QT Interval Dispersion and Cardiac Sympathovagal Balance Shift in Rats With Acute Ethanol Withdrawal

Background: Dysregulation of autonomic nervous system function and impaired homogeneity of myocardial repolarization are 2 important mechanisms for the genesis of ventricular arrhythmias in nonalcoholic subjects. Our previous study suggested that acute ethanol withdrawal promoted the shift of cardiac sympathovagal balance toward sympathetic predominance and reduced the vagal tone, which were related to a higher incidence of ventricular arrhythmia and related death. However, the homogeneity of myocardial repolarization and its relation with the cardiac sympathovagal balance are unknown, especially in alcoholic subjects. The aim of the present study was to clarify these points. Methods: Male Wistar rats were treated with a continuous ethanol liquid diet for 49 days, and then subjected to 1‐day withdrawal and 1‐day withdrawal with 7‐day carvedilol (can block the sympathetic nervous system completely via β1, β2, and α adrenergic receptors) pretreatment. The cardiac sympathovagal balance and homogeneity of myocardial repolarization were evaluated based on the heart rate variability (HRV) and QT interval dispersion (QTd: dynamic changes in QT interval duration). Results: The increase in QTd was observed only in rats at 1‐day withdrawal, but not in nonalcoholic, continuous ethanol intake, and 1‐day withdrawal with 7‐day carvedilol pretreatment rats. At 1‐day withdrawal, the low‐frequency power/high‐frequency power (LF/HF) ratio in HRV was elevated and correlated with the QTd. The increased QTd and elevated LF/HF ratio were normalized by the 7‐day carvedilol pretreatment in rats at 1‐day ethanol withdrawal. Conclusions: In rats with an abrupt termination of the chronic continuous ethanol intake, the homogeneity of myocardial repolarization impaired and correlated with the cardiac sympathovagal balance. Carvedilol pretreatment is associated with a reduction in both the QTd and LF/HF ratio, raising the possibility that the cardiac sympathovagal balance shift may be responsible for the impaired homogeneity of myocardial repolarization, and that β‐blocker pretreatment may decrease the mortality risk during alcoholic withdrawal.     

Reduced intercellular coupling leads to paradoxical propagation across the Purkinje-ventricular junction and aberrant myocardial activation

Ventricular tachycardia is a common heart rhythm disorder and a frequent cause of sudden cardiac death. Aberrant cell-cell coupling through gap junction channels, a process termed gap junction remodeling, is observed in many of the major forms of human heart disease and is associated with increased arrhythmic risk in both humans and in animal models. Genetically engineered mice with cardiac-restricted knockout of Connexin43, the major cardiac gap junctional protein, uniformly develop sudden cardiac death, although a detailed electrophysiological understanding of their profound arrhythmic propensity is unclear. Using voltage-sensitive dyes and high resolution optical mapping techniques, we found that uncoupling of the ventricular myocardium results in ectopic sites of ventricular activation. Our data indicate that this behavior reflects alterations in source-sink relationships and paradoxical conduction across normally quiescent Purkinje-ventricular muscle junctions. The aberrant activation profiles are associated with wavefront collisions, which in the setting of slow conduction may account for the highly arrhythmogenic behavior of Connexin43-deficient hearts. Thus, the extent of gap junction remodeling in diseased myocardium is a critical determinant of cardiac excitation patterns and arrhythmia susceptibility.     

Alcohol and rhythm disorders

Cardiovascular disease is the main cause of mortality in chronic alcoholics. There is a clear association between excessive alcohol consumption and the risk of sudden cardiac death. The pro-arrhythmogenic effect of ethanol could be responsible for some of these cases of arrhythmia and sudden death in subjects with an alcoholic cardiomyopathy and also in those with an apparently normal heart. In any case of supraventricular or ventricular arrhythmia in a chronic alcoholic or in an occasional heavy drinker, the potential role of alcohol consumption in the initiation of these disorders should be considered. In all cases, patient management consists of detoxification and abstaining from alcohol consumption, but the withdrawal period is particularly critical as regards the risk of ventricular arrhythmias.     

Arrhythmias in Cardiac Amyloidosis: Challenges in Risk Stratification and Treatment

Cardiac amyloidosis occurs secondarily to the deposition of insoluble protein fibrils in cardiac tissue leading to progressive myocardial dysfunction, clinical heart failure, and arrhythmia. In recent years, increasing awareness and improved screening have resulted in an increased prevalence of cardiac amyloidosis, with contemporary estimates reporting a prevalence of 18-55 cases per 100,000 person-years, accounting for > 13% of heart failure hospitalizations. The arrhythmic manifestations of cardiac amyloidosis can range from conduction-system disease and bradyarrhythmias to atrial fibrillation and sudden cardiac death. Bradyarrhythmias and conduction system disease may occur secondarily to amyloid infiltration, but the timing of pacemaker implantation remains unclear. When available, biventricular pacing should be considered in symptomatic patients, particularly in those expected to receive a high burden of ventricular pacing (> 40%). The management of atrial fibrillation can be challenging, because contemporary agents for rate and rhythm control may be poorly tolerated in patients with cardiac amyloidosis. Patients with cardiac amyloidosis also have a high rate of intracardiac thrombus and should be anticoagulated in the presence of atrial fibrillation (regardless of CHADS₂ score). We generally consider transesophageal echocardiography before cardioversion regardless of anticoagulation status or duration of arrhythmia. Ventricular arrhythmias may also occur in patients with cardiac amyloidosis, and decisions surrounding implantable cardioverter-defibrillator implantation should balance the risks of ventricular arrhythmia and sudden cardiac death with the competing risks of worsening heart failure and noncardiac death. In this review, we cover the primary arrhythmic manifestations of cardiac amyloidosis and discuss their management considerations.     

Circadian variation in ventricular electrical instability associated with coronary artery disease

Although sudden cardiac deaths and ischemic cardiac events clearly occur in a circadian pattern, such a pattern has not been shown for primary arrhythmic events. Because primary arrhythmic events are thought to play an important role in sudden cardiac death, a large series of ventricular stimulation studies was analyzed to determine whether circadian variation in ventricular electrical instability exists. If such a circadian variation could be shown, it could have implications for the conduct and interpretation of electrophysiologic testing and the etiology of circadian variation in sudden cardiac death. Results of 2 drug-free ventricular stimulation studies performed 4 to 28 hours apart in each of 162 patients with coronary artery disease were analyzed. Rate and duration of induced arrhythmia, number of extrastimuli required to induce arrhythmia and changes in these factors between the 2 tests in each patient were analyzed. Comparisons were made by half-day, by hour and in a temporally continuous manner to eliminate errors associated with any single method. No significant circadian variation was found in any electrophysiologic measure of ventricular electrical instability despite adequate statistical power. These findings show that the time of day during which ventricular stimulation tests are performed does not affect test results, and therefore does not need to be controlled during electrophysiologic studies. If these findings are parallel to those in ambulatory patients with coronary artery disease, then circadian changes in ventricular electrical instability may not play as important a role in the circadian pattern of sudden cardiac death as had been previously thought.     

The value of the clinical history to assess prognosis of patients with ventricular tachycardia or ventricular fibrillation after myocardial infarction

Multivariate analysis using 70 variables in 200 patients who suffered from ventricular tachycardia or ventricular fibrillation after myocardial infarction detected eleven variables that were associated with an increased risk of sudden arrhythmic death and cardiac death during a mean follow-up period of 2 years. Four of the 11 variables came from the patient's clinical history: (1) cardiac arrest at the time of the first spontaneous episode of arrhythmia, (2) New York Heart Association functional class for dyspnoea = III, (3) ventricular tachycardia or ventricular fibrillation occurring early (after 3 days and within 2 months) after myocardial infarction, (4) multiple myocardial infarctions before the first episode of ventricular tachyarrhythmia. Total mortality, incidence of sudden arrhythmic death and of non-sudden cardiac death increased with an increasing number (zero, one, two, three, four) of variables seen in individual patients. Patients with zero or one variable had an incidence of sudden death of 2.8% and a 4.2% incidence of non-sudden cardiac death at 26 months, while patients with more than two variables had a 13.5% and a 20.3% incidence respectively of sudden and non-sudden cardiac death. The strongest predictor of sudden death was the occurrence of cardiac arrest during the first spontaneous episode of ventricular arrhythmia. The strongest predictor of non-sudden cardiac death was the New York Heart Association functional class. The use of the four variables to stratify risk revealed seven subgroups of patients with incidences of sudden death ranging from 0 to 28%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Risk of ventricular arrhythmia in patients with myocardial infarction and non-obstructive coronary arteries and normal ejection fraction

AIM To assess the arrhythmic determinants and prognosis of patients presenting with myocardial infarction and nonobstructive coronary arteries(MINOCA)with normal ejection fraction(EF).METHODS This is an observational analysis of 131 MINOCA patients with normal EF.Three cardiac magnetic resonance(CMR)diagnosis classes were recognized according to the late gadolinium enhancement(LGE)pattern:Myocardial infarction(MI)(n=34),myocarditis(n=47),and"no LGE"(n=50).Ventricular events occurring during hospitalization were recorded and the entire population was followed-up at 1 year.RESULTS Ventricular arrhythmia was observed in 18(13.8%)patients during hospitalization.The"no LGE"patients experienced fewer ventricular events than the MI and myocarditis patients[4.0%vs 26.5%and 14.9%,respectively(P=0.013)].There was no significant difference between the MI and myocarditis groups.On multivariate analysis,LGE transmural extent[OR=1.52(1.08-2.15),P=0.017]and ST-segment elevation[OR=4.65(1.61-13.40),P=0.004]were independent predictors of ventricular arrhythmic events,irrespective of the diagnosis class.Finally,no patient experienced sudden cardiac death or ventricular arrhythmia recurrence at 1-year.CONCLUSION MINOCA patients with normal EF presented no 1-year cardiovascular events,irrespective of the CMR diagnosis class.LGE transmural extent and ST segment elevation at admission are risk markers of ventricular arrhythmia during hospitalization.     

Detection of patients at risk for sudden heart death by long-term ECG. The role of life-threatening ventricular arrhythmias

Recognition of patients at risk of sudden cardiac death and prevention of such lethal events represent important and, for the most part, unresolved problems in clinical cardiology. From pathologic-anatomical and clinical studies of instances of sudden death it is known that in more than 80% the lethal electrical events, that is ventricular fibrillation, are attributable to myocardial ischemia, usually due to coronary artery disease. Experience in experimental studies as well as in treatment of patients with myocardial infarction on coronary care units has shown that certain types of arrhythmias such as frequent, multiform, repetitive and early-occurring (R-on-T) ventricular premature beats, in particular, may be associated with sudden arrhythmic cardiac death. Accordingly, in 1971, Lown and Wolf proposed a system for grading of ventricular arrhythmias and their severity which assumed world-wide importance for clinical and prognostic studies. This system of classification contains quantitative and qualitative criteria and is ordered in part on exclusion and in part on hierarchy, in which it is implied that the hierarchy of ventricular premature beats corresponds with that of the risk of death. Since the system enables only semiquantitative delineation of ventricular arrhythmias whose absolute number, however, within a given observation period appears to be of prognostic relevance and, additionally, since the Lown system is encumbered by the fact that classification is based only on the most severe arrhythmia with subsequent loss of information regarding concurrent arrhythmias of lesser severity, Bigger and his associates, in 1978, suggested a modification to provide quantification of all ventricular premature beats. In addition to the problems inherent to grading ventricular premature beats, further problems are also incurred with respect to spontaneous variability of ventricular arrhythmias. Based on statistical considerations and clinical studies accordingly, adequate assessment of complex ventricular arrhythmias prerequisites continuous monitoring for a period of 24 to 48 hours. Furthermore, for the exact recognition and quantitative detection of ventricular arrhythmias, the reliability of the individual systems for continuous ECG monitoring plays an important role since, by no means, have they all been validated in arrhythmia-detection capabilities. Since 1971, a number of clinical studies have shown, in particular, that complex ventricular arrhythmias are of important prognostic relevance in characterization of patients at risk of sudden cardiac death. The results may be summarized as follows: Ventricular premature beats can be found frequently in     

Usefulness of programmed ventricular stimulation in predicting future arrhythmic events in patients with cardiac sarcoidosis

The utility of programmed ventricular stimulation to predict future arrhythmic events in patients with cardiac sarcoidosis is unknown. Similarly, the long-term benefit of implantable cardioverter-defibrillators (ICDs) in cardiac sarcoidosis has not been established. Thirty-two consecutive patients with cardiac sarcoidosis underwent programmed ventricular stimulation. Patients with spontaneous or inducible sustained ventricular arrhythmias (n = 12) underwent ICD insertion. All study patients were followed for the combined arrhythmic event end point of appropriate ICD therapies or sudden death. Mean length of follow-up to sustained ventricular arrhythmia or sudden death was 32 +/- 30 months. Five of 6 patients (83%) with spontaneous sustained ventricular arrhythmias and 4 of 6 patients (67%) without spontaneous but with inducible sustained ventricular arrhythmias received appropriate ICD therapy. Two of 20 patients (10%) with neither spontaneous nor inducible sustained ventricular arrhythmias experienced sustained ventricular arrhythmias or sudden death. Programmed ventricular stimulation predicted subsequent arrhythmic events in the entire population (relative hazard 4.47, 95% confidence interval [CI] 1.30 to 15.39) and in patients who presented without spontaneous sustained ventricular arrhythmias (relative hazard 6.97, 95% CI 1.27 to 38.27). No patient with an ICD died of a primary arrhythmic event. In patients with spontaneous or inducible sustained ventricular arrhythmias, mean survival from first appropriate ICD therapy to death or cardiac transplant was 60 +/- 46 months, with only 2 patients dying or reaching transplant at study end. In conclusion, programmed ventricular stimulation identifies patients with cardiac sarcoidosis at high risk for future arrhythmic events. ICDs effectively terminate life-threatening arrhythmias in high-risk patients, with significant survival after first appropriate therapy.     

Arrhythmic sudden death in children

Sudden death (SD) in childhood is rare, representing only 10% of paediatric mortality after one year of age. The individual risk is estimated between 1 in 20.000 and 1 in 50.000 per year. In case of a negative autopsy for cardiac morphologic anomalies, the most presumable cause remains a genetically-determined malignant primary ventricular arrhythmia. Rhythmic sudden cardiac death can be categorized as a complication of a cardiomyopathy (dilated or hypertrophic), or as a primary channelopathy without any structural heart disease. Primary ventricular arrhythmias include long QT syndrome, Brugada syndrome, short QT syndrome and Polymorphic Ventricular Tachycardia. The diagnosis of such syndromes relies upon specific ECG anomalies, personal history of family members, eventually echocardiography and drug challenge. For some of these diseases, morbid genes have been identified thus rendering possible the management of pre symptomatic or undiagnosed family members within specialized multidisciplinary teams. In case of sudden arrhythmic death in children, the parents and siblings must be examined Rescued sudden death exposes to a high risk of recurrence. In such patients, the automatic implantable defibrillator has dramatically improved survival.     

Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia

Sarcomere protein gene mutations cause hypertrophic cardiomyopathy (HCM), a disease with distinctive histopathology and increased susceptibility to cardiac arrhythmias and risk for sudden death. Myocyte disarray (disorganized cell-cell contact) and cardiac fibrosis, the prototypic but protean features of HCM histopathology, are presumed triggers for ventricular arrhythmias that precipitate sudden death events. To assess relationships between arrhythmias and HCM pathology without confounding human variables, such as genetic heterogeneity of disease-causing mutations, background genotypes, and lifestyles, we studied cardiac electrophysiology, hypertrophy, and histopathology in mice engineered to carry an HCM mutation. Both genetically outbred and inbred HCM mice had variable susceptibility to arrhythmias, differences in ventricular hypertrophy, and variable amounts and distribution of histopathology. Among inbred HCM mice, neither the extent nor location of myocyte disarray or cardiac fibrosis correlated with ex vivo signal conduction properties or in vivo electrophysiologically stimulated arrhythmias. In contrast, the amount of ventricular hypertrophy was significantly associated with increased arrhythmia susceptibility. These data demonstrate that distinct somatic events contribute to variable HCM pathology and that cardiac hypertrophy, more than fibrosis or disarray, correlates with arrhythmic risk. We suggest that a shared pathway triggered by sarcomere gene mutations links cardiac hypertrophy and arrhythmias in HCM.     

Bedside programmed ventricular stimulation for sudden death risk stratification

BACKGROUND: Patients with myocardial infarction and left ventricular dysfunction are at risk for sudden death. This research was conducted to determine the applicability and safety of a bedside programmed stimulation protocol to determine the risk for sudden death in these patients. METHODS: Four hundred and twelve patients with acute myocardial infarction were studied. Left ventricular ejection fraction was evaluated by means of an echocardiogram. Ventricular arrhythmia, late potentials and heart rate variability were determined by means of Holter recordings. Fifty patients (60 +/- 14-year-old; 85% male) presented a left ventricular ejection fraction lower than 0.40 (0.36 +/- 0.10) associated with late potentials, low heart rate variability or ventricular arrhythmia greater than Lown I. After a central venous access was placed under fluoroscopy guidance and ECG monitoring, a quadripolar catheter was advanced to the right ventricular apex to perform programmed ventricular stimulation with up to three extrastimuli. The patients were followed-up to determine in-hospital morbidity and/or mortality. RESULTS: No patient suffered complications. Ventricular tachycardia or ventricular fibrillation was induced in six patients. All of them received amiodarone and in five an automatic cardioverter-defibrillator was implanted. After a 22 +/- 6 month follow-up, five patients had received appropriate discharges from the implanted device and none had suffered from arrhythmic sudden death. CONCLUSION: Bedside programmed stimulation is a safe and useful means for sudden death risk stratification in post myocardial infarction patients. It moreover presents the advantage of being cheaper than conventionally used procedures.     

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.     

右室相关心律失常的临床和基础

冠心病或心肌病所致左室结构和电重构是室性心律失常和心源性猝死发生的主要原因.近20年来,右室相关心律失常已受到工作者重视,其好发于青壮年患者,易导致心源性猝死,基础研究尤其是分子遗传学的发展推动了人们对右室相关心律失常发病机制、诊断和预后的认识和理解.右室相关心律失常多见于致心律失常型右室心肌病、Brugada综合征、...     

Sudden arrhythmic cardiac death--mechanisms, resuscitation and classification: the Seattle perspective

Ventricular fibrillation (VF) is the first recorded arrhythmia in 75% of patients who have a sudden cardiovascular collapse. Rarely (1%) does sustained ventricular tachycardia (VT) alone cause collapse and unconsciousness. Whether all VF begins as VT is unknown. Early application of cardiopulmonary resuscitation and rapid defibrillation are essential to ensure survival and satisfactory neurologic recovery. During the last 2 years in Seattle, the initial resuscitation rate for VF was 269 of 447 patients (60%), with 114 of 447 patients (26%) surviving long-term. Survivors of VF have a high overall risk of recurrent VF, with many univariate risk factors identified: evidence of poor left ventricular function (history of congestive heart failure, prior myocardial infarction [MI] or low ejection fraction), extensive coronary artery disease, absence of a new MI (either Q wave or non-Q wave) with VF, male gender, advanced age, complex or high-frequency ventricular ectopy on Holter recording, inducibility at electrophysiologic study, exercise-induced angina or hypotension, and smoking. Classification of cardiac deaths as arrhythmic or nonarrhythmic is important in interpreting the therapeutic response. However, because many patients have chronic symptoms, timing of the onset of a new event is difficult. Furthermore, accurate timing of an event does not guarantee correct classification. Sudden death is not necessarily arrhythmic, nor is all arrhythmic death sudden. Total cardiac mortality may be a simpler and more relevant end point to measure the overall effect of antiarrhythmic therapy.     

Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress

Arrhythmias following cardiac stress are a key predictor of death in healthy population. Carbon monoxide (CO) is a ubiquitous pollutant promoting oxidative stress and associated with hospitalization for cardiovascular disease and cardiac mortality. We investigated the effect of chronic CO exposure on the occurrence of arrhythmic events after a cardiac stress test and the possible involvement of related oxidative stress. Wistar rats exposed chronically (4?weeks) to sustained urban CO pollution presented more arrhythmic events than controls during recovery after cardiac challenge with isoprenaline in vivo. Sudden death occurred in 22% of CO-exposed rats versus 0% for controls. Malondialdehyde (MDA), an end-product of lipid peroxidation, was increased in left ventricular tissue of CO-exposed rats. Cardiomyocytes isolated from CO-exposed rats showed higher reactive oxygen species (ROS) production (measured with MitoSox Red dye), higher diastolic Ca(2+) resulting from SR calcium leak and an higher occurrence of irregular Ca(2+) transients (measured with Indo-1) in comparison to control cells after a high pacing sequence. Acute treatment with a ROS scavenger (N-acetylcysteine, 20?mmol/L, 1?h) prevented this sequence of alterations and decreased the number of arrhythmic cells following high pacing. Chronic CO exposure promotes oxidative stress that alters Ca(2+) homeostasis (through RYR2 and SERCA defects) and thereby mediates the triggering of ventricular arrhythmia after cardiac stress that can lead to sudden death.     

Therapeutic approach for patients with catecholaminergic polymorphic ventricular tachycardia: state of the art and future developments

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by bidirectional or polymorphic ventricular arrhythmias under conditions of increased sympathetic activity in young patients with structurally normal hearts. Patients with CPVT are at high risk of developing life-threatening ventricular arrhythmias when untreated. A wide variety of arrhythmic event rates on conventional therapy, with β-blockers as the cornerstone, has been reported. Here, we systematically review all available studies describing the efficacy of β-blocker therapy for prevention of arrhythmic events in CPVT. Because of heterogeneity between the studies, a random-effects meta-analysis model was used to assess the efficacy of β-blocker therapy in preventing any arrhythmic event [syncope, aborted cardiac arrest (ACA), and sudden cardiac death (SCD)], near-fatal arrhythmic events (ACA and SCD), and fatal arrhythmic events. Eleven studies including 403 patients, of whom 354 (88%) had a β-blocker prescribed, were identified. Mean follow-up ranged from 20 months to 8 years. Estimated 8-year arrhythmic, near-fatal, and fatal event rates were 37.2% [95% confidence interval (CI): 16.6-57.7], 15.3% (95% CI: 7.4-23.3), and 6.4% (95% CI: 3.2-9.6), respectively. In addition, we review the recent developments in alternate chronic treatment options for CPVT patients, including calcium channel blockers, flecainide, left cardiac sympathetic denervation, and implantable cardioverter defibrillators. A new treatment strategy is proposed, including a stepwise addition of the alternate treatment options to β-blockers in patients who do not respond sufficiently to this first-line therapy. Finally, future developments in chronic treatment options and acute treatment options of ventricular arrhythmias are discussed.     

Arrhythmia in chronic respiratory insufficiency

Ventricular arrhythmias are frequent in chronic pulmonary disease. Hypoxemia, right ventricular enlargement, associated left ventricular dysfunction and iatrogenic factors are potential determinants of the density and complexity of these arrhythmias. Its prognostic meaning in chronic pulmonary disease and its relationship with the elevated prevalence of sudden cardiac death in these patients, are not well known. Meanwhile, the therapeutic anti-arrhythmic strategy is dominated by the correction of the etiologic factors, namely continuous oxygen therapy which decreases ventricular arrhythmia and prolongs survival. Holter 24 hours monitoring is a useful diagnostic tool in management of these patients.     

Prediction of life-threatening arrhythmias--still an unresolved problem

A major challenge in current cardiology is to predict who will die suddenly from ventricular arrhythmias. Ventricular arrhythmias are the most common cause of sudden cardiac death, occurring in about 1-2:1,000 inhabitants yearly, and is most frequently due to coronary artery disease. Patients with increased risk of ventricular arrhythmias can be offered medical treatment and ultimately an implantable cardioverter defibrillator (ICD). Left ventricular ejection fraction (EF) is currently the main risk stratification tool used to select patients for ICD therapy. However, EF is insufficient in predicting arrhythmic risk. A number of techniques have been presented to improve arrhythmic risk stratification without having reached clinical utility. Conduction abnormalities and dispersion of action potential duration forms the substrate for malignant ventricular arrhythmias in infarcted tissue as in several cardiomyopathies. The ability to assess electrical dispersion in patients noninvasively has been limited. Myocardial strain by echocardiography has been presented as an accurate tool for assessing myocardial function and timing. Inhomogeneous and dispersed myocardial contraction has been related to the occurrence of ventricular arrhythmias and seems to be a promising tool in risk stratification. This review focuses on arrhythmia mechanisms and novel echocardiographic tools for assessing risk of ventricular arrhythmias.     

Programmed electrical stimulation to determine the need for antiarrhythmic therapy in patients with complex ventricular ectopic activity

Patients with complex ventricular ectopy (greater than or equal to Lown grade III) and organic heart disease (OHD) are at increased risk for sudden cardiac death. Despite this fact, many such patients will remain free of symptomatic ventricular arrhythmia and thus are unnecessarily exposed to antiarrhythmic drug toxicity and arrhythmic potentiation. Programmed stimulation (PS) was used to direct therapy in 88 patients with asymptomatic ventricular ectopy complicating OHD. Thirty-three had inducible ventricular tachycardia (VT) and underwent treatment. The 55 patients without inducible VT (less than or equal to 6 repetitive ventricular responses) are the focus of this study. Three patients required treatment for persistent cardiac awareness. The remaining 52 have been followed for 22 months off antiarrhythmic drugs and all have remained free of subsequent major arrhythmic events. Therefore, in patients with complex ventricular ectopy, OHD, and absence of prior symptomatic ventricular arrhythmia, PS identifies patients at low risk for future disabling or life-threatening arrhythmic episodes and patients with absence of inducible VT can usually be managed without antiarrhythmic drugs.