Author + information
- Received October 30, 2004
- Revision received December 8, 2004
- Accepted December 21, 2004
- Published online April 5, 2005.
- Christian Bruch, MD⁎,⁎ (, )
- Michael Gotzmann⁎,
- Jörg Stypmann, MD⁎,
- Frauke Wenzelburger, MD†,
- Markus Rothenburger, MD†,
- Matthias Grude, MD⁎,
- Hans H. Scheld, MD, FESC, FETCS†,
- Lars Eckardt, MD‡,
- Günter Breithardt, MD, FESC, FACC⁎ and
- Thomas Wichter, MD, FESC⁎
- ↵⁎Reprint requests and correspondence:
Dr. Christian Bruch, Universitätsklinikum Münster, Medizinische Klinik und Poliklinik C (Kardiologie und Angiologie), Albert-Schweitzer-Str. 33, D-48129 Münster, Germany
Objectives This prospective study tested whether Doppler echocardiographic variables add incremental value to QRS duration in determining the prognosis of patients with chronic heart failure (CHF) and systolic dysfunction.
Background Diastolic dysfunction frequently is observed in patients with CHF, but its prognostic impact relative to that of QRS duration is unknown.
Methods A total of 193 patients with CHF and an ejection fraction <45% were enrolled prospectively. Echo measurements included left ventricular dimensions/volumes, ejection fraction, mitral early/late diastolic velocity ratio, deceleration time, and tissue Doppler mitral annular velocities. The mitral filling pattern was classified as either restrictive (RFP) or nonrestrictive. A cardiac event (cardiac death or urgent cardiac transplantation) was defined as combined study end point.
Results During a follow-up of 385 ± 270 days, 24 patients suffered an event (cardiac death, n = 21; urgent transplantation, n = 3). The RFP, QRS duration, left ventricular systolic diameter, and mitral annular early diastolic velocity were independent predictors of an event. In patients with QRS duration >144 ms, the outcome was markedly poorer in the presence of RFPs as compared with their absence. Similarly, despite a QRS duration ≤144 ms, the outcome was worse in the presence of a RFP. A risk-stratification model based on the three strongest independent predictors separated groups into those with good prognosis and those with high, intermediate, and low event-free survival rates.
Conclusions In subjects with CHF and systolic dysfunction, transmitral flow patterns add incremental value to QRS duration in determining the prognosis.
Despite advances in the medical management of patients with chronic heart failure (CHF), morbidity and mortality remain high (1). The prolongation of the QRS interval has been identified as an independent predictor of adverse outcome (2). However, in patients with CHF, echo-Doppler indices of diastolic filling also provide prognostic information, and a restrictive filling pattern (RFP) is indicative of a poor prognosis (3). This prospective study tested whether Doppler echocardiographic variables add incremental value to QRS duration in determining the prognosis of patients with CHF and systolic dysfunction.
Two hundred seventy-one patients were recruited consecutively from our outpatient CHF clinic, which is jointly run by the Departments of Cardiology/Angiology and Cardiothoracic Surgery in our institution. Inclusion criteria were a history of CHF according to Framingham criteria (4), left ventricular ejection fraction (LVEF) <45%, and clinical stability after at least two months on standard medical therapy. Patients with congenital heart disease (n = 4), malignancy (n = 2), severe valvular disease (n = 6), atrial fibrillation (n = 28), or under permanent pacemaker stimulation (n = 27) were excluded. Follow-up information was obtained during routine ambulatory visits but also by telephone contact with patients or their physicians. All patients gave their informed consent before study entry.
Electrocardiography (ECG) analysis
QRS duration was measured in a 12-lead ECG using leads V3to V6(interobserver and intraobserver correlations for QRS duration: 0.97 and 0.98, respectively).
All patients underwent a standard echo examination, including the assessment of transmitral peak early and late diastolic velocities (E, A) and deceleration time (DT). A RFP was defined by an E/A ratio >2, a DT <150 ms, and a mitral annular E′ velocity <8 cm/s (5). Tissue Doppler imaging (TDI)-derived peak systolic (S′), early (E′), and late (A′) diastolic velocities were derived from the septal and lateral mitral annulus and averaged for each patient (6). Interobserver and intraobserver correlations for conventional echo measurements and TDI variables reached 0.94 and 0.98, respectively.
Outcome measurements and statistical analysis
Death from a cardiac cause or urgent cardiac transplantation was considered as the combined study end point. Numerical values are expressed as mean ± SD. Continuous variables were compared between groups using an unpaired ttest (for normally distributed variables) or Mann-Whitney Utest (for non-normally distributed variables). The chi-square test was used to compare categoric variables. Clinical, ECG, and echo variables were evaluated for the combined study end point in a univariate Cox proportional hazard model. All variables with a significant association were entered in a multivariate Cox model to identify independent predictors of outcome. Receiver operating characteristic curves were generated to define cut-off values for independent predictors. Event-free survival was analyzed by the Kaplan-Meier method, and survival curves were compared by the log-rank test. Independent predictors identified by the multivariate Cox proportional hazard survival model were used to derive a prognostic index to classify patients into different risk groups. A p value of <0.05 was considered significant.
During a follow-up of 385 ± 270 days, 24 patients suffered an event (cardiac death, n = 21; urgent cardiac transplantation, n = 3) and thus reached the study end point. Eleven patients were censored (elective cardiac transplantation, n = 9; death from noncardiac cause, n = 2).
Patients with or without event did not differ significantly with respect to the etiology of CHF, but QRS duration was significantly longer in patients with an event (Table 1).In such patients, LVEF and DT were reduced, and RFP was more frequent (Table 2).The independent predictors of an event identified by the multivariate Cox analysis are listed in Table 3.
In patients with a QRS duration >144 ms, the event-free survival was significantly lower than in patients with a QRS duration ≤144 ms (event-free survival rate of 69% vs. 90%, p = 0.0021) (Fig. 1).In patients with a QRS duration >144 ms, the presence of a RFP indicated a poor prognosis (event-free survival rate 51% vs. 79% in those with a non-RFP, p = 0.023) (Fig. 2A).Likewise, in patients with a QRS duration ≤144 ms, a RFP indicated a less-favorable outcome than that in patients without RFP (event-free survival rate rate 59% vs. 97%, p < 0.0001) (Fig. 2B).
Construction of a noninvasive risk score
The noninvasive predictive model was based on the three strongest independent predictors, i.e., presence of a RFP, QRS duration >144 ms, and left ventricular systolic diameter index >2.75 cm/m2. Very low-, low-, intermediate-, and high-risk groups were identified by the absence of any risk factor or the presence of one, two, or three risk factors with an event-free survival of 100%, 91%, 64%, and 41%, respectively (Fig. 3).
This study is the first to combine the prognostic impact of the ECG and the echocardiogram, two methods that are routinely used in the follow-up of patients with CHF. The main finding is that a RFP provides independent prognostic information that is incremental to QRS duration in patients with CHF.
Given the increasing number of individuals affected by CHF, risk stratification is of tremendous importance. In such patients, QRS prolongation is a known predictor of adverse outcome. Shamim et al. (2) found a mortality of 50% in CHF patients with a QRS duration >140 ms as opposed to a mortality of 23% in the remaining patients. However, our study and others show that although QRS prolongation has prognostic value, there is a substantial overlap of QRS duration between patients with or without event (Table 2). In this setting, the assessment of diastolic function added incremental prognostic information. In CHF patients with or without QRS prolongation, outcome was significantly worse in the presence of a RFP (Figs. 2A and 2B). These findings are in line with observations by Hansen et al. (7), who found an incremental value of a RFP to peak oxygen consumption in determining the prognosis in patients with CHF.
Our findings indicate that a combination of predictive factors more accurately predicts the individual risk than a single parameter or cut-off value. In our risk model, in the presence of two or three risk factors, outcome was significantly worse as compared with the presence of ≤1 risk factor. In the absence of any risk factor, no patient suffered a cardiac event during follow-up (Fig. 3). The variables considered in our model are readily available in the daily clinical setting and are cost-effective, enabling serial follow-up examinations. Other markers, such as natriuretic peptides or TDI analysis of left ventricular asynchrony (8), may have added further prognostic information but were not considered in the present analysis.
For the TDI-derived mitral annular E′ velocity, Wang et al. (9) recently reported an incremental predictive power for cardiac mortality compared with standard clinical and echo measurements. However, in their study, patients with various cardiac diseases and a wide range of resting LVEFs were analyzed. Thus, the prognostic impact of a RFP and E′ may vary in subsets of CHF patients with different etiologies and resting LVEF.
Because patients with severe valvular disease, atrial fibrillation, permanent pacemaker stimulation, or primary diastolic heart failure were excluded, our results should not be extrapolated to these patient populations.
- Abbreviations and acronyms
- peak late diastolic mitral filling velocity
- peak late diastolic mitral annular velocity
- chronic heart failure
- deceleration time
- peak early diastolic mitral filling velocity
- peak early diastolic mitral annular velocity
- left ventricular ejection fraction
- restrictive filling pattern
- peak systolic mitral annular velocity
- tissue Doppler imaging
- Received October 30, 2004.
- Revision received December 8, 2004.
- Accepted December 21, 2004.
- American College of Cardiology Foundation
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