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Best CRT outcomes with LBBB and prolonged QRS
Major finding: Patients with LBBB and a prolonged QRS interval (150 ms or more) had the lowest mortality at 1 month, 1 year, and 3 years, as well...
The results from EchoCRT fit well with the results of a meta-analysis that my associates and I recently ran on data from 3,782 heart failure patients treated with CRT in five trials sponsored by Medtronic. The results showed that QRS duration was a powerful predictor of the effects of CRT on morbidity and mortality.
The meta-analysis results confirmed the benefit of CRT in patients with mild, moderate, or severe heart failure symptoms, in sinus rhythm, and with a QRS duration of at least 140 msec, and in these patients CRT is standard of care. The results also showed that the benefits from CRT diminish as the QRS duration goes below 140 msec. Patients with a QRS duration of 130-139 msec are in a gray zone. If they need a defibrillator, then making it a CRT device makes sense, but if no device implant is planned then continued attempts at medical treatment are probably better than going to CRT.
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I would avoid CRT in patients with a QRS of less than 130 msec, and now the EchoCRT results show evidence of harm in these patients. A lot of patients with a QRS duration of 120-129 msec have been receiving CRT devices when the chances of benefit are small. This might be a treatment of last resort, but only when you have exhausted all the other treatment alternatives.
The meta-analysis also showed that QRS duration was the only independent predictor of CRT outcomes (Eur. Heart J. 2013 [doi:10.1093/eurheartj/eht290]). QRS morphology – whether or not there is a left bundle branch block – was not a significant factor relative to QRS duration. The EchoCRT results also showed that echocardiography used to diagnose left-ventricular dyssynchrony failed to identify a subgroup of patients with a narrow QRS duration who benefited from CRT.
Dr. John G.F. Cleland is professor of medicine at the University of Hull (England). He has been a consultant to Biotronik, St. Jude, and Medtronic. He made these comments in an interview.
AT THE ESC CONGRESS 2013
AMSTERDAM – Patients with severe heart failure and a narrow QRS duration who received cardiac resynchronization therapy had more than twice the rate of cardiovascular deaths as patients who did not undergo active CRT treatment in a multinational randomized study with 809 patients.
The study’s enrollment criteria focused on patients with a QRS duration of less than 130 msec, and in this group active CRT produced no benefit, compared with the CRT function turned off in control patients for the study’s primary efficacy endpoint of death from any cause or first hospitalization for worsening heart failure.
In addition, during an average 19 months’ follow-up, patients in the CRT-on group had an all-cause death rate nearly five percentage points above the controls, an 80% relatively increased hazard, and a cardiovascular death rate also five percentage points above the controls, a greater than two-fold relative hazard, Dr. Johannes Holzmeister said at the annual congress of the European Society of Cardiology.
Both increased hazard rates were statistically significant and were a "surprising, unexpected finding," said Dr. Holzmeister, a cardiologist at the University of Zurich.
"This is the final nail in the coffin for CRT in patients with only slightly-prolonged QRS," commented Dr. Douglas P. Zipes, a professor and electrophysiologist at Indiana University in Indianapolis.
Existing recommendations from the American College of Cardiology and American Heart Association (J. Am. Coll. Cardiol. 2013 [doi:10.1016/j.jacc2013.05.019]) restrict unequivocal endorsement of CRT to heart failure patients with a QRS duration of at least 150 msec and say that CRT can be useful for patients with New York Heart Association class II, III, or IV heart failure, left bundle branch block (LBBB), and a QRS duration of 120-149 msec. Recommendations from the European Society of Cardiology are more permissive, calling CRT recommended for patients in sinus rhythm with a QRS duration of at least 120 msec, LBBB morphology on their QRS wave, and an ejection fraction of at least 35% who are expected to remain in good functional status for more than 1 year (Eur. Heart J. 2012;33:1787-847).
The ESC recommendations also say that CRT should be considered in patients with a QRS duration of at least 150 msec, irrespective of their QRS morphology.
It seems like many patients with shorter QRS durations have been receiving CRT treatment. During his report at the meeting, Dr. Holzmeister cited data from a 2008-2009 European-wide survey of CRT patients by the European Heart Rhythm Association, which showed that, 4-5 years ago, 9% of patients in Europe who received a CRT device had a QRS duration of less than 120 msec and another 10% of the CRT recipients had durations of 120-129 msec (Eur. Heart J. 2009;30:2450-60).
Substantial numbers of patients continue to receive CRT treatment with a QRS duration of 120-129 msec, a treatment that the data indicate should be a "last resort," said Dr. John G.F. Cleland, professor of medicine and a heart failure specialist at the University of Hull (England).
Although existing society recommendations sanction CRT for selected heart failure patients with a QRS duration of 120-149 msec, many experts have become convinced that the field needs a new set of QRS criteria.
"I think the cutoff for CRT implantation should be 150 msec," said Dr. Gordon F. Tomaselli, professor of cardiology and an electrophysiologist at Johns Hopkins University in Baltimore. "Patients with a QRS duration of less than 150 msec, particularly without left bundle branch block, should probably not get CRTs unless some special circumstances are present," he said in an interview.
"This reinforces the conclusion that we should not use CRT devices in heart failure patients with a QRS duration of less than 130 msec," commented Dr. Stefan D. Anker, professor and cardiologist at Charitè Hospital in Berlin and designated discussant for Dr. Holzmeister’s talk at the meeting. Dr. Anker called CRT use in patients with QRS durations of 130-149 msec uncertain and in need of more evidence for efficacy and safety from trials. "What is certain is that in patients with a QRS of 150 msec or greater there is a strong mortality reduction with CRT," he said.
The Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT) study randomized 809 patients with a QRS duration of less than 130 msec and left ventricular ejection fraction of 35% or less, and also required that patients meet criteria for having left-ventricular dyssynchrony detected by echocardiography. All patients received a CRT device, which was turned on in 404 patients. The study began in August 2008, and enrollment stopped on March 13, 2013, because of futility and a potential for harm.
Major finding: Patients with LBBB and a prolonged QRS interval (150 ms or more) had the lowest mortality at 1 month, 1 year, and 3 years, as well...