Correspondence

Cardiac-Resynchronization Therapy

N Engl J Med 2008; 358:1865-1866April 24, 2008

Article

To the Editor:

A QRS duration longer than 120 msec is the only validated selection criterion for cardiac-resynchronization therapy (CRT). However, observational studies have shown a high prevalence of mechanical dyssynchrony in patients with narrow QRS complexes. Beshai et al. (Dec. 13 issue)1 report on the Cardiac Resynchronization Therapy in Patients with Heart Failure and Narrow QRS (RethinQ) study, the first randomized trial examining the performance of CRT in this specific population. Its negative results must be interpreted from the perspective of the study methods used. Patient selection was based on echocardiographic criteria, which, in the Predictors of Response to Cardiac Resynchronization Therapy (PROSPECT) trial, were found to be technically challenging and poorly reproducible.2 Consequently, whether these patients presented with true cardiac dyssynchrony is uncertain. Furthermore, analysis of peak oxygen consumption, the primary end point in the RethinQ study, failed to show a benefit of CRT in the only other study in which it was used,3 in contrast to positive trends observed with more robust secondary end points. Now that the benefits conferred by CRT with respect to morbidity and mortality have been established,4,5 the clinical relevance of a mechanistic study based on functional assessment appears to be questionable.

Further investigations are needed before definitive conclusions regarding the effects of CRT in patients with a narrow QRS complex can be drawn.

Claude Daubert, M.D.
Christophe Leclercq, M.D., Ph.D.
University Rennes 1, 35000 Rennes, France
jean-claude.daubert@chu-rennes.fr

5 References

1. 1

   Beshai JF, Grimm RA, Nagueh SF, et al. Cardiac-resynchronization therapy in heart failure with narrow QRS complexes. N Engl J Med 2007;357:2461-2471
   Full Text | Web of Science | Medline

2. 2

   Yu CM, Abraham WT, Bax J, et al. Predictors of Response to Cardiac Resynchronization Therapy (PROSPECT) -- study design. Am Heart J 2005;149:600-605
   CrossRef | Web of Science | Medline

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
   CrossRef | Web of Science | Medline

4. 4

   Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150
   Full Text | Web of Science | Medline

5. 5

   Cleland JGF, Daubert J-C, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539-1549
   Full Text | Web of Science | Medline

To the Editor:

Beshai et al. report that in patients with heart failure and narrow QRS complexes, CRT did not improve peak oxygen consumption or measures of left ventricular remodeling. Bleeker et al., however, recently showed that in patients who have heart failure with preexisting left ventricular dyssynchrony and a wide QRS complex, echocardiographic evidence of resynchronization is mandatory for a clinical response and left ventricular remodeling.1 Although this does not necessarily hold true for patients with a narrow QRS complex, it would be interesting to know whether effective resynchronization, as evidenced by echocardiography, was achieved in patients randomly assigned to the CRT group as compared with controls.

Hielko Miljoen, M.D.
Bernard P. Paelinck, M.D., Ph.D.
Christiaan J. Vrints, M.D., Ph.D.
University Hospital Antwerp, 2650 Edegem, Belgium
hielko.miljoen@uza.be

1 References

1. 1

   Bleeker GB, Mollema SA, Holman ER, et al. Left ventricular resynchronization is mandatory for response to cardiac resynchronization therapy: analysis in patients with echocardiographic evidence of left ventricular dyssynchrony at baseline. Circulation 2007;116:1440-1448
   CrossRef | Web of Science | Medline

Author/Editor Response

Daubert and Leclercq make the same comments about our study that Daubert previously expressed.1 They take issue with the choice of peak oxygen consumption as the primary end point and the echocardiographic methods used for patient selection. Regarding the primary end point, RethinQ is the first randomized study to examine the role of CRT in patients with chronic heart failure and a narrow QRS duration. Therefore, before large-scale trials are conducted, studies that examine the effects of this therapy on functional measures that have been shown to predict the outcome in patients with chronic heart failure are essential. In that regard, there are ample data that show the prognostic power of peak oxygen consumption.2 Indeed, studies that were powered to examine the effect of CRT on functional measures in patients with a wide QRS complex were conducted and published before the morbidity and mortality trials referred to by Daubert and Leclercq.3 It is not clear to us what “robust secondary end points” they had in mind. However, in the RethinQ study, CRT had a consistent absence of favorable effects on important measures such as volumes, ejection fraction, quality-of-life score, and 6-minute walking distance.

The reproducibility of the methods selected is an important point. Echocardiographic data (including tissue Doppler measurements) were acquired only after significant training and qualification of clinical sites, with careful ongoing monitoring. Data analysis was equally meticulous. In contrast to the PROSPECT study, in the RethinQ trial, interobserver variability for tissue Doppler measurement of opposing-wall mechanical delay was low. Therefore, we are confident that the patients in our study were correctly identified.

We agree with Miljoen et al. that additional analysis is needed to understand the underlying reasons for our results, including the effect of CRT on mechanical dyssynchrony. We are conducting this and other analyses at this time.

In summary, we reiterate our opinion that additional studies are needed, but only after a careful understanding of the mechanisms of dyssynchrony in this unique group. We do not believe that it is prudent to extend the conclusions of studies in patients with a wide QRS complex to those with a normal duration.

John F. Beshai, M.D.
University of Chicago, Chicago, IL 60637
jbeshai@medicine.bsd.uchicago.edu

Richard A. Grimm, D.O.
Cleveland Clinic Foundation, Cleveland, OH 44195

Sherif F. Nagueh, M.D.
Methodist Hospital, Houston, TX 77030

3 References

1. 1

   Daubert J-C. Resynchronization therapy in patients with narrow QRS complex (discussant). In: Late breaking clinical trials, American Heart Association Scientific Sessions, Orlando, FL, November 4–7, 2007.
   

2. 2

   Wasserman K, Hansen JE, Sue DY, Stringer WW, Whipp BJ. Principles of exercise testing and interpretation. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2005.
   

3. 3

   Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 2001;344:873-880
   Full Text | Web of Science | Medline