Attenuation of severity of myocardial ischemia during repeated daily ischemic episodes.

OBJECTIVES: The purpose of this study was to assess whether the severity of myocardial ischemia would be attenuated by repeated daily ischemic episodes, recorded by ambulatory electrocardiographic monitoring (AEM). BACKGROUND: Repetitive ischemic episodes induced by brief coronary occlusions in animal experiments and in humans during balloon coronary angioplasty produce preconditioning. We wanted to assess whether this phenomenon also exists during daily ischemic episodes. METHODS: Twenty-one patients with known coronary artery disease and ischemia on exercise testing and AEM were requested to walk a distance known to have previously caused myocardial ischemia on three consecutive occasions. Walking time was approximately 15 min and was followed by 5 min of rest. RESULTS: Mean maximal heart rate during the three walks was similar; however, the mean maximal ST segment depression decreased significantly from 2.21 mm during the first walk to 1.61 mm and 1.43 mm, respectively, on the second and third walks (p = 0.001). Ischemia duration was also significantly reduced on the second and third walks by 56% from 514 to 228 and 254 s, respectively (p = 0.012). The heart rate at onset of ischemia (ischemic threshold) increased from 99 beats/min on the first walk to 101 beats/min on the second walk and to 106 beats/min on the third walk (p = 0.058). CONCLUSIONS: This study demonstrated attenuation of myocardial ischemia with an associated increase in ischemic threshold in patients with repeated and adjacent ischemic episodes. This form of myocardial protection is likely to be encountered in patients during ordinary activity and may represent the clinical counterpart of myocardial preconditioning.

Ischemic threshold during two exercise testing protocols and during ambulatory electrocardiographic monitoring.

OBJECTIVES: The aim of this study was to examine the dependence of the ischemic threshold during exercise testing on the exercise protocol employed and to determine the relation between the ischemic thresholds observed during exercise and during daily activity. BACKGROUND: The ischemic threshold (heart rate at 1-mm ST segment depression) during daily activity has been reported to be lower than that observed during exercise testing. Recent reports have hypothesized that this difference is probably dependent on the exercise protocol employed. METHODS: Twenty-two patients with known coronary artery disease, not receiving antianginal medications, were evaluated by repeated exercise testing according to the Bruce and the modified Davidson protocols and by 48-h ambulatory electrocardiographic monitoring. RESULTS: Although the heart rate at 1-mm ST segment depression was somewhat lower with the Davidson than with the Bruce protocol (112 +/- 14 vs. 115 +/- 14 beats/min), the rate-pressure product at 1-mm ST segment depression was similar during the two protocols (16,900 +/- 4,000 vs. 17,700 +/- 3,600). The mean heart rate (100 + 12 beats/min) at 1-mm ST segment depression during ambulatory ischemic episodes (n = 137) was significantly lower than that observed during both exercise protocols (p < 0.001 for both comparisons). CONCLUSIONS: Exercise-induced ischemia occurs at a relatively fixed threshold that is mainly dependent on myocardial oxygen demand and is independent of the exercise protocol employed. Ischemia on ambulatory monitoring, however, occurs at a much more variable threshold that is commonly lower than that observed during exercise and is therefore dependent on other factors in addition to increased demand.

Natural history of left ventricular thrombi: their appearance and resolution in the posthospitalization period of acute myocardial infarction.

A series of 198 consecutive patients with acute myocardial infarction were prospectively studied before hospital discharge and during 24.0 +/- 8.6 months of follow-up. A predischarge thrombus was found in 38 (31%) of 124 patients with anterior infarction but in none of 74 patients with inferior infarction (p less than 0.001). Early thrombolytic therapy in 34 patients did not decrease the rate of thrombus occurrence. Acute anterior infarction, ejection fraction less than or equal to 35% and apical dyskinesia or aneurysm (but not akinesia) were significantly related to the appearance of thrombus during hospitalization by stepwise logistic regression analysis. Echocardiographic follow-up of 159 patients for at least 6 months (mean 26.6 +/- 8.4) revealed that thrombus disappeared in 14 (48%) of 29. Disappearance of thrombus was related to predischarge apical akinesia (but not dyskinesia) and to warfarin therapy during the follow-up period. A new thrombus first appeared after hospital discharge in 13 of 130 patients, and in 7 of the 13 it resolved during further follow-up. Thus, 30% (13 of 42) of thrombi in these patients appeared after discharge from the hospital. Three factors were related to occurrence of new thrombi during the follow-up period: deterioration in left ventricular ejection fraction, predischarge ejection fraction less than or equal to 35% and ventricular aneurysm or dyskinesia. Systemic embolism occurred in six patients, all with a predischarge thrombus (p less than 0.001). Mobility of the thrombus was the only variable significantly related to subsequent embolic events (p = 0.001) by logistic regression analysis. Thus, the predischarge echocardiogram identifies patients with thrombus and those at highest risk of embolic events. It can indicate patients who are likely to have thrombus resolution and those at risk of developing a new thrombus after hospital discharge. Follow-up echocardiograms may help in guiding the length of long-term anticoagulant therapy. Four additional patients with a predischarge apical mobile thrombus (not part of the consecutive series) received thrombolytic therapy. In two of the four, lysis of thrombus was achieved without complications, but systemic embolism occurred in the other two, and proved fatal in one.

Disopyramide-induced Torsade de Pointes.

Recurrent ventricular tachycardia (torsade de pointes) is a serious and sometimes fatal arrhythmia occurring usually with quinidine therapy. Four patients experienced ventricular tachycardia after receiving conventional doses of disopyramide phosphate (600 mg/day) for recurrent atrial fibrillation-two of them in combination with amiodarone hydrochloride. Isoproterenol hydrochloride infusion was effective in three patients, while ventricular pacing promptly abolished ventricular ectopic beats and the ventricular tachycardia in the fourth patient. Torsade de pointes is more likely to occur in patients with severe repolarization delay and sinus bradycardia or atrioventricular block, and its appearance in four patients within a period of nine months after the introduction of disopyramide treatment in our service raises the possibility that this is not a rare complication of this drug, especially if used in combination with other QT interval-prolonging agents.

Effect of exercise on cerebral circulation.

The effect of supine physical exercise on cerebral blood flow (CBF) was measured in 30 normal subjects with the 133Xe inhalation technique. The CBF measurements were correlated to changes in PCO2, heart rate, and blood pressure, and to cardiac output and right atrial pressure in 10 of the subjects who underwent Swan-Ganz catheterization. No significant change was found in CBF during physical exercise, although a marked increase in cardiac output, blood pressure, and right atrial pressure and a mild decrease in PCO2 were found. Cerebrovascular resistance increased by 38%, in contrast to a decrease of 33% in the peripheral vascular resistance. The factors that affect the mechanism of cerebrovascular autoregulation during exercise are discussed.

Analysis of risk factors in 532 survivors of first myocardial infarction hospitalized in Jerusalem.

During the period January 1979-March 1983, we have conducted in Jerusalem a case control study of all patients under the age of 65 surviving their first diagnosed myocardial infarction, in order to evaluate the importance of the conventional risk factors and to detect additional factors through quantifying plasma apolipoprotein concentrations. As a control group, we have chosen a sample from a previously studied Jewish population (LRC study), representative of the adult Jerusalemite population, parents of children born during 1958-1961. To complete the younger age group missing in the LRC population, we added a population studied in the Kiryat Yovel district of Jerusalem. We report here the results obtained from interviews and analysis of 532 cases (448 males and 84 females), and 869 controls (457 males and 412 females). In order to overcome the effects of age and ethnic origin on the risk factors, we have divided our populations according to age and country of origin of their fathers. Age, sex, smoking, history of high blood pressure, diabetes, elevated plasma triglycerides and/or cholesterol, and decrease in plasma HDL cholesterol, emerged as the most powerful and significant risk factors in this study. Other putative risk factors such as socioeconomic status, dietary habits, physical activity and obesity index were not found to be significantly different between cases and controls. It is noteworthy that smoking was more important as a risk factor in the younger age groups, whereas hypertension and diabetes were more important in the older age groups, particularly in females. The differences in lipid levels were considerably more prominent in the young age groups in both sexes. Myocardial infarction was observed more frequently in patients of European or American extractions. Apolipoproteins A-I, A-II, E and B determined in this study were shown to be affected partly by age and country of origin. Apo E and apo B levels were significantly higher and Apo A-I significantly lower in patients with myocardial infarction when compared to controls.

Clinical outcome of silent myocardial ischemia.

Asymptomatic coronary artery disease can be detected by an abnormal electrocardiogram at rest, by a positive exercise test result unaccompanied by pain, or by the demonstration of silent ischemic episodes during daily activities. However, the clinical outcome of patients with silent myocardial ischemia has not yet been clearly defined. In a study of 356 patients with documented coronary disease--211 of whom had previous myocardial infarction--the prognostic information of spontaneous ST-segment depression was found to be independent of that associated with a positive exercise test result, ejection fraction, and extent of arteriographically documented coronary artery disease. Patients with asymptomatic ischemia had a higher coronary event rate than those without ischemia. Cardiac event rates followed a similar pattern for patients with silent, symptomatic and mixed ischemia--whether or not there was previous myocardial infarction.

Holter recording during treadmill testing in assessing myocardial ischemic changes.

One hundred forty-four patients underwent a Bruce protocol treadmill exercise test during which an electrocardiogram (ECG) was recorded simultaneously with a 2-channel Holter recorder with bipolar V3- and V5-like leads and by a conventional 12-lead system. Sixty-eight patients had no ST depression on either the Holter or on the 12-lead ECG during the exercise test, whereas in 70 patients ischemic changes were recorded by both methods; thus, in 138 of the 144 patients (96%), the results of the 2 tests were concordant. The severity of ST depression, as judged by the heart rate at which ischemic changes were first noted and the maximal ST depression observed, were similar on both recording systems. The Holter system identified 6 of the 7 patients whose ischemic changes were confined to the inferior wall on the 12-lead ECG. The addition of the V3 lead as a second ischemic lead increased the ischemia detection by 10%. Ninety-five patients also underwent coronary arteriography. In these patients the sensitivity of the Holter system during exercise in detecting significant coronary artery disease was 81% and that of 12-lead ECG was 84%, the specificity was 85% and 85%, respectively, and the positive predictive value 91% and 91%, respectively. Thus, the 2-channel Holter recording system with bipolar V3- and V5-like leads was as accurate as the 12-lead system in detecting ischemic changes during exercise and proved that ambulatory monitoring system can reliably reproduce ST segment.

Mibefradil in the treatment of chronic stable angina pectoris: comparative studies with other calcium antagonists.

The ability of mibefradil, a new T-channel-selective calcium antagonist, to improve exercise tolerance and silent ischemic parameters in patients with chronic stable angina was compared in 3 separate trials with 2 other commonly used calcium antagonists: diltiazem SR (120 mg/twice daily) and amlodipine (10 mg/day). Compared with amlodipine, mibefradil 100 mg given once daily over a 3-week period resulted in a statistically significantly larger increase from baseline in total exercise tolerance test (ETT) duration (treatment difference of 40.9 sec, p = 0.04), time to onset of angina (treatment difference 61.2 sec, p < 0.001), and time to onset of ischemia (treatment difference of 54.4 sec, p = 0.004). The decrease in weekly anginal episodes was 58% with mibefradil versus 19% with amlodipine, and the reduction in nitroglycerin consumption was 58% with mibefradil versus a 10% increase with amlodipine. The decrease in the number of silent ischemic episodes detected by a 48-hour Holter recording was significantly larger (p = 0.03) with mibefradil 100 mg (88%) compared with amlodipine 10 mg (38%). Similarly, a larger decrease in the duration of silent ischemia was observed with mibefradil (69%) compared with that seen with amlodipine (38%). The preliminary results of a second trial comparing mibefradil with amlodipine were consistent with the first demonstrating that the improvement for all 3 ETT parameters was larger for mibefradil (ETT duration: 55.2 sec; delay in onset angina: 74.2 sec; time to onset of ischemia: 63.6 sec), but in this trial the treatment differences did not reach statistical significance. In the trial comparing mibefradil (100 mg once daily) with diltiazem SR (120 mg twice daily), both compounds had equivalent effects on all ETT parameters tested. Mibefradil produced a 21% increase in exercise duration compared with a 20% increase with diltiazem. Although mibefradil yielded larger increases in the time to onset of angina and the time to onset of 1-mm ST-segment depression (42% and 38%, respectively) than did diltiazem (34% and 25%, respectively), the treatment differences did not reach statistical significance. Both mibefradil and diltiazem SR were associated with at least a 70% reduction from baseline in anginal frequency and nitroglycerin consumption. Mibefradil-treated patients showed greater decreases in heart rate and the rate-pressure product at each stage of the ETT than patients treated with amlodipine or diltiazem SR. All 3 drugs were well tolerated. However, compared with mibefradil, amlodipine and diltiazem SR produced a higher incidence of leg edema. In conclusion, the effectiveness of mibefradil in improving all 3 ETT parameters was greater than that of amlodipine and equivalent to that of diltiazem SR. Moreover, mibefradil provided greater reductions in the heart rate and cardiac workload than did the other 2 drugs.

Improvement in ischemic parameters during repeated exercise testing: a possible model for myocardial preconditioning.

Repeated short episodes of coronary occlusion in experimental animals, and in humans during balloon angioplasty, cause myocardial preconditioning. This study examines whether myocardial ischemia induced by repeated exercise testing can reduce the extent of ischemia induced by subsequent exercise tests. Twenty-six patients with positive stress tests underwent 3 treadmill exercise tests at 30-minute intervals. Two additional tests were performed on each of the previous 2 days in order to eliminate and/or reduce the training effect. All 3 exercise tests were of similar work load. In spite of that, total ischemic time was markedly shortened from 633 to 399 seconds (p <0.0001) as well as the recovery time from 259 to 126 seconds (p <0.0001) between the first and the second tests. There was no further improvement on the third test. Time to 1-mm ST depression was prolonged from 487 to 593 seconds (p = 0.004) and double product at 1-mm ST depression was increased in the second test from 20,322 to 22,325 mm Hg/second (p = 0.008), implying a higher ischemic threshold. An improvement of > or = 10% in < or = 1 ischemic parameter was observed in 25 of the 26 patients and in > or = 2 of the ischemic parameters in 76% of the patients. Improvement in ischemic parameters develops during repeated exercise induced ischemia in most patients. We suggest that this phenomenon, which was previously known as "warm up," is the clinical counterpart of myocardial preconditioning which develops not only during ischemia caused by reduction in coronary flow, but also during demand-induced ischemia.

Ventricular ectopic activity during myocardial ischemic episodes in ambulatory patients.

The association between ventricular ectopic activity (VEA) and ischemic episodes during everyday activities was investigated in ambulatory patients with stable angina pectoris. Seventy-five consecutive patients with proven coronary artery disease, ischemic episodes on Holter monitoring and positive treadmill tests, but without known ventricular arrhythmias, were prospectively studied. In these 75 patients, a total of 719 ischemic episodes were recorded during 127 twenty-four-hour monitoring periods. Forty-three patients had either no or only very low baseline VEA (less than 14 ventricular premature complexes [VPCs]/24 hours); none of these patients had increased VEA during any ischemic episode. However, among 32 patients who had greater than or equal to 14 VPCs/24 hours (average 243 VPCs/24 hours), increased VEA during ischemic episodes was observed in 11 (31%). These 11 patients had a total of 174 ischemic episodes and the increased VEA appeared in 47 (27%) of the episodes. During 40 of the ischemic episodes the number of single VPCs increased significantly compared to the baseline background VEA: during 4 episodes trigeminy appeared and during another 3 bigeminy was observed. More complex VEA was not observed. Among the 11 patients with increased VEA, only 4 developed VPCs during treadmill testing. No correlation was found between the severity of the ischemic episodes (degree of ST depression and duration of ischemia) and the increased VEA. In 83% of these episodes the increased VEA appeared during the last (possibly reperfusion) phase. No correlation was found between the appearance of ventricular arrhythmias during ischemic episodes and the presence or absence of chest pain at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of metoprolol in reducing myocardial ischemic threshold during exercise and during daily activity.

In a study of 48 patients with coronary artery disease and evidence of ischemia during exercise and daily life, metoprolol reduced the threshold of myocardial ischemia in a dose-dependent manner. This effect of beta blockers is probably due to increased coronary tone.

Myocardial ischemia during daily activities and stress.

Twenty-four-hour, 2-channel Holter monitoring during daily activities was performed in 210 patients; during the same day a Bruce protocol treadmill test was also performed and the electrocardiogram was recorded using the same Holter system. Significant ST-segment depression was observed during daily activities in 97 patients, while similar changes were recorded during the treadmill test in 122 patients. Thus, 77% of patients with ST depression during the provocation of the treadmill test had ischemic episodes during their everyday life. On the other hand, 3 patients with proven significant coronary artery disease had spontaneous ischemic episodes during daily activities, but had a negative stress test. The ischemic changes during daily activity developed at a lower heart rate than during stress testing (94 beats/min vs 109 beats/min, respectively, p less than 0.05). A total of 351 ischemic episodes were recorded during daily activities, 241 (69%) of these were asymptomatic. In 46 patients all episodes were asymptomatic, in 15 all were symptomatic, while in 36 both symptomatic and silent episodes were detected. The mean duration of the symptomatic episodes was 13.7 minutes and that of the asymptomatic ones was 14.9 minutes (difference not significant). The degree of ST depression in these 2 groups was also similar. Because of more advanced symptomatology in 143 patients, coronary arteriography was performed; 43 had normal and 100 had pathologic coronary arteries. In this selected group, the sensitivity of Holter monitoring during daily activity was 87% and during stress 97%; the specificity during daily activity was 95% and during stress 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Day-to-day variability of myocardial ischemic episodes in coronary artery disease.

Twenty patients with chronic stable angina pectoris, proved coronary artery disease, positive treadmill stress test response, and at least 2 episodes of ischemia per day underwent 72 hours of Holter monitoring during daily activities. During this period they had 389 ischemic episodes: 104 (27%) symptomatic and 285 (73%) silent. Marked variability was observed between patients in the number of ischemic episodes (range 2 to 15 per day, mean 6.5), duration of ischemia (range 6 to 419 minutes/day, mean 76.5), maximal ST depression (range 1 to 6 mm, mean 3.4) and heart rate at the beginning of ST depression (range 75 to 105 beat/min, mean 91). The day-to-day variability in individual patients between the different days in the number of ischemic episodes was 36%, in duration 51%, and in maximal degree of ST depression 31%. Only 9% variability was noted in heart rate at the beginning of ST depression. Similar day-to-day variability in individual patients was noted in the symptomatic and silent episodes. For clinical purposes of evaluation of ischemia during daily activities, 1 day of monitoring appears to be sufficient because within the first day, 78% of the maximal number of ischemic episodes, 64% of their duration, and 84% of the maximal degree of ST depression were detected. However, for evaluation of anti-ischemic drugs at least 2 monitoring days are required.

Prognostic significance of ischemic episodes in patients with previous myocardial infarction.

This study assessed the prognostic significance of ischemic changes during daily activity as recorded by ambulatory electrocardiographic monitoring in a group of 224 low-risk postinfarction patients. Of the 224 patients studied, 74 (33%) had transient ischemic episodes on Holter monitoring. During the 28 months of follow-up the frequency of cardiac events (cardiac death, reinfarction, hospitalization for unstable angina, balloon angioplasty or coronary bypass surgery) was 51% among those with ischemic episodes on Holter monitoring, compared with 12% in those without such changes (p less than 0.0001). The 74 patients with positive results in their exercise tests and Holter monitoring had a 51% event rate, compared with 20% among the 44 patients with a positive exercise test result but negative Holter results (p less than 0.001). The event rate in those without ischemic changes either on the exercise test or on Holter was only 8.5%. Among patients with good (greater than 40%) or reduced (less than 40%) left ventricular ejection fraction, those with transient ST depression on Holter had a significantly higher cardiac event rate compared with those without it. A similar event rate was found in patients with only silent, only symptomatic and with silent and symptomatic ischemic episodes.

Characteristics of silent and symptomatic myocardial ischemia during daily activities.

In 191 patients with proven coronary artery disease, 24-hour Holter monitoring detected 587 transient episodes of ST depression during daily activities. Of that total, 424 episodes were silent (72.3%) and 163 were symptomatic (27.7%). There were no statistically significant differences between silent and symptomatic episodes as to their mean duration (15.1 vs 14.3 minutes, respectively), heart rate at onset of ST depression (93 vs 96 beats/min, respectively), heart rate at the time of maximal ST depression (114 beats/min, both) and mean maximal ST depression (1.9 vs 2.0 mm, respectively). Of the 191 patients, 104 (55%) had only silent episodes, 33 (17%) only symptomatic episodes and 54 (28%) had both types ("mixed"). All patients, regardless of episode type, were of similar age, received comparable medical therapy, had a similar extent of angiographically documented coronary artery disease and similar episode characteristics. However, mixed-episode patients had significantly more ischemic episodes per day (4.8) than silent-episode (2.6) and symptomatic-episode (1.9) patients (p less than 0.001 for both) and a longer total period of daily ischemia (60 minutes), than the other 2 groups (36 and 28 minutes, respectively, p less than 0.001 for both). Of the 191 patients, 97 (51%) had had a previous myocardial infarction. The characteristics of their silent and symptomatic episodes were similar to the 94 (49%) patients without infarction, except for a longer duration of the silent episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Early right atrial pacing after myocardial infarction. I. Comparison with early treadmill testing.

Right atrial (RA) pacing and modified treadmill testing (TT) were performed in 111 patients recovering from acute myocardial infarction (MI) before hospital discharge to determine whether ischemic responses are more common with RA pacing than with TT and whether the prognosis could be better determined by the results of 1 test compared with the other. Patients with predischarge congestive heart failure, chest pain, physical disability or age older than 70 years were excluded. Ischemic responses were significantly more frequent during RA pacing than during TT (41% vs 34%, p = 0.02). The results of the 2 tests were concordant in 102 patients (92%): Both were positive in 37 and both negative in 65. In 8 patients, results of RA pacing were positive and results of TT were negative; only 1 patient had positive TT and negative RA pacing responses. The higher percentage of positive responses during RA pacing than during TT can be attributed to the significantly higher pressure-rate product achieved during pacing (18,773 vs 16,831 mm Hg/min, p less than 0.001). The ischemic threshold, defined as the pressure-rate product at which an ischemic change was first noted in a particular patient, was almost identical in both tests. During a mean follow-up period of 16 months, 10 patients had recurrent MI; 8 had positive predischarge RA pacing but only 5 had positive TT responses (p = 0.008). Six patients died; in 3 RA pacing responses were positive and in 2 TT responses were positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Early right atrial pacing after myocardial infarction. II. Results in 77 patients with predischarge angina pectoris, congestive heart failure, or age older than 70 years.

Seventy-seven consecutive postinfarction patients who had either predischarge angina pectoris or congestive heart failure, or who were older than 70 years of age, underwent right atrial (RA) pacing before hospital discharge. In 60% of these patients, ischemic changes developed during RA pacing; this high yield of positive response indicates advanced coronary arterial disease. During a mean follow-up of 15 months, these patients had a high mortality rate (18%) and a reinfarction rate of 9%. RA pacing separated this a priori high-risk group into lower- and higher-risk subsets. Of the 46 patients with a positive RA pacing response, 6 had reinfarction, while none of the 31 patients with a negative RA pacing response had reinfarction (p = 0.04); 10 of the 14 cardiac deaths were among the patients who had positive RA pacing responses at discharge (p = not significant). Thus, of the 20 major cardiac events, 16 occurred among those with positive RA pacing responses (p less than 0.05). Predischarge clinical symptoms, however, were not good predictors of subsequent major cardiac events. We conclude that RA pacing can be safely performed even in high-risk and elderly patients and a positive response can identify those who have a poorer prognosis. Therefore, for postinfarction patients who, according to the prevailing criteria, are excluded from treadmill testing, we advocate the use of RA pacing.

Magnesium therapy for torsades de pointes.

This is the first report of the successful use of magnesium sulfate (MgSO4) in 3 consecutive patients with torsades de pointes (TdP). In 1 patient, TdP was induced by a combination of quinidine and amiodarone, in the second by procainamide, and in the third by an overdose of imipramine. The QT intervals before TdP were 0.70, 0.64 and 0.56 second, respectively. A bolus of 1.0 to 2.0 g MgSO4 25% abolished the TdP in all 3 patients; but in the third patient, because of recurrent TdP, a second bolus of 1.0 g and a continuous 24-hour infusion of 1.0 mg/min were administered, preventing TdP. There was no immediate shortening in the QT interval in any patient after MgSO4. Magnesium can be given safely even in patients with acute myocardial infarction, angina pectoris or systemic hypertension, conditions in which isoproterenol is contraindicated; it can be applied faster than temporary cardiac pacing; and its use for TdP appears worthy of additional trials.