Development Of Malignant Ventricular Arrhythmias Research Articles

Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphism in coronary disease and malignant ventricular arrhythmias.

It has been reported that patients carrying the angiotensin-converting enzyme (ACE) deletion DD genotype with the angiotensin II type 1 (AT1) C allele are at increased risk for myocardial infarction. The frequency distribution of the ACE and AT1 receptor gene polymorphism and their possible relation regarding malignant ventricular arrhythmias in patients with coronary artery disease (CAD) and left ventricular dysfunction was determined. The ACE I/D and AT1 A/C polymorphisms (using polymerase chain reaction) in 100 Caucasian patients suffering from CAD with a history of malignant ventricular arrhythmias treated with an implantable cardioverter defibrillator (ICD group) was compared to 127 age-matched Caucasian patients with CAD and no history of malignant ventricular arrhythmias (control group). All patients had reduced left ventricular ejection fraction of < 40% and were comparable regarding sex distribution, body mass index, ACE-inhibitor treatment, lipid status and duration of CAD. The prevalence of DD/CC in the ICD group was significantly higher (19% versus 10%, p < 0.0001). The risk for malignant ventricular arrhythmias was associated with the combination of ACE D and AT1 C alleles (odds-ratio: 2.4, 95% confidence interval 1.41 to 3.94, p < 0.001). The distribution of ACE and AT1 genotypes was not different between the two group. Patients with coronary artery disease and left ventricular dysfunction carrying ACE D and AT1 C alleles are at increased risk for development of malignant ventricular arrhythmias. Because of available pharmacological inhibitors, these results may have clinical implications for the prevention of sudden cardiac death.

QT dispersion predicts ventricular arrhythmia in pediatric cardiomyopathy patients referred for heart transplantation

Background QT dispersion has been used in stratifying risk for sudden death in adults with dilated cardiomyopathy, but its role in the pediatric population has not been delineated. Methods We reviewed electrocardiograms in pediatric patients with dilated cardiomyopathy referred for heart transplantation, to evaluate the role of QT dispersion in predicting malignant arrhythmias in these patients. Three groups were defined: Group I ( n = 13) had dilated cardiomyopathy and malignant ventricular arrhythmias, Group II ( n = 13) had dilated cardiomyopathy with no ventricular arrhythmias and Group III ( n = 30) consisted of normals. QT dispersion was defined as the duration of the shortest QT subtracted from that of the longest. In addition, the standard deviation of the QT intervals was calculated for each ECG, using 12 leads. Results QT dispersion was significantly prolonged in Group I (97 ± 33 msec) compared to Group II (74 ± 19 msec) and Group III (42 ± 17 msec). QT standard deviation was also prolonged in Group I (30 ± 11 msec) vs Group II (22 ± 5 msec) and Group III (13 ± 4 msec). Using a threshold value of 90 msec for QT dispersion or 25 msec for QT standard deviation, a sensitivity of 78% and a specificity of 70% was obtained for identifying patients who would subsequently develop ventricular arrhythmias. Conclusions In pediatric heart transplant candidates with dilated cardiomyopathy, QT dispersion and QT standard deviation identify patients at higher risk for the development of malignant ventricular arrhythmia. This simple test can be helpful in the evaluation and management of these patients awaiting transplantation.

Holter monitoring in Chagas' heart disease.

Electrocardiographic rhythm disturbance evaluation by Holter monitoring is increasingly becoming a useful methodologic tool for risk stratification as well as for therapeutic assessment in patients with Chagas' disease. Furthermore, late potential analyses, now being directly obtained from Holter recording has promising perspectives in enhancing identification of patients with high risk profiles for development of malignant ventricular arrhythmias. In addition, recently incorporated to Holter studies, heart rate variability analysis will certainly contribute to a better understanding of the characteristic autonomic nervous system disarray that commonly affects chagasic patients.

Mechanisms and models to predict a QT c effect

Prolongation of the QT Interval with consequent ventricular tachyarrhythmias may arise in the context of bradycardia (pause dependent) or may reflect sympathetic imbalances (adrenergic dependent). The normal repolarization process of ventricular myocardial cells is not entirely synchronous; some cells recover early and some later, resulting in a normal heterogeneity in refractoriness among ventricular cells during the inscription of the T wave. If the normal heterogeneity in ventricular repolarlzation is increased, as can occur following administration of some class IA and class III antiarrhythmic agents, then the QT interval will be prolonged. All-or-none action potentials can be evoked only in cells that have repolarized to a critical membrane potential of about −60 mV. Thus, the late-recovering cells (which terminate the T wave) may still be refractory and incapable of generating propagated action potentials while the early-recovering cells (which initiate the T wave) are fully excitable. In normal hearts, the period between repolarization of the earliest and the latest cells is insufficient to allow even very premature ventricular beats that occur early during the T wave (R-on-T phenomenon) to precipitate a sustained tachyarrhythmia. When the recovery process among ventricular cells becomes more inhomogeneous, however, as in the prolonged QT syndrome, the accompanying increased heterogeneity in ventricular repolarization and refractoriness can lead to the development of malignant ventricular arrhythmias, including torsades de pointes. Any drug that increases the dispersion of the repolarization process may prolong the QT interval and raise the potential for arrhythmias. QT prolongation and ventricular arrhythmias may also stem from the presence of early afterdepolarizations (EADs). The occurrence of EADs at the plateau level as well as near repolarization membrane levels leads to inhomogeneities in recovery and refractoriness. Accordingly, the accompanying increase in QT interval and dispersion of refractoriness can lead to the development of malignant arrhythmias. A rise in adrenergic tone and sympathetic tone imbalance has also been implicated in congenital and other prolonged QT syndromes. The contribution of sympathetic imbalance to QT prolongation and arrhythmias has been demonstrated in a number of animal models. In humans, sympathetic imbalance plays a particularly important role in the congenital prolonged QT syndromes.

Regulation of QT interval during postural transitory changes in heart rate in normal subjects

A lack of homogeneity, and the presence of intrinsic abnormalities in ventricular myocardial repolarization are thought to be important mechanisms underlying the development of malignant ventricular arrhythmias. 1–4 These abnormalities are believed to be reflected, at least in part, in the finding of a relative elongation in the QT interval to the preceding RR interval. 5,6 Although the QT-RR relation has been examined clinically as a static relation (QTc), 7 it appeared important to evaluate it in the framework of the dynamic QT response to transitory changes in heart rate, because it is possible in some cases that the abnormalities in the ventricular repolarization process that could precipitate malignant ventricular arrhythmias emerge only in its dynamic response, and not in a static relation. Although some studies have reported the response of the QT interval to the sudden and sustained changes in heart rate produced by strenuous exercise, 5,6,8 this method appears impractical, particularly for evaluating patients with malignant ventricular arrhythmias. In this study, we developed a microcomputer-based, automated technique for assessing the beat-to-beat QT-RR relation to examine the dynamic response of the QT interval to transitory changes in the heart rate during the head-up tilt test.

Effects of hydrochlorothiazide, amiloride, and lisinopril on the metabolic, hemodynamic, and electrocardiographs responses to increased plasma epinephrine

I n the treatment of cardiovascular disease, such as hypertension and heart failure, minor metabolic side effects of the long-term pharmacologic treatment might be of importance. Thus, diuretics may jnduce a potentially’arrhythmogenic hypokalemial and have negative effects on the glucose metabolism, and both diuretics and l3 blockers may have adverse effects on blood lipid levels2 that might increase the risk of coronary artery disease, despite the benefits provided by these drugs’ antihypertensive actions. In experimental settings, an infusion of epinephrine given at a rate to obtain serum concentrations comparable to those seen in acute myocardial infarction has profound metabolic and electrocardiographic effects that are known to facilitate the development of malignant ventricular arrhythmias.3 These effects of epinephrine may be aggravated by some drugs commonly prescribed in cardiovascular disorders.” This study investigated the effects of pretreatment with hydrochlorothiazide, amiloride, and lisinopril on the response to an epinephrine infusion. were analyzed: potassium, magnesium, calcium, phosphate, urate, albumin, creatinine, and blood glucose. An electrocardiographic recording was made during the infusion and for the following 30 minutes. The recordjng was analyzed for heart rate, T-wave amplitude, QRS duration, and QT interval. Systolic and diastolic (phase V) blood pressures were also determined. Prior to the epinephrine infusion, the volunteers were pretreated in random order for 14 days with: (1) placebo, (2) hydrochlorothiazide (HCTZ) 50 mg daily, (3) amiloride 10 mg daily, and (4) lisinopril 20 mg daily. Each volunteer received all of the pretreatments (Latin square design). The results were expressed as mean +: standard deviation. For statistical analysis, a multivariate analysis of variance for repeated measurements (MANOVA) was used with time during epinephrine infusion and the various pretreatments as within-subject factors.