Active Voice: The Heart – A New Victim of Cancer-Induced Cachexia
By Reid Hayward, Ph.D.
Viewpoints presented in SMB commentaries reflect opinions of the authors and do not necessarily represent positions or policies of ACSM.
Reid Hayward, Ph.D., is a professor of exercise science in the School of Sport and Exercise Science at the University of Northern Colorado in Greeley, Colorado. He also is the director of the University of Northern Colorado Cancer Rehabilitation Institute. He has been a member of ACSM more than 25 years.
This commentary presents Dr. Hayward’s views on the topic of the research article that he and his co-author had published together. Their research paper appeared in the June 2018 issue of Medicine & Science in Sports & Exercise® (MSSE).
Clinicians have long recognized the cardiovascular consequences of cancer treatment – a concern that is primarily focused on heart failure associated with anthracycline exposure. However, it has more recently become apparent that a wide range of anti-cancer agents cause cardiotoxicities that can encompass heart failure, hypertension, vascular disease, arrhythmias, metabolic disorders and systolic/diastolic dysfunction. This has led to the development of an emerging discipline that focuses on the intersecting aspects of cardiovascular disease and cancer – a discipline termed “cardio-oncology.” Since its inception, this field has developed at a rapid pace and has resulted in the establishment of cardio-oncology programs in medical academic institutions and major health care systems. Our need to understand these cardiovascular-cancer interactions is highlighted by the fact that women over the age of 65 who are diagnosed with early- stage breast cancer are more likely to die of cardiovascular complications than from cancer. In addition, it is now recognized that treatment-related cardiac death is the primary noncancer cause of mortality in adult survivors of childhood malignancies.
Attempts to identify and develop strategies to attenuate these cardiovascular complications is of utmost importance. To that end, our group has spent more than 15 years investigating the effects of exercise on doxorubicin-induced cardiac dysfunction. We have shown previously that both endurance and resistance exercise protect against doxorubicin cardiotoxicity, while preserving the anti-neoplastic effects of the drug. This exercise-induced cardioprotection has been associated with a preservation of contractile proteins, a normalization of autophagic flux, and a reduction in cardiac doxorubicin tissue accumulation resulting from an upregulation in multidrug resistance proteins.
Although a great deal of attention has been focused on the cardiovascular toxicities related to cancer treatment, less attention has been paid to the cardiovascular toxicities of the cancer itself. The term “cardiac cachexia” is most often associated with heart disease, but in the field of oncology it can be used to describe cancer-induced cardiac atrophy, remodeling and dysfunction. Tumor-bearing animals have been shown to exhibit dilated cardiomyopathy, cardiac remodeling, increased autophagy and deleterious alterations in cardiac contractile proteins. Studies have reported that cancer patients who died because of cancer cachexia showed a 25 percent reduction in heart weight when compared with cancer patients not diagnosed with cachexia. Other published evidence indicates that extensive cardiac fibrosis is observed postmortem in all cancer patients regardless of the presence of clinically diagnosed cachexia. Cardiac complications in cancer patients, particularly cancer-induced complications, remain underdiagnosed and, thus, are commonly not addressed in the clinical setting.
Recently, our group sought to determine if chronic endurance exercise could mitigate the cardiac complications associated with cancer-induced cardiac cachexia. As reported in the June 2018 issue of MSSE, we investigated the effects of voluntary wheel running on cardiac function, myosin heavy chain isoform distribution and the expression of autophagy proteins in rats inoculated with mammary adenocarcinoma cells. Tumor-bearing animals showed cardiac atrophy, cardiac dysfunction, abnormal myosin heavy chain isoform distribution and autophagic dysregulation. Chronic endurance exercise preserved cardiac mass and normalized both systolic and diastolic cardiac function in tumor-bearing animals. Furthermore, exercise attenuated the negative shift in myosin heavy chain isoform expression and autophagic flux. Overall, exercise protected the heart against cancer-induced cardiac cachexia and the functional deficits that accompany this syndrome.
The fatigue and weakness associated with cancer-induced cachexia historically have been attributed to skeletal muscle wasting, but it is possible that cardiac insufficiency may be an equally contributing factor. These new findings demonstrate that exercise may be one effective strategy to offset the debilitating effects of cancer-induced cardiac cachexia. It is yet one more example that highlights the benefits of structured exercise in cancer survivors. As advocates for Exercise is Medicine®, exercise professionals working with cancer survivors need to consider exercise strategies to specifically target not only the cancer treatment-related cardiotoxicities, but also the cardiotoxicities resulting from the cancer itself.