CRT Can Reverse HF From Cancer Chemotherapy: MADIT-CHIC

May 14, 2019

SAN FRANCISCO — People with heart failure (HF) caused by cancer chemotherapy were generally left out of the big cardiac resynchronization therapy (CRT) trials; they are barely mentioned at all in guidelines.

But such patients who get a CRT device after meeting electrocardiographic and other criteria for the treatment may significantly improve in terms of myocardial structure and function, as well as symptoms.

That was demonstrated, at least over a 6-month follow-up, in the small and single-group but prospective Multicenter Automatic Defibrillator Implantation Trial–Chemotherapy Induced Cardiomyopathy (MADIT-CHIC) study, presented here at the Heart Rhythm Society 2019 Scientific Sessions.

About 40% of the study's 30 patients improved by at least one NYHA functional class after device implantation, and overall their mean left ventricular ejection fraction (LVEF) went up by 11 percentage points (P < .001). Collectively they showed significant improvements in end-systolic and end-diastolic diameters and volumes.

Only one of the patients showed no LVEF increase over the follow-up, Jagmeet P. Singh, MD, DPhil, Massachusetts General Hospital, Boston, who presented the MADIT-CHIC results here at the meeting, told | Medscape Cardiology.

The patients had been evaluated by cardio-oncologists at 12 centers, who helped ensure that their HF wasn't from coronary disease or other causes, and was likely due to chemotherapy-induced cardiomyopathy (CHIC), he said.

All of them had received chemotherapy 6 or more months before receiving a biventricular pacemaker for CRT, for which they had a standard class I or II indication, including symptoms with reduced LVEF and a prolonged QRS interval on guideline-directed meds. All had left-bundle-branch block (LBBB).

Clinicians treating patients with a history of cancer may not be vigilant about possible chemotherapy cardiac effects if it's been a long time since the last treatment, Singh observed. Signs of CHIC may not manifest for years, and there's almost no guidance from guidelines or trials.

However, he said, "I think if they have chemo-induced cardiomyopathy, and they have some evidence of a conduction defect on the electrocardiogram, they'd be a great candidate for resynchronization therapy."

Indeed, regardless of whether such patients were omitted from the trials, "I think what this study will show us is that if you meet the criteria for a CRT device, then you should get a CRT device," Jodie L. Hurwitz, MD, North Texas Heart Center, Dallas, not connected with MADIT-CHIC, told | Medscape Cardiology.

The study provides the best available data on treating CHIC, which are "surely striking. The CRT response is dramatic in this homogeneous group of patients studied for the first time," said the invited discussant after Singh's presentation, Kenneth A. Ellenbogen, MD, Virginia Commonwealth University, Richmond.

Although MADIT-CHIC had big limitations as a study, including its observational nature, lack of a control group, few patients, and follow-up limited to 6 months, he noted, it should still be influential. "In terms of clinical equipoise, I'm not so sure that many of us would have argued that a control group was necessary."

Ellenbogen said clinicians should keep a high level of suspicion for CHIC in cancer survivors who show signs of HF. "And for patients who have cancer-induced chemotherapy who qualify for CRT, we can be pretty positive and pretty optimistic when we talk to those patients about their response to CRT."

The treatment is most appropriate, however, if the HF persists over the long term, despite optimal medical therapy. Symptoms may often abate in patients who continue on good cardiovascular medical therapy after the end of chemotherapy, pointed out Yong-Mei Cha, MD, Mayo Clinic, Rochester, Minnesota, after Singh's presentation. What does that say about the best time to initiate CRT in those who remain eligible?

"There are some patients who actually develop cardiomyopathy in close proximity to having received chemotherapy, and I think the norm is to immediately start them on beta blockers and ACE inhibitors or angiotensin receptor blockers, and treat them with a decongestive line of therapy," Singh replied.

"Some of them actually reverse back, and do pretty well in the long term." That's why patients in the study had to be at least 6 months past their chemotherapy before receiving a CRT device; the actual range was 18 months to almost 25 years.

"They were all on optimal medications by the time they got their devices, which I would say is probably essential."

The cohort's mean age was 63 years, and 26 of the 30 were women. Three-quarters of the patients had received anthracyclines, well known to be cardiotoxic, and a similar percentage had received chemotherapy for breast cancer; others had been treated for lymphoma or sarcoma.

Their mean LVEF went from 28% at baseline to 39% after 6 months of CRT (P < .001), the primary end point. Significant reverse myocardial remodeling was also evident on core-lab echocardiography readings at 6 months, with no differences in the effects by age, sex, NYHA class, LVEF, or QRS duration.

Proportional Change in Echocardiographic Indicators of Remodeling From Baseline to 6 Months in MADIT-CHIC
Echo Parameter Change (%) From Baseline
to 6 Months
LVEF +38
LV end-diastolic volume –18
LV end-systolic volume –30
LV end-diastolic diameter –7
LV end-systolic diameter –14
LV mass –19
LV = left ventricular; all changes, P < .001

All had an LVEF below 35%, and 57% were in NYHA class 2 on optimal meds, with the rest in class 3; 97% were on beta blockers. The mean QRS interval was 151 ms.

"As cardio-oncology is becoming more of a well known, established program across the country, there are better and more involved strategies for cancer surveillance," Singh said in an interview.

"Now, you see that after 10 or 15 years many of them actually end up having cardiac disease, which may be ischemic in some or it may be purely chemo-induced cardiomyopathy," he said. Yet once identified as cancer patients, they might not be as likely to see a cardiologist. Perhaps, he said, that will change as cardio-oncology grows as a field.

MADIT-CHIC was supported by Boston Scientific. Singh discloses consulting for Abbott, Biotronik, Boston Scientific, Medtronic, St. Jude Medical, Microport, Back Beat, Impulse Dynamics, EBR, and Toray, and being involved with research sponsored by Abbott and Boston Scientific. Hurwitz discloses receiving honoraria for speaking or consulting fees from Medtronic. Ellenbogen and Cha report no relevant conflicts.

Heart Rhythm Society (HRS) 2019 Scientific Sessions: Abstract S-LBCT02-04. Presented May 10, 2019.

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