6. Mebrate Y, Willson K, Manisty CH, et al. Dynamic CO 2 therapy in periodic breathing: a modeling study to determine optimal timing and dosage. J Appl Physiol 2009;107:696 –706. 7. Bradley TD, Logan AG, Kimoff RJ, et al., for the CANPAP Investi- gators. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005;353:2025–33. Treating Asymptomatic Chemotherapy-Induced Cardiac Dysfunction A Chance That Cardiologists and Oncologists Should Not Miss We have read the work by Yoon et al. (1) with great interest. The authors point out that many cancer survivors showing cardiac dysfunction after oncologic therapy do not receive treatment consistent with heart failure guidelines, particularly if they are in the asymptomatic phase of this form of cardiomyopathy. More- over, they state that it is not clear whether treatment of asymp- tomatic cardiac dysfunction in cancer patients decreases the risk of developing symptomatic heart failure and adverse cardiac events and that no prospective studies have ever evaluated this topic. However, some stronger and more recent evidence than that reported by the authors—like the work by Haq et al. (2), dating back to 1985, in which patients were treated with only digoxin and diuretics— have been provided with regard to treatment of chemotherapy-induced left ventricular dysfunction with modern heart failure therapy. A few years ago, Tallaj et al. (3) reported that the cardiac prognosis of chemotherapy-induced cardiomyopathy can be positively affected when patients are treated with angiotensin-converting enzyme inhibitors and that the addition of a beta-blocker might further improve the clinical outcome and reverse left ventricular dysfunction. Moreover, in a recently pub- lished prospective study, considering a population of 201 patients with anthracycline-induced cardiomyopathy, we demonstrated that an early treatment including angiotensin-converting enzyme inhibitor and beta-blocker, started within 6 months from the end of chemotherapy, allows for a complete recovery of left ventricular ejection fraction and positively impacts cardiac outcome (4). Notably, the clinical benefit was more evident in asymptomatic patients; indeed, most patients showing a complete recovery from cardiac dysfunction were either asymptomatic or had a low New York Heart Association functional class at the time heart failure therapy was initiated. This suggests that early detection of asymp- tomatic left ventricular dysfunction or even of subclinical cardio- toxicity (early increase of troponin I preceding left ventricular dysfunction) (5) is of paramount importance to successfully treat or prevent cardiotoxicity. Therefore, monitoring of cardiotoxicity, exclusively on the basis of symptoms evaluation, might miss the opportunity to early detect cardiac injury in a still-reversible stage. Finally, we strongly agree with Yoon et al. (1) that oncologists and cardiologists should better collaborate in the assessment of patients receiving potentially cardiotoxic agents, because therapy decisions involving the same patients might potentially mean exchanging one fatal disease for another. *Daniela Cardinale, MD, PhD Alessandro Colombo, MD Carlo M. Cipolla, MD *Cardiology Unit European Institute of Oncology Via Ripamonti 435 20141 Milan Italy E-mail: daniela.cardinale@ieo.it doi:10.1016/j.jacc.2010.11.046 REFERENCES 1. Yoon GJ, Telli ML, Kao DP, et al. Left ventricular dysfunction in patients receiving cardiotoxic cancer therapy: are clinicians responding optimally? J Am Coll Cardiol 2010;56:1644 –50. 2. Haq MM, Legha SS, Choksi, et al. Doxorubicin-induced congestive heart failure in adults. Cancer 1985;56:1361–5. 3. Tallaj JA, Franco V, Rayburn BK, et al. Response of doxorubicin- induced cardiomyopathy to the current management strategy of heart failure. J Heart Lung Transplant 2005;24:2196 –201. 4. Cardinale D, Colombo A, Lamantia G, et al. Anthracycline-induced cardiomyopathy. Clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol 2010;55:213–20. 5. Cardinale D, Colombo A, Sandri MT, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin- converting enzyme inhibition. Circulation 2006;114:2474 – 81. Reply We greatly appreciate the letter from Dr. Cardinale and colleagues regarding our recent paper on the care of cancer patients who have developed treatment-emergent left ventricular dysfunction (1). We wholeheartedly concur that monitoring of cardiotoxicity by screening for symptoms of heart failure alone misses the vast majority of individuals with cardiotoxicity—an observation seen time and time again in clinical trials (2,3). Assigning nonspecific symptoms (e.g., fatigue, edema) to heart failure is often particularly challenging in this patient population, because such symptoms can easily be mistakenly attributed to noncardiac side effects of chemotherapy or to the underlying malignancy itself. Hence, our findings that only one-third of patients with asymptomatic left ventricular dysfunction received therapy with angiotensin-converting enzyme inhibitors or beta- blockers demonstrate substantial room for improvement. We do not believe that the optimal screening/treatment prac- tices for these patients are definitively clear. Thanks to the groundbreaking work in Italy by Cardinale et al. (4,5), there is strong (albeit single-center) evidence for a strategy of screening for subclinical cardiotoxicity with troponin in patients treated with high-dose chemotherapy or trastuzumab and in initiating angiotensin-converting enzyme inhibitor therapy in the troponin- positive cohort. The same group also demonstrated that therapy with enalapril +/- carvedilol was more effective when instituted early in the setting of anthracycline-induced cardiomyopathy (6)—although, given that patients were not randomized in the study, it is possible that patients with late-presentations were “self-selected” as individuals who by definition had not recovered from early acute injury without intervention. In the older cited study by Tallaj et al. (7), the vast majority of patients had severe symptomatic heart failure, a population in whom treatment with conventional heart failure therapy has a more definitively clear role. In recent years, there has been tremendous growth of new cancer therapies, many of which have off-target cardiac side effects 1790 Correspondence JACC Vol. 57, No. 17, 2011 April 26, 2011:1787–91 brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by Elsevier - Publisher Connector