Jan Pool

QT interval prolongation predicts cardiovascular mortality in an apparently healthy population.

BackgroundIn myocardial infarction patients, heart rate-adjusted QT interval (QT), an electrocardiographic indicator of sympathetic balance, is prognostic for survival. Methods and ResultsIn a 28-year follow-up, the association between QT, and all-cause, cardiovascular, and ischemic heart disease mortality was studied in a population of 3,091 apparently healthy Dutch civil servants and their spouses, aged 40–65 years, who participated in a medical examination during 1953–1954. Moderate (QTc, 420–440 msec) and extensive (QTc, more than 440 msec) QTc prolongations significantly predict all-cause mortality during the first 15 years among men (adjusted respective relative risks [RRs], 1.5 and 1.7) and among women (RRs, 1.7 and 1.6). In men, cardiovascular (RRs, 1.6 and 1.8) and ischemic heart disease mortality (RRs, 1.8 and 2.1) mainly account for this association. In women, the association cannot be attributed specifically to cardiovascular and ischemic heart disease mortality. RRs for a subpopulation without any sign of heart disease at baseline are similar. The same is observed for QT, prolongation after light exercise, although in this situation most associations are not statistically significant, probably because of smaller numbers in the QTc prolongation categories. ConclusionsOur results suggest that QT, contributes independently to cardiovascular risk. If autonomic imbalance is an important mechanism, it might be speculated that changes in life-style (e.g., with regard to physical exercise and smoking) may have a preventive impact.

QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest.

BackgroundQTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance. Methods and ResultsIn the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventric-ular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazetts formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction < 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compared with a QTc of 440 msec or less (95% confidence interval: 1.4, 3.9). In contrast, in patients with evidence of cardiac dysfunction, the relative risk of QTc prolongation was 1.0 (0.5, 1.9). Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks. ConclusionsThese data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death. (Circulation 1991;83:1888—1894)

Heart rate variability from 24-hour electrocardiography and the 2-year risk for sudden death.

BACKGROUND Low heart rate variability has been implicated as a risk factor for sudden death. However, no large epidemiological studies using sudden death as an outcome event have been reported. METHODS AND RESULTS A total of 6,693 consecutive patients who underwent 24-hour ambulatory ECG were followed up for 2 years; of these, 245 patients died suddenly. Clinical data at the time of 24-hour ambulatory ECG were collected for all patients who died suddenly and for a random sample of 268 patients from the study cohort. In all patients in sinus rhythm with or without occasional supraventricular arrhythmias at the 24-hour ECG (193 patients who died suddenly and 230 patients from the sample), heart rate variability parameters were derived. Patients with low short-term RR interval variability (mean during 24 hours of per-minute standard deviations [SD] of RR intervals < 25 msec) had a 4.1-fold higher risk (95% confidence interval [CI], 2.6, 8.1) for sudden death than patients with high short-term variability (> or = 40 msec); after adjustment for age, evidence of cardiac dysfunction, and history of myocardial infarction, the relative risk was 2.6 (95% CI, 1.4, 5.1). The crude relative risk of long-term RR interval variability (SD during 24 hours of per-minute means of RR intervals < 8 msec) was 4.4 (95% CI, 2.6, 7.7); after adjustment for the same risk factors, it was 2.2 (95% CI, 1.2, 4.1). Patients with a minimum heart rate > or = 65 beats per minute had a double risk of sudden death compared with those with a minimum heart rate < 65 beats per minute (adjusted relative risk, 2.1; 95% CI, 1.3, 3.6). CONCLUSIONS These findings support the theory that patients with low parasympathetic activity (low short-term RR interval variability) have an increased risk for sudden death independent of other risk factors.

Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen Study.

BackgroundHeart-rate-adjusted QT-interval (QTc) is prognostic of sudden death in myocardial infarction patients. So far, population studies have yielded conflicting results on the predictive value of QTc for coronary heart disease morbidity and mortality. Therefore, we investigated this in a longitudinal study of middle-aged and elderly men. Methods and ResultsFrom 1960 to 1985, 877 middle-aged men were followed and repeatedly examined in the Zutphen Study. In 1985 the remaining cohort was extended to 835 elderly men from the same birth cohort and followed until 1990. Men with prolonged QTc (420 ms1/2 or more) had a higher risk of myocardial infarction and coronary heart disease death relative to men with QTc less than 385 ms1/2. Ageadjusted coronary heart disease mortality rate ratios were 4.3 (95% confidence interval, 1.3 to 13.8) in middle-aged men and 3.3 (95% confidence interval, 1.0 to 11.6) in elderly men. These associations could not be attributed to prevalent heart disease and were independent of other cardiovascular risk factors. ConclusionsThese results indicate that within the normal range of QTc in the general population, men with long QTc are at higher risk for coronary heart disease. Because QTc is easily determined, it may provide a valuable contribution to risk stratification.

QTc duration is associated with levels of insulin and glucose intolerance. The Zutphen elderly study.

Prolongation of heart rate-adjusted QT length (corrected QT interval [QTc]) is associated with elevated risk of coronary heart disease and sudden death. This may have to do with autonomic cardiac control. Because insulin is known to stimulate sympathetic activity, we studied the association of insulin level and glucose tolerance with QTc. In 1990, 383 elderly men 70–89 years of age without previous myocardial infarctions or known diabetes had a 12-lead electrocardiogram recorded and glucose tolerance determined in the frame of an ongoing follow-up study. QTc was significantly associated with fasting glucose, insulin, and C-peptide and glucose levels 60 and 120 min after an oral glucose load. For fasting C-peptide and the area under the glucose curve (AUGC), this association could not be explained by the concomitant occurrence of other risk factors of coronary heart disease. Furthermore, fasting C-peptide and the AUGC were independently additive predictors of QTc duration. The difference in QTc between men in the extreme quintiles of both variables was 22 ms. QTc prolongation seems to be part of the insulin resistance syndrome. The association may be explained by increased sympathetic activity induced by high insulin levels. An additional explanation could be an effect of high insulin, impaired glucose utilization, or both on membrane activity of myocardial cells.

Physical training and relaxation therapy in cardiac rehabilitation assessed through a composite criterion for training outcome

One hundred fifty-six myocardial infarction patients were randomly assigned to either exercise plus relaxation and breathing therapy (treatment A, n = 76) or to exercise training only (treatment B, n = 80). Effects on exercise testing showed a more pronounced training bradycardia and a remarkable improvement in ST abnormalities in treatment A (p less than 0.005). A model was developed to integrate the various exercise parameters into a single measure for training benefit. Approximately half the patients showed a training success, with a more positive and less negative outcome in treatment A (p = 0.09). The odds for failure were 0.25 for treatment A and 0.51 for treatment B (odds ratio: 2.04; 95% confidence interval, 0.94 to 4.6). Thus the risk of failure was reduced by half when relaxation was added to exercise training. These results indicate that exercise training is not successful in all MI patients and that relaxation therapy enhances training benefit.

Psychic effects of physical training and relaxation therapy after myocardial infarction

The psychological impact of exercise training and relaxation therapy was investigated in 156 myocardial infarction patients. They were randomly assigned to either exercise plus relaxation and breathing therapy (Treatment A: n = 76) or exercise training only (Treatment B: n = 80). Patients in Treatment A improved on three out of eight psychological measurements (anxiety, well-being, feelings of invalidity). No change was demonstrable in Treatment B. The difference between the treatments was significant for wellbeing (p less than 0.005). Physical outcome, measured by exercise testing was positive in about half of the patients (Treatment A: 55%, Treatment B: 46%). A negative outcome occurred less in Treatment A (p less than 0.05). Training success was not associated with psychic benefit. The association differed for the two treatments. It was concluded that exercise training was effective for some but not for all cardiac patients, and that a psychic effect of exercise could not be demonstrated. Relaxation therapy enhanced physical and psychic outcome of rehabilitation.

ST segment and T wave characteristics as indicators of coronary heart disease risk: The Zutphen study

OBJECTIVES This study evaluated the predictive value of T wave amplitude and ST segment level on lead I for angina pectoris, a first myocardial infarction, sudden death and coronary heart disease death in middle-aged and elderly men. BACKGROUND Certain ST-T wave characteristics may reflect favorable autonomic cardiac control. Slight ST segment elevation has been reported to indicate a low risk of coronary heart disease mortality. METHODS A total of 876 men, born between 1900 and 1920, participated in periodic medical examinations and were followed up with respect to morbidity and mortality from 1960 to 1985. In 1985, the remaining cohort was extended to 836 elderly men from the same birth cohort who were followed up until 1990. Relative risks in categories of T wave amplitude and ST segment level were estimated by survival analysis. RESULTS Both middle-aged and elderly men with T wave amplitudes > or = 0.15 mV had a lower risk of myocardial infarction, coronary heart disease death and sudden death than men with T wave amplitudes 0.05 to 0.15 mV. The adjusted relative risk of coronary heart disease death was 0.5 (95% confidence interval [CI] 0.2 to 1.0); in men with T wave amplitude < or = 0.05 mV, relative risk was 2.0 (95% CI 1.3 to 3.1). Slight ST segment elevation was also associated with decreased risk: relative risk 0.5 (95% CI 0.3 to 1.0) compared with the isoelectric ST segment level. In men with ST segment depression, relative risk was 2.2 (95% CI 1.4 to 3.4). The association of T wave amplitude and ST segment level were independent of each other. CONCLUSIONS In addition to the elevated risk of coronary heart disease that is associated with ST-T wave abnormalities, we observed that normal variations in repolarization characteristics are predictive of future heart disease.

Success and failure of exercise training after myocardial infarction: Is the outcome predictable?

One hundred fifty-six patients underwent a 5 week daily exercise training program after recovery from acute myocardial infarction. Outcome was assessed on the basis of exercise testing, integrating the measurements into a single outcome measure consisting of three categories (positive, n = 79; negative, n = 42; no change, n = 35). This composite criterion served as the end point for determining the predictability of a positive (training success) and negative (training failure) outcome. With use of logistic regression analysis, the baseline variables of clinical information, exercise data and psychosocial variables were able to identify patients with training success, as well as patients with failure (correct classification rates 81% and 85%, respectively). The characteristics of patients for whom training was beneficial differed from those of patients with a negative outcome. Work status before infarction was the single most important predictor of success, but it did not determine failure. Psychologic variables (type A behavior, well-being, depression) were important for predicting failure, but not for predicting success. Cardiac state and physical fitness largely determined training success. It is concluded that the physical benefit of exercise training in patients after myocardial infarction is highly predictable. Validation will make it possible to optimally apply exercise training as a therapeutic modality in these patients.

The Cardiac Infarction Injury Score and coronary heart disease in middle-aged and elderly men: The Zutphen study

The Cardiac Infarction Injury Score (CIIS), based on electrocardiographic characteristics, was developed as a measure to determine the presence of myocardial infarctions. In the present study the association of the CIIS with coronary morbidity and mortality was investigated among middle-aged and elderly men. A cohort of 877 men, born between 1900 and 1919, was followed and repeatedly examined from 1960 onwards. In 1985 the remaining cohort was extended to 836 elderly men from the same birth cohort, and followed until 1990. In both middle-aged and elderly men with high CIIS the prevalence of (silent) previous myocardial infarction and the occurrence of ST-T abnormalities were increased. Five-year relative risks of men with CIIS 20 or more relative to men with CIIS < 5 were 2.2 (95% confidence interval: 1.2-4.1) for angina pectoris, 2.4 (1.4-4.0) for myocardial infarction and 5.8 (3.4-9.9) for coronary heart disease death. Thus, the CIIS is associated with risk of coronary heart disease in apparently healthy middle-aged as well as elderly men.