Author + information
- Daniel J. Lenihan, MD∗ ()
- ↵∗Address for correspondence:
Dr. Daniel J. Lenihan, Cardio-Oncology Center of Excellence, Cardiovascular Division, Washington University in St. Louis, 660 South Euclid Avenue, Campus Box 8086, St. Louis, Missouri 63110.
In this issue of JACC: Heart Failure, Jones et al. (1) report on a comprehensive prospective cardiovascular assessment of patients with cancer who have no evidence of left ventricular dysfunction by sophisticated testing and who are undergoing therapy that is known to be potentially cardiotoxic (and are considered a patient who is at Stage A HF according to the ACC/AHA staging system according to the American College of Cardiology [ACC]/American Heart Association [AHA] Stage A heart failure [HF]). The authors detail cardiac structural changes that occurred in a substantial percentage of patients; however, the good news is that most of the patients did not progress further down the ACC/AHA HF staging system from Stage A (a patient at high risk for development of HF) to Stage B (patients with structural abnormalities including evidence of left ventricular remodeling without symptoms of HF) (1). It would be alarming if a high percentage of patients actually progressed to symptomatic HF (Stage C), and that would certainly raise important questions about the overall utility of the treatment for cancer. Another key component of this report is that a variety of cancers were included, which enhances our knowledge base beyond that of primarily breast cancer studies in cardio-oncology to date (1).
The authors are to be commended for the careful description of cardiovascular (CV) risk factors, monitoring of symptoms, and detailed sophisticated cardiac imaging that was used in conducting this study. It is not only with such a complete CV assessment of patients undergoing potentially cardiotoxic cancer treatment that we can collectively understand how often CV toxicity occurs but also how standard clinical measurements can uncover those who may be developing subclinical CV damage (and therefore becoming a patient with Stage B HF). It was the vision of the leaders in cardiology years ago that the ACC/AHA staging system would be more inclusive of patients who are likely to develop symptomatic HF and that we could collectively intervene with prevention or early detection strategies to forestall the epidemic of HF that we are experiencing (2). The current report is evidence that this visionary strategy can actually be applied in practice.
There are some important details to emphasize about these data and highlight areas that can be enhanced in future studies. For example, the authors acknowledge that their study did not have enough patients or statistical power to determine whether certain cardioprotective medications may attenuate the progression to Stage B HF. Only approximately 25% of the total population studied was receiving angiotensin-converting enzyme (ACE) inhibitor, and there was no clear protective signal from these limited data. As noted by the authors, there has been a suggestion that certain cardioprotective medications may actually prevent progression from Stage A to Stage B HF during cancer treatment (3). One such study, the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial, was able to demonstrate that candesartan (an angiotensin receptor blocker [ARB]) prevented development of Stage B HF (4) in patients receiving predominantly anthracycline-based chemotherapy and that this strategy of using ACE inhibitor or ARB in high-risk patients (such as those with diabetes mellitus or peripheral vascular disease) is strongly suggested by the current HF guidelines. It is also highly notable that, according to the data presented here, a transition rate of nearly 20% to Stage B HF should definitely be considered a high-risk situation and that cancer treatment results in a higher rate of HF progression than diabetes or peripheral vascular disease alone. As such, including “cardiotoxins” such as cancer therapy in the summary figure for the HF staging system is absolutely justified. In fact, “potentially cardiotoxic cancer therapy” would be more accurate to include in the HF guideline summary figure.
One disappointing feature of this careful study is that cardiac biomarkers are not reported. I would be curious if some combination of sophisticated cardiac biomarkers could allow a stratification of those patients at highest risk, who would benefit from cardioprotective therapy. If specific CV-based biomarkers could reliably identify those patients, then this would usher in an era of personalized medicine in cardio-oncology. There have been a variety of biomarker-based studies over the years, but differences in assay techniques or timing of measurement have unfortunately provided significant uncertainty to the findings. However, I hope that improved technology may lead to meaningful changes in the current biomarker paradigm for cardio-oncology. One such study suggested that a combination of elevated markers may predict cardiac dysfunction (5), whereas another novel cardiac biomarker that is dependent on the mechanism of cardiac injury from the cancer treatment (6) may be useful in identifying high-risk patients to target cardioprotective therapy.
Overall, I congratulate Jones et al. (1) for this excellent report detailing the impact of cancer therapy on CV function in a broad population of patients. This study serves as a wake-up call for cardiology to actually apply the visionary ACC/AHA guidelines and staging system for our collective patients in cardio-oncology. Identifying those patients undergoing treatment for cancer at high risk for heart failure and applying the best preventive therapy are the overarching goals. “To B or not to B” is certainly the question we have in cardio-oncology.
↵∗ Editorials published in JACC: Heart Failure reflect the views of the authors and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Dr. Lenihan has reported that he has no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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