Relation between ventricular repolarization duration and cardiac cycle length during 24-hour Holter recordings. Findings in normal patients and patients with long QT syndrome.

BACKGROUND. The interval from the R wave to the maximum amplitude of the T wave (RTm) contains the heart rate dependency of ventricular repolarization. METHODS AND RESULTS. A computer algorithm was developed to quantify the RTm and preceding RR intervals for each of more than 50,000 beats on 24-hour ambulatory electrocardiographic (Holter) recordings to evaluate the dynamic relation between repolarization duration and cycle length. The relation of RTm to the preceding RR interval (RTm/RR slope) was determined by the best-fit linear regression equation between these two parameters. Eleven normal subjects and 16 patients with long QT syndrome (LQTS) were investigated. Six of the normal subjects had Holter recordings obtained before and after beta-blocker therapy. beta-Blockers were associated with a significant (p = 0.005) reduction in the RTm/RR slope from 0.13 +/- 0.02 to 0.10 +/- 0.02. The mean value of the RTm/RR slope was significantly (p = 0.003) larger in the LQTS patients (0.21 +/- 0.08) than in normal subjects (0.14 +/- 0.03). CONCLUSIONS. These findings indicate that 1) quantification of the dynamic relation between ventricular repolarization and RR cycle length can be obtained on a large number of Holter-recorded heart beats; 2) beta-blockers reduce the RTm/RR slope in normal patients; and 3) LQTS patients have an exaggerated delay in repolarization at long RR cycle lengths.     

Comparison of right atrial pacing soon after myocardial infarction with treadmill testing 6 months later

Seventy-four patients recovering from acute myocardial infarction underwent right atrial pacing before hospital discharge, and treadmill exercise testing 6 months later. The early right atrial pacing test was positive in 32 patients (43 percent) and the late treadmill test was positive in 32 patients (42 percent). The results of the two tests were concordant in 77 percent of the patients, 23 with an ischemic response and 34 with a normal response on both tests. In nine patients a positive right atrial pacing test was followed by a negative treadmill test, and in eight patients a negative pacing test was followed by a positive treadmill test. A positive right atrial pacing test at hospital discharge had an 81.0 percent predictive accuracy for a positive late treadmill test; chest pain, congestive heart failure or increased cardiothoracic ratio at discharge had a predictive value of only 52.9, 42.8 and 42.8 percent, respectively. Both the early right atrial pacing test and the late treadmill test were positive in a significantly higher proportion of patients with inferior or subendocardial infarction than of patients with anterior myocardial infarction. During early right atrial pacing the mean maximal heart rate achieved was higher than that during late treadmill testing (148 versus 133 beats/min) and the mean systolic blood pressure was lower (137 versus 162 mm Hg), but the pressure-rate product was similar on the two tests (20,282 versus 21,455 mm Hg/min). This finding may explain the similar frequency of ischemic responses to the two tests. These results indicate that the response to right atrial pacing soon after myocardial infarction is a good predictor for the presence or absence of an ischemic response to treadmill testing 6 months later. Thus, early right atrial pacing at the time of hospital discharge may be used to determine the pace of rehabilitation and short-term prognosis.     

Effects of nisoldipine on myocardial ischemia during exercise and during daily activity

The antiischemic properties of nisoldipine, a dihydropyridine calcium antagonist, were assessed in a multicenter, double-blind, placebo-controlled trial by repeated exercise testing and 72-hour ambulatory electrocardiographic monitoring in 82 patients with coronary artery disease. Patients with positive treadmill stress test results and greater than or equal to 2 ischemic episodes per 24 hours were included in this study. Administration of all chronic antiischemic medications except beta blockers were discontinued. During the first week all patients received placebo twice daily. During the second and third weeks, 41 patients received nisoldipine 10 mg and 41 patients received placebo twice daily. In the placebo group there were no changes in exercise parameters or in ambulatory electrocardiographic parameters. In the nisoldipine group, exercise duration increased from 403 to 448 seconds (p = 0.0035), time to 1 mm of ST depression increased from 224 to 298 seconds (p = 0.002), time to pain increased from 241 to 321 seconds (p = 0.01), and maximal ST depression was reduced from 2.6 to 2.3 mm (p = 0.002). Among the ambulatory electrocardiographic parameters in the nisoldipine group, only the number of episodes was reduced, from 14.4 to 11.6 (p = 0.0013) per patient. There was no significant reduction in total ischemic time (132 vs 120 minutes per patient). No significant side effects were observed. This is the largest clinical trial to date on the effects of nisoldipine on myocardial ischemia. The results indicate that nisoldipine was effective in improving all exercise parameters and only partially effective in suppressing ischemia during daily activity.     

Modulating effects of age and gender on the clinical course of long QT syndrome by genotype

OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration. BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited. METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations (LQT1), 209 cases of LQTS caused by the HERG potassium channel gene mutations (LQT2), and 81 cases of LQTS caused by the SCN5A sodium channel gene mutation (LQT3) gene carriers. The probability of cardiac events (syncope, aborted cardiac arrest, or sudden death) was analyzed by genotype, gender, and age (children < or = 15 years and adults 16 to 40 years). In addition, the risk of sudden death and lethality of cardiac events were evaluated in 1,075 LQT1, 976 LQT2, and 324 LQT3 family members from families with known genotype. RESULTS: During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19% and 18%), and higher in LQT1 and LQT2 males (5% and 6%) than in LQT1 and LQT2 females (2% for both). CONCLUSIONS; Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.     

Prognostic significance of nonfatal myocardial reinfarction. Multicenter Diltiazem Postinfarction Trial Research Group

In most risk stratification and intervention postinfarction trials, cardiac mortality is used as the major outcome end point either alone or in combination with nonfatal reinfarction. However, the independent risk carried by nonfatal reinfarction for subsequent cardiac death has not been quantified. The prognostic significance of nonfatal reinfarction was determined from the multicenter diltiazem trial data base of 1,234 patients treated with placebo followed up for 1 to 4 years after acute myocardial infarction. One hundred sixteen patients had at least one nonfatal reinfarction, 14 (12%) of whom subsequently experienced cardiac death. Of the remaining 1,118 patients without nonfatal reinfarction, 110 (9.8%) experienced cardiac death. Compared with event-free patients, patients with nonfatal reinfarction were more likely (p less than 0.05) to be women, to have had an infarction before their index event and to have had prior cardiac-related symptoms. Cox survivorship analyses, using pertinent baseline clinical variables along with nonfatal reinfarction as a time-dependent predictor variable, revealed that nonfatal reinfarction carried a significant and independent risk for subsequent cardiac mortality (hazard ratio 3.0, p = 0.002), which was greater than that carried by other significant predictor variables (New York Heart Association functional class, pulmonary congestion on chest radiograph, blood urea nitrogen level, predischarge Holter-recorded ventricular premature complexes and radionuclide ejection fraction). The cardiac mortality risk associated with nonfatal reinfarction was further increased in patients whose index event was their first infarction (hazard ratio 5.4, p = 0.0006). Thus, nonfatal reinfarction carries a strong, significant and independent risk for subsequent cardiac death in patients surviving an acute myocardial infarction.     

Clinical and genetic variables associated with acute arousal and nonarousal-related cardiac events among subjects with long QT syndrome

In patients with the long QT syndrome (LQTS), the occurrence of cardiac events (syncope or cardiac arrest) is frequently associated with acute arousal caused by exercise, swimming, emotion, or noise. However, cardiac events may also occur during sleep or with ordinary daily activities. The purpose of this study was to determine whether there are differential clinical, electrocardiographic, and genetic features among LQTS patients who experienced cardiac events with and without acute arousal. We identified 1,325 patients with cardiac events from the International LQTS Registry. Based on the precipitating conditions of the first event, 427 patients were classified as arousal, 345 as nonarousal, and the remaining 553 were unknown (not classifiable). Gene linkage was known in 78 of the 772 patients with classifiable first events. The age at first cardiac event was significantly younger in the arousal than the nonarousal group (11.7 vs. 15.5 years, respectively; p<0.001). The arousal-type patients had a higher rate of subsequent cardiac events during follow-up after the index event than the nonarousal-type patients (p = 0.02). Arousal-related cardiac events occurred in 85% of LQT1, 67% of LQT2, and 33% of LQT3 patients (p = 0.008). This study provides evidence that the genotype is an important determinant of the LQTS phenotype in terms of arousal and nonarousal-related cardiac events.