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The European Society of Cardiology

Influence of QRS prolongation on the natural history of CHF

Luigi Padelettia,*, Marzia Giaccardia,b, Federico Turrenia,b, Nicola Musillia, Andrea Colellaa, Paolo Pieragnolia, Antonio Micheluccia, Giuseppe Ricciardia and Maria Cristina Porciania

a Institute of Internal Medicine and Cardiology, University of Florence, Florence, Italy
b Department of Cardiovascular Rehabilitation, Don Gnocchi Foundation, Florence, Italy

Received 3 May 2004; accepted 24 May 2004.

* Luigi Padeletti, Institute of Internal Medicine and Cardiology, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. Tel.: +39-055-4277634; fax: +39-055-4378638
elettrofisiologia{at}dfc.unifi.it

Abstract

Aims To evaluate the influence of QRS prolongation on the natural history of chronic heart failure (CHF).

Methods The results of several studies carried out from 1951 to 2003 were analysed.

Results (a) Isolated left bundle branch block (LBBB) is associated with an increased risk of developing cardiovascular disease and increased cardiac mortality; (b) investigations on the effect of right bundle branch block (RBBB) on mortality have yelded conflicting results; (c) the effects of the association of LBBB with left axis deviation (LAD) on further LV function deterioration remain controversial; (d) LBBB in CHF is associated with a significantly higher all-cause and sudden cardiac death mortality.

Conclusions LBBB is unequivocably associated with greater disease severity and mortality in patients with CHF.

Key Words: Heart failure • QRS duration • Bundle branch block • Mortality

Introduction

The concept of bundle branch block (BBB) was introduced in 1909 by Eppinger and Rothberger.1 A large amount of literature related to the anatomy, electrophysiology, hemodynamics, and clinical and prognostic significance of BBB has accumulated since their original paper. The numerous studies on the prognostic significance of BBB have produced different results, because of different types of population samples and study designs. The first section of this review discusses the prognostic importance of BBB in subjects screened by the ECG, the second one is mainly focused on the effects of prolonged duration of QRS complex on the clinical outcome of patients with congestive heart failure (CHF).

BBB in ECG screened population

During 30 years of follow-up, Eriksson et al. found in a random-sampled population of 855 men who were 50 years old in 1963, 82 patients (9.6%) with BBB. The prevalence of BBB increased with age and RBBB was more common than LBBB. No increased mortality in the BBB population was observed. The heart volumes at the age of 50 years were consistently larger among those who developed BBB, and among the same subjects a diagnosis of CHF during follow-up was significantly more common.2

From 1968 to 1993, the Irish Heart Foundation screened a population of 110,000 subjects for the presence of cardiovascular disease and its risk factors.3 The prevalence of BBB without heart disease was 0.28%, and isolated right bundle branch block (RBBB) was significantly more prevalent than isolated left bundle branch block (LBBB); the prevalence of each abnormality significantly increased with age. During a 30 years follow-up period, isolated LBBB was associated with an increased risk of developing overt cardiovascular disease and increased mortality while an excellent long-term prognosis was associated with isolated RBBB. The Manitoba study4 investigated a cohort of healthy men (pilots of the Royal Canadian Air Force) during an average follow-up of 29 years. LBBB developing in men over 45 years of age, was associated with an increased mortality usually within the first 5 years of development. The 5-years incidence of sudden death as the first manifestation of heart disease was 10 times greater in men with LBBB than in those without it.

Rotman and Triebwasser5 in 1975 reported the ten-year experience with BBB at the USAF School of Aerospace Medicine. Though the prevalence of coronary artery disease and hypertension was significantly higher in the LBBB group, no significant differences were noted between the RBBB and LBBB groups with regard to follow-up morbidity or mortality.

The Framingham study on newly acquired LBBB and RBBB6 showed that in the 10 years after block was detected the cumulative cardiovascular disease mortality rate in subjects with LBBB and RBBB was significantly higher than in age matched members free from BBB. There was a definite trend indicating a higher mortality from cardiovascular disease in the population with LBBB, but the difference did not achieve statistical significance for the small number of cases. In men, but non in women, LBBB was associated with a significant greater prevalence of cardiac enlargement and CHF, when compared to RBBB.

In a large cohort of patients without heart failure both LBBB and RBBB were associated with increased mortality during 6 years follow-up and after adjustment for potential confounders (demographic, clinical, exercise and nuclear scintigraphic parameters), complete RBBB remained associated with a 50% greater risk of death, similar to that associated with complete LBBB.7 These results differ from those of the Reykjavik Study, where total mortality and other causes of death were not associated with RBBB either by univariate or multivariate analysis.8

The effects of isolated BBB on left ventricular function were retrospectively investigated by Lee et al.9 After a mean follow up period of 52 months – adjusting for differences due to age, sex, hypertension, hyperlipidemia, and diabetes mellitus – left ventricular ejection fraction diminished by –7.3±12% per year in the isolated LBBB cohort versus –1.9±4% in isolated RBBB cohort and –1.1±3% reduction in the isolated nonspecific intraventricular delay (IVCD) cohort (). These data indicate that subjects with LBBB but not RBBB or IVCD have a significant risk of developing LV dysfunction over time. In patients with LBBB, the QRS duration was shown to have a significant inverse correlation with EF and a value of 170 ms or more was identified as a marker of significant LV dysfunction.10 In the study of Murkofsky et al.11 the presence of a nonspecific prolonged QRS complex (>0.10 s) in the absence of typical features of RBBB or LBBB was highly specific, but relatively insensitive, for predicting LV dysfunction, since also a normal QRS duration did not reliably excluded abnormal LVEF.

Left axis deviation (LAD) in patients with LBBB presumably reflects the abnormality in the activation of the left ventricle, which could reflect septal, distal Purkinje system, or left ventricular tissue abnormalities.

While Dhingra et al.12 reported that among patients with LBBB, those with LAD have a higher incidence of myocardial dysfunction and a higher cardiovascular mortality than those with a normal axis, in the study of Das et al.10 the presence of LAD in LBBB does not signify a further decrease in ejection fraction (EF).

A subanalysis of the Manitoba study13 showed that in apparently healthy men with RBBB, right and left axis deviation occur more commonly than in those without this conduction disturbance but no adverse long-term prognosis was demonstrated.

Thus the studies based on ECG screening indicate that:

  1. Isolated LBBB is associated with an increased risk of developing cardiovascular disease and increased cardiac mortality.
  2. Investigations of the effect of RBBB on mortality have yielded conflicting results.
  3. The effects of the association of LBBB with LAD on further LV function deterioration remain controversial.

BBB in congestive heart failure

In patients with CHF the presence of IVCD was found to be the most powerful prognostic predictor among the simple ECG parameters with a stepwise increase in mortality as a grade increase in the duration of IVCD occurs.14 Data from UK-HEART study database evidenced that patients with a QRS duration >150 ms when compared to those with a duration <=150 ms had significantly greater LV end-diastolic and end-systolic diameters, less low-frequency R–R interval spectral power and 5-year increased mortality.15 A recent prospective study16 performed in ICD implanted patients in NYHA class III CHF, showed a significantly higher relative risk for cardiac mortality, sudden cardiac death, and event rate – intended as recurrence rates of ventricular tachycardia (VT), fast ventricular tachycardia (FVT) and ventricular fibrillation (VF) – in the group with broader QRS (>150 ms). Quite surprisingly, outcome did not differ significantly matching patients by (EF) inferior or superior to 35%.

Due to the growing importance of cardiac resynchronization therapy (CRT) in the management of patients with CHF, this section of the article will focus mainly on the effects of LBBB in the presence of LV dysfunction.

Left bundle branch block and left ventricular function
From the first experience by Wiggers17 in 1925 many other studies have suggested that an abnormal ventricular activation pattern due to LBBB or right ventricular apex pacing is associated with a decreased ventricular LV function with alterations in regional myocardial perfusion and structural changes. In patients with LBBB a reversal of the normal sequence between right and left ventricular mechanical events occurs, right ventricular systole and diastole markedely preceding that of the left ventricle, with LV isovolumic contraction and relaxation phases lengthening, and diastolic filling time shortening. This reversal of the normal sequence between right and left ventricular mechanical events results in a dynamic interventricular asynchrony with altered interventricular septal motion, and reduced septal contribution to left ventricular ejection fraction.18 In patients with dilated cardiomyopathies an increase of pre-ejection and relaxation times has been shown to prolong mitral regurgitation. This effect directly impairs diastolic function by shortening the time available for the left ventricle to fill to an extent likely to limit stroke volume.19 Dilated cardiomyopathy hearts with a LBBB display early activation of the septal wall, associated with lateral wall pre-stretch. This is followed by a delayed lateral contraction at higher stress and further systolic stretch of the early activated septum. This inhomogeneous temporal activation results in worsened myocardial performance, as indicated by a rightward shift and narrowing of the pressure–volume loop.20 There are also important regional and global metabolic and energetic consequences that develop from dyssynchrony. The prematurely activated myocardium develops less overall work consuming less energy, which is largely wasted with respect to ejection, because pressure remains low. Infact, according to recent data much of the early septal motion in the present of LBBB occurs prior to closure of the mitral valve. Contraction of the late activated free wall, in contrast, occurs under a higher load with a higher metabolic demand. This causes wasting work in stretching the more compliant early-activated territory rather than contributing to ejection. As a consequence, the net effect is a reduction in chamber efficiency.21

LBBB in congestive heart failure
The first important contribution in this field is represented by the study carried out on 555 patients with LBBB during the years 1937 to 1948 at the Massachussets General Hospital.22 The relationship between QRS complex duration and heart size, as determined by X-ray, showed that the percentage of patients with marked cardiac enlargement increased as the QRS width increased. Moreover when the patients were arranged according to the size of their hearts at the time when LBBB was first diagnosed, a definite relationship between the size of the heart and survival time was found.

Fifty years later Gottipaty et al.23 evaluated the resting baseline ECG in patients with symptomatic dilated cardiomyopathy, enrolled in the VEST trial: cumulative survival from all-cause mortality decreased proportionally with QRS duration and the relative risk in the widest QRS (>220 ms) group was five times greater than the in narrowest (<90 ms) one.

Baldasseroni et al.24 analyzed the large Italian Network on CHF Registry of unselected outpatients with CHF of different causes. Complete LBBB was diagnosed in 1391 of 5517 patients (25%) and was associated with a significantly increased 1-year mortality rate from any cause and sudden death.

The retrospective analysis of the CHF-STAT database25 examined patients followed for a median time of 45 months, and showed that the prolongation of the QRS duration on resting ECG is a predictor of both total mortality and sudden death in patients with ischemic or nonischemic cardiomyopathy, NYHA class II to IV heart failure, and at least 10 PVCs per hour. However only LBBB was associated with worse survival.

There is increasing evidence that CRT can improve ventricular systolic performance in patients with dilated cardiomyopathies and LBBB, an effect thought to be due to improving contraction synchrony rather than enhancing contractility since this improvement occurs without an increase in myocardial energy consumption.21

CRT has been shown to reverse the mechanical abnormalities associated with severe conduction delay, to improve patient's symptoms, functional capacity and quality of life.26–28 Vogt et al.29 analyzed the course of intrinsic IVCD in thenative ECG after 1 year of successful CRT, in comparison with the initial ECG, in the patients of the PATH-CHF study group, the almost totality of them presenting LBBB. Only a few patients showed shortening of nonpaced QRS complex over time and a significant evidence of remodeling of the intrinsic ECG was lacking.

We conclude that complete LBBB is unequivocally associated with greater disease severity and mortality in patients with congestive HF.

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