Anthracycline-induced cardiomyopathy (AIC) may progress to end-stage heart failure requiring mechanical circulatory support or orthotopic heart transplantation (OHT). Previous studies have described important clinical differences between AIC and nonischemic cardiomyopathy (NIC) cohorts requiring these advanced interventions. Therefore, we sought to extend this literature by comparing echocardiographic parameters, treatment strategies, and the prognosis between matched patients from these cohorts. This is a retrospective matched cohort study. All patients who received a ventricular assist device or OHT at a large Canadian center were reviewed (n = 421; 1988 to 2015) and subjects with clinical and pathologic evidence of AIC were included (n = 17, 4.0%). A comparison cohort with idiopathic NIC from the same database, matched 3:1 for age, gender, ethnicity, and year of heart failure onset was selected. The Mann-Whitney rank-sum and Fisher’s exact tests were used for comparisons. Patients with AIC were predominantly women (70.6%) with heart failure diagnosed at age 40.2 ± 15.8 and 8.3 ± 8.9 years after anthracycline treatment. Compared with NIC, no differences were seen in co-morbidities, echocardiographic measures, the proportion of patients receiving a defibrillator, ventricular assist device, or OHT, the incidence of graft failure, and all-cause mortality. In contrast to other studies, AIC was not associated with a higher incidence of right ventricular dysfunction. A greater proportion of patients with AIC developed cancer (recurrence or new primary) post-OHT (21.4% vs 2.3%, p = 0.042). In conclusion, we demonstrate that when matched cohorts of patients with end-stage heart failure secondary to AIC and idiopathic NIC are compared, they are similar with respect to co-morbidities, degree of ventricular dysfunction, and advanced therapeutics used. The prognosis with OHT is also similar.
A proportion of patients with anthracycline-induced cardiomyopathy (AIC) will progress to end-stage heart failure requiring advanced therapeutic interventions. Registry-based studies have demonstrated a favorable 10-year survival in patients with AIC receiving OHT compared with unmatched cohorts with other causes of end-stage heart failure. However, OHT may not be a feasible option for all patients with AIC as a cancer-free status for at least 5 years is often required for candidacy. Mechanical circulatory support has evolved as an alternative that can be considered for destination or bridge therapy. Recent studies have helped alleviate some of the long-term concerns associated with using ventricular assist devices (VAD) for patients with previous cancer treatment but have reported more frequent concomitant right ventricular dysfunction. These investigations compared cohorts with differences in baseline age, gender, body surface area, and co-morbidities that may have masked or accentuated outcomes. Therefore, a matched comparison will build on existing literature relating to the management and prognosis of patients with AIC with end-stage heart failure. Our aim was to describe the echocardiographic parameters, advanced cardiac interventions, and clinical outcomes in patients at a large Canadian heart failure center with end-stage heart failure secondary to AIC receiving VAD and/or OHT and compare these findings to a “matched cohort” with idiopathic NIC.
Methods
This is a retrospective matched cohort study approved by the Research Ethics Board of our institution. A total of 421 patients with VAD implantation and/or OHT have been recorded in the University Health Network Heart Function Program’s database (February 1988 to December 2015). From this, subjects with a diagnosis of AIC were identified. There were 170 patients with a diagnosis of idiopathic NIC; a comparison cohort was created which was matched 3:1 with AIC for age, gender, ethnicity, and year of heart failure diagnosis (n = 51). This matching criterion was selected to avoid secular trends in management and to reflect recent evidence that patient demographic characteristics influence the interpretation of ventricular size and function. None of the patients with NIC had a history of malignancy. There were no study exclusions.
All patients were managed through the Heart Function Program with no loss to follow-up. Patient information was obtained through hospital electronic medical records, performed in duplicate, 1 month apart, to ensure completeness and accuracy of data extraction. Cardiac investigations, biopsies, VAD implantations, and OHTs were solely performed at our institution. Archived echocardiograms were reviewed by a cardiologist with level III echocardiography certification, and all measurements were performed in accordance with the American Society of Echocardiography guidelines by an experienced sonographer blinded to patient’s group membership. Cardiac specimens were also obtained from all patients either at the time of VAD implantation (apical core sample), OHT, or autopsy (portion of left ventricle to whole heart explant). These specimens were reviewed and reported by a single pathologist with expertise in cardiovascular pathology using light microscopy, electron microscopy, and immunohistochemistry. A diagnosis of AIC was based on a combination of a (1) supportive history of anthracycline exposure along with (2) light microscopy findings of myocyte vacuoles, myofibrillar dropout, and fibrosis in the absence of a pathologic signature of another type of cardiomyopathy, and an electron microscopy finding of loss of myofibrils and significant dilation of the sarcoplasmic reticulum. Study patients were followed for clinical events until January 1, 2016.
All data distribution was first assessed using histograms, skewness, and kurtosis. Continuous variables were expressed as mean ± SD and compared using the Mann-Whitney rank-sum test. Discrete variables were expressed as number and percentage of total and compared using a 2-tailed Fisher’s exact test. Statistical analyses were performed using SAS Enterprise 9.2 (Cary, North Carolina). A p value <0.05 was considered statistically significant.
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