Evidence-Based Oncology June 2015
Advancing Patient Care in Cardio-Oncology: The ACC.15 Cardio-Oncology Intensive
While many advances in cancer therapeutics have significantly impacted the cardiovascular (CV) health of cancer patients and cancer survivors, transforming lives and growing the population of patients living with and surviving the disease, they have also created a need for a comprehensive and revised approach to the CV care of these patients. Professional medical societies have a long-standing legacy of improving patients’ health by providing and developing education, training, clinical guidance, and research resources for their members. To better assist its growing membership in these ways, the American College of Cardiology (ACC) formed a Cardio-Oncology Working Group charged with assessing existing practices along with the needs of patients and professionals in this field. The Group conducted a nationwide survey focused on cardio-oncology services, gathering opinions from CV division chiefs and fellowship training directors. This helped identify important challenges, including the need for broader educational opportunities and training.1
ACC.15 Cardio-Oncology Intensive
Traditionally, cardio-oncology has been represented at national cardiology conferences with cardiotoxicity-related sessions embedded in focused clinical pathways – most commonly, heart failure and CV imaging. These sessions successfully highlighted novel developments within specific areas, but struggled with introducing a broader interdisciplinary dialogue and bringing multiple stakeholders to the stage. In collaboration with the organizing committee of the 64th Annual Scientific Sessions (ACC.15), chaired by Athena Poppas, MD; and Jeffrey T. Kuvin, MD, Working Group members designed a Cardio-Oncology Intensive a half-day program focused on highly relevant clinical questions in the CV care of patients with cancer and cancer survivors. The aim of the Intensive, which took place March 16, 2015, in San Diego, was to initiate a dynamic conversation on different aspects of care, and utilize novel presentation formats to facilitate audience participation and learning. Importantly, all debates and panel discussions included members of both cardiology health teams and oncology health teams, thereby allowing the audience to glean perspectives on patient care from both sides of the aisle.
The Intensive opened with an overview that consisted of a cardiologist’s perspective of cardio-oncology, followed by an oncologist’s perspective. The cardiologist, Pamela Douglas, MD, MACC, FASE, of Duke University, called for guidelines and a multidisciplinary approach to the care of these patients, highlighting overlap and common risk factors such as smoking, obesity, poor nutrition, and inflammation shared by cancer and heart disease patients. Subsequently, oncologist Susan Dent, MD, of the Ottawa Hospital Cancer Centre and the University of Ottawa took the stage and underscored the rising trend in mortality due to heart disease in breast cancer survivors, calling for collaboration between both groups as an important aid in avoiding heart damage when possible.
The Intensive session included 4 case presentations that covered areas of CV risk prediction and cardioprotection strategies in patients undergoing cancer therapies, delivery of comprehensive care in cancer survivorship, and management of patients treated with vascular endothelial growth factor (VEGF) signaling pathway inhibitors. Here we highlight a case that presented current challenges in CV risk stratification and brought to the table experts in CV imaging, biomarkers for risk stratification, oncology treatment, and CV risk modeling.
A 68-year-old African American woman with new diagnosis of stage III diffuse large B-cell lymphoma was referred for an evaluation of CV risk prior to initiation of planned chemotherapy treatment. Her medical history included left-sided infiltrating ductal carcinoma of the breast (stage IIIB, hormone receptor–negative and HER2 receptor-negative) at age 31 years, for which she received left modified radical mastectomy, post mastectomy chest wall irradiation, and doxorubicin, cyclophosphamide, and paclitaxel chemotherapy. Her history was also significant for hypertension controlled with medications, obesity, 7-year history of type 2 diabetes mellitus, and shoulder arthritis. Her medications included metformin, chlorthalidone, simvastatin, aspirin, ibuprofen, and insulin with meals. The physical exam revealed elevated blood pressure but normal CV exam without elevated jugular venous pressure. She denied angina-like symptoms. The electrocardiogram (ECG) showed normal sinus rhythm, and troponin I and brain natriuretic peptide (BNP) were within normal ranges. The patient underwent a stress echocardiogram (ECHO) with myocardial strain assessment that demonstrated mildly reduced systolic function at rest with overall LVEF of 50% and abnormal global longitudinal strain value of -14.5% (Figure 1). There was preserved contractility during stress, without regional wall motion abnormalities. The patient’s medical therapy was optimized by introduction of an ACE-inhibitor and a beta-blocker: lisinopril and carvedilol, respectively. Blood pressure lowering was pursued to a goal of less than 130/80 mm Hg. Chlorthalidone was stopped to allow titration of ACE-inhibitor and beta-blocker. Simvastatin was switched to pravastatin while on chemotherapy, and ibuprofen was discontinued. Therapeutic lifestyle changes were recommended, including increasing walking and other exercise, improved diet (referral to a dietician was provided), as well as stress reduction. She was treated with 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone regimen (R-CHOP) with dexrazoxane infusions. She had a good outcome and continues to be followed.
The conversation began with a discussion on elevated CV risk in light of planned therapy with R-CHOP. With a history of treatment for breast cancer that included 240 mg/m2 of doxorubicin in the past, planned R-CHOP treatment was raising the cumulative doxorubicin dose to a high value of 540 mg/m2. The panel recognized the lack of randomized data for cardiac prevention in this patient and necessary extrapolation from CV data derived in different cohorts.
Use of Strain Imaging
Thomas Marwick, MD, PhD, MPH, cardiologist at the Menzies Research Institute, Tasmania, and formally of the Cleveland Clinic, reviewed the evidence for incremental value of ECHO strain imaging in predicting cardiotoxicity in patients undergoing cancer treatment.2 Normal ranges and important technical considerations were discussed, including imaging and post processing, as well as variations in strain data interpretation related to regional heterogeneity, load independence, and different vendors.3 The understanding of these concepts will be critical for wider clinical implementation of strain, including in the care of patients with different malignancies, as well as in the design of clinical studies investigating the utility of strain in guiding cardioprotective treatment.
Use of Biomarkers
Daniel Lenihan, MD, cardiologist at the Vanderbilt Heart and Vascular Institute in Nashville, discussed the role of BNP as a biomarker and predictor of cardiotoxicity that showed promise in smaller trials.4 While we await the completion of the ongoing multicenter PREDICT study, the audience is directed to its positive preliminary findings presented at recent national meetings.5
Use of Cardiac MR
W. Gregory Hundley, MD, FACC, FAHA, cardiologist at the Wake Forest Baptist Health, highlighted the advantages of using cardiac magnetic resonance, including high accuracy and reproducibility of ventricular volume measurements of a particular value in patients undergoing serial imaging. He also described novel data on extracellular volume measurement using T1 mapping as a promising new marker of cardiotoxicity.6,7
Oncology Treatment Considerations
Erica Mayer, MD, MPH, oncologist at Dana-Farber Cancer Institute, commented on the success of triple-negative breast cancer treatment in this patient 30 years prior to her presentation with the second malignancy, and highlighted the national trend of decreasing the use of anthracyclines in the treatment of patients with breast cancer.8 The consideration of dexrazoxane was discussed, as was the need for prospective evaluation of this and other cardioprotective agents in conjunction with specific oncology regimens.
Models to Predict CV Risk
CV risk prediction models in patients with cancer are scarce and Jersey Chen, MD, MPH, cardiologist and clinical development physician at AstraZeneca, presented recently published risk score data for cardiomyopathy and heart failure in patients with breast cancer who received trastuzumab. This model utilized the Surveillance, Epidemiology and End Results (SEER)-Medicare database and identified 7 risk factors including age, adjuvant chemotherapy, coronary artery disease, atrial fibrillation, diabetes mellitus, hypertension. and renal failure.9 The model was contrasted with another cardiac risk score derived among clinical trial participants that identified age and baseline left ventricular ejection fraction as the only important contributors of risk in patients receiving trastuzumab therapy.10 Further need for validation of these models in clinical practice was highlighted, as well as the need for development of CV risk prediction in patients with other malignancies.
The Intensive continued with case presentations and a discussion of how to deliver comprehensive care to patients, highlighted by expert commentaries on cancer survivorship and exercise. The talk on the cardiotoxic effects of the VEGF signaling pathway inhibitors focused on the need for and approaches to ischemia evaluation. The debate on the cardiotoxicity related to radiation therapy presented novel modalities, posing the question of whether radiation effects continue to be an ongoing concern. Each of these clinical areas (and more which could not be addressed within the allotted time) represents a unique need and opportunity for growth and collaboration among oncologists, cardiologists, and other medical staff, as well as among various CV subspecialties involved in the evaluation of cancer patients presenting with CV disease and/or risk factors.
Rapid developments in oncology and cardiology have created a durable need for platforms that allow knowledge exchange and interdisciplinary education. The ACC.15 Cardio-Oncology Intensive successfully joins the effort to advance scientific dialogue and bridge gaps in clinical practice through education and collaboration. As we plan the next Intensive, it is important to note broad areas of partnership that will need to be developed in order advance CV care of patients with cancer and cancer survivors. They include but are not limited to:
- collaborations in clinical guidelines and documents development;
- education and clinical training;
- database and registry building; and
- basic, clinical, translational, and epidemiology research.1
1. Barac A, Murtagh G, Carver JR et al. Council clinical perspective: cardiovascular health of patients with cancer and cancer survivors: a roadmap to the next level. J Am Coll Cardiol. In press.
2. Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2014;27:911-939.
3. Negishi K, Negishi T, Kurosawa K, et al. Practical guidance in echocardiographic assessment of global longitudinal strain. JACC Cardiovasc Imaging. 2015;8:489-492.
4. Ky B, Putt M, Sawaya H, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol. 2014;63:809-816.
5. Ky B, Warneke D, Lenihan DJ, et al. Clinical risk prediction in anthracycline cardiotoxicity. J Clin Oncol. 2014;32:5S(suppl): abstract 9624.
6. Jordan JH, D'Agostino RBJ, Hamilton CA, et al. Longitudinal assessment of concurrent changes in left ventricular ejection fraction and left ventricular myocardial tissue characteristics after administration of cardiotoxic chemotherapies using t1-weighted and t2-weighted cardiovascular magnetic resonance. Circ Cardiovasc Imaging. 2014;7:872-879.
7. Kongbundansuk S, Hundley WG. Noninvasive imaging of cardiovascular injury related to the treatment of cancer. JACC Cardiovasc Imaging. 2014;7:824-838.
8. Serrurier K, Hwang J, JP McGuire, Griffin AC, Melisko ME, Rugo HS. Chemotherapy treatment patterns for early-stage breast cancer (ESBC): decreasing use of anthracycline-based regimens. J Clin Oncol. 2012;30(suppl 27): abstract 141.
9. Ezaz G, Long JB, Gross CP, Chen J. Risk prediction model for heart failure and cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Heart Assoc. 2014;3:e000472.
10. Romond EH, Jeong JH, Rastogi P, et al. Seven-year follow-up assessment of cardiac function in NSABP b-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with acp plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012;30:3792-3799.