Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy.

BACKGROUND: Three types of anthracycline-induced cardiotoxicities are currently recognized: acute, early-onset chronic, and late-onset chronic. However, data supporting this classification are lacking. We prospectively evaluated incidence, time of occurrence, clinical correlates, and response to heart failure therapy of cardiotoxicity. METHODS AND RESULTS: We assessed left ventricular ejection fraction (LVEF), at baseline, every 3 months during chemotherapy and for the following year, every 6 months over the following 4 years, and yearly afterward in a heterogeneous cohort of 2625 patients receiving anthracycline-containing therapy. In case of cardiotoxicity (LVEF decrease >10 absolute points, and <50%), heart failure therapy was initiated. Recovery from cardiotoxicity was defined as partial (LVEF increase >5 absolute points and >50%) or full (LVEF increase to the baseline value). The median follow-up was 5.2 (quartile 1 to quartile 3, 2.6-8.0) years. The overall incidence of cardiotoxicity was 9% (n=226). The median time elapsed between the end of chemotherapy and cardiotoxicity development was 3.5 (quartile 1 to quartile 3, 3-6) months. In 98% of cases (n=221), cardiotoxicity occurred within the first year. Twenty-five (11%) patients had full recovery, and 160 (71%) patients had partial recovery. At multivariable analysis, end-chemotherapy LVEF (hazard ratio, 1.37; 95% confidence interval, 1.33-1.42 for each percent unit decrement) and cumulative doxorubicin dose (hazard ratio, 1.09; 95% confidence interval, 1.04-1.15 for each 50 mg/m(2) increment) were independent correlates of cardiotoxicity. CONCLUSIONS: Most cardiotoxicity after anthracycline-containing therapy occurs within the first year and is associated with anthracycline dose and LVEF at the end of treatment. Early detection and prompt therapy of cardiotoxicity appear crucial for substantial recovery of cardiac function.

Prevention of Atrial Fibrillation in High-risk Patients Undergoing Lung Cancer Surgery: The PRESAGE Trial.

OBJECTIVE: We performed a prospective, randomized clinical study to assess whether prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, reduces the incidence of postoperative atrial fibrillation. BACKGROUND: Postoperative atrial fibrillation is a well recognized complication after lung cancer surgery, with an incidence as high as 30%. Perioperative increase of NT-proBNP has been demonstrated to be a strong independent predictor of postoperative atrial fibrillation in this setting. METHODS: NT-proBNP concentration was measured 24 hours before surgery and soon after surgery in 1116 patients. Three hundred twenty (29%) patients showed a high NT-proBNP value and were enrolled: 108 were assigned to the metoprolol group, 102 to the losartan group, and 110 to the control group. RESULTS: Overall, the incidence of postoperative atrial fibrillation was 20% (n = 64); it was significantly lower in the metoprolol and losartan groups compared with the control group [6%, 12%, and 40%, respectively; relative risk 0.19, 95% confidence intervals (CIs), 0.09-0.37; P < 0.001 in the metoprolol group; and 0.29, 95% CI, 0.16-0.52; P < 0.001 in the losartan group). No significant difference was found when the metoprolol and losartan groups were directly compared (P = 0.21). CONCLUSIONS: A prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with high NT-proBNP levels, significantly reduced the occurrence of postoperative atrial fibrillation.

Managing cardiotoxicity of chemotherapy.

OPINION STATEMENT: The increase in survivorship of cancer patients makes the understanding of the available options for prevention and treatment of cardiotoxicity induced by antineoplastic agents a crucial topic both for cardiologists and oncologists. The most frequent and typical clinical manifestation of cardiotoxicity is asymptomatic or symptomatic left ventricular dysfunction, which may progress to overt heart failure. It may be induced not only by conventional cancer therapy, like anthracyclines, but also by new antitumoral targeted therapy such as trastuzumab. The current standard for monitoring cardiac damage during antineoplastic treatment, mainly based on the quantification of left ventricular ejection fraction, detects cardiac toxicity only when a functional impairment has already occurred. Evaluation of cardiac biomarkers such as troponin, however, has shown excellent sensitivity in the early detection of cardiotoxicity by the identification of patients with subclinical cardiac injury that precedes the development of cardiac dysfunction. The use of angiotensin-converting enzyme inhibitors in patients with troponin elevation during chemotherapy may be an effective tool to prevent left ventricular ejection fraction reduction and late cardiac events. There are no well established recommendations for treatment of cancer patients who develop cardiac dysfunction. Angiotensin-converting enzyme inhibitors and beta-blockers have proven to be effective in this setting. However, there are concerns in using these medications in cancer patients, and therefore the tendency is to treat patients only if symptomatic. However, the clinical benefit of these medications may be more evident in asymptomatic patients, and the recovery of cardiac function strongly depends on the amount of time elapsed from the end of chemotherapy to the start of heart failure therapy. This observation suggests that the early detection of cardiac damage is crucial and early use of angiotensin-converting enzyme inhibitors and beta-blockers should be considered in patients with left ventricular dysfunction induced by antineoplastic agents.