Prognosis and predictors of functional recovery at follow-up in patients with anthracyclines cardiomyopathy

Abstract

Purspose: Cardiomyopathy (CMP) due to anthracyclines chemotherapy (ACT) is considered to have a poor prognosis, but pump function may improve with early treatment with ACE-inhibitors (ACE-I). We evaluated the long-term follow-up (f-u) of a group of patients (pts) with ACT-CMP observed over a 25 year period, to assess prognosis, causes of death and predictors of functional recovery. Methods: The study group included 133 pts (women/men 101/32, mean age 53±13 years at diagnosis) with CMP due to ACT (symptomatic or not) diagnosed between 1984 and 2011. Inclusion criteria: 1) congestive heart failure after ACT, with ejection fraction (EF) by echocardiogram (echo) ≤ 50%; or EF 10% compared to a pre-ACT echo; 2) no other detectable causes of CMP; 3) more than 6 months follow-up after diagnosis of CMP. Cardiologic examination, ECG and echo were done at diagnosis, after 3, 6, 12 months and then yearly. Cardiovascular therapy was prescribed according to the clinical knowledge at different periods of time. Patients were considered responders if EF increased to >50%, or at least by 10% above baseline value. Primary endpoints: cardiovascular mortality, recovery of EF at 12 months. Secondary end points: factors predictive of therapeutic response. Results: The f-u lasted 6-204 months (median 22). Seventy eight (57%) pts died: 63 of cancer disease progression, 2 of cardiac failure, 13 of other causes. The mean NYHA class decreased from 2.1±0.8 to 1.7±0.6 at 3 months, 1.6±0.6 at 6 months, 1.5±0.6 at 12 months (p <0.0001). At last f-u 68 pts were in NYHA class 1; EF was 22%-65% (median 53%). The responders were 26% at 3 months, 45% at 6 months, 52% at 12 months, and 57% at last f-u. Of all responders, 67% of pts were on monotherapy with BB (beta blockers) and 56% with ACE-I. The addition of BB to initial therapy with ACE-I brought the responders from 56% to 64%, while in patients previously treated with BB, addition of ACE-I did not induce any further improvement. By multivariable logistic analysis, independent predictors of recovery of EF were: smaller end-diastolic diameter, higher fractional shortening or EF at diagnosis; combination therapy with ACE-I and BB; BB monotherapy (p = 0.001). Conclusions: The prognosis of CMP due to ACT is not as poor as previously described, and mortality is mainly linked to the tumor. The extent of left ventricular remodeling at baseline can affect the degree of recovery of EF during f-u. Therapy with ACE-I and, mostly, with BB is effective in improving the clinical and echocardiographic conditions.