History Of Sustained Ventricular Tachyarrhythmias Research Articles

Brugada syndrome and abnormal splicing of SCN5A in myotonic dystrophy type 1

In patients with myotonic dystrophy type 1 (DM1), the mechanisms underlying sudden cardiac death, which occurs in up to 1/3 of patients, are unclear. To study the potential role of Brugada syndrome in ventricular tachyarrhythmias and sudden death in DM1 patients. We screened 914 adult patients included in the DM1 Heart Registry during 2000-2009 for the presence of type 1 Brugada pattern on electrocardiogram (ECG). We also performed direct sequencing of SCN5A in patients with Brugada pattern. Further, we analysed SCN5A splicing on ventricular myocardial specimens harvested during cardiac transplantation in a 45-year-old patient with DM1 and three controls with inherited dilated cardiomyopathy. A type 1 Brugada pattern was present on the ECG of seven of 914 patients (0.8%), including five with a history of sustained ventricular tachyarrhythmia or sudden death, who fulfilled the criteria for Brugada syndrome. SCN5A sequencing was normal in all patients. Ventricular myocardial specimen analysis displayed abnormal splicing of SCN5A exon 6, characterized by over-expression of the 'neonatal' isoform, called exon 6A, in the patient with DM1, but not from the controls. Our findings suggest a potential implication of Brugada syndrome in sudden death in DM1, which may be related to missplicing of SCN5A. Our findings provide a new insight into the pathophysiology of heart disease in DM1.

QT dispersion, a simple tool to predict ventricular tachyarrhythmias and/or sudden cardiac death after myocardial infarction

Recent studies showed contradictive results of the relation between QT dispersion and the occurrence of ventricular tachyarrhythmias and/or sudden cardiac death. In addition, beta adrenoreceptors blocking agents, which are known to decrease the incidence of lethal arrhythmias after myocardial infarction, administered to the majority of patients in those studies population. Since β-blocker as secondary prevention drug was underutilized at National Cardiovascular Center Harapan Kita, this study was performed to find out the relation between QT dispersion and ventricular tachyarrhythmias and/or sudden cardiac death after previous myocardial infarction. The QT interval duration, QT dispersion and clinical variables of 36 postinfarction patients with history of sustained ventricular tachyarrhythmias and/or sudden cardiac death (event group) were compared with 75 postinfarction patients without such events (control group). QT dispersion differed significantly between study groups and was increased in the event group (115 ± 41 msec vs 81 ± 25 msec, p < 0.001). Corrected maximal QT interval duration was also prolonged in the event group (534 ± 56 vs 501 ± 35 msec, p < 0.001). Regression analysis showed that increasing QT dispersion was related to the occurrence of ventricular tachyarrhythmias and/or sudden cardiac death with OR of 3.2, 4, and 5.8 for cut-off point of 80, 90, and 100 msec respectively. The QT dispersion could predict the occurrence of ventricle tachyarrhythmias and/or sudden cardiac death in patient with AMI. This study confirmed that the QTd remain useful in free of beta blocking agents state. (Med J Indones 2005; 14: 230-6)

12.8 ICD for primary and secondary prevention of sudden death in patients with dilated cardiomyopathy

Background and Aim: Although some patients (pts) with dilated cardiomyopathy (DC), also without history of sustained ventricular tachyarrhythmias, may be considered at high risk of sudden death (SD), the role of implantable defibrillator (ICD) for primary prevention remains uncertain. I P 481 HEALTH STATUS AND THE IMPACT OF ANXIETY ON

Long-term prognostic value of time domain analysis of signal-averaged electrocardiography in idiopathic dilated cardiomyopathy

The aim of this study was to evaluate the long-term prognostic value of signal-averaged electrocardiography (SAECG) in idiopathic dilated cardiomyopathy (IDC). Time domain analysis of SAECG was assessed in 131 patients with angiographically confirmed IDC (age 52 ± 12 years; 108 men; left ventricular ejection fraction 33 ± 12%) using specific criteria in 44 patients with bundle branch block. Late potentials (LP) on SAECG were present in 27% of the patients. Patients with LP had a similar left ventricular ejection fraction and a similar left ventricular end-diastolic diameter than patients with a normal SAECG. With a follow-up of 54 ± 41 months, 24 patients suffered cardiac death and 19 had major arrhythmic events (sudden death, resuscitated ventricular fibrillation, or sustained ventricular tachycardia). Patients with LP had an increased risk of all-cause cardiac death (RR 3.3, 95% confidence interval 1.5 to 7.5, p = 0.004) and of arrhythmic events (RR 7.2, 95% confidence interval 2.6 to 19.4, p = 0.0001). Using multivariate analysis, only LP on SAECG (p = 0.001), reduced SD of all normal-to-normal intervals (SDNN) (p = 0.002), increased pulmonary capillary wedge pressure (p = 0.005), and history of sustained ventricular tachyarrhythmia (p = 0.02) predicted cardiac death. A history of previous sustained ventricular tachyarrhythmia (p = 0.0001), reduced SDNN (p = 0.003), and LP on SAECG (p = 0.006) were the only independent predictors of major arrhythmic events. Results were not altered when considering separately patients with or without bundle branch block, or after exclusion of patients with a history of sustained ventricular tachyarrhythmia. This study is one of the first to suggest that LP on SAECG is an independent predictor of all-cause cardiac death and is of high interest for arrhythmia risk stratification in IDC.

JTc prolongation with d,l-sotalol in women versus men

Women are at increased risk for torsades de pointes associated with a variety of drugs that prolong ventricular repolarization, but few data exist regarding possible sex differences in extent of repolarization changes with these medications.We sought to compare JTc interval responses in women and men during treatment with d,l-sotalol. The study cohort consisted of 1,897 patients (26% women) with available baseline and ≥1 on-drug electrocardiogram from a database involving patients exposed to oral d,l-sotalol without developing torsades de pointes. The mean lowest and highest daily d,l-sotalol dose, normalized for weight, was not significantly different between sexes. At each dosing extreme, on-drug JTc was significantly longer in women (p ≤0.0002). Statistically independent predictors of on-drug JTc included gender (p = 0.003), baseline JTc (p = 0.0001), dose (p = 0.0001), serum creatinine (p ≤0.03), and history of sustained ventricular tachyarrhythmias (p = 0.01). In both men and women, as baseline JTc increased, the drug-induced increment in JTc became progressively smaller. Thus, in response to d,l-sotalol, JTc intervals become longer in women than in men. This sex difference is independent of dose and not solely attributable to the known gender disparity in baseline JTc. The greater propensity of women to drug-induced torsades de pointes may represent the most extreme expression of a basic sex difference in the response to medications that prolong ventricular repolarization.

Management of patients with life-threatening ventricular tachyarrhythmias in the defibrillator era: the need to differentiate.

Patients with a history of sustained ventricular tachyarrhythmias form an extremely inhomogeneous group with respect to presenting arrhythmia, underlying cardiac disease, and therefore, risk of dying suddenly. For subgroups such as ventricular tachycardia in the absence of underlying cardiac disease, radiofrequency catheter ablation offers cure. In others, implantation of a cardioverter defibrillator already appears to have gained the therapy of first choice, leaving only a secondary role to antiarrhythmic drugs. It must be emphasized however, that these new therapeutic strategies have their pros and cons like the older, seemingly out-fashioned approaches of noninvasively or invasively guided antiarrhythmic drug therapy or empiric amiodarone treatment. Until the advent of controlled randomized trials comparing the implantable cardioverter defibrillator (ICD) with the best other, usually medical form of treatment, physicians must continue to base their individual therapeutic decisions on circumstantial published and personal experience. In doing so, the recent achievements of catheter ablation and defibrillator implantation have definitely improved patient care, but have not made antiarrhythmic drugs jobless. With all the alternatives at hand, it remains a challenging task to weigh the benefits and risks of the various approaches against each other in an attempt to tailor the antiarrhythmic intervention to the very individual need of the patient.

719-5 Clinical Correlates and Prognostic Significance of the Frequency of Episodes of Nonsustained Ventricular Tachycardia in the Electrophysiologic Study versus Electrocardiographic Monitoring Trial (ESVEM)

Nonsustained ventricular tachycardia (VTns) predicts mortality in several settings but its significance in patients (pts) with a history of sustained ventricular tachyarrhythmias is unknown. Pts in ESVEM were randomized to guidance method and to drug independent of VTns events. We grouped pts (n = 486) by frequency of VTns events on baseline 48hr drug-free HM: Gl ≡ No VTns (n = 70), G2 ≡ >0 to <0.25 runs/h (n = 190). G3 ≡ ≥0.25 to <1 runs/h (n = 109), G4 ≡ ≥ 1 runs/h (n = 117). There were no significant differences (p > 0.05) between groups with respect to age, ejection fraction, functional class, presenting arrhythmia, prior exposure to antiarrhythmic drugs or guidance method. Data are presented in order of group number (Gr1, 2, 3, 4, respectively). Significant differences were observed for sex (29, 8, 13, 15%female; p = 0.0008), previous myocardial infarction (6%, 10%, 22%, 23%; p = 0.0002), PVC/h (136, 146, 300, 735; p < 0.0001), pairs/h (1, 3,12, 60; p < 0.0001), and mean heart rate (77, 74, 74, 80 bpm; p = 0.0008). Because the significance of VTns may vary in pts with different disorders, an analysis was restricted to pts with ischemic heart disease (IHD, n = 414). Significant differences were observed for age (63, 65, 64, 67 yr; p = 0.01). sex (23, 6, 10,9%female, p = 0.0028). years since last myocardial infarction (MI) (3.7, 8.9, 9.1, 7.9yr; p < 0.0001), history of operative revascularization (8%, 29%, 30%, 38%; p = 0.0003), for PVC/h (151, 149,286, 769 PVC/h; p < 0.0001). mean pairs/h (1, 3, 12,62; P < 0.0001). mean heart rate (76, 74, 76, 81 bpm; p = 0.004), but not for ejection fraction, functional class, presenting arrhythmia, previous exposure to antiarrhythmic drugs, number of Mis, or angina since last MI. Variables based on presence/absence, on continuous and on stratified frequency measures of VTns events and the above variables were entered into a Cox proportional hazards regression model for: 1) pts discharged on a drug predicted to be effective, 2) all randomized pts (intention-to-treat), 3) pts with IHD. None of the VTns variables were significant independent predictors of arrhythmia recurrence or all-cause mortality. We conclude that significant clinical differences exist between groups of pts with different frequencies of VTns events. However, measures of VTns event frequency were not predictors of arrhythmia recurrence or mortality in this group of patients with known ventricular tachyarrhythmias.

Effect of oral sotalol on systemic hemodynamics and programmed electrical stimulation in patients with ventricular arrhythmias and structural heart disease

We explored the central hemodynamic responses to oral sotalol during dose titration in patients with ventricular arrhythmias who underwent programmed ventricular stimulation. Twelve patients were included in the study, 9 with a history of sustained ventricular tachyarrhythmias (6 postmyocardial infarction and 3 with cardiomyopathy) and 3 with a history of nonsustained ventricular tachycardia postmyocardial infarction. Left ventricular ejection fractions were <45% in 10 patients, and <35% in 5; the mean ejection fraction was 37% (range 20–51%). Sotalol prevented the induction of ventricular tachycardia in each of 3 patients wtth nonsustained ventricular tachycardia and in 6 of 9 wtth sustained ventricular tachycardia at baseline study. At peak action (2 hours) after sotalol loading (mean dose, 167 mg orally twice daily), the hemodynamic effects included bradycardia, decreased cardiac index, increased left ventricular filling pressure and systemic vascular resistance, and no change in stroke volume or stroke work index. One patient was not continued on sotalol, owing to an excessive increase in the pulmonary capillary wedge pressure, despite the lack of symptomatic heart failure. Congestive heart failure in association with marked bradycardia developed in another patient, who had suppression of inducible ventricular tachycardia after sotalol loading; this patient was managed wtth a reduction in the dose of sotalol and a regimen of digoxin and furosemide, and has been well compensated and without a recurrence of sustained ventricular tachycardia for more than 4 years. Ventricular tachycardia has been controlled wtth sotalol, without hemodynamic deterioration, in 6 of these patients. The evidence supports the idea that, despite its β-adrenergic blocking effects, sotalol can be used, albeit with some caution, even in patients with compromised left ventricular systolic function.

Results of electrophysiological testing and long-term follow-up in patients sustaining cardiac arrest only while receiving type IA antiarrhythmic agents.

Therapeutic management of patients sustaining a cardiac arrest while receiving antiarrhythmic agents can be difficult since the role of the drug in possibly facilitating the arrhythmia is often difficult to define. To determine if the response to programmed stimulation could give insight into which patients may have experienced a drug-induced cardiac arrest, we studied 29 patients (61 +/- 9 years) with no prior history of sustained ventricular tachyarrhythmias (VT) who suffered a cardiac arrest only while receiving type Ia antiarrhythmic agents. Patients with documented myocardial infarction, acute ischemia, electrolyte abnormalities, or torsade de pointes were excluded from the study. Twenty-four patients had coronary artery disease with prior myocardial infarction (ejection fraction 28% +/- 9%) and five patients had idiopathic dilated cardiomyopathy (ejection fraction 31% +/- 6%). During baseline electrophysiological testing, 19 patients (66%) had inducible sustained ventricular arrhythmias: uniform VT, n = 14 (group I), polymorphic VT or ventricular fibrillation, n = 5 (group II). Ten patients (group III) had no inducible sustained ventricular arrhythmias. To determine if rechallenge with a type Ia agent could facilitate induction of a sustained ventricular arrhythmia in group III, eight patients underwent ten electrophysiological studies during therapy with either procainamide or quinidine. Only two patients developed sustained VT in response to programmed stimulation. Patients in groups I and II received therapy guided by electrophysiological testing, including antiarrhythmic agents alone (n = 8), subendocardial resection (n = 4), or an implantable cardioverter defibrillator (n = 7). Patients in group III received antiarrhythmic agents empirically (n = 3), or for treatment of atrial tachyarrhythmias (n = 2) or nonsustained VT (n = 1). In addition, four patients in group III received an implantable cardioverter defibrillator. During a mean follow-up of 28 +/- 27 months (range: 1 day-84 months) 13 patients died suddenly or received a defibrillator shock preceded by syncope or presyncope: group I: n = 5; group II: n = 2; group III: n = 6. (1) most patients sustaining a cardiac arrest only in the presence of type Ia antiarrhythmic agents have inducible sustained VT in the absence of antiarrhythmic agents, and (2) the risk of recurrent VT persists in patients without inducible sustained arrhythmias in the drug-free state, regardless of whether they manifest inducible arrhythmias after rechallenge with a type Ia agent.

The effects of atrial pacing on the signal-averaged electrocardiogram in patients with coronary artery disease

The effects of atrial pacing on the signal-averaged electrocardiogram were studied in 14 patients with remote myocardial infarction and a history of cardiac arrest or sustained ventricular tachycardia (group I) and in 13 patients with coronary artery disease and no history of sustained ventricular tachyarrhythmia (group II). Recordings of the signal-averaged electrocardiogram were obtained at control and during atrial pacing at rates of 80, 100, and 120 beats/min. All patients had recordings analyzed from at least two paced rates. At control, the mean high frequency total duration of the QRS complex (HFTD) was significantly longer in group I versus group II patients (123 +/- 5.6 versus 111 +/- 3.5 msec, p less than 0.05). Although the duration of the QRS signal under 40 microV (D40) was higher in group I versus group II patients (42 +/- 4.7 versus 32.4 +/- 3.5 msec) and the root mean square amplitude of the terminal 40 msec QRS (RMSA) was lower in the group I patients (27 +/- 7.5 versus 38.1 +/- 8.8 microV), these differences did not achieve statistical significance. There was no effect of atrial pacing on the measured signal-averaged parameters of HFTD, D40, and RMSA. Although there was a difference between group I and group II at each paced rate analyzed, atrial pacing did not help to further stratify the groups. In patients with coronary artery disease, atrial pacing is not a useful method of stratifying high-risk patients. Changes in serial signal-averaged electrocardiograms from the same patient are not due to heart rate variability.

Limited value of programmed electrical stimulation from multiple right ventricular pacing sites in clinically sustained ventricular fibrillation or ventricular tachycardia associated with coronary artery disease

One-hundred and fifty patients with coronary artery disease and a documented history of sustained ventricular tachyarrhythmias were studied to determine if programmed electrical stimulation (PES) from a second right ventricular (RV) pacing site optimizes the induction of such sustained arrhythmias. The first PES test was performed from 2 RV pacing sites (apex and outflow tract or septum) using the apex first in each patient. All patients underwent a second PES within 6 to 24 hours of the first; both studies used up to 4 ventricular extrastimuli, in the absence of antiarrhythmic treatment. The second PES was performed from a single RV apical site using a pacing catheter retained from the first study. During the first day's study, 74 patients (49%) had sustained ventricular tachycardia induced from the RV apex. Only 11 of the remaining 76 patients (7% of the total group) were inducible exclusively from a second RV pacing location during the first day's testing. Seven of these 11 patients, as well as 15 additional patients who did not have ventricular tachycardia induced from either site on the first day's study, were inducible from the RV apex during the second drug-free study. Among patients with sustained ventricular tachyarrhythmias, limiting PES to a single RV site, with the option of performing a second study in those who are initially noninducible is more effective in inducing sustained ventricular tachyarrhythmias than is PES performed from 2 RV pacing sites.

Safety and efficacy of encainide for malignant ventricular arrhythmias

The antiarrhythmic effect of encainide was evaluated in 140 patients with documented symptomatic ventricular tachycardia or ventricular fibrillation refractory to conventional agents. In 102 patients with reproducible spontaneous arrhythmia, noninvasive methods, including ambulatory monitoring and exercise testing, were used to evaluate drug efficacy, while in the remaining 38 patients electrophysiologic testing was performed. Side effects necessitated drug discontinuation in 10 patients before noninvasive evaluation. Of the remaining 92 patients 44 (48%) responded to encainide. Of the 38 patients who underwent electrophysiologic study, 1 discontinued encainide because of side effects and in 4 patients the spontaneous occurrence of sustained ventricular tachycardia precluded repeat study. Of the remaining 33 patients, 10 (30%) were rendered noninducible with encainide. The drug was more effective in those with a left ventricular ejection fraction >35% (p < 0.03) and in those presenting with nonsustained ventricular tachycardia. Side effects were reported in 53 of 140 patients (38%) and were primarily nausea, vomiting, headaches and tremors. Aggravation of arrhythmia occurred in 4% of patients with a history of nonsustained arrhythmia and in 25% of those with a history of sustained ventricular tachycardia or ventricular fibrillation. Worsening of arrhythmia was not related to mean dose of drug, mean blood level or electrocardiographic changes; it was more likely to occur in patients with a markedly reduced left ventricular ejection fraction (average 32%) and in those with a history of sustained ventricular tachyarrhythmia (p < 0.05). Long-term encainide therapy was continued in 48 patients. After a mean follow-up of 25 months (range 2 to 74 months), 6 patients died suddenly (6% per year) and 3 patients had nonfatal recurrence. An additional 5 patients died from congestive heart failure unrelated to the drug and encainide was discontinued in 5 because of side effects. The remaining 29 patients have been maintained on encainide for an average of 36 months. It is concluded that encainide is an effective and well-tolerated drug that improves the survival in a selected group of drug-resistant patients at risk of sudden death. However, like other antiarrhythmic drugs encainide has the potential for cardiac side effects, especially aggravation of arrhythmia, and caution must be exercised in its use.

Utility of ambulatory electrocardiographic monitoring for predicting recurrence of sustained ventricular tachyarrhythmias in patients receiving amiodarone

The prognostic implications of changes in ventricular ectopic activity on serial 24 hour ambulatory electrocardiographic (Holter) recordings were prospectively evaluated in 107 patients with a history of sustained ventricular tachyarrhythmias treated with amiodarone for at least 30 days. Twenty-seven patients (25%) had insufficient ventricular ectopic activity (less than 10 ventricular premature complexes/h and no repetitive forms) on baseline Holter recordings for serial statistical analysis. In 53 (66%) of the remaining 80 patients, serial 24 hour Holter monitor recordings showed efficacy of treatment, defined as a 75% decrease in ventricular premature complexes, a 95% decrease in ventricular couplets and absence of ventricular tachycardia. During a mean follow-up period of 14.2 +/- 9.9 months, 34 (32%) of the 107 patients had recurrence of a sustained ventricular tachyarrhythmia. Holter recording correctly predicted nine recurrences and correctly identified 37 patients who did not experience a recurrence. Holter efficacy failed to predict recurrence of a sustained ventricular tachyarrhythmia in 16 patients, and 18 patients remained free of recurrence despite failure to achieve Holter efficacy. The positive predictive value of Holter monitoring efficacy was 33% and the negative predictive value was 70%; however, these differences were not statistically significant by chi-square analysis. Similar results were obtained using Holter recordings performed relatively early in therapy (6 weeks and 4 months). Of the 27 patients without significant ventricular ectopic activity on the baseline Holter recording, 9 had an arrhythmia recurrence despite continued infrequent ventricular premature complexes and no repetitive forms on subsequent recordings. The recurrence rate in this group (33%) was similar to the overall recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS)