Heart Failure and Cancer ― A Comorbid Risk That Is No Longer Underestimated ―
Article ID: CJ-20-0888
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Article ID: CJ-20-0888
Onco-cardiology/cardio-oncology is a clinical interdisciplinary continuum between malignant disease and cardiovascular disease. Notably, the multidirectional approach is essential for directing this interdisciplinary research because cancer per se causes cardiovascular events, namely heart failure (HF), ischemic heart disease, arrhythmias and thrombosis,1 and because multiple types of anticancer drugs and therapies cause cardiovascular disorders, such as HF, arrhythmias, atherosclerotic disease and hypertension.2–4
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In addition, recent advances in cancer treatment promote the number of “cancer survivors” who are appreciated to have higher cardiovascular risks due to the cancer therapeutics-related cardiac dysfunction (CTRCD) and the progression of natural cardiovascular risks by aging (Figure).5 Thus, the more intense and practical care that is required for these patients. In the meantime, establishment of clinical evidence and clinical research is warranted.
Cancer and heart failure (HF) as comorbidity: disease-specific and shared risks. Cancer and HF share event risk factors associated with the development or worsening of the disease condition. Active cancer causes inflammation, cachexia, and anemia, which are known risk factors for worsening HF. Vice versa, HF primarily promotes chronic inflammation and neurohormonal activation, which also presumably contribute to cancer progression. In addition, cancer and HF shares common disease risks (green ovals). CTRCD, cancer therapeutics-related cardiac dysfunction.
In this issue of the Journal, Kaneko et al report real-world evidence regarding the relationship between cancer and the risk of in-hospital death in patients with HF in Japan.6 Based on a retrospective cohort study using the large-scale Diagnosis Procedure Combination (DPC) database (n=447,818), they found that the concomitant presence of cancer was independently associated with higher in-hospital mortality of patients hospitalized for HF. The key findings of their study are summarized as follows. (1) Cancer was diagnosed in approximately 6% of patients hospitalized for HF. (2) Infectious complications were more frequently (5.3%) seen in patients with cancer. (3) The presence of cancer was independently associated with a higher in-hospital mortality (10.0%, P<0.001). However, there remained a critical limitation due to the nature of DPC database.
First, lack of information regarding the cause of death and cancer status limited exploration of the causal relationship between cancer and the worsening of HF. The authors’ added discussion regarding this point of concern is that patients with cancer are generally at high risk for complications such as thrombotic events and infections,6 which is supposed to be one of the major reasons for the poorer prognosis regardless of HF.
Second, the lack of information regarding the active status of cancer and the choice of cancer treatment. In patients with active cancer, cancer-related chronic inflammation causes cardiovascular events.7 Also, advanced-stage cancer causes malnutrition that promotes cachexia and anemia, which are known risk factors for worsening HF.8 In other word, progression of cancer could be associated with advances in the risk of HF.
Information regarding the regimen of anticancer treatment is also crucial for understanding the cause of death in patients with CTRCD. For instance, the anthracycline-related regimen is broad spectrum and effective for malignant lymphoma, and solid cancers such as breast cancer and gastrointestinal cancers. However, anthracyclines sometimes cause irreversible myocardial damage.2 Anthracycline-induced cardiotoxicity is generally dose-dependent and often occurs within 1 year after the termination of therapy, but there are reports of late-onset of chronic progressive toxicity.9
Chemotherapy is not the exclusive option in cancer treatment. Thoracic radiation therapy is an effective treatment for several malignancies, such as bulky lymphoma and breast cancer. However, mediastinal radiation therapy accelerates the process of atherosclerosis, resulting in early-onset coronary artery disease. It may also cause cardiomyopathy and valvular disease such as aortic regurgitation, and chronic pericardial diseases such as constrictive pericarditis.10 Furthermore, it is noteworthy that cancer survivors treated with both anthracycline and radiation exhibit the highest risk of experiencing cardiac events.11
Lastly, there are insufficient data regarding the “shared” risks such as aging, hypertension, diabetes, smoking, alcohol and obesity,12 which are common risk factors for not only the onset of cancer but also for worsening HF. In patients with these comorbid risks, greater attention should be paid to the development of cardiovascular disease not only during the active cancer stage but also in the survivor stage.
In summary, this study confirmed the clinical significance regarding cancer as a comorbidity that should no longer be underestimated in Japanese HF patients. The present study will facilitate more clinical studies to address the cause-and-effect relationship between cancer and HF to reduce mortality in those who are suffering from these worst causes of death in the Japanese population.
T.M. is a member of Circulation Journal’ Editorial Team.
