Ellamae Stadnick

Canadian Cardiovascular Society Guidelines for Evaluation and Management of Cardiovascular Complications of Cancer Therapy

Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.

Prognostic Value of Rubidium-82 Positron Emission Tomography in Patients After Heart Transplant

Background—Cardiac allograft vasculopathy is a key prognostic determinant after heart transplant. Detection and risk stratification of patients with cardiac allograft vasculopathy are problematic. Positron emission tomography using rubidium-82 allows quantification of absolute myocardial blood flow and may have utility for risk stratification in this population. Methods and Results—Patients with a history of heart transplant undergoing dipyridamole rubidium-82 positron emission tomography were prospectively enrolled. Myocardial perfusion and left ventricular ejection fraction were recorded. Absolute flow quantification at rest and after dipyridamole stress as well as the ratio of mean global flow at stress and at rest, termed myocardial flow reserve, were calculated. Patients were followed for all-cause death, acute coronary syndrome, and heart failure hospitalization. A total of 140 patients (81% men; median age, 62 years; median follow-up, 18.2 months) were included. There were 14 events during follow-up (9 deaths, 1 acute coronary syndrome, and 4 heart failure admissions). In addition to baseline clinical variables (estimated glomerular filtration rate, previously documented cardiac allograft vasculopathy), relative perfusion defects, mean myocardial flow reserve, and mean stress myocardial blood flow were significant predictors of adverse outcome. Conclusions—Abnormalities on rubidium-82 positron emission tomography were predictors of adverse events in heart transplant patients. Larger prospective studies are required to confirm these findings.

The Prognostic Value of Rb-82 Positron Emission Tomography in Patients Following Heart Transplant

Background—Cardiac allograft vasculopathy is a key prognostic determinant after heart transplant. Detection and risk stratification of patients with cardiac allograft vasculopathy are problematic. Positron emission tomography using rubidium-82 allows quantification of absolute myocardial blood flow and may have utility for risk stratification in this population. Methods and Results—Patients with a history of heart transplant undergoing dipyridamole rubidium-82 positron emission tomography were prospectively enrolled. Myocardial perfusion and left ventricular ejection fraction were recorded. Absolute flow quantification at rest and after dipyridamole stress as well as the ratio of mean global flow at stress and at rest, termed myocardial flow reserve, were calculated. Patients were followed for all-cause death, acute coronary syndrome, and heart failure hospitalization. A total of 140 patients (81% men; median age, 62 years; median follow-up, 18.2 months) were included. There were 14 events during follow-up (9 deaths, 1 acute coronary syndrome, and 4 heart failure admissions). In addition to baseline clinical variables (estimated glomerular filtration rate, previously documented cardiac allograft vasculopathy), relative perfusion defects, mean myocardial flow reserve, and mean stress myocardial blood flow were significant predictors of adverse outcome. Conclusions—Abnormalities on rubidium-82 positron emission tomography were predictors of adverse events in heart transplant patients. Larger prospective studies are required to confirm these findings.

Reduced Myocardial Flow in Heart Failure Patients With Preserved Ejection Fraction

Background—There remains limited insight into the pathophysiology and therapeutic advances directed at improving prognosis for patients with heart failure with preserved ejection fraction (HFpEF). Recent studies have suggested a role for coronary microvascular dysfunction in HFpEF. Rb-82 cardiac positron emission tomography imaging is a noninvasive, quantitative approach to measuring myocardial flow reserve (MFR), a surrogate marker for coronary vascular health. The aim of this study was to determine whether abnormalities exist in MFR in patients with HFpEF without epicardial coronary artery disease. Methods and Results—A total of 376 patients with ejection fraction ≥50%, no known history of obstructive coronary artery disease, and a confirmed diagnosis of heart failure (n=78) were compared with patients with no evidence of heart failure (n=298), further stratified into those with (n=186) and without (n=112) hypertension. Global and regional left ventricular MFR was calculated as stress/rest myocardial blood flow using Rb-82 positron emission tomography. Patients with HFpEF were more likely to be older, female, and have comorbid hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, anemia, and renal dysfunction. HFpEF was associated with a significant reduction in global MFR (2.16±0.69 in HFpEF versus 2.54±0.80 in hypertensive controls; P<0.02 and 2.89±0.70 in normotensive controls; P<0.001). A diagnosis of HFpEF was associated with 2.62 times greater unadjusted odds of having low global MFR (defined as <2.0) and remained a significant predictor of reduced global MFR after adjusting for comorbidities. Conclusions—HFpEF, in the absence of known history for obstructive epicardial coronary artery disease, is associated with reduced MFR independent of other risk factors.

An International Survey of Health Care Providers Involved in the Management of Cancer Patients Exposed to Cardiotoxic Therapy.

Cardiotoxicity is the second leading cause of morbidity and mortality in cancer survivors. The objective of this international cardiac oncology survey was to gain a better understanding of current knowledge and practice patterns among HCPs involved in the management of cancer patients exposed to potentially cardiotoxic drugs. Between 2012 and 2013, we conducted an email-based survey of HCPs involved in the management of cardiac disease in cancer patients. 393 survey responses were received, of which 77 were from Canadian respondents. The majority of respondents were cardiologists (47%), followed closely by medical oncologists. The majority of respondents agreed that cardiac issues are important to cancer patients (97%). However, only 36% of total respondents agreed with an accepted definition of cardiotoxicity. While 78% of respondents felt that cardiac medications are protective during active cancer treatment, only 51% would consider prescribing these medications up-front in cancer patients. Although results confirm a high level of concern for cardiac safety, there continues to be a lack of consensus on the definition of cardiotoxicity and a discrepancy in clinical practice between cardiologists and oncologists. These differences in opinion require resolution through more effective research collaboration and formulation of evidence-based guidelines.

Clinical Experience of Patients Referred to a Multidisciplinary Cardiac Oncology Clinic: An Observational Study

Cardiotoxicity is the second leading cause of long-term morbidity and mortality among cancer survivors. The purpose of this retrospective observational study is to report on the clinical and cardiac outcomes in patients with early stage and advanced cancer who were referred to our multidisciplinary cardiac oncology clinic (COC). A total of 428 patients were referred to the COC between October 2008 and January 2013. The median age of patients at time of cancer diagnosis was 60. Almost half of patients who received cancer therapy received first-line chemotherapy alone (169, 41.7%), of which 84 (49.7%) were exposed to anthracyclines. The most common reasons for referral to the cardiac oncology clinic were decreased LVEF (34.6%), prechemotherapy assessment (11.9%), and arrhythmia (8.4%). A total of 175 (40.9%) patients referred to the COC were treated with cardiac medications. The majority (331, 77.3%) of patients were alive as of January 2013, and 93 (21.7%) patients were deceased. Through regular review of cardiac oncology clinic referral patterns, management plans, and patient outcomes, we aim to continuously improve delivery of cardiac care to our patient population and optimize cardiac health.

Unusual Cause of an Ejection Murmur: Myxoma in the Left Ventricular Outflow Tract

We present the case of a healthy, asymptomatic 50-year-old woman with a systolic ejection murmur who was found to have an obstructive left ventricular outflow tract mass. Transthoracic echocardiography revealed a large mobile mass attached to the basal anterior septum of the left ventricle. Surgical resection was performed and a benign left ventricular outflow tract myxoma was diagnosed. The patients postoperative course was unremarkable. We describe the clinical presentation and role of 2- and 3-dimensional transthoracic and transesophageal echocardiography in surgical management.

Evaluation, prevention and management of cancer therapy-induced cardiotoxicity: a contemporary approach for clinicians.

Purpose of review While targeted therapies have improved cancer outcomes, unique cardiovascular toxicities are increasingly recognized, particularly when administered sequentially after anthracyclines or radiation. Patients with cancer therapy-induced cardiotoxicity benefit from collaborative care involving cardiology and oncology, leading to a new interdisciplinary field called cardio-oncology. The present review will highlight contemporary clinical issues in cardio-oncology. Recent findings Recently, risk factors for cancer therapy-induced cardiotoxicity have been evaluated in real-world rather than in clinical trial patients. Biomarkers and advanced echocardiography are emerging as sensitive tools for preclinical identification of cancer therapy-induced cardiotoxicity. Single-center studies suggest that cancer therapy-induced cardiotoxicity responds to prompt heart failure medical treatment, and such therapy may even prevent cardiotoxicity. Summary Modern cancer therapy has short-term cardiac risk that may require collaborative management by clinicians with expertise in cardiology and oncology. The increased effectiveness of modern cancer therapy is resulting in a growing population of cancer survivors who are at long-term risk for cardiovascular disease. The present review of contemporary clinical issues in cardio-oncology will be of interest to healthcare providers who manage cardiotoxicity during cancer therapy, and who follow patients who survive cancer but face increased long-term cardiovascular risk.

Abstract P2-07-06: Obesity, dyslipidemia, and diabetes as risk factors for trastuzumab-related cardiotoxicity in breast cancer patients

Background. Clinical trials have demonstrated an increased risk of cancer treatment related cardiac dysfunction (CTCD) during trastuzumab(H) therapy. Diabetes, dyslipidemia, and obesity are also known risk factors for cardiovascular disease. The primary objective of this study was to evaluate the incidence of asymptomatic drop in left ventricular ejection fraction (AD-LVEF) and symptomatic CTCD (S-CTCD) in women with BC and co-morbidities receiving H, referred to a dedicated cardio-oncology clinic (COC). Methods. This was a retrospective cohort study of women with BC (all stages) referred to The Ottawa Hospital COC between 2008 and 2015, who received chemotherapy (CT) and H. Data collected included: demographics, reason for referral, cardiac testing (MUGA/ECHO) co-morbidities (diabetes, dyslipidemia) and cardiac outcomes. Obesity defined as body mass index > 30. Symptomatic CTCD include SOB, PND, orthopnea, peripheral edema, congestive heart failure. Asymptomatic drop in LVEF defined as decrease of at least 15% from baseline; normal LVEF, or a decrease of at least 10% in LVEF, less than 53%. Results. Chemotherapy (A-CT) followed by H, 62 received H without A-CT. 139 patients with no history diabetes, dyslipidemia, or obesity, referred with AD-LVEF (68%), with S- CTCD (30%), pre-CT assessment (2%). Obesity (O) pre-existing co-morbidity in 63 (26%) patients, (20 (32%) with S-CTCD, 40 (63%) referred with AD-LVEF, 3(5%) referred for pre-CT assessment). Dyslipidemia (L) – 52 (21%); referred with S-CTCD 15; 29%), with AD-LVEF 31 (60%), pre-CT assessment 6 (11). Diabetes (D) – 29 (12%) - (6 (21%) with S-CTCD, 19 (66%) referred with AD-LVEF, 4(13%) referred for pre-CT assessment). Combination of two or three conditions significantly increase incidence of S-CTCD: O+L – 67%, O+D – 69%, O+L+D – 72%. Combination of obesity and other conditions significantly increase incidence of S-CTCD: O+L – 67%(Relative Risk -2.2, p=0,04), O+D – 69% (RR-2.3, p=0,02), O+L+D – 72% (RR-2.4, p=0,08). Conclusion. The combination of two or three co-morbidities significantly increases the incidence of S-CTCD. BC patients experiencing CTCD with pre-existing history of diabetes, dyslipidemia, and obesity may require more proactive strategies for prevention, detection and treatment of cardiotoxicity during trastuzumab-based treatment. Citation Format: Aseyev O, Johnson C, Turek M, Stadnick E, Law A, Gosh N, Dent S. Obesity, dyslipidemia, and diabetes as risk factors for trastuzumab-related cardiotoxicity in breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-06.

Myocardial Viability: From PARR-2 to IMAGE HF - Current Evidence and Future Directions

Ischemic heart failure is a growing disease with high morbidity and mortality. Several studies suggest the benefit of viability imaging to assist revascularization decision, but there is controversy. Multiple imaging modalities can be used to accurately define hibernating myocardium; however, the best approach remains uncertain. This review will highlight current evidence and future directions of viability imaging assessment.