1. 1093
The physiological underpinning for cardiac resynchroni-
zation therapy (CRT) began with Carl Wiggers in 1925.
He showed that when contraction of the heart was induced by
direct cardiac electric stimulation, the early phase of contrac-
tion of the heart was slowed and myocardial tension developed
more gradually.1
Wiggers explained these findings by differ-
ences in the order of excitation of the ventricle. Subsequent
studies by a number of investigators highlighted the fact that
a left bundle-branch block conduction pattern was associated
with dyssynchronous contraction that exacerbated left ven-
tricular systolic dysfunction. Few people appreciate the fact
that Dr Morton Mower, who was involved in the development
of the implantable cardioverter defibrillator,2,3
also developed
the patent for cardiac resynchronization therapy in 19904
that
was assigned to CPI/Guidant and subsequently licensed to
Medtronic.
In 1994, Cazeau et al5
reported 1 patient with widened QRS
and advanced heart failure who achieved dramatic improve-
ment with biventricular pacing. Various short-term animal and
clinical hemodynamic studies showed significant improve-
ment in cardiac function when both right and left ventricles of
a diseased heart with conduction disturbance were preexcited
(biventricular pacing),6
and similar findings were observed
recently with univentricular left ventricular stimulation in
the compromised heart with conduction block.7
Central to
all these studies was that dyssynchronous contraction associ-
ated with disturbed left ventricular conduction improved with
direct left ventricular pacing.
A series of large randomized trials, including
COMPANION,8
CARE-HF,9
MADIT-CRT,10
and RAFT,11
have documented the safety and efficacy of biventricular car-
diac reynchronization pacing in patients with various degrees
of severity of heart failure. All the studies involved patients
with wide QRS complexes, with the best results observed in
those with left bundle-branch block. Cardiac guideline recom-
mendations followed in 2008,12
with a recent update in 201213
emphasizing the importance of wide QRS and left ventricular
conduction disturbance as the best substrate for CRT efficacy.
The article by Thibault et al14
in Circulation involves a
small randomized trial of CRT in patients with heart failure
and narrow QRS (<120 ms) using exercise duration at 1 year
as the primary end point. The Thibault trial was designed in
2002 and initiated in 2003, and it appears to be based on an
observational study reported in 2003 by Achilli et al.15
The
Achilli study enrolled patients with refractory heart failure
(HF) and incomplete left bundle-branch block (narrow QRS)
together with echocardiographic evidence of interventricular
and intraventricular asynchrony. There were 38 patients with
QRS >120 ms and 14 patients had a narrow QRS <120 ms.
The CRT benefit was similar in patients with wide or narrow
QRS. It should be emphasized that the authors put the word
narrow in quotes (“narrow”) in the title and throughout the
article when referring to QRS <120 ms because many of the
patients had QRS durations <100 ms. The authors concluded
that “cardiac resynchronization therapy may be helpful in
patients with echocardiographic evidence of interventricular
and intraventricular asynchrony and incomplete left bundle-
branch block”.15
It is surprising that Thibault et al.14
initiated their study
based on limited findings in the literature, and their study
did not include echocardiographic evidence of dyssynchrony.
The average QRS duration was 104+9 ms, with many of the
enrolled patients with QRS <100 ms. There were 12 enrolling
centers, and the study ran for 8 years from 2003 to 2011 with
a total enrollment of only 85 patients in the study. That means
that, on average, each center enrolled <1 patient per center
per year. It is surprising that the Data and Safety Monitoring
Board waited 8 years to terminate the study because of futility
and safety concerns.
After Thibault et al initiated their study but before
publication in Circulation, there were several reports of
variable CRT efficiacy in heart failure patients with narrow
QRS complexes. In a small observational study by Bleeker et
al16
involving 66 studied patients with low ejection fraction
and left ventricular dyssynchrony on tissue doppler imagaing,
the 33 patients with QRS <120 ms had left ventricular reverse
remodeling with CRT comparable with the 33 patients with
QRS complex >120 ms. A larger randomized trial by Beshai
et al17
involved 172 patients with the primary end point an
increase in peak oxygen consumption of at least 1.0 mL per
kilogram of body weight per minute during cardiopulmonary
exercise testing at 6 months after randomization. The CRT-
treated patients did not improve peak oxygen consumption
when compared with the nontreated control group. The results
of this randomized study were not very encouraging that CRT
would be beneficial in patients with narrow QRS complexes.
What have we learned from the large MADIT-CRT trial
regarding CRT efficacy and QRS duration? CRT was sig-
nificantly more effective when the QRS duration was >150
ms than in the 130 to 149 ms range,10
and female patients
(Circulation. 2013;127:1093-1094.)
© 2013 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.113.001363
The opinions expressed in this article are not necessarily those of the
editors or of the American Heart Association.
From the University of Rochester Medical Center, Rochester, NY.
Correspondence to Arthur J. Moss, MD, Professor of Medicine
(Cardiology), Heart Research Follow-Up Program, University of
Rochester Medical Center, 265 Crittenden Blvd, CU 420653, Rochester,
NY 14642-0653. E-mail heartajm@heart.rochester.edu
Narrow QRS Is Not the Right Substrate for
Cardiac Resynchronization Therapy
Arthur J. Moss, MD
Editorial

2. 1094 Circulation March 12, 2013
were the only ones who achieved significant CRT benefit
with QRS of 130 to 149 ms.18
Heart failure patients with left
bundle-branch block conduction obtained excellent benefit
from CRT, and there was no appreciable benefit from CRT
in patients with right bundle-branch block or intraventricular
conduction delay.19
It is quite clear that CRT does not achieve a favorable
result in patients with QRS durations <120 ms. On the other
hand, mechanical left ventricular dyssynchrony, an impor-
tant myocardial substrate for effective CRT, is exacerbated
by abnormal excitation of the left ventricle with a wide QRS
duration, especially when a left bundle branch conduction
disturbance is present. Although many factors influence the
cardiac responsiveness to CRT (lead position, type of cardio-
myopathy [ischemic versus nonischemic], extent and severity
of the myocardial damage, and sex), wide QRS complex and
left bundle-branch block are excellent electric biomarkers for
identification of heart failure patients who are likely to benefit
from resynchronization therapy.
Disclosures
Dr Moss reports a research grant from Boston Scientific to the
University of Rochester, of which he is a principal investigator.
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Key Words: Editorials ■ cardiac resynchronization therapy