Mechanism Of Sudden Cardiac Death Research Articles

Mechanism of sudden cardiac death in coronary artery disease

An 87-year-old lady with hypertension being her only cardiovascular risk factor was investigated for dyspnoea and chest oppression three years ago, and acute coronary syndrome could be excluded. She stayed asymptomatic for a longer period, but was admitted again with similar symptoms and suspected atrial fibrillation. Twice, 12-lead-ECG and cardiac biomarkers were within normal limits. 24-hour-Holter monitoring was ordered to document atrial fibrillation. Twenty hours later she was found unconscious in her room. Circulation was restored within five minutes after immediate mechanical and electrical resuscitation. The first documented rhythm had been ventricular fibrillation. As the 12-lead ECG then showed ST-segment elevation in all anterior leads, PCI of a critical stenosis of the proximal LAD was performed (fig. 1, 2). The patient fully recovered and was sent home ten days later. Analysis of the Holter ECG revealed that in a moment without ST depression or ST elevation in any of the three leads, an extrasystole with a relatively short coupling interval of 330 ms (QT interval just before the event: 430 ms) induced a fast ventricular tachycardia (fig. 3) at a heart rate of 260/min. Due to the severe anterior wall ischaemia, the ventricular tachycardia rapidly degenerated into ventricular fibrillation lasting until external defibrillation (fig. 4).

Orgasm Associated Incontinence (Climacturia) Following Radical Pelvic Surgery: Rates of Occurrence and Predictors

Orgasm associated incontinence, that is the inadvertent leakage of urine at orgasm, has received little attention in the literature. We evaluated the rate of occurrence of orgasm associated incontinence following radical pelvic surgery as well as its associated factors and predictors. From January 2005 to March 2006, 696 patients were evaluated for post-radical pelvic surgery sexual dysfunction. A database was created, and descriptive statistics, chi-square analysis and logistic regression analysis were used to evaluate associated factors and predictors. Of 475 patients 96 (20%) reported orgasm associated incontinence following radical pelvic surgery. The incidence was significantly less in the cystoprostatectomy group than in the open and laparoscopic radical prostatectomy groups (p <0.05). Orgasm associated incontinence was more commonly found within 12 months following surgery vs greater than 12 months (RR 0.81, 95% CI 0.72-0.92, p <0.01) and in patients with orgasm associated pain (RR 1.09, 95% CI 1.01-1.16, p <0.01) and penile length loss (RR 1.32, 95% CI 1.09-1.59, p <0.01). On multivariate analysis all factors associated on univariate analyses remained predictive. Orgasm associated incontinence was not associated with patient age, the degree of nerve sparing, surgical margin status, seminal vesicle or lymph node involvement, preoperative erectile function, nocturnal erections, libido level or daytime continence. Orgasm associated incontinence occurs in a fifth of men (96 of 475) following radical pelvic surgery. The incidence of orgasm associated incontinence is greater with radical prostatectomy than with radical cystectomy and it is unrelated to the type of prostatectomy performed (open vs laparoscopic). Orgasm associated incontinence is more likely to be reported within year 1 following surgery and in men who complain of orgasmic pain and/or penile shortening.

Protagonist: Routine screening of all athletes prior to participation in competitive sports should be mandatory to prevent sudden cardiac death

For centuries it was a mystery why cardiac arrest occurred in high-level athletes who previously had achieved extraordinary exercise performance with no complaints of symptoms. The cause was generally ascribed to myocardial infarction, even though evidence of ischemic myocardial necrosis was rarely reported. Now it is clear that the most common mechanism of sudden cardiac death (SCD) during sports activity is abrupt ventricular fibrillation as a consequence of a wide spectrum of cardiovascular diseases, either acquired or congenital.

Mechanisms of sudden cardiac death

Despite recent advances in preventing sudden cardiac death (SCD) due to cardiac arrhythmia, its incidence in the population at large has remained unacceptably high. Better understanding of the interaction among various functional, structural, and genetic factors underlying the susceptibility to, and initiation of, fatal arrhythmias is a major goal and will provide new tools for the prediction, prevention, and therapy of SCD. Here, we review the role of aberrant intracellular Ca handling, ionic imbalances associated with acute myocardial ischemia, neurohumoral changes, and genetic predisposition in the pathogenesis of SCD due to cardiac arrhythmia. Therapeutic measures to prevent SCD are also discussed.

Mechanism of sudden cardiac death in pigs with viable chronically dysfunctional myocardium and ischemic cardiomyopathy

Pigs with viable chronically dysfunctional myocardium and ischemic cardiomyopathy are at high risk of sudden cardiac death (SCD). We sought to identify the arrhythmic mechanism of SCD, the relation to changes in left ventricular (LV) function, and inducibility of malignant arrhythmias before SCD. Juvenile pigs (n = 72) were instrumented with chronic stenoses on proximal left anterior descending and circumflex arteries. Survival was only 29% 3 mo after instrumentation, and all deaths were sudden and without prodromal symptoms of heart failure. Triphenyltetrazolium chloride staining demonstrated necrosis in only nine animals averaging 2.3 +/- 0.9% of the LV, with no difference between SCD animals and survivors. Implantable loop recorders (n = 13) documented both ventricular fibrillation (n = 6) and bradyasystole (n = 2) as the arrhythmic mechanism of death. Although regional and global function were depressed [anteroseptal wall thickening 1.8 +/- 0.2 vs. 4.2 +/- 0.2 mm in Sham animals (P < 0.001); fractional shortening 21 +/- 2 vs. 31 +/- 1% in Sham animals (P < 0.01)], there were no differences between SCD animals and survivors. LV mass increased in animals with ischemic cardiomyopathy and was greater in animals with SCD (4.0 +/- 0.2 vs. 3.1 +/- 0.1 g/kg in survivors; P < 0.001). Serial programmed ventricular stimulation failed to induce any sustained arrhythmias. We conclude that pigs with viable dysfunctional myocardium and globally reduced LV function have a high rate of SCD with a spectrum of arrhythmias similar to patients with ischemic cardiomyopathy. The risk is independent of necrosis but appears to increase with LV hypertrophy. Like patients with ischemic cardiomyopathy, programmed stimulation is insensitive to predict SCD when viable dysfunctional myocardium is the pathological substrate.

Fever as a Precipitant of Idiopathic Ventricular Fibrillation in Patients with Normal Hearts

Ventricular fibrillation (VF) is the main mechanism of sudden cardiac death. The clinical precipitants of sudden cardiac death due to idiopathic VF are poorly characterized. Emerging evidence implicates triggers originating predominantly from the distal Purkinje arborization and the right ventricular outflow tract. We report three patients without structural heart disease or repolarization abnormalities in whom a febrile illness was the only concurrent disease associated with unexpected sudden cardiac death due to VF storm. An automated defibrillator was implanted in all three patients. In one patient with persistent recurrent VF episodes, mapping demonstrated the origin of these triggers was from the Purkinje arborization of the anterior wall of the right ventricle. Ablation at a site of earliest activation during ectopy, where pace mapping was concordant and Purkinje potential preceded the onset of ventriculogram, resulted in suppression of all arrhythmias. After follow-up of 22, 9, and 18 months in the three patients, no ventricular arrhythmias have been recorded. We present a series of patients in whom an apparently benign febrile illness was associated with malignant ventricular arrhythmias in the absence of cardiac disease or other factors known to precipitate sudden cardiac death. Physicians should be aware of this possible phenomenon in cases of febrile illness associated with syncope.

Hibernating Myocardium

The inability to reproduce spontaneous ventricular fibrillation in an animal model of chronic coronary artery disease has limited advances in understanding mechanisms of sudden cardiac death (SCD). Swine with hibernating myocardium arising from a chronic left anterior descending coronary artery (LAD) occlusion have a high rate of SCD that parallels the poor clinical survival of medically treated patients with hibernating myocardium. Kaplan-Meier analysis (n=426) demonstrated a cumulative mortality of 49% after 5 months that was almost entirely attributable to spontaneous SCD. Using implantable loop recorders, ventricular fibrillation was documented as the arrhythmic mechanism of death in all animals (n=10) and was usually preceded by ventricular tachycardia (n=8). Physiological studies before SCD (n=7) demonstrated total LAD occlusion and collateral-dependent myocardium (n=5), excluding acute occlusion as a major trigger of arrhythmia. The physiological substrate of hibernating myocardium was present before SCD, with reductions in LAD perfusion (SCD 0.79+/-0.13 versus 0.80+/-0.08 mL/min per g) and wall thickening (SCD 28+/-3% versus 22+/-3%) that were similar to survivors (n=14). Triphenyltetrazolium chloride infarcts among animals with SCD were infrequent (4 of 32) and small, averaging 4.6% of LV mass. Histology (n=4) showed postmortem changes but no acute inflammation nor contraction band necrosis. These data support the notion that hibernating myocardium is a pathophysiological substrate at high risk of SCD. This is independent of changes in functional stenosis severity, acute myocardial necrosis, or fibrotic scar. Thus, regional adaptations that promote myocyte survival in the setting of chronic repetitive ischemia result in a substrate with enhanced vulnerability to lethal arrhythmias and SCD.

Prediction of sudden cardiac death: appraisal of the studies and methods assessing the risk of sudden arrhythmic death.

Since the recognition of the high incidence of cardiac arrest as the mechanism of sudden cardiac death (SCD), medical scientists and clinicians have sought methods to predict and prevent these events. Significant progress has already been made in the prediction and prevention of life-threatening arrhythmias during the last decade. This progress is highlighted by the outcomes of 4 recently published randomized studies demonstrating that the implantable cardioverter defibrillator (ICD) provides a mortality benefit compared with conventional drug therapy in highly specific subsets of patients.1–4 In parallel with intervention studies, several observational studies and reports have raised an optimistic notion that arrhythmic death can be predicted by methods potentially useful for widespread screening programs.5–10 Despite the evidence-based data and practical recommendations for indications of ICD therapy,11 utilization of this therapy has not been uniformly implemented worldwide, and screening of patients at potential high risk for arrhythmic death has not become a routine clinical practice. In addition to economic and educational factors, this may be due to methodological problems in the designs of a number of the completed observational and randomized intervention studies that confound the interpretation of the results and general application of the procedures. In this report, we analyze the problems of predicting arrhythmic deaths and the advantages and limitations of the various methods and studies, and we evaluate the need for new and better studies and methods of risk stratification. Three types of clinical research designs have been used to estimate the efficacy of interventions and the accuracy of methods for predicting sudden arrhythmic death: (1) observational follow-up studies, (2) case-control studies, and (3) randomized intervention designs. Observational studies are based on baseline assessment of 1 or more risk variables and subsequent follow-up of predefined patient groups. These studies have been most commonly used in the …

Role of Purkinje conducting system in triggering of idiopathic ventricular fibrillation

Ventricular fibrillation is the main mechanism of sudden cardiac death, but the source of its spontaneous initiation has not been mapped. 16 patients were investigated by electrography and radiofrequency ablation after resuscitation from recurrent idiopathic ventricular fibrillation. Triggers of ventricular fibrillation originated from various locations within the Purkinje system in 12 patients and from the ordinary myocardial muscle in four. The accuracy of mapping was confirmed by acute elimination of triggers by radiofrequency delivery, and there was no recurrence of ventricular fibrillation in 14 patients. Long-term follow-up is necessary to establish that ablation is curative and avoids use of a defibrillator.

Sympathetic nerve sprouting, electrical remodeling and the mechanisms of sudden cardiac death.

The purpose of this article is to review the nerve sprouting hypothesis of sudden cardiac death. It is known that sympathetic stimulation is important in the generation of sudden cardiac death. For example, there is a diurnal variation of sudden death rate in patients with myocardial infarction. Beta blockers, or drugs with beta blocking effects, are known to prevent sudden cardiac death. It was unclear if the cardiac nerves in the heart play only a passive role in the mechanisms of sudden death. To determine if nerve sprouting and neural remodeling occur after myocardial infarction, we performed immunocytochemical studies of cardiac nerves in explanted native hearts of transplant recipients. We found that there was a positive correlation between nerve density and a clinical history of ventricular arrhythmia. Encouraged by these results, we performed a study in dogs to determine whether or not nerve growth factor (NGF) infusion to the left stellate ganglion can facilitate the development of ventricular tachycardia (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD). The results showed that augmented myocardial sympathetic nerve sprouting through NGF infusion plus atrioventricular (AV) block and MI result in a 44% incidence (four of nine dogs) of SCD and a high incidence of VT in the chronic phase of MI. In contrast, none of the six dogs (with AV block and MI) without NGF infusion died suddenly or had frequent VT episodes. Based on these findings, we propose the nerve sprouting hypothesis of ventricular arrhythmia and SCD. The hypothesis states that MI results in nerve injury, followed by sympathetic nerve sprouting and regional (heterogeneous) myocardial hyperinnervation. The coupling between augmented sympathetic nerve sprouting with electrically remodeled myocardium results in VT, VF and SCD. Modification of nerve sprouting after MI may provide a novel opportunity for arrhythmia control.

What do implantable cardioverter/defibrillators teach us about the mechanisms of sudden cardiac death?

Almost two decades of experience with the ICD have resulted in a better understanding of the nature of life-threatening ventricular tachyarrhythmias. The most pertinent achievements in this respect stem from clinical follow-up observations in patients with important clinical entities such as dilated cardiomyopathy or the Brugada syndrome. For instance, patients with dilated cardiomyopathy presenting with syncope and a negative electrophysiological study have been shown to have a high incidence of appropriate usage of their ICD. On the other hand, relative little has been gained from the extensive electrogram storage capabilities of third and fourth generation ICDs. Basically, careful evaluation of these electrograms has confirmed previous anecdotal data obtained from analysis of Holter recordings of patients who died suddenly while wearing the ECG recorder. In most instances, VT/VF episodes are triggered by relatively late-coupled premature beats whereas short--long--short sequences have been observed only in few patients. One future research avenue concerns the more detailed analysis of changes in cardiac autonomic tone preceding the occurrence of sustained ventricular tachyarrhythmias which can be assessed from the electrogram storage of the ICD.

Sudden Cardiac Death in Mitral Valve Prolapse.

To the Editor: I read with interest the excellent report on sudden cardiac death with apparently normal heart by Chugh et al.1 Of note was the finding that 28 of 270 hearts (10%) had pathological criteria for mitral valve prolapse. In addressing the association between mitral valve prolapse and sudden cardiac death, the authors classified these hearts as having a nonspecific structural abnormality. Such an assumption is open to question. Evidence to date suggests that the predominant mechanism of sudden cardiac death in mitral valve prolapse is fatal ventricular …

Interpretation and Application of Stored Electrograms

Detailed recordings of the electrical events surrounding delivered or aborted implantable cardioverter de~brillator (ICD) therapy has improved dramatically our outpatient management of patients with complex ventricular arrhythmias. Current generation ICDs offer an array of diagnostic storage features including electrogram recordings from ventricular, and more recently, atrial leads. Review of stored electrograms allows the clinician to: (1) retrospectively identify the rhythm diagnosis that prompted device therapy, (2) recognize problems with overand undersensing and lead integrity and (3) gain insights into the triggers of ventricular tachycardia (VT) and mechanisms of sudden cardiac death.

What have we learned about cardiac arrhythmias?

No subspecialty in cardiology has undergone a more radical transformation in the last half century than has clinical cardiac electrophysiology. From the creation of the coronary care unit (CCU), with its concept of intensive monitoring of patients who have cardiac arrhythmias, to understanding the genetics of ion channel disturbances responsible for inherited cardiac arrhythmias, clinical cardiac electrophysiology has evolved into an established discipline credited with improving and saving hundreds of thousands of lives. In this review, we will highlight the top 10 significant advances responsible for this remarkable transformation. ### Ambulatory ECG Recording the ECG in the ambulatory individual provided the ability for the first time to obtain online information in an active individual. Begun by Holter and Gengerelli1 in 1949, the initial device weighed 85 pounds and was strapped to the back. The most modern version is implanted subcutaneously and can monitor the cardiac rhythm for long time periods.2 Ambulatory ECG has led to many new insights, including an understanding of the mechanisms of sudden cardiac death, causes of syncope, and the concept of painless ischemia. All implantable pacemakers and cardioverter/defibrillators (ICDs) have the ability to record the cardiac rhythm, which is a useful adjunct to decision making. ### The CCU A major step forward in reducing death from myocardial infarction was the introduction of the CCU,3 where continuous monitoring of cardiac rhythm and hemodynamic status allowed early recognition and correction of life-threatening complications.4 Closed-chest cardiac massage and defibrillation became important life-saving measures, and the value of the well-trained nurse in this milieu became clear. The CCU also taught us to develop short- and long-term risk profiles of the patient, based on ECG, hemodynamic, and enzymatic findings. The concept of warning arrhythmias emerged along with the use of prophylactic lidocaine administration.5 Neither stood the test of time.6 7 The …

Interaction of septadian and circadian rhythms in life-threatening ventricular arrhythmias in patients with implantable cardioverter-defibrillators

Previous studies have shown that life-threatening ventricular arrhythmias display both circadian and septadian (day of the week) periodicity. We hypothesized that assessing the relation between these circadian and septadian rhythms may provide important pathophysiologic information about the mechanism of sudden cardiac death. Using the database from a population of 683 consecutive patients with a third-generation implantable cardioverter-defibrillator (ICD), we examined the time pattern of ICD activations for rapid (prospectively defined as cycle length <280 ms) tachycardias for each day of the week. A total of 5,270 arrhythmic episodes were analyzed. Despite the fact that event distribution was significantly nonuniform (p <0.001) for both circadian and septadian analyses, the circadian pattern was strikingly similar for each day of the week with a relatively broad peak between 9 a.m. and 6 p.m. and a long nadir between 9 p.m. and 6 a.m. We conclude that the trigger factors responsible for the daily circadian distribution of life-threatening ventricular arrhythmias in a population with ICDs are similar throughout the week and may thus be unrelated to the standard work week. These data suggest that the physiologic modulators of circadian and septadian rhythms may be different.

Fibromuscular dysplasia of small coronary arteries and fibrosis in the basilar ventricular septum in mitral valve prolapse

The mechanism of sudden cardiac death in patients with mitral valve prolapse is poorly understood. Twenty-four hearts from patients with mitral valve prolapse who suddenly died (mean age 34 ± 8 years) and 16 trauma control hearts (mean age 30 ± 7 years) were histologically studied. Dysplasia of the atrioventricular nodal artery was present in 18 of 24 hearts with mitral valve prolapse and four of 16 controls hearts ( p = 0.003). The degree of luminal narrowing, as morphometrically measured, was significantly greater in hearts with mitral valve prolapse ( p = 0.003). The degree of fibrosis in the base of the ventricular septum, as calculated by computerized morphometry, was greater in hearts with mitral valve prolapse ( p = 0.0002) and independent of age, sex, and heart weight ( p = 0.005). We conclude that arterial dysplasia in mitral valve prolapse may contribute to sudden cardiac death mediated by ventricular fibrosis. (AM Heart J 1997;134:282-91.)

Erythrocyte magnesium and prostaglandin dynamics in chronic sleep deprivation.

The mechanism of sudden cardiac death occurring in patients with chronic fatigue is controversial. This study was designed to define a hypothesis that coronary arterial spasm and thrombus formation can occur during chronic fatigue. For evaluating the feasibility of coronary arterial spasm, erythrocyte magnesium (Mg) was measured. Blood coagulability was evaluated by the change of prostaglandin concentration. Subjects included 16 healthy male volunteers (mean age 21.6 +/- 2.5 years). Test conditions were as follows: (A) control state: a day following a night of good sleep; (B) temporary sleep deprivation: a day preceded by < 3 h of sleep; (C) chronic sleep deprivation: a day preceded by a month during which sleep lasted < 60% of that in condition (A) above. The erythrocyte Mg concentration was measured by the atomic absorption method. The plasma concentration of thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in eight subjects by radioimmunoassay method. (1) Mean erythrocyte Mg concentration was significantly less in chronic sleep deprivation (1.1 +/- 0.4 mg/dl) than in the control state (1.8 +/- 0.4 mg/dl, p < 0.01) or in temporary sleep deprivation (1.6 +/- 0.4, p < 0.01). (2) The level of thromboxane B2 was significantly higher during chronic sleep deprivation than under control conditions (104.4 +/- 78.0 vs. 20.4 +/- 9.0 pg/ml, p < 0.05). (3) There were no significant intergroup differences in 6-keto-prostaglandin F1 alpha level. These findings could support the hypothesis that coronary arterial spasm and thrombus formation occur in chronic sleep deprivation.

Sudden cardiac death, ventricular arrhythmias and hypertensive left ventricular hypertrophy

To evaluate the relationship between sudden cardiac death, ventricular arrhythmias and left ventricular hypertrophy in patients with hypertension. Epidemiological studies assessing the importance of left ventricular hypertrophy as a risk factor for sudden cardiac death, studies assessing the prevalence of arrhythmias in left ventricular hypertrophy and studies assessing whether there is an electrophysiological substrate in the hypertrophied myocardium for ventricular dysrhythmias. Current evidence indicates that left ventricular hypertrophy is a risk factor for sudden cardiac death and that ventricular arrhythmias are more prevalent in hypertensive patients with than in those without left ventricular hypertrophy. However, there is a lack of evidence that these dysrhythmias are important as an underlying mechanism for sudden cardiac death, and there is no clear evidence that the hypertrophied myocardium is, itself, an arrhythmogenic substrate for malignant ventricular dysrhythmias. One possible mechanism for sudden cardiac death is myocardial ischaemia, either as a consequence of associated coronary disease or due to left ventricular hypertrophy, but this remains unproved. There is currently no evidence that the ventricular ectopic activity seen in patients with hypertensive left ventricular hypertrophy is a marker for sudden cardiac death. Clarification of the mechanisms involved in sudden cardiac death will help in selecting appropriate preventive and therapeutic strategies for these patients.

Left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: Increase in gradient after exercise

To define alterations in the magnitude of the left ventricular outflow tract gradient during supine exercise, 10 patients with hypertrophic obstructive cardiomyopathy were studied under basal conditions and during exercise and recovery with simultaneous invasive hemodynamic measurements, particularly of the peak to peak systolic pressure gradient across the left ventricular outflow tract. Basal outflow pressure gradient ranged from 0 to 89 mm Hg (average 37.4 +/- 9.6). No increase was observed during 5 min of exercise (average 29.6 +/- 10 mm Hg, range 0 to 91; p = NS), even though arterial blood pressure, heart rate and cardiac index increased significantly in association with a decrease in peripheral vascular resistance. However, a rapid and highly significant increase in left ventricular outflow gradient occurred after exercise was completed (average 83.5 +/- 11.4 mm Hg, range 10 to 130; p less than 0.001), while arterial blood pressure, heart rate and cardiac index closely approached basal levels and total peripheral vascular resistance increased. In contrast to previous assumptions regarding the behavior of the outflow gradient in hypertrophic cardiomyopathy, obstruction to left ventricular outflow increases after rather than during supine exercise. Rapid changes in preload during recovery represent the most likely explanation for the postexercise development of outflow obstruction. New considerations regarding the mechanisms of sudden cardiac death and the therapeutic approach in patients with hypertrophic cardiomyopathy may result from this pathophysiologic observation.

Sudden Cardiac Death After Myocardial Infarction

Recent advances in the understanding of the mechanisms of sudden cardiac death have been paralleled by technical advances in diagnosis and treatment, involving ambulatory Holter monitoring and the use of implantable defibrillators. Risk factors predisposing toward sudden cardiac death in the postmyocardial infarction setting and in patients with congestive heart failure include the presence of ventricular ectopy [greater than 10 premature ventricular contractions (PVC) per hour], frequent episodes of ventricular pairs and nonsustained ventricular tachycardia on 24-hour Holter monitoring, and a depressed left ventricular ejection fraction. Additional risk factors for sudden cardiac death in coronary artery disease include arterial stenosis in coronary vessels supplying intact myocardium remote from the infarction site, the presence of late potentials on the signal averaged ECG, and attenuation of the normal variation in heart rate. The ability to induce sustained ventricular tachycardia (SVT) on electrophysiological testing is highly predictive of sudden cardiac death after myocardial infarction. Conversely, the ease of suppression of the induced tachycardia with antiarrhythmic agents is correlated with the risk of subsequent lethal ventricular arrhythmia. The detrimental effect of frequent ventricular ectopy (greater than 10 PVC/h) on survival in coronary artery disease is particularly pronounced in patients with moderately well preserved left ventricular function [ejection fraction (EF) greater than 30%], thereby suggesting that these patients may be better served by antiarrhythmic therapy than those with severely depressed left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)