Think Resynchronization Therapy for Heart Failure Benefits "Narrow-QRS" Patients? RethinQ

November 07, 2007

November 7, 2007 (Orlando, FL) - Patients with systolic heart failure and echocardiographic LV dyssynchrony do not objectively benefit from cardiac resynchronization therapy (CRT) when their QRS duration is less than 130 ms, according to a randomized trial that argues against using CRT in so-called narrow-QRS patients [ 1, 2].

In a prospectively defined subgroup analysis, however, the study, called Cardiac Resynchronization Therapy in Patients with Heart Failure and Narrow QRS (RethinQ) did see a functional benefit from CRT among patients with a QRS duration of >120 msec to <130 msec, consistent with current recommendations indicating the pacing therapy at the 120-msec threshold or above. Functional outcomes were measured primarily by changes in peak O 2 consumption after six months.

A "narrow" QRS is usually defined as being <120 msec, observed lead author Dr John F Beshai (University of Chicago, IL). When RethinQ was designed, he told heartwire , all CRT trials had included patients with QRS intervals from 120 msec to 130 msec, "but when you actually look at the mean values of the patients in those trials, they're at greater than 150 and upward of 160 msec. We wanted to include this intermediate group of patients between 120 and 130 msec so that we might be able to pick up information regarding mechanical dyssynchrony. It was part of the design to capture a patient population that had not been very well studied."

Beshai presented the RethinQ findings here at the American Heart Association 2007 Scientific Sessions the same day they were published online in the New England Journal of Medicine.

QRS duration has been criticized as at best a weak predictor of CRT response, and echo measures of dyssynchrony--especially those from tissue-Doppler imaging (TDI)--have been explored as potential ways to sharpen the identification of heart-failure patients most likely to benefit. Because entry into the trial required echo evidence of dyssynchrony, which was provided primarily by TDI, the results of RethinQ are consistent with the view that QRS criteria can complement echo parameters in predicting CRT response.

The study randomized 172 patients in NYHA functional class 3 who had an LVEF <35%, a QRS interval <130 msec, and echo-defined mechanical dyssynchrony to receive a CRT-defibrillator device with the CRT feature turned either on or off (87 and 85 patients, respectively). At least 90% of the population were on beta blockers and either ACE inhibitors or angiotensin receptor blockers.

At the six-month evaluation, which was performed in 76 CRT patients and 80 of the controls, there was no difference between the groups in the primary end point: the rate of at least a 1.0-mL/kg-per-minute improvement in peak O 2 consumption at six months. The values were 46% for CRT-treated patients and 41% for controls (p=0.63).

Nor were there differences in change in quality of life as measured by the Minnesota Living with Heart Failure Questionnaire or in six-minute-walk distance, LVEF, end-diastolic and -systolic volumes or diameters, or degree of mitral regurgitation.

In the only measured parameter to show a significant difference in the overall population, 54% of the CRT group and 29% of the control group (p=0.006) improved by at least one NYHA functional class.

During his RethinQ presentation, Beshai was cautious regarding the NYHA finding's importance, because the end point is subjectively assessed, and the CRT-related improvement is out of step with the null findings for more objective measures. During the panel discussion following his presentation, however, he downplayed the possibility that it represented a placebo effect, as study participants were carefully blinded to treatmentassignment.

In a prospectively planned analysis, CRT-treated patients, compared with controls, showed significant improvement in peak O 2 consumption (p=0.02) among those with a QRS interval >120 msec, but not among patients with QRS <120 msec. NYHA class improved significantly regardless of QRS duration. There were no similar differences in quality-of-life scores or six-minute-walk distance.

Patients on CRT showed significantly better improvement in NYHA class compared with controls regardless of whether they had ischemic or nonischemic cardiomyopathy. CRT significantly improved six-minute-walk distance among nonischemics (p=0.01) but not patients with ischemic disease. There were no significant responses in peak O 2 consumption or quality of life by type of cardiomyopathy.

As the assigned discussant for Beshai's presentation, Dr Jean-Claude Daubert (University Hospital, Rennes, France) questioned the use of change in peak O 2 consumption as the primary end point in RethinQ. He said the same functional end point had been shown in the MIRACLE-ICD 2 [ 3] trial to be less reliable than "more robust" end points based on clinical outcomes or volumetric responses, such as change in LV end-systolic volume.

RethinQ, Daubert said, "has raised an important question relevant to clinical practice, but due to methodological choices, was unable to provide any clear response to the question asked." Pending further, differently designed investigations, he said, "CRT cannot be recommended in heart-failure patients with normal QRS."

The trial was supported by St Jude Medical, from which Beshai reports receiving consulting fees and grant support; he also reports being a consultant to AtriCure. As noted in the paper, other RethinQ coauthors report receiving grant support or lecture and/or consulting fees from St Jude, Medtronic, General Electric, and Boston Scientific. Daubert reports being a consultant to or on an advisory board for Medtronic and St Jude.

  1. Beshai JF, Grimm RA, Nagueh SF, et al. Cardiac-resynchronization therapy in heart failure with narrow QRS complexes. N Engl J Med 2007; DOI:10.1056/NEJMoa0706695. Available at: .

  2. Beshai JF. Resynchronization therapy in patients with narrow QRS (RethinQ). American Heart Association 2007 Scientific Sessions; November 6, 2007; Orlando, FL. Late-breaking-clinical trials 3.

  3. Abraham WT, Young JB, Leon AR, et al. Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction, an indication for an implantable cardioverter-defibrillator, and mildly symptomatic chronic heart failure. Circulation 2004; 110:2864-2868. Abstract

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