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MADIT-CHIC: CRT aids patients with chemotherapy-induced cardiomyopathy

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MADIT-CHIC gives us the best data we have

No guideline currently addresses using cardiac resynchronization therapy to treat chemotherapy-induced cardiomyopathy. The findings from MADIT-CHIC showed a striking benefit from treatment with cardiac resynchronization therapy of a magnitude we would expect to see in patients with nonischemic cardiomyopathy. Patients showed improvements in all measures of cardiac performance.

Dr. Kenneth A. Ellenbogen, professor of medicine, Virginia Commonwealth University, Richmond, Va. Mitchel L. Zoler/MDedge News

Dr. Kenneth A. Ellenbogen

This small, nonrandomized study is limited by its short-term follow-up, but it gives us the best data we have so far on this topic, and the results were striking. The response that patients had to CRT was dramatic and homogeneous in a group of patients studied for the first time: those with chemotherapy-induced cardiomyopathy (CHIC).

It appears that CHIC can take as long as decades to appear in a patient, but we now need to have a high level of suspicion for this complication. We need to come up with better ways to monitor development of CHIC in patients who have received cancer chemotherapy so that we can give eligible patients this beneficial treatment. We can be optimistic about the potential for benefit from CRT in these patients.

Kenneth A. Ellenbogen, MD , is chief of cardiology and a professor of medicine at Virginia Commonwealth University in Richmond, Va. He has been a consultant to Boston Scientific, Medtronic, and St. Jude; he has received honoraria from Biotronik; and he has received research funding from Boston Scientific and Medtronic. He made these comments as the designated discussant for the MADIT-CHIC report.



– Patients with cardiomyopathy secondary to cancer chemotherapy who qualified for cardiac resynchronization therapy (CRT) by having a wide QRS interval showed a virtually uniform, positive response to this treatment in a multicenter study with 30 patients.

Dr. Jagmeet P. Singh chief of cardiology at Massachusetts General Hospital and professor of medicine at Harvard Medical School in Boston Mitchel L. Zoler/MDedge News

Dr. Jagmeet P. Singh

This is the first time this therapy has been prospectively assessed in this patient population.

The results “show for the first time that patients with chemotherapy-induced cardiomyopathy [CHIC] who meet criteria for CRT show significant improvement in left ventricular function and clinical symptoms in the short term” during follow-up of 6 months, Jagmeet P. Singh, MD, said at the annual scientific sessions of the Heart Rhythm Society.

Dr. Singh acknowledged that, with 30 patients, the study was small, uncontrolled, had a brief follow-up of 6 months, and was highly selective. It took collaborating investigators at 12 U.S. centers more than 3.5 years to find the 30 participating patients, who had to meet very specific criteria designed to identify true CHIC. Nonetheless, Dr. Singh considered the results convincing enough to shift practice.

Based on the results, “I would certainly feel comfortable using CRT in patients with CHIC,” said Dr. Singh, associate chief of cardiology at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston. “If a patient has CHIC with a wide QRS interval and evidence for a conduction defect on their ECG, they are a great candidate for CRT. The results highlight that there is a cohort of patients who develop cardiomyopathy after chemotherapy, and these patients are often written off” and until now have generally received little follow-up for their potential development of cardiomyopathy. Dr. Singh expressed hope that the recent emergence of cardio-oncology as a subspecialty will focus attention on CHIC patients.

The MADIT-CHIC (Multicenter Automatic Defibrillator Implantation Trial – Chemotherapy-Induced Cardiomyopathy) study enrolled patients with a history of exposure to a cancer chemotherapy regimen known to cause cardiomyopathy who had no history of heart failure prior to the chemotherapy. All patients had developed clinically apparent heart failure (New York Heart Association functional class II, III, or IV) at least 6 months after completing chemotherapy, had no other apparent cause of the cardiomyopathy as ascertained by a cardio-oncologist, and were on guideline-directed medical therapy. Enrolled patients also had to have a class I or II indication for CRT, with a left ventricular ejection fraction of 35% or less, a QRS interval of at least 120 milliseconds, sinus rhythm and left bundle branch block, or no left bundle branch block and a QRS of at least 150 milliseconds.

Just over three-quarters of the patients had received an anthracycline drug, and 73% had a history of breast cancer, 20% a history of leukemia or lymphoma, and 7% had a history of sarcoma. The patients averaged 64 years of age, and 87% were women. CRT placement occurred 18-256 months after the end of chemotherapy, with a median of 188 months.

The study’s primary endpoint was the change in left ventricular ejection fraction after 6 months, which increased from an average of 28% at baseline to 39% at follow-up, a statistically significant change. Ejection fraction increased in 29 of the 30 patients, with one patient showing a flat response to CRT. Cardiac function and geometry significantly improved by seven other measures, including left ventricular mass and left atrial volume, and the improved ejection fraction was consistent across several subgroup analyses. Patients’ NYHA functional class improved by at least one level in 41% of patients, and 83% of the patients stopped showing clinical features of heart failure after 6 months on CRT.

MADIT-CHIC received funding from Boston Scientific. Dr. Singh has been a consultant to Abbott, Back Beat, Biotronik, Boston Scientific, EBR, Impulse Dynamics, Medtronic, Microport, St. Jude, and Toray, and he has received research support from Abbott and Boston Scientific.

SOURCE: Singh JP et al. HRS 2019, Abstract S-LBCT02-04.

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