QRS duration is of prognostic relevance in patients with several underlying heart diseases. Short-term data also show the prognostic value of QRS duration in lower risk groups of patients. The aim of this study was to investigate the long-term prognostic value of QRS duration in patients with known or suspected coronary artery disease. The study cohort consisted of 512 patients (308 men, mean age 60 ± 11 years) who underwent myocardial perfusion imaging (MPI) for the evaluation of suspected or known coronary artery disease. Follow-up data were collected to assess the prognostic value of QRS duration, alongside clinical characteristics and MPI results. End points were cardiac death and cardiac death or nonfatal myocardial infarction (MI). During a mean follow-up of 8.6 ± 5.2 years, 290 patients (60%) died, with 139 deaths (27%) attributable to cardiac causes. Nonfatal MI occurred in 28 patients (6%), and 127 patients (25%) underwent late coronary revascularization (>3 months). Patients with QRS duration <120 ms had annualized cardiac death rates and cardiac death or nonfatal MI rates of 2.2% and 2.3%, respectively, compared with those of 4.1% and 4.4% in patients with QRS duration ≥120 ms. Multivariate models identified QRS duration ≥120 ms as an independent predictor of both end points, on top of clinical characteristics and MPI results. In conclusion, QRS duration ≥120 ms is an independent predictor of cardiac death and cardiac death or nonfatal MI, after adjustment for clinical characteristics and MPI results.
Surface 12-lead electrocardiography (ECG) is a valuable tool for diagnostics because of its low cost and simplicity. These features also make ECG an attractive option for cardiac risk stratification. Several studies have reported the prognostic value of QRS duration in patients with heart failure, left ventricular systolic dysfunction, and acute coronary syndrome. Recent studies have also aimed to assess the prognostic value of QRS duration in the general population and in groups of lower risk patients on a short term. As long-term data in the latter group of patients are lacking, this study aimed to assess the long-term prognostic value of QRS duration in patients with known or suspected coronary artery disease (CAD) referred for myocardial perfusion imaging (MPI) for the evaluation of myocardial ischemia.
Methods
The study population consisted of 512 patients (308 men, 204 women, mean age 60 ± 11 years) referred for MPI for evaluation of suspected or known CAD. This study was not subject to the Dutch Medical Research Involving Human Subjects Act. Therefore, approval from the local research ethics committee to conduct this prospective follow-up study was not required at the time of enrollment. Moreover, the study was conducted according to the Declaration of Helsinki. All patients consented participation in this study. An assessment of cardiac risk factors was done before the procedure. Hypertension was defined as a blood pressure ≥140/90 mm Hg or treatment with antihypertensive medication. Diabetes mellitus was defined as a fasting glucose level of ≥140 mg/dl or the need for insulin or oral hypoglycemic agents. Hypercholesterolemia was defined as a total cholesterol level of ≥247 mg/dl or treatment with lipid-lowering medication.
Twelve-lead surface ECG was performed at rest, digitally stored, and analyzed by an experienced observer unaware of any other data, according to recommendations for the standardization and interpretation of the electrocardiogram. QRS duration was calculated as the mean of 3 separate measurements using a dedicated computer system (Mortara Instruments, Bilthoven, The Netherlands). The dobutamine-atropine stress test was performed as described. Dobutamine was injected intravenously up to a maximum dose of 40 μg/kg/min. If the test end point was not reached at a maximum dose of dobutamine, up to 1 mg of atropine was administered intravenously. Blood pressure, heart rate, and electrocardiogram were monitored continuously. Test end points were achievement of target heart rate (85% of maximum age-predicted heart rate), horizontal or downsloping ST-segment depression of >2 mm, ST-segment elevation of >1 mm in patients without previous myocardial infarction (MI), severe angina, systolic blood pressure decrease of >40 mm Hg, blood pressure of >240/120 mm Hg, or significant arrhythmia. Metoprolol was available to reverse the (side) effects of dobutamine or atropine if these did not revert spontaneously after termination of dobutamine infusion.
Approximately 1 minute before the termination of the stress test, an intravenous dose of 370 MBq technetium-99m tetrofosmin was administered. For resting studies, 370 MBq tetrofosmin was injected at least 24 hours after the stress study. Image acquisition was performed with a triple-head gamma camera system (Prism 3000 XP; Picker International, Cleveland, Ohio). For each study, 6 oblique (short axis) slices from the apex to the base and 3 sagittal (vertical long axis) slices were defined. Each of the 6 short-axis slices was divided into 8 equal segments. The septal part of the 2 basal slices was excluded from analysis because this region corresponds to the fibrous portion of the interventricular septum and normally exhibits reduced uptake. The interpretation of the MPI was performed semiquantitatively by visual analysis assisted by analysis of the circumferential profiles. Stress and rest tomographic views were reviewed side by side by an experienced observer who was unaware of each patient’s clinical data. A reversible perfusion defect was defined as a perfusion defect on stress images that partially or completely resolved at rest in ≥2 contiguous segments or slices in the 47-segment model. A fixed perfusion defect was defined as a perfusion defect on stress images in ≥2 contiguous segments or slices, which persists on rest images in the 47-segment model. An abnormal study was considered in the presence of a fixed or reversible perfusion defect (or both).
Follow-up data were obtained in 2011. The mean follow-up period was 8.6 ± 5.2 years, and the median follow-up for all survivors was 13.4 years. Outcome data were obtained by a questionnaire, evaluation of hospital records, contacting the patient’s general practitioner, and/or review of civil registries. The cause of death was retrieved at Statistics Netherlands ( www.cbs.nl ). The date of the last review or consultation was used to calculate the follow-up time. Outcome events were cardiac death and cardiac death or nonfatal MI. Cardiac death was defined as death caused by acute MI, significant cardiac arrhythmias, or refractory congestive heart failure. Sudden death occurring without another explanation was included as cardiac death.
Values were expressed as mean ± standard deviation or number (%) and compared using the Student t test or chi-square test. The probability of survival was calculated using the Kaplan–Meier method, and survival curves were compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression models were used to assess the prognostic value of QRS duration in relation to the outcomes described previously. All variables were forced to enter the model simultaneously. The risk of a variable was expressed as a hazard ratio with a corresponding 95% confidence interval (CI). A p value <0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 22 (IBM Corp., Armonk, New York).
Results
Clinical characteristics are presented in Table 1 . ECG at rest demonstrated a QRS duration ≥120 ms in 115 patients (22%), of which 41patients (36%) had a right bundle branch block, 19 patients (17%) had a left bundle branch block, 1 patients (1%) had Wolff-Parkinson-White syndrome, and 54 patients (46%) had an unspecified intraventricular block. QRS duration ≥120 ms was significantly more observed in men and in patients with a previous MI, congestive heart failure, and an abnormal MPI result.
| Variable | All patients (n = 512) | QRS duration <120ms (n = 397) | QRS duration ≥120 ms (n = 115) | p value |
|---|---|---|---|---|
| Age (years) | 60 ± 11 | 60 ± 11 | 62 ± 10 | 0.062 |
| Men | 308 (60%) | 224 (56%) | 84 (73%) | <0.005 |
| Hypertension | 232 (45%) | 178 (45%) | 54 (47%) | 0.688 |
| Smoker | 137 (27%) | 104 (26%) | 33 (29%) | 0.594 |
| Hypercholesterolemia | 175 (34%) | 135 (34%) | 40 (35%) | 0.877 |
| Diabetes mellitus | 91 (18%) | 71 (18%) | 20 (17%) | 0.903 |
| Prior heart failure | 88 (17%) | 49 (12%) | 39 (34%) | <0.001 |
| Old myocardial infarction | 152 (30%) | 106 (27%) | 46 (40%) | <0.05 |
| Prior CABG | 83 (16%) | 56 (14%) | 27 (23%) | <0.01 |
| Prior PCI | 92 (18%) | 70 (18%) | 22 (19%) | 0.7 |
| ACE inhibitor | 149 (29%) | 104 (26%) | 45 (39%) | <0.01 |
| Betablocker | 204 (40%) | 163 (41%) | 41 (36%) | 0.297 |
| Calcium channel blocker | 229 (45%) | 170 (43%) | 59 (51%) | 0.04 |
| Diuretic | 126 (25%) | 80 (20%) | 46 (40%) | <0.001 |
| Nitrate | 159 (31%) | 118 (30%) | 41 (36%) | <0.01 |
An abnormal MPI was observed in 297 patients (58%). This included fixed defects in 143 patients (28%) and reversible defects in 154 patients (30%). Of the 154 patients with reversible defects, 107 patients (21%) had partially reversible defects and 47 patients (9%) had completely reversible defects. During follow-up, 290 patients (57%) died, of which 139 deaths (27%) were attributed to cardiac causes. Nonfatal MI occurred in 28 patients (6%), and late coronary revascularization (>3 months) was performed in 127 patients (25%).
During the 8.6 ± 5.2 year follow-up period, annualized cardiac death rates were 3.0% in patients with an abnormal MPI compared to 2.1% patients with normal MPI (p = 0.0375). Cardiac death or nonfatal MI occurred at a rate of 3.2% in the abnormal MPI group compared to 2.3% in the normal MPI group (p = 0.0185). Annualized cardiac death rates were 2.2% in patients with QRS duration <120 ms and 4.1% in patients with QRS duration ≥120 ms (p <0.0001). Cardiac death or nonfatal MI occurred at a rate of 2.3% in patients with QRS duration <120 ms and 4.4% in patients with QRS duration ≥120 ms (p <0.0001).
Kaplan–Meier survival curves for the end points cardiac death and cardiac death or nonfatal MI are presented in Figures 1 and 2 . A significantly longer event-free survival for patients with QRS duration <120 ms was seen for both end points. In Figures 3 and 4 , survival is shown according to the combination of QRS duration and MPI results. QRS duration <120 ms and a normal MPI were associated with a favorable prognosis, and the combination of QRS duration ≥120 ms and an abnormal MPI was associated with an adverse prognosis. An intermediate prognosis was observed in patients with normal QRS duration and an abnormal MPI and in patients with QRS duration ≥120 ms and normal MPI. This pattern was observed in both end points.
Univariate analysis results for each end point are presented in Tables 2 and 3 . QRS duration ≥120 ms was a strong predictor of cardiac death and cardiac death or nonfatal MI. An abnormal MPI was associated with an increased risk of cardiac death and cardiac death or nonfatal MI.
