM from two commonly employed gated SPECT packages [4D-MSPECT (4DM) and Quantitative Perfusion SPECT (QPS)] with the 3-dimensional reference standard, CT angiography (CTA). METHODS: Comparisons were made in 56 patients (mean age 61.4 +/- 14.6; 32% female) referred for dual-isotope or low-dose/high-dose Tc-99m-tetrofosmin rest/stress MPI and cardiac CTA (mean 1.5 +/-4.5 months apart). LVM measurement was performed for both CTA and MPI by two independent observers blinded to clinical information. RESULTS: Correlation with CTA was best for post-stress MPI than at rest; thus, post-stress values are reported. Values obtained with each of the techniques were very highly reproducible (interobserver correlation r = 0.99 for each technique). The mean LVM values were 142 g by CTA, 145 g by 4DM, and 135 g by QPS (P = NS for CTA vs SPECT, but P < .001 for 4DM vs QPS). There was moderately good correlation between CTA and SPECT LVM data (r = 0.74 and 0.72 for 4DM and QPS, respectively; both P < .001). However, on Bland-Altman analysis there was significant overestimation of lower values and underestimation of higher CT LVM values by both QPS and 4DM (both r = 0.68 and 0.69, P < .001). The limits of agreement relative to CT LVM were wide (-52.1 g to 64.1 g for QPS; and -60.0 g to 53.5 g for 4DM). CONCLUSIONS: SPECT and CTA give reproducible measures of LVM. Using CTA as the reference standard, the mean SPECT LVM values are similar, but lower values are overestimated and higher values are underestimated. Thus, the SPECT values are not substitutable for CTA without mathematical correction.

Pre-Diagnosis Exercise and Cardiovascular Events in Primary Breast Cancer: Women's Health Initiative.

OBJECTIVES: The purpose of this study was to investigate whether pre-diagnosis exercise reduces the risk of subsequent cardiovascular events (CVEs) in women with primary breast cancer. BACKGROUND: Cardiovascular disease (CVD) is the leading nonmalignant cause of death in patients with cancer, and it is the leading cause of death in women with primary breast cancer who are older than 65 years of age. METHODS: Using a prospective design, 4,015 patients with confirmed diagnosis of primary breast cancer enrolled in the Women's Health Initiative (WHI) completed a self-report questionnaire assessing leisure-time physical activity (i.e., exercise) in metabolic equivalent task (MET) hours per week. Age- and multivariable-adjusted Cox proportional hazards models were used to estimate associations between pre-diagnosis exercise and new-onset CVEs (i.e., heart failure [HF], myocardial infarction [MI], angina, coronary revascularization, peripheral arterial disease [PAD], carotid artery disease, transient ischemic attack [TIA], stroke, and cardiovascular death). RESULTS: Median follow-up was 12.7 years and 8.2 years for cardiovascular disease (CVD) mortality and CVEs, respectively, with 324 CVEs, including 89 MIs, 49 new diagnoses of HF, and 215 CVD deaths. In multivariable analysis, the incidence of composite CVEs decreased across increasing total MET h/week categories (p = 0.016). Compared with <2.5 MET-hours per week, the adjusted hazard ratio (HR) was 0.80 (95% confidence interval [CI]: 0.59 to 1.09) for 2.5 to <8.6 MET h/week; 0.9 (95% CI: 0.64 to 1.17) for 8.6 to <18 MET h/week; and 0.63 (95% CI: 0.45 to 0.88) for ≥18 MET h/week. CONCLUSION: Pre-diagnosis exercise exposure is associated with a significant graded reduction in subsequent CVEs in long-term survivors of primary breast cancer.

"Mass-ive" infarction: case report and review of myocardial metastatic malignancies.

Metastatic cancers to the heart are uncommon but occur up to 20 to 40 times more frequently than primary tumors of the heart. Cardiac metastases from lung cancer are rarely diagnosed ante mortem and usually cause no symptoms or signs. In this case report cardiac metastasis from a primary adenosquamous cancer of the lung presented as myocardial infarction in a 61-year-old man. His diagnosis was made and confirmed via multimodality imaging of the heart, which is also reviewed in depth.

Cardiovascular health disparities: a systematic review of health care interventions.

Racial and ethnic disparities in cardiovascular health care are well documented. Promising approaches to disparity reduction are increasingly described in literature published since 1995, but reports are fragmented by risk, condition, population, and setting. The authors conducted a systematic review of clinically oriented studies in communities of color that addressed hypertension, hyperlipidemia, physical inactivity, tobacco, and two major cardiovascular conditions, coronary artery disease and heart failure. Virtually no literature specifically addressed disparity reduction. The greatest focus has been African American populations, with relatively little work in Hispanic, Asian, and Native American populations. The authors found 62 interventions, 27 addressing hypertension, 9 lipids, 18 tobacco use, 8 physical inactivity, and 7 heart failure. Only 1 study specifically addressed postmyocardial infarction care. Data supporting the value of registries, multidisciplinary teams, and community outreach were found across several conditions. Interventions addressing care transitions, using telephonic outreach, and promoting medication access and adherence merit further exploration.

Prediction of coronary heart disease by erectile dysfunction in men referred for nuclear stress testing.

BACKGROUND: Recent evidence suggests a strong link between erectile dysfunction (ED) and atherosclerotic vascular disease. Stress myocardial perfusion single-photon emission computed tomography (MPS) is a widely used noninvasive imaging modality that allows diagnosis of coronary heart disease and stratification of cardiovascular risk. We sought to determine the relationship between ED and coronary heart disease in men referred for MPS. METHODS: A total of 221 men referred for MPS were prospectively screened for ED with a validated questionnaire. Patient characteristics, MPS findings, and exercise results were correlated with ED. RESULTS: Erectile dysfunction was present in 54.8% of the patients. Patients with ED exhibited more severe coronary heart disease (MPS summed stress score >8) (43.0% vs 17.0%; P<.001) and left ventricular dysfunction (left ventricular ejection fraction <50%) (24.0% vs 11.0%; P=.01) than those without ED. Erectile dysfunction was associated with a shorter exercise time (8.0 vs 10.1 minutes; P<.001) and lower Duke treadmill score (4.4 vs 8.4; P<.001). Multivariate analysis showed ED to be an independent predictor of severe coronary heart disease (odds ratio, 2.50; 95% confidence interval, 1.24-5.04; P = .01) and high-risk MPS findings (summed stress score >8, transient ischemic dilation, or left ventricular ejection fraction <35%) (odds ratio, 2.86; 95% confidence interval, 1.43-5.74; P = .003). CONCLUSIONS: Erectile dysfunction is common in men referred for MPS, is associated with markers of adverse cardiovascular prognosis, and is an independent predictor of severe coronary heart disease and high-risk MPS findings. These results suggest that questioning about sexual function may be a useful tool for stratifying risk in individuals with suspected coronary heart disease.

American Society of Clinical Oncology Summit on Addressing Obesity Through Multidisciplinary Provider Collaboration: Key Findings and Recommendations for Action.

OBJECTIVE: Given the increasing evidence that obesity increases the risk of developing and dying from malignancy, the American Society of Clinical Oncology (ASCO) launched an Obesity Initiative in 2013 that was designed to increase awareness among oncology providers and the general public of the relationship between obesity and cancer and to promote research in this area. Recognizing that the type of societal change required to impact the obesity epidemic will require a broad-based effort, ASCO hosted the "Summit on Addressing Obesity through Multidisciplinary Collaboration" in 2016. METHODS: This meeting was held to review current challenges in addressing obesity within the respective health care provider communities and to identify priorities that would most benefit from a collective and cross-disciplinary approach. RESULTS: Efforts focused on four key areas: provider education and training; public education and activation; research; and policy and advocacy. Summit attendees discussed current challenges in addressing obesity within their provider communities and identified priorities that would most benefit from multidisciplinary collaboration. CONCLUSIONS: A synopsis of recommendations to facilitate future collaboration, as well as examples of ongoing cooperative efforts, provides a blueprint for multidisciplinary provider collaboration focused on obesity prevention and treatment.

Haemodynamic instability secondary to cardiac involvement by lymphoma.

Cardiac involvement in lymphomas is not uncommon, but it is often missed due to the variability in its presentation. We present a case of bradycardia and complete heart block resulting in haemodynamic instability in a patient with recurrent diffuse large B-cell lymphoma. Timely diagnosis and appropriate management of such patients is crucial and requires a high index of suspicion. Our patient required temporary pacemaker implantation and intravenous corticosteroid therapy. His complete heart block and bradycardia eventually resolved after a course of radiation therapy.

Hypothyroid cardiomyopathy in a patient post-doxorubicin chemotherapy.

Hypothyroidism may cause decreased cardiac output and heart failure-and when severe, bradycardia and pericardial effusions may develop. Chemotherapies, particularly doxorubicin, are known and often irreversible causes of cardiomyopathy. As such, when cardiomyopathy develops in patients who have been exposed to anthracycline chemotherapy, the importance of ruling out other reversible causes such as hypothyroidism cannot be overstated. We present a case of acute systolic heart failure in a patient post-doxorubicin chemotherapy and radiation therapy for alveolar rhabdomyosarcoma, found to have severe hypothyroidism as a reversible cause of cardiomyopathy.