Incidence and outcomes of cancer treatment-related cardiomyopathy among referrals for advanced heart failure

Abstract

Background: Approximately 2-3% of patients undergoing advanced heart failure therapies such as left ventricular assist devices (LVAD) and orthotropic heart transplantation (OHT) have chemotherapy-related cardiomyopathy, according to analyses of large databases such as United Network for Organ Sharing (UNOS) or Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registries. While these studies have shown similar survival outcomes post-interventions, these databases by definition exclude patients referred for advanced therapies but do not receive them, and thus there is little data on overall outcomes of such patients. Given the lack of nuance in the diagnoses in large registries and the possibility that many cancer treatment-related cardiomyopathy (CCMP) patients might be misclassified by the generic "non-ischemic" or "dilated" cardiomyopathies, we investigated the incidence and clinical outcomes of CCMP patients among advanced heart failure (HF) referrals at a single high volume institution. Methods: All referrals from 2013 to 2016 were evaluated for type of cardiomyopathy, with careful chart review. Outcomes such as LVAD, OHT and death were compared between CCMP and other cardiomyopathies. Results: Of 553 referrals for advanced HF, 19 (3.4%) were for CCMP. There was a higher percentage of patients receiving advanced therapies in the CCMP vs. non-ischemic cardiomyopathy (NICMP) and ischemic cardiomyopathy (ICMP) (42.1% vs 30.2% vs 33.6%, not significant). Of the CCMP patients, 3 had OHT directly, 2 had LVAD followed by OHT, and 3 had LVADs as bridge to candidacy or destination therapy. Fifty-eight percent of the CCMP did not receive LVAD or OHT compared to 69.8% and 66.3 of the NICMP and ICMP, respectively (p = 0.0388). Independent of type of advanced therapy, survival was significantly higher in the CCMP group compared to NICMP and ICMP (93.3% vs 84.8% vs 73.8%, respectively P = 0.0021 for 1 year, 93.3% vs 76.2% vs 58.3%, respectively, P = < 0.0001 for 3 year). Conclusions: In a single institution, CCMP accounts for more than 3% of all referrals for advanced HF therapies and almost 8% of NICMP. Contrary to concerns for previous cancer and sequelae of cancer treatment excluding patients for advanced therapies, a higher percentage of CCMP underwent advanced HF therapies and with similar outcomes. This is the first study to show that among patients referred for advanced therapies, CCMP patients do not have inferior outcomes compared to other cardiomyopathies regardless of the selected management strategy.

Severe Cardiac Toxicity Induced by Cancer Therapies Requiring Intensive Care Unit Admission

“…Araujo-Gutierrez et al (145) analyzed all the referrals for advanced HF of a tertiary-care center, showing that 3.4% of patients were CCMP, but the percentage was high as 7.8% in the subset of idiopathic, non-ischemic cardiomyopathy. Though not reaching statistical significance, there was a higher percentage of patients receiving LV assist device (LVAD) as bridge to transplant (BTT).…”

Sex-Related Differences in Dilated Cardiomyopathy with a Focus on Cardiac Dysfunction in Oncology

“…These differences result from the presence of women specific forms of primary disease and sex-specific biological response. The most common forms of CRCD are secondary to breast cancer treatment, which is strongly sexoriented, followed by hematological malignancies [22,51]. Women with CRCD that progressed to DCM are older, have smaller end-diastolic volume index, have higher left ventricular EF, have a lower burden of scar at CMR, have a worse NYHA class but a better long-term prognosis, and have higher rate of previous chemotherapy exposure compared with women with the diagnosis of primary DCM [52][53][54].…”

“…In this setting, DCM can be the ending phase of a pathological process that is usually defined more broadly as chemotherapy-related cardiac dysfunction (CRCD). It is reported that CRCD can affect up to 10% of cancer survivors [22], even though incidence is variable according to the definition used. The heterogeneity of definitions adopted by different societies is summarized in Table 1 [23,24].…”

“…The heterogeneity of definitions adopted by different societies is summarized in Table 1 [23,24]. CRCD progresses to end-stage HF in 2-3% of cases according to retrospective studies [22,[25][26][27][28]; up to 2.5% of patients requiring LVAD or transplantation have CRCD in UNOS or INTERMACS registries [22,[25][26][27][28]. Both DCM in general and CRCD in particular are influenced by sex in terms of clinical characteristics and outcomes.…”

<p>Is it possible to prevent chemotherapy-induced heart failure with cardiovascular drugs - the review of the current clinical evidence</p>

“…Cardiovascular diseases and cancer are the most common death causes in the USA and Europe, although long-term survival of oncological patients has increased in the last years, reaching 64% of 5-year survival rate, 41% of 10-year survival rate and 15% of 20-year survival rate. Moreover, many patients suffer from both of these conditions – a situation which may result from cardiotoxicity of anticancer treatment 1,2. The most frequent symptom of such cardiotoxicity is LVEF (left ventricular ejection fraction) reduction which may indicate the development of left ventricular dysfunction and lead to congestive heart failure.…”