Seasonal variation in sudden cardiac death after experimental myocardial infarction

The authors studied the incidence of sudden death by monitoring the ECG after ligation of the left anterior descending coronary artery in 184 dogs. A significant number of sudden deaths (46 dogs) occurred in the cold weather months, November-February (42%), compared to the summer months, July and August (6%). All deaths resulted from ventricular tachyarrhythmias (greater than or equal to 300/min) and occurred between 13 and 22 hours after coronary artery ligation. The survivors (138 dogs) were subjected to electrophysiological study, during which a significantly higher number showed induced sustained monomorphic ventricular tachycardia (VT) (heart rate greater than or equal to 300/min) during the winter months than during the summer months. Heart weight and infarct mass were not significantly different throughout the year. Higher sympathetic tone or catecholamine levels may account for the seasonal variation in sudden death during evolving myocardial infarction.     

Prediction of sudden cardiac death after myocardial infarction in the beta-blocking era

OBJECTIVES: This study assessed the predictive power of arrhythmia risk markers after an acute myocardial infarction (AMI). BACKGROUND: Several risk variables have been suggested to predict the occurrence of sudden cardiac death (SCD), but the utility of these variables has not been well established among patients using medical therapy according to contemporary guidelines. METHODS: A consecutive series of 700 patients with AMI was studied. The end points were total mortality, SCD, and nonsudden cardiac death (non-SCD). Nonsustained ventricular tachycardia (nsVT), ejection fraction (EF), heart rate variability, baroreflex sensitivity, signal-averaged electrocardiogram (SAECG), QT dispersion, and QRS duration were analyzed (n = 675). Beta-blocking therapy was used by 97% of the patients at discharge and by 95% at one and two years after AMI. RESULTS: During a mean (+/-SD) follow-up of 43 +/- 15 months, 37 non-SCDs (5.5%) and 22 SCDs (3.2%) occurred. All arrhythmia risk variables differed between the survivors and those with non-SCD (e.g., the standard deviation of N-N intervals was 98 +/- 32 vs. 74 +/- 21 ms [p < 0.001] and the QRS duration was 103 +/- 22 vs.89 +/- 16 ms [p < 0.001]). Sudden cardiac death was weakly predicted only by reduced EF (<0.40; p < 0.05), nsVT (p < 0.05), and abnormal SAECG (p < 0.05), but not by autonomic markers or standard ECG variables. The positive predictive accuracy of EF, nsVT, and abnormal SAECG as predictors of SCD was relatively low (8%, 12%, and 13%, respectively). CONCLUSIONS: The common arrhythmia risk variables, particularly the autonomic and standard ECG markers, have limited predictive power in identifying patients at risk of SCD after AMI in the beta-blocking era.     

Out-of-hospital sudden cardiac death: a comparative study spanning 10 years

Incidence, etiology and time zones of sudden cardiac deaths were compared for 1986 and 1976. Totals of 1,140 cases of acute endogeneous deaths, 590 in 1986 and 550 in 1976, were sent for coroner's inquest in Kanagawa Prefecture. These were the materials for the present study. Sudden cardiac deaths included 239 (46.1%) in 1986 and 137 (37.4%) cases in 1976 in males, and 81 (47.1%) in 1986 and 74 (40.0%) cases in 1976 in females. There were 129 (21.9%) and 163 (29.6%) cases with cerebral hemorrhages in 1986 and 1976, respectively. The acute cardiac death was the most frequent cause among acute endogenous deaths, and it approximately doubled among males during an interval of 10 years. It was related to a marked increase in ischemic heart disease (from 89 to 170 cases) in males compared to a slight increase among females (from 58 to 76 cases). Non-ischemic acute cardiac deaths were frequently noted in males; 38 (27.7%) and 27 (11.4%) cases in 1976 and 1986, respectively. In ischemic heart disease, deaths most frequently occurred about midnight (from 12 a.m. to 1 a.m.) or in the evening (from 5 p.m. to 6 p.m.), and deaths due to acute cardiac failure occurred during sleep. Time zones of evening deaths in ischemic heart disease corresponded to the report of Muller et al., but, the peak about midnight was not reported. This difference may be explained by the circadian rhythm theory, however, heavy alcohol intake and spasmogenicity in the Japanese people may also play roles in midnight deaths.     

KCNJ11 polymorphisms and sudden cardiac death in patients with acute myocardial infarction

PURPOSE: Patients with an acute myocardial infarction (AMI) are of high risk to develop ischemia-induced ventricular arrhythmias, leading to sudden cardiac death (SCD) in about one third of all AMI patients. The individual susceptibility to ischemia-induced arrhythmias may be modified by polymorphisms in genes encoding ion channels. The cardiac ATP-dependent potassium channel (K(ATP)) current is generated by ion channels encoded by the KCNJ11 gene and the SUR2a gene. Opening of the K(ATP) channel during ischemia results in action potential shortening in various studies and may therefore influence the outcome of AMI patients. METHODS: Using a three-primer strategy, we sequenced the complete coding and adjacent 5' and 3' sequences of the intronless KCNJ11 gene (1.3 kb) prospectively in two groups. Patients of group 1 (n = 84) survived three or more transmyocardial infarctions without developing any ventricular arrhythmias. Patients of group 2 died suddenly from their first myocardial infarction (n = 86), most of them witnessed SCDs. RESULTS: We identified a total of six known polymorphisms (K23E, A190A, L267V, L270V, I337V, and K281K) and two new polymorphisms (L267L, 3'UTR +62 G/A). The allele, genotype, and haplotype frequencies did not differ between the two groups. All polymorphisms were found to be in Hardy-Weinberg equilibrium. In addition, we identified two novel missense mutations in a highly conserved region of the gene in two patients of group 2 (P266T and R371H) with yet unknown functional consequences. CONCLUSION: In this study of AMI patients, SCD was not related to polymorphisms in the KCNJ11 gene.     

Non-arrhythmic therapy of ventricular tachyarrhythmias and sudden cardiac death after acute myocardial infarction

The management of ventricular tachyarrhythmias and prevention of sudden cardiac death after acute myocardial infarction (AMI) underwent important evolution. In the CAST study, encanaide and other antiarrhythmic drugs were not only ineffective but also increased mortality after myocardial infarction. Amiodarone had some beneficial effect on arrhythmic events without improving survival, and ICDs failed to improve outcome early after AMI. In comparison, short and long term survival benefits of beta blockers, angiotensine converting enzyme inhibitors and aldosterone antagonists after AMI is well established. This review discusses the role of non-arrhythmic therapy in the prevention of ventricular tachyarrhythmia's and sudden cardiac death after AMI.     

Plasma concentrations of fibrinolytic factors in the subacute phase of myocardial infarction predict recurrent myocardial infarction or sudden cardiac death

BACKGROUND: The prognostic value of plasma concentrations of tissue type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein has been reported in patients with coronary artery disease. However, the association between cardiac events and these factors during the acute and subacute phases of myocardial infarction (MI) is unknown. The purpose of this study was to determine whether elevated plasma concentrations of t-PA, PAI-1, and C-reactive protein in patients with MI are associated with future recurrent MI or sudden cardiac death. METHODS: We studied 106 consecutive patients who survived a confirmed first MI between 1993 and 1998 in our hospital. The control group consisted of 50 patients who had no significant coronary artery stenosis. Blood samples were obtained at the time of admission for acute MI and on the 28th day after admission. Patients were followed for a mean of 50 months after these measurements. The primary end points were sudden cardiac death and fatal or nonfatal acute MI. RESULTS: Of the 92 patients who were available for follow-up, 10 had cardiac events. Both the plasma t-PA and PAI-1 concentrations were elevated on day 1 of acute MI compared to the control group and decreased by day 28, but remained higher than those in the controls. Plasma C-reactive protein concentration was also elevated on day 1 and decreased by day 28. Using a stepwise variable choice model of Cox proportional hazards analysis including these fibrinolytic factors and C-reactive protein, only the t-PA concentration in the subacute phase was a significant predictor of cardiac events (relative risk per S.D. 3.20, P<0.01). We further found that independent of other risk factors, an elevated t-PA concentration was predictive of cardiac events. CONCLUSIONS: This study reveals that a rise in endogenous t-PA concentration during the subacute phase of MI could predict recurrent MI or sudden cardiac death.     

QT dispersion as a risk factor for sudden cardiac death and fatal myocardial infarction in a coronary risk population.

OBJECTIVE: To evaluate the efficacy of head up tilt guided treatment with metoprolol and clonidine in preventing the recurrence of syncope in patients with malignant vasovagal syncope. PATIENTS: 20 patients (9 men and 11 women, mean age 33 (SD 17), range 14 to 62 years) with severe symptoms. DESIGN: Randomised double blind crossover trial; efficacy was assessed by head up tilt testing. RESULTS: Metoprolol was more effective than clonidine in abolishing syncope (19/20 v 1/20, P < 0.001) but clonidine showed some beneficial effects on time to syncope and severity of hypotension in 12 patients. During an average follow up of 15 (3) months there was a significant reduction in the recurrence of symptoms compared with the previous year in patients who had tilt up guided treatment (18 metoprolol, 1 clonidine). CONCLUSIONS: Treatment guided by head up tilting is a reliable method of treating patients with malignant vasovagal syndrome. Metoprolol was an effective long term treatment for preventing syncope. High doses were more effective and a careful dose titration period helped to minimise withdrawal symptoms and side effects.     

Prodromata of myocardial infarction and sudden death.

A sample of 160 hospitalized, acute myocardial infarction patients and 138 individuals who died prior to hospitalization from acute coronary heart disease were studied to determine the incidence and duration of prodromal symptoms and action taken to cope with the symptoms. Seventy percent of the in-hospital subsample (IHS) and 64% of the out-hospital subsample (OHS) reported prodromata. The OHS reported a significantly longer median duration of symptoms than the IHS (29 versus 10.5 days). Sixty-seven percent of the IHS reported new or accelerated anginal symptoms as the most frequently occurring symptom, in contrast to 35% for the OHS. Twenty-seven percent of the IHS and 36% of the OHS consulted a physician about symptoms. Individuals in both subgroups, especially chronically diseased patients, considered their symptoms manageable. Likewise, when contacted, their physicians may have viewed these symptoms as manageable. Patients with a high risk of myocardial infarction and sudden death were significantly more likely to have consulted physicians during the prodromal phase than low-risk patients. A clearly delineated prodromal syndrome is needed so that both lay and medical communities can effectively respond to and intervene during the prodromal phase of acute myocardial infarction and sudden cardiac death.     

Psychosocial and physiological predictors of sudden cardiac death after healing of acute myocardial infarction

Several major prospective studies that have examined the relation between type A behavior and cardiac mortality have failed to find an association. Since psychosocial factors have been implicated in the etiology of sudden cardiac death, it is possible that this association may emerge if sudden cardiac death is distinguished as an outcome distinct from other cardiac mortality. Predictors of sudden death and other cardiac outcomes were examined using data from the Recurrent Coronary Prevention Project, a 4.5-year prospective clinical trial of 1,012 postinfarction patients begun in San Francisco in 1978. A unique set of risk factors was found for the differing outcomes: sudden cardiac death had predominantly psychosocial predictors while nonsudden cardiac death and nonfatal recurrences were predominantly predicted by biologic factors. Type A behavior was an independent predictor of sudden, but not nonsudden, cardiac death in this population (p = 0.04). These results are the first demonstration of a direct relation between stress and sudden cardiac death in a large prospective clinical study, and provide insight into the failure of past prospective studies to find an association between type A behavior and cardiac mortality.