Cardio-Oncology Corner

Deep dive: Cancer-related therapies and advanced HF

As the field of cardio-oncology is burgeoning, there is increased awareness of the potential cardiotoxicity of cancer treatments and a focus on early detection and prevention. Nevertheless, some patients develop HF so advanced that they need end-organ interventions such as mechanical circulatory support devices or heart transplantation. Analysis of heart transplant and mechanical circulatory support databases informs much of what we know about outcomes, although these are largely limited to patients with HF who received anthracycline-based chemotherapy. Although the incidence of stage D (refractory) HF due to chemotherapy is estimated to be approximately 2% to 3%, various reports from transplant registries show that the incidence is increasing.

There are unique considerations for the eligibility of mechanical circulatory support and heart transplantation in this population, including the potential effect of mediastinal radiation therapy on perioperative complications. The data, however, are very limited in this area. In addition, due to the concern for recurrence of malignancy — especially in the setting of systemic immunosuppression — many centers have a requirement for a 5-year cancer-free interval before acceptance for heart transplantation. Finally, single-center studies indicated that chemotherapy cardiomyopathy due to doxorubicin, for example, had a markedly worse prognosis compared with idiopathic dilated cardiomyopathy or ischemic HF.

Barry Trachtenberg

INTERMACS analysis

Analysis of the INTERMACS registry from 2006 to 2011 showed that 2% of patients with a left ventricular assist device placed had a history of chemotherapy cardiomyopathy. Patients with chemotherapy cardiomyopathy were more likely to receive the LVAD with a strategy of destination therapy compared with other LVAD recipients. Importantly, patients were twice as likely to require a right VAD (19% vs. 9%) as those without a history of cancer, likely due to the global cardiac dysfunction caused by the chemotherapy. Thus, careful consideration should be given to alternative strategies such as total artificial heart or heart transplantation in eligible patients who are determined before implant to have a high risk for right ventricle failure. Despite the increased risk for RV failure, patients with chemotherapy cardiomyopathy had similar survival compared with all other patients. The increased risks may have been mitigated because patients with chemotherapy cardiomyopathy had fewer comorbidities and were younger.

ISHLT registry analysis

In addition, an analysis from the International Society for Heart and Lung Transplantation (ISHLT) registry from 2000 to 2008 compared patients with chemotherapy cardiomyopathy and dilated nonischemic cardiomyopathy. There was also no difference in overall survival between the two groups. The data showed a higher incidence of malignancies in the chemotherapy cardiomyopathy group within 1 year of heart transplantation (5% vs. 2% in control group), although five of nine cancers were skin cancers. There was no increased risk for death due to recurrent cancers, a finding that was also replicated in analysis of the United Network for Organ Sharing (UNOS) database.

More data needed

These databases are not only limited by lack of information on specific chemotherapy regimens and dosages, but they may also be subject to misclassification of patients with chemotherapy cardiomyopathy under more generic terms such as “nonischemic” or “idiopathic” cardiomyopathy. In our single-center study analyzing outcomes of patients with chemotherapy cardiomyopathy referred for advanced therapies, we found that we had indeed failed to properly designate 60% and 40% of our chemotherapy cardiomyopathy patients appropriately to the UNOS and INTERMACS registries, respectively.

Finally, our knowledge on the outcomes of advanced therapies is mainly confined to anthracycline-based chemotherapy. As the use of targeted therapies such as tyrosine kinase and VEGF inhibitors as well as cancer immunotherapy, including immune checkpoint inhibitors, continues to expand considerably, the implications for those that develop stage D HF from these therapies remain wholly unknown. As cancer survivorship continues to increase and the proportion of patients undergoing mechanical circulatory support or heart transplantation due to chemotherapy cardiomyopathy increases, more data are needed on their unique complications and outcomes.

Disclosure: Trachtenberg reports no relevant financial disclosures.

As the field of cardio-oncology is burgeoning, there is increased awareness of the potential cardiotoxicity of cancer treatments and a focus on early detection and prevention. Nevertheless, some patients develop HF so advanced that they need end-organ interventions such as mechanical circulatory support devices or heart transplantation. Analysis of heart transplant and mechanical circulatory support databases informs much of what we know about outcomes, although these are largely limited to patients with HF who received anthracycline-based chemotherapy. Although the incidence of stage D (refractory) HF due to chemotherapy is estimated to be approximately 2% to 3%, various reports from transplant registries show that the incidence is increasing.

There are unique considerations for the eligibility of mechanical circulatory support and heart transplantation in this population, including the potential effect of mediastinal radiation therapy on perioperative complications. The data, however, are very limited in this area. In addition, due to the concern for recurrence of malignancy — especially in the setting of systemic immunosuppression — many centers have a requirement for a 5-year cancer-free interval before acceptance for heart transplantation. Finally, single-center studies indicated that chemotherapy cardiomyopathy due to doxorubicin, for example, had a markedly worse prognosis compared with idiopathic dilated cardiomyopathy or ischemic HF.

Barry Trachtenberg

INTERMACS analysis

Analysis of the INTERMACS registry from 2006 to 2011 showed that 2% of patients with a left ventricular assist device placed had a history of chemotherapy cardiomyopathy. Patients with chemotherapy cardiomyopathy were more likely to receive the LVAD with a strategy of destination therapy compared with other LVAD recipients. Importantly, patients were twice as likely to require a right VAD (19% vs. 9%) as those without a history of cancer, likely due to the global cardiac dysfunction caused by the chemotherapy. Thus, careful consideration should be given to alternative strategies such as total artificial heart or heart transplantation in eligible patients who are determined before implant to have a high risk for right ventricle failure. Despite the increased risk for RV failure, patients with chemotherapy cardiomyopathy had similar survival compared with all other patients. The increased risks may have been mitigated because patients with chemotherapy cardiomyopathy had fewer comorbidities and were younger.

ISHLT registry analysis

In addition, an analysis from the International Society for Heart and Lung Transplantation (ISHLT) registry from 2000 to 2008 compared patients with chemotherapy cardiomyopathy and dilated nonischemic cardiomyopathy. There was also no difference in overall survival between the two groups. The data showed a higher incidence of malignancies in the chemotherapy cardiomyopathy group within 1 year of heart transplantation (5% vs. 2% in control group), although five of nine cancers were skin cancers. There was no increased risk for death due to recurrent cancers, a finding that was also replicated in analysis of the United Network for Organ Sharing (UNOS) database.

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More data needed

These databases are not only limited by lack of information on specific chemotherapy regimens and dosages, but they may also be subject to misclassification of patients with chemotherapy cardiomyopathy under more generic terms such as “nonischemic” or “idiopathic” cardiomyopathy. In our single-center study analyzing outcomes of patients with chemotherapy cardiomyopathy referred for advanced therapies, we found that we had indeed failed to properly designate 60% and 40% of our chemotherapy cardiomyopathy patients appropriately to the UNOS and INTERMACS registries, respectively.

Finally, our knowledge on the outcomes of advanced therapies is mainly confined to anthracycline-based chemotherapy. As the use of targeted therapies such as tyrosine kinase and VEGF inhibitors as well as cancer immunotherapy, including immune checkpoint inhibitors, continues to expand considerably, the implications for those that develop stage D HF from these therapies remain wholly unknown. As cancer survivorship continues to increase and the proportion of patients undergoing mechanical circulatory support or heart transplantation due to chemotherapy cardiomyopathy increases, more data are needed on their unique complications and outcomes.

Disclosure: Trachtenberg reports no relevant financial disclosures.