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.

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.

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.

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.

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.

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.

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.

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.

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.

A comparative assessment of coronary artery calcification on chest CT scans of patients referred to a cardio-oncology clinic.

BACKGROUND: The presence and burden of coronary artery calcium (CAC) is a strong predictor of cardiovascular events. In an effort to gain insight into the utility of CAC for coronary artery disease (CAD) screening in cancer patients with heart disease, we sought to determine the presence and burden of CAC detected on routine chest CT in patients referred to a cardio-oncology clinic, comparing them to a conventional cardiology clinic with the general population as controls. METHODS: Patients from the cardio-oncology clinic, general cardiology clinic, and the general clinic population at Rush University Medical Center who had a chest CT as part of their previous treatment were identified. Each CT scan was evaluated for presence, extent, and severity of CAC by 3 independent readers. RESULTS: In multivariate analysis, when compared with cardio-oncology clinic, CAC was more prevalent in the CT scans of cardiology patients (p = 0.04), but not the general clinic population (p = 0.5); CAC extent (p = 0.05) and severity (p = 0.05) was significantly higher in the cardiology patients but the extent (p = 0.05) and severity (p = 0.92) was similar in the general clinic population. CONCLUSION: Despite being matched by age and sex, controlling for other major cardiovascular risk factors, patients referred to our cardio-oncology clinic had similar and less prevalent/severe CAC burden compared with the general population and conventional cardiology clinics respectively. Whether this translates to less utility of CAC for CAD screening, or to less overall coronary events in a cardio-oncology clinic, is of interest.

Cardiovascular Health of Patients With Cancer and Cancer Survivors: A Roadmap to the Next Level.

Many existing and emerging cancer therapies have a significant effect on the cardiovascular health of patients with cancer and cancer survivors. This paper examines current aspects of interdisciplinary cardio-oncology clinical care delivery and education in the United States and outlines how these data provide a platform for future development of the field. We present the results of the nationwide survey on cardio-oncology services, practices, and opinions, conducted among chiefs of cardiology and program directors, which demonstrate ranges of clinical activities and identify significant interest for increased educational opportunities and expert training of cardiovascular physicians in this field. The survey respondents recognized clinical relevance but emphasized lack of national guidelines, lack of funds, and limited awareness and infrastructure as the main challenges for development and growth of cardio-oncology. We discuss potential solutions to unmet needs through interdisciplinary collaboration and the active roles of professional societies and other stakeholders.

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.

Strategies for treating lipids for prevention: risk stratification models with and without imaging.

Cardiovascular disease (CVD) remains the leading cause of mortality both in the United States and worldwide. Traditional risk factors are essential to CVD risk prediction and explain a significant portion of the between-population and between-individual variance in CVD. Nonetheless, due to the large size of the group, a substantial portion of cardiovascular events occur in individuals predicted to be at low risk based on traditional risk factor models such as the Framingham risk score. The problem is that by disregarding this low risk group, a significant proportion of events are ignored and deemed 'unpreventable'. As such, it is imperative to find new ways to improve CVD risk prediction and thereby apply preventive measures to persons more likely to develop 'preventable' disease. Focus has consequently shifted towards identification of novel markers to improve cardiovascular risk prediction. We review the role of various risk stratification models, and assess the incorporation of imaging markers to guide treatment for lipids in prevention of CVD.

Long-term change in alcohol-consumption status and variations in fibrinogen levels: the coronary artery risk development in young adults (CARDIA) study.

OBJECTIVE: To examine long-term associations between change in alcohol-consumption status and cessation of alcohol use, and fibrinogen levels in a large, young, biracial cohort. DESIGN: Analysis of covariance models were used to analyse participants within the Coronary Artery Risk Development in Young Adults Study (CARDIA) cohort who had fibrinogen and alcohol use data at year 7 (1992-1993; ages 25-37) and year 20 examinations. SETTING: 4 urban US cities. PATIENTS: 2520 men and women within the CARDIA cohort. MAIN OUTCOME MEASURES: 13-year changes in alcohol use related to changes in fibrinogen. RESULTS: Over 13 years, mean fibrinogen increased by 71 vs 70 mg/dL (p=NS) in black men (BM) versus white men (WM), and 78 vs 68 mg/dL (p<0.05) in black women (BW) versus white women (WW), respectively. Compared with never-drinkers, there were smaller longitudinal increases in fibrinogen for BM, BW and WW (but a larger increase in WM) who became or stayed drinkers, after multivariable adjustment. For BM, WM and WW, fibrinogen increased the most among persons who quit drinking over 13 years (p<0.001 for WM (fibrinogen increase=86.5 (7.1) (mean (SE))), compared with never-drinkers (fibrinogen increase=53.1 (5.4)). CONCLUSIONS: In this young cohort, compared with the participants who never drank, those who became/stayed drinkers had smaller increases, while those who quit drinking had the highest increase in fibrinogen over 13 years of follow-up. The results provide a novel insight into the mechanism for the established protective effect of moderate alcohol intake on cardiovascular disease outcomes.

13-year long-term associations between changes in traditional cardiovascular risk factors and changes in fibrinogen levels: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

OBJECTIVE: Cross-sectional and prospective studies have linked cardiovascular events and traditional risk factors (TRFs) with higher plasma fibrinogen levels. In a young cohort, we sought to determine longitudinal associations between changes in/development of TRFs and fibrinogen levels over 13 years. METHODS: We included 2525 adults from the CARDIA study, aged 25-37 with fibrinogen and TRFs measured at year 7 (study baseline; 1992-1993); and year 20 (follow-up). Multiple linear regressions were used to compare mean changes in fibrinogen to TRFs. RESULTS: Mean fibrinogen increased by 71 mg/dL vs. 70 mg/dL (p = NS) in black vs. white men, and 78 mg/dL vs. 68 mg/dL (p < 0.05) in black vs. white women, respectively over 13 years. After multivariable adjustments, fibrinogen generally rose with increasing BMI (p < 0.001; all sex/race groups), LDL cholesterol, log triglycerides and diastolic blood pressure; and fell with increasing HDL cholesterol and physical activity. 13-year increase in fibrinogen for persons who quit smoking or became non-obese were comparable (p = NS) to that of never-smokers and never-obese persons. CONCLUSIONS: Among young black and white men and women with few baseline cardiovascular risk factors, fibrinogen tracked longitudinally with changes in TRFs over 13 years through middle age. There was a strong inverse longitudinal relationship between modifiable risk factors (weight loss/smoking cessation) and 13-year change in fibrinogen. Our study helps provide some insight into the role of fibrinogen as a disease marker in the associations between fibrinogen and CVD.