Relation of silent myocardial ischemia to ventricular arrhythmias and sudden death

Silent myocardial ischemia is common in the clinical spectrum of coronary disease. Ambulatory electrocardiographic monitoring has provided the most objective evidence of silent ischemia, but the phenomenon has also been detected in patients with coronary artery disease through analysis of exercise-induced ischemic ST-segment alterations, scintigraphic myocardial perfusion defects and left ventricular wall motion abnormalities. Silent myocardial ischemia frequently occurs in patients with stable angina, unstable angina, myocardial infarction and completely asymptomatic coronary artery disease. In each of these groups, silent ischemia has been associated with an increased risk of subsequent cardiac events. However, it remains unclear whether silent ischemia is directly involved in the occurrence of these events, possibly by provoking ventricular arrhythmias. Only limited data are available on the relation between silent ischemia and arrhythmias in myocardial infarction, vasospastic angina, coronary angioplasty, exercise testing and ambulatory electrocardiography. However, fortuitous ambulatory monitoring coincident with sudden death has detected ischemia associated with lethal arrhythmias in some individual cases. This suggests that an ischemia-arrhythmia association may be important in certain patients at certain times, possibly in combination with other factors.     

The Management of the Older Adult Patient with Anomalous Left Coronary Artery from the Pulmonary Artery Syndrome: A Presentation of Two Cases and Review of the Literature

ALCAPA (anomalous left coronary artery from pulmonary artery) syndrome is a rare congenital abnormality that involves an anomalous insertion of the left coronary artery into the pulmonary artery. Ninety percent of patients present in the first year of life with signs and symptoms of heart failure or sudden cardiac death secondary to chronic myocardial ischemia. There have been an increasing number of reports of ALCAPA patients surviving to adulthood. There seems, however, to be a tendency to die suddenly in the third decade of life. Adult survivors are either asymptomatic or present with mitral regurgitation, cardiomyopathy, myocardial ischemia, or malignant arrhythmias. The management of the older patient presenting with symptoms resulting from ischemia and progressive left ventricular dysfunction remains a challenge. Treatment is largely based on guidelines for adult congenital heart disease management and an extrapolation of evidence from heart failure practice. Currently, surgical reimplantation of the anomalous coronary onto the aorta is the mainstay of treatment. The management of heart failure, sudden cardiac death, and ventricular arrhythmia present problems that are not addressed by reimplantation of the anomalous vessel alone. In this report, we present two cases with different modes of presentation and discuss treatment options.     

Ventricular arrhythmias and Q-Tc interval during stress-ECG

Q-T prolongation is well-known to be related to ventricular arrhythmias in a number of clinical circumstances. The purpose of this study was to determine whether heart rate corrected Q-T interval (QTc) may indicate susceptibility to ventricular arrhythmias during stress testing. QTc was determined at rest, during submaximal and maximal bicycle work load in normals and patients with remote myocardial infarction, documented coronary artery disease (CAD) and in a group of patients with different cardiac diseases and premature ventricular beats during exercise testing (PVC). Ventricular arrhythmias were graded according to Lown. Q-Tc interval significantly increased in all groups of those patients having complex ventricular arrhythmias (Lown greater than or equal to III). In patients with ischemic S-T segment depression during stress testing, QTc was only lengthened if complex ventricular arrhythmias were present. Q-Tc lengthening in stress testing is assumed to be associated with occurrence of ventricular premature beats rather than ischemia. There is evidence that abnormal repolarization due to imbalance of the autonomic nervous system induces ventricular arrhythmias. Monitoring of Q-Tc interval during stress testing is warranted and may be useful to predict future cardiac events such as sudden cardiac death.     

Myocardial ischemia and ventricular fibrillation: pathophysiology and clinical implications

Ventricular fibrillation (VF) and myocardial ischemia are inseparable. The first clinical manifestation of myocardial ischemia or infarction may be sudden cardiac death in 20-25% of patients. The occurrence of potentially lethal arrhythmia is the end result of a cascade of pathophysiological abnormalities that result from complex interactions between coronary vascular events, myocardial injury, and changes in autonomic tone, metabolic conditions and ionic state of the myocardium. It is also related to the time from the onset of ischemia. Within the first few minutes there is abundant ventricular arrhythmogenesis usually lasting for 30 min. Triggers for ischemic VF occur at the border zone or regionally ischemic heart. The border zone of ischemia is the predominant site of fragmentation. Acute ischemia opens K(ATP) channels and causes acidosis and hypoxia of myocardial cells leading to a large dispersion in repolarization across the border zone. Abnormalities of intracellular Ca2+ handling also occur in the first few minutes of acute myocardial ischemia and may be an important cause of arrhythmias in human coronary artery disease. Substrate on the other hand transforms triggers into VF and serves to maintain it through fragmentation of waves in the ischemic zone. Thrombin levels, stretch, catecholamine, genetic predisposition, etc. are some of these factors. Reentry models described are spiral wave reentry, 3 dimensional rotors, reentry around 'M' cells and figure-of-eight reentry. Continuing efforts to better understand these arrhythmias will help identify patients of myocardial ischemia prone to arrhythmias.     

Prevention of sudden death in patients with coronary artery disease: do lipid-lowering drugs play a role?

Ventricular arrhythmias are the most common cause of sudden cardiac death in patients with coronary artery disease. Since treatment of hypercholesterolemia in patients with coronary artery disease reduces the risk of major coronary events by about 30%, one could speculate that this treatment could also result in a reduction of arrhythmic episodes in high-risk patients. In this review, the importance of myocardial ischemia as a trigger for ventricular arrhythmias, as well as the available data that suggest a possible effect of anti-ischemic treatments, including lipid-lowering drugs, on these arrhythmias are presented. Also, possible mechanisms and future research to test the hypothesis that lipid-lowering drugs can reduce life-threatening ventricular arrhythmias are discussed.     

冠心病猝死的相关因素分析

目的探讨冠心病患者心脏性猝死的发生率及其相关因素。方法回顾分析46例冠心病患者住院期间发生心脏性猝死的有关临床资料,男性32例,女性14例,年龄38-83（49．5±10．7）岁。收集患者的诱因、心电图（ECG）、超声心动图、动态心电图、X线胸片、心电监护、电解质等资料,根据患者相关项目逐项进行分析。结果46例猝死患者占同期冠心病总住院数的2．2％。多数发生猝死的冠心病患者存在一定高危因素,电解质紊乱、Lown3-5级室早、高度房室传导阻滞、束支传导阻滞、心脏扩大、左室肥厚、心功能不全、持续心肌缺血等因素均可触发致命性心律失常;猝死起始的ECG类型及其演变过程多有一定规律性。结论冠心病患者的心脏性猝死发生率为2．2％。冠心病患者发生猝死与电解质紊乱、Lown3-5级室早、高度房室传导阻滞、束支传导阻滞、心脏扩大、左室肥厚、心功能不全、持续心肌缺血等高危因素密切相关。有效控制危险因素能大大降低冠心病猝死发生率。     

Angina pectoris, myocardial infarction and sudden cardiac death with normal coronary arteries: a clinicopathologic study of 9 patients with progressive systemic sclerosis

The syndrome of angina pectoris or acute myocardial infarction without obstructive coronary artery disease has been the subject of much interest. We studied nine autopsied patients with progressive systemic sclerosis and evidence of ischemic heart disease but morphologically normal coronary arteries. Three patients had angina pectoris and three others chest pains of unknown etiology, six had ventricular arrhythmias, four had clinically suspected acute myocardial infarction, and eight had sudden cardiac death. At autopsy extensive focal myocardial necrosis was present in seven patients and myocardial scarring in all nine, but all patients had widely patent intramural and extramural coronary arteries. The finding of contraction band myocardial necrosis in seven of the eight patients who experienced sudden death suggests that the myocardial damage was a consequence of reperfusion of focally nonperfused myocardium, and thus due to a myocardial Raynaud's phenomenon. Patients with PSS may provide a model of spasm of intramyocardial vessels causing angina pectoris or myocardial infarction with morphologically normal coronary arteries.     

How to evaluate sudden cardiac death risk after myocardial infarction?

Sudden cardiac death is the mode of death of more than half of coronary heart disease patients. Preventing sudden cardiac death involves prevention of ventricular arrhythmias occurrence as well as the treatment by an implantable cardioverter defibrillator. The evaluation of sudden cardiac death risk should consider the underlying cardiopathy, the associated coronary risk factors and all pharmacological treatment efficient to reduce ventricular remodeling and myocardial ischemia. Only significant low ejection fraction and positive ventricular testing in some cases are now considered are now considered by the current French recommendations for cardioverter defibrillator implantation in primary prevention. However, other noninvasive markers such as heart rate variability and T wave alternans are of interest in sudden cardiac death risk stratification after myocardial infarction.     

Ventricular arrhythmias in patients with rest angina: correlation with ST segment changes and extent of coronary atherosclerosis

Major ventricular arrhythmias occurring concurrently with myocardial ischemia are presumed to be the most frequent mechanism for sudden cardiac death. Two hundred eighteen catheterized patients with angina pectoris at rest were reviewed to identify clinical, ECG, and arteriographic features that might correlate with the presence of serious ventricular arrhythmias occurring during episodes of rest pain. Ventricular arrhythmias during episodes of rest pain were significantly more common in patients who manifested transient ST segment elevation in the anterior leads and in patients with marked transient ST segment shifts (greater than 5 mm). Ventricular arrhythmias during episodes of rest pain were not more common in patients with extensive coronary artery disease.     

Role of coronary artery spasm in ischemic heart disease. Therapeutic implications

The term coronary artery spasm should not be used interchangeably with the specific clinical syndrome "variant angina" since it does occur in other acute and chronic ischemic heart disease syndromes. The term coronary artery spasm should not be applied to patients with ischemic heart disease unless there is clinical, angiographic, and physiologic evidence of its presence. The diagnosis of coronary artery spasm is confirmed by angiography, i.e. change in caliber of the coronary arteries plus evidence of ischemia. Probable diagnosis is in patients who have the syndrome of variant angina, i.e. rest angina associated with ST segment elevation on the electrocardiogram. One can be highly suspicious that the spasm is at work in patients who have rest angina, especially those with unstable angina. One can be suspicious of patients who have variable effort angina or walk-through angina. Coronary artery spasm is a possibility in patients with an acute myocardial infarction or acute re-infarction and is also possible that sudden death in patients with normal coronary arteries can be related to coronary artery spasm. Coronary artery spasm is the usual cause of myocardial ischemia in patients with rest angina without effort angina. This has also commonly been documented in patients with rest and effort angina. There are isolated reports suggesting that patients with effort angina pectoris also develop coronary artery spasm. Coronary artery spasm has been documented to occur in association with acute myocardial infarction. Whether coronary artery spasm is the cause or the result of myocardial infarction has not been determined at this time. However, the recent combined use of intracoronary nitroglycerin and intracoronary streptokinase in patients with acute myocardial infarction has shown reversal of totally obstructed arteries and suggests the relationship between coronary artery disease, coronary artery spasm, and in situ coronary thrombosis. The incidence of sudden death in patients with documented coronary artery spasm is unknown. But, since complete heart block and/or ventricular tachycardia occur during episodes of coronary artery spasm, it is not unreasonable to assume that some patients have died as a result of these rhythm disturbances. The prognosis of patients with coronary artery spasm seems to depend on the presence or absence of severe coronary atherosclerosis, i.e. those with severe disease have a worse prognosis. Current therapy of patients with coronary artery spasm involves the use of nitrates and calcium antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)     

Sudden death during ambulatory Holter monitoring

Four cases of sudden cardiac death during ambulatory Holter monitoring are described. All had coronary arterial disease. Two patients were on antiarrhythmic drug therapy and both had a prolonged QTc-interval on their resting electrocardiogram. The predominant rhythm was sinus rhythm in all. In one patient, severe bradycardia terminated in asystole. In the remaining 3 patients, ventricular flutter (which was initiated in 2 instances by a short run of polymorphous ventricular tachycardia) degenerated into ventricular fibrillation. The lethal event was triggered once by an early cycle ventricular premature beat and twice by late cycle ventricular premature beats. There was no specific pattern of warning arrhythmias preceding sudden cardiac death. Signs of ischemia/sympathetic overactivity preceding sudden cardiac death were found in 3 patients. Autopsy studies were performed in 2 patients and revealed acute ischemic myocardial damage.     

Coronary artery bypass grafting in the management of ventricular arrhythmias in patients with coronary artery disease

This review analyzes the role of coronary artery bypass grafting in ventricular arrhythmia associated with exertion, problematic sustained ventricular tachycardia, and sudden cardiac death associated with documented ventricular arrhythmia, or first manifestation of coronary artery disease. Specifically discussed is the role of acute ischemia in initiating and perpetuating ventricular arrhythmia. Coronary artery bypass grafting is indicated as a curative intervention for ventricular arrhythmia, but in only one rare instance: exercise-induced ischemia associated with problematic sustained ventricular arrhythmia, when the tachycardia is documented as being induced by acute ischemia. In other instances, indications for coronary artery bypass grafting follow the current guidelines based on clinical trials. Patients with the most severely damaged coronary artery anatomy associated with impaired left ventricular dysfunction have their life expectancy significantly prolonged after coronary artery bypass grafting. These results have been presented as evidence that coronary artery bypass grafting prevents ventricular arrhythmia and sudden cardiac death by modifying the two most powerful predicting factors of sudden cardiac death: coronary artery anatomy and left ventricular function.     

Silent myocardial ischemia in men with systemic hypertension and without clinical evidence of coronary artery disease.

The prevalence, characteristics and circadian pattern of silent myocardial ischemia, and its association with ventricular arrhythmias was studied in hypertensive men aged 35 to 70 years (mean 61) without clinical cardiac disease. Participants were withdrawn from diuretic treatment and received 1 month of oral electrolyte repletion with 40 mmol of potassium chloride, and 400 mg of magnesium oxide daily. Twenty-four-hour Holter monitoring was then performed. Episodes of silent myocardial ischemia occurred in 50 of 186 men (27%) and lasted from 2 to 289 minutes (mean 30 and median 18). Statistical analysis comparing the interval from midnight to 6 A.M. with each of the other three 6-hour time intervals revealed that participants were less likely to have silent myocardial ischemia in this period (p less than 0.01 for each comparison) than at other times of the day. There was little difference in the proportion of men with a frequent or complex ventricular arrhythmia during the entire day or within 1 hour of the silent myocardial ischemic episode (or during a comparable time period) comparing those with to those without silent myocardial ischemia. These findings indicate that silent myocardial ischemia occurs in approximately 25% of an older population of hypertensive men without history of symptomatic cardiac disease. The circadian pattern of frequency of silent ischemic events in men free of clinical cardiac disease is similar to that reported for patients with cardiac disease and coincides with that reported for sudden death. There was no significant association between silent myocardial ischemia and ventricular arrhythmias.     

Myocardial perfusion scintigraphy in patients with mitral valve prolapse: Its advantage over stress electrocardiography in diagnosing associated coronary artery disease and its implications for the etiology of chest pain

Patients with mitral valve prolapse (MVP) frequently experience chest pain which may, expecially in older subjects and males, be difficult to differentiate from angina pectoris. Electrocardiographic (ECG) changes, ventricular arrhythmias, metabolic abnormalities and rare reports of myocardial infarction and sudden death further suggest the presence of an ischemic process in these patients. The recognition of accompanying coronary artery disease (CAD) and exclusion of other causes of ischemia, therefore, may be important in determining the prognosis and appropriate therapy for such patients.     

Koronare Herzkrankheit – Bedeutung der Ischämiebeseitigung für das Arrhythmieverhalten

Myocardial ischemia induces redistribution of different ions (H(+), K(+), Na(+), Ca(++)) across the cardiomyocyte membrane, as well as the loss of intracellular ATP content. This results in changes in the electrical properties including shortening of the action potential, appearance of delayed afterpotentials, and a modified refractoriness of the cardiomyocyte. These changes may induce or support malignant cardiac arrhythmias. Supersensitivity of sympathetic denervated myocardium may further support the electrical instability of ischemic myocardium.Virtues of studies indicate that patients with coronary artery disease who develop complex arrhythmias during or after exercise bear a substantially increased risk for sudden cardiac death. Other studies report about arrhythmic stabilization and reduced mortality if patients with reversible myocardial ischemia receive complete revascularization. However, none of these studies is without methodological flaws. Due to the lack of methodologically sound studies in sufficiently large patient cohorts, the question whether complete coronary revascularisation improves the prognosis of patients with coronary artery disease and which strategy (medical, interventional, or surgical) warrants the best outcomes remains open.     

Ventricular tachyarrhythmias,myocardial ischemia,and sudden cardiac death in patients with hypertensive heart disease

Hypertensive heart disease is increasingly considered to be a strong and independent risk factor for sudden cardiac death. Ventricular tachyarrhythmias in these patients are common and mainly the result of electrophysiologic abnormalities and increased electrical vulnerability of the hypertrophic myocardium. However, proarrhythmia in the hypertrophic heart often is facilitated and aggravated by electrolyte disturbances, the sympathoadrenergic tone, transient blood pressure crisis, and especially by the occurrence of myocardial ischemia. Myocardial ischemia in the setting of hypertensive heart disease may result from stenotic lesions in large and/or small coronary artery vessels and, in the absence of both, will result from the altered cellular oxygen supply and consumption in the hypertrophic myocardium. Recent studies have shown that acute and transient myocardial ischemia are common in many hypertensives, often fail to be symptomatic, and that the dynamic interaction of left ventricular hypertrophy, transient myocardial ischemia, and ventricular tachyarrhythmias may provide a crucial link for the high incidence of sudden cardiac death in patients with hypertensive heart disease.     

Ventricular arrhythmias in ischemic heart disease

Ventricular arrhythmias remain the leading cause of death from coronary artery disease. This review summarizes current thinking in several areas relating to the pathophysiology, prognosis, and therapy of ventricular arrhythmias associated with acute and chronic coronary artery disease syndromes. The experimental basis of arrhythmias in the setting of acute myocardial ischemia and chronic myocardial infarction is described, stressing the important pathophysiologic differences between these two conditions. The effects of the autonomic nervous system as a key modulator of ischemic arrhythmogenesis are discussed. Insights, derived from endocardial mapping studies, into the nature of ventricular tachycardia in humans with chronic myocardial infarction are described, including implications for risk stratification and therapy to prevent arrhythmia recurrence. Current therapeutic principles are discussed in the management of ventricular arrhythmias associated with coronary artery disease, including pharmacologic approaches, surgical and catheter ablation, and automatic implantable cardioverting and defibrillating devices.     

Hypertension,left ventricular hypertrophy,and sudden death

Left ventricular hypertrophy (LVH), a form of end-organ damage in hypertension, is associated with increased incidence of sudden cardiac death (SCD). This review explores the possible mechanisms behind this phenomenon. SCD in LVH could be thrombotic/ischemic or arrhythmic (eg, myocardial ischemia, even in the absence of significant coronary artery disease, may be one important factor). Abnormalities of flow-mediated dilatation, endothelial function, and a hypercoagulable state are well-observed abnormalities in association with hypertension and LVH, although their precise contributory role is as yet undefined in the pathogenesis of sudden death. Electrophysiologic abnormalities are also well documented in LVH, and such patients are more predisposed to arrhythmias. In the past decade, many studies have investigated the regression of LVH, and recent studies are addressing whether the latter translates into a prognostic benefit.     

Timing and triggers of transient myocardial ischemia

Use of exercise tolerance testing and new techniques of ambulatory electrocardiographic monitoring to more objectively measure myocardial ischemia have enabled clinicians to better recognize the magnitude, timing and variable characteristics of transient ischemic events. These commonly occurring events in patients with coronary artery disease have a diurnal pattern strikingly similar to that reported for catastrophic cardiovascular events such as myocardial infarction, sudden cardiac death and stroke. Whether those factors that contribute to reversible ischemic events are similar to those causing infarction and sudden death has not been resolved. However, the parallel increase in morning activity for these related phenomena suggests that a better understanding of the triggers of reversible myocardial ischemia may help improve understanding of the causes of myocardial infarction and sudden cardiac death.     

Ventricular Fibrillation and Polymorphic Ventricular Tachycardia with Critical Coronary Artery Stenosis:

ICD Therapy and CABG for Sudden Death. Introduction: Previous studies have suggested that coronary artery bypass surgery is sufficient to prevent recurrence of sudden death in patients with critical coronary artery stenosis presenting with ventricular fibrillation or polymorphic ventricular tachycardia. We present our experience in patients with one or more episodes of sudden death associated with documented ventricular fibrillation or polymorphic ventricular tachycardia and severe operable coronary artery disease who underwent defibrillator implant at the time of bypass surgery. Methods and Results: Fifty-eight consecutive patients (age 63 ± 8 years) were included in this study. Eighteen of the 58 patients had no evidence of previous myocardial infarction. The mean ejection fraction was 37 ± 13%. All patients underwent electrophysiologic study before and after revascularization. At the time of first defibrillator discharge, each patient was reevaluated to exclude the presence of ischemia. The benefits of defibrillator implant were estimated comparing the projected survival based upon defibrillator discharge preceded by syncope or presyncope with survival curves generated including total death and sudden plus cardiac death. After a mean follow-up of 4.6 ± 2 years, 22 patients received appropriate shocks preceded by syncope or presyncope, and an additional 19 patients received asymptomatic shocks. At 4 years, survival free of total death was 71.2%, and the projected survival was 58.8% (P < 0.05). Multivariate analysis showed that ejection fraction lower than 30% and induction of arrhythmia with one or two extrastimuii (S2, S3) were independent predictors for defibrillator discharge. None of the remaining variables including age, gender, number of bypasses, history of myocardial infarction, and type of arrhythmias induced were predictive for death and occurrence of shocks. Conclusions: In patients with ventricular fibrillation and polymorphic ventricular tachycardia, bypass surgery does not protect from recurrence of life-threatening arrhythmias, and, as in our population, defibrillator implant may have significant impact on survival.