Prognostic value of ventricular arrhythmia in hypertensive patients

OBJECTIVE: Hypertensive left ventricular hypertrophy (LVH) is associated with increased risk of arrhythmias and mortality. However, no clinical study demonstrated a significant relation between ventricular arrhythmias and mortality in systemic hypertension. DESIGN AND METHODS: To evaluate the prognostic value of arrhythmogenic markers in systemic hypertension, we included between 1987 and 1993. 214 hypertensive patients, 59.1 +/- 12.8 years old, without symptomatic coronary disease, myocardial infarction, systolic dysfunction, electrolyte disturbances or antiarrhythmic therapy. At inclusion, an ECG, a 24 h Holter ECG (204 patients) with Lown classification of ventricular arrhythmias, an echocardiography (reliable in 187 patients) with left ventricular mass index and ejection fraction calculation, a SAECG (125 patients, enrolled after 1988) with ventricular late potentials (LP) were recorded. QT interval dispersion (QTd) was calculated on 12 leads standard ECG and LVH was appreciated. RESULTS: At baseline echocardiographic LVH was recorded in 63 patients (33.7%) with normal ejection fraction (75 +/- 7.4%). Non-sustained ventricular tachycardia (Lown IVb) was found in 33 pts (16.2%) and LP in 27 patients (21.6%). After a mean follow up of 42.4 +/- 26.8 months, all-cause mortality was 11.2% (24 patients); 17 patients died of cardiac causes (7.9%); of these 9 patients (4.2%) died suddenly. In univariate analysis, age, strain pattern of LVH, advanced Lown classes and abnormal QT dispersion (> 80 ms) were significantly related to global, cardiac and sudden death (p < or = 0.01). Left ventricular mass index was closely related to cardiac mortality (p = 0.002). LP failed to predict mortality. In multivariate analysis, only Lown class IVb was an independent predictor of global and cardiac mortality, increasing the risk of global death 2.6 fold [1.2-6.0] (CI 95%) and the risk of cardiac death 3.5 fold [1.2-9.7] (CI 95%). CONCLUSIONS: In hypertensive patients the presence of non-sustained ventricular tachycardia on 24 h Holter has a prognostic value.     

Long-term outcome and prognostic determinants in children with hypertrophic cardiomyopathy

OBJECTIVES: We sought to determine clinical, angiographic, and echocardiographic predictors of survival in children with isolated hypertrophic cardiomyopathy (HCM) in a large pediatric centre. BACKGROUND: Sudden death is a catastrophic outcome of HCM in childhood but has been difficult to predict. Current therapies might provide for improved outcome if factors identifying high risk can be identified. METHODS: Records of 99 patients diagnosed with HCM from 1958 to 1997 at <18 yr were reviewed for clinical, angiographic (n = 62) and echocardiographic (n = 83) predictors of survival outcome. The effects of clinical characteristics on sudden death (including resuscitated sudden death) were individually tested in Cox's proportionate hazard modeling. RESULTS: Seventy-one subjects were male. Median age at diagnosis was 5.0 yr with a medical follow-up interval of 4.8 yr. Thirty-seven of 97 patients had a family history of HCM. Ambulatory electrocardiograms (ECG) in 78 patients demonstrated supraventricular tachycardia in 16 and ventricular tachycardia in 21. Death or resuscitated sudden death occurred in 18 patients. Sudden death rate was 2.7%/yr after age 8 yr. Cox's proportionate survival modeling revealed increased corrected QT interval (QTc) dispersion on ECG (relative risk [RR] 1.61 per 20 ms increment, p < 0.0003), ventricular tachycardia (VT) on ambulatory ECG (RR 3.75, p < 0.006) and myocardial bridging of the LAD coronary (RR 12.0, p < 0.003) to be associated with reduced time to death or resuscitated sudden death. CONCLUSIONS: Detailed assessment of ECGs, ambulatory ECGs, and coronary angiography can assist in identifying which children with HCM are at risk for sudden death.     

QT dispersion, daily variations, QT interval adaptation and late potentials as risk markers for ventricular tachycardia

AIMS: The aim of the study was to determine the value and correlation between QT dispersion, daily variations in the QT interval and late potentials as risk markers for ventricular tachycardia. METHODS AND RESULTS: QT dispersion was defined as the difference between the longest and the shortest QT interval in 12 electrocardiographic leads, QTc variability as the difference between the maximal and minimal QTc interval during 24-h Holter monitoring and QT interval adaptation as the regression line between heart rate and the uncorrected QT interval. One hundred and forty-five patients, 3 months after myocardial infarction were included in the study. QT dispersion significantly increased with the severity of arrhythmia (modified Lown's classification; P< 0.001). The level of 80 ms was associated with ventricular tachycardia with a sensitivity of 72.7% and a specificity of 86.4%. The greater daily variability of the QTc interval in patients with ventricular tachycardia was insignificant (P > 0.05). QT interval adaptation did not discriminate between patients with ventricular tachycardia from those in other groups. Late potentials were associated with ventricular tachycardia with a sensitivity of 50% and a specificity of 90.3%. CONCLUSION: Large QT dispersion and late potentials were risk markers for ventricular tachycardia, but there was no correlation between QT dispersion, daily variations in the QT interval and late potentials in patients 3 months after myocardial infarction.     

Nonsustained ventricular tachycardia in severe heart failure. Independent marker of increased mortality due to sudden death. GESICA-GEMA Investigators

BACKGROUND: The goal of the study was to determine the prognostic value of nonsustained ventricular tachycardia (NSVT) in total mortality in severe congestive heart failure (CHF) and in death modes. NSVT is associated with an increased mortality in CHF. However, the predictive value of NSVT as a marker for sudden death or death due to progressive heart failure has not been determined. METHODS AND RESULTS: Five hundred sixteen patients from the GESICA trial (33.4% with NSVT) were initially studied with the results of 24-hour Holter and 2 years of follow-up. Within 2 years, 87 of 173 patients (50.3%) with NSVT and 106 of 343 patients (30.9%) without NSVT died. Relative risk (RR) was 1.69 (95% confidence interval [CI], 1.27 to 2.24; P < .0002), and Cox proportional hazard analysis was 1.62 (95% CI, 1.22 to 2.16; P < .001). Sudden death increased from 8.7% (30 of 343) to 23.7% (41 of 173) in patients with NSVT (RR, 2.77; 95% CI, 1.78 to 4.44; P < .001). Progressive heart failure death was also increased from 17.5% (60 of 343) to 20.8% (36 of 173) (P = .22). Quantitative analysis of 24-hour Holter (first 295 patients) demonstrated that couplets had a similar RR to that of NSVT for both total mortality (RR, 1.81; 95% CI, 1.22 to 2.66; P < .002) and sudden death (RR, 3.37; 95% CI, 1.57 to 7.25; P < .0005). Couplets and/or NSVT (ventricular repetitive beats) were even more predictive for sudden death (RR, 10.1; 95% CI, 1.91 to 52.7; P < .01). CONCLUSIONS: In patients with CHF, NSVT is an independent marker for increased overall mortality rate and sudden death. The absence of NSVT and ventricular repetitive beats in a 24-hour Holter indicates a low probability of sudden death.     

Peroxidase activity of liver microsomal vitamin D 25-hydroxylase and cytochrome P450 1A2 catalyzes 25-hydroxylation of vitamin D3 and oxidation of dopamine to aminochrome

OBJECTIVES: This study sought to determine the long-term risk of sudden cardiac death in patients with hemodynamically stable sustained ventricular tachycardia complicating coronary artery disease. BACKGROUND: The prognosis and risk of sudden cardiac death in patients with a history of myocardial infarction and ventricular tachyarrhythmias have not been clearly defined. Prior studies are limited by a short follow-up period and by inclusion of patients with heterogeneous cardiac diseases and presenting arrhythmias. METHODS: A retrospective cohort analysis was performed on data from 124 patients, followed up for a mean of 36 +/- 30 months, who received electrophysiologically guided therapy for hemodynamically stable ventricular tachycardia after remote myocardial infarction. RESULTS: Seventy-eight patients were treated pharmacologically (medical group), and 46 patients underwent map-guided subendocardial resection (surgical group). Nine patients (7.3%) died suddenly, 5 (4.0%) died of noncardiac causes, 9 (7.3%) died of a perioperative complication, and 20 (23.4%) died of other cardiac causes. At 1, 2 and 3 years, sudden death occurred at cumulative rates of 2 +/- 1%, 3 +/- 2% and 7 +/- 3%, whereas total mortality was 20 +/- 4%, 28 +/- 4% and 32 +/- 5% (mean +/- SD). Sudden cardiac death (p = 0.047) and total mortality (p = 0.036) were higher in patients with multivessel disease and were similar for both treatment groups. CONCLUSIONS: Although the overall mortality in postinfarction patients presenting with hemodynamically stable ventricular tachycardia treated with electrophysiologically guided antiarrhythmic therapy is high, the risk of sudden death in these patients appears to be low (average 2.4%/year).     

Citalopram in the treatment of obsessive-compulsive disorder: an open pilot study

PURPOSE: To evaluate QT dispersion in hypertensive patients, with and without left ventricular hypertrophy, and compare with normal persons. METHODS: Thirty eight patients (21 male and 17 female, age 55 +/- 15 years) underwent echocardiography and simultaneous 12 lead, vertically aligned, electrocardiogram at 50 mm/s speed. No patient was on antiarrhythmic therapy. There were 19 non-hypertensive patients that constituted the control group (G-I). Group II was constituted by the other 19 patients, who were hypertensives. This group was further divided in group II-A (9 patients without left ventricular hypertrophy) and group II-B (10 patients with left ventricular hypertrophy). QT dispersion was obtained by the difference between the longest and the shortest QT registered. RESULTS: QT dispersion was significantly increased on hypertensive patients, both with and without left ventricular hypertrophy, when compared to controls (G-I 31 +/- 9 ms, G-II 52 +/- 15 ms. P < 0.0001; G-IIa 46 +/- 10 ms and G-IIb 56 +/- 18 ms X G-I, p < 0.0005). In hypertensive patients, there was no statistically significant difference between group II-A and group II-B. CONCLUSION: We conclude that QT dispersion is significantly increased on hypertensive patients when compared to non-hypertensive individuals and that such increase, occurs before left ventricular hypertrophy develops. These findings suggest that, in hypertensive patients, electrical changes in left ventricular myocardium can precede structural and morphological abnormalities. Such findings offer new insights into the mechanisms related to enhanced mortality among hypertensive patients.     

QT interval as a cardiac risk factor in a middle aged population

OBJECTIVE: To evaluate the value of QT interval as a cardiac risk factor in middle aged people. METHODS: The association between QT interval and cardiac risk factors and mortality in a middle aged Finnish population of 5598 men and 5119 women was evaluated over a 23 year follow up. To adjust the QT interval confidently for heart rate, a nomogram was constructed from the baseline electrocardiograms separately for men and women. RESULTS: Nomogram-corrected QT interval (QTNc) prolongation was associated with elevated blood pressure and signs of cardiovascular disease; QTNc shortening was associated with smoking. Over 10% prolongation of QTNc predicted death in men with heart disease: adjusted relative risk (RR) was 2.17 (95% confidence interval 0.67-7.45) for sudden death; 2.12 (1.25-3.59) for total cardiovascular mortality; and 1.92 (1.23-3.00) for all cause mortality. In healthy men the increase in RR was not significant: sudden death, 1.48 (0.67-3.25); total cardiovascular mortality, 1.25 (0.92-1.70); all cause mortality, 1.21 (0.96-1.53). However, healthy men with long QTNc in the lowest heart rate quartile exhibited an RR of 2.75 (1.00-7.40) for sudden death. Over 10% shortened QTNc predicted cardiovascular death in men with heart disease who smoked; RR 3.72 (1.45-9.54). Non-smoking men with short QTNc had low mortality risks irrespective of possible signs of cardiovascular disease. The trends in mortality risks were similar but weaker for women. CONCLUSIONS: In a middle aged population, prolonged QT interval predicts cardiac mortality in men with signs of cardiovascular disease. In women and healthy men this risk is weak and may reflect subclinical heart disease. A shortened QT interval predicts death in men with heart disease who smoke.     

Syncope and ventricular arrhythmias in hypertrophic cardiomyopathy are not related to the derangement of coronary microvascular function

Non-sustained ventricular tachycardia on Holter and syncope have been considered risk factors for sudden death in hypertrophic cardiomyopathy. AIMS: In these patients the coronary vasodilator reserve is impaired despite normal coronaries, so we evaluated the correlation between the severity of coronary vasodilator reserve impairment and the occurrence of syncope and non-sustained ventricular tachycardia. METHODS AND RESULTS: Eighty-four patients with hypertrophic cardiomyopathy (62 males, age 43 +/- 12 years) had a two-dimensional echocardiographic study and a 48-h Holter. Myocardial blood flow was measured by positron emission tomography, at baseline and after dipyridamole, and the coronary vasodilator reserve was computed as dipyridamole myocardial blood flow/baseline myocardial blood flow. In 27 patients, subendocardial and subepicardial myocardial blood flow was measured in the septum and the subendocardial/subepicardial ratio was computed. Twenty of 84 patients had at least one syncopal episode, and 26 had at least one run of non-sustained ventricular tachycardia on Holter. Baseline and dipyridamole myocardial blood flow, coronary vasodilator reserve, and baseline and dipyridamole subendocardial/subepicardial myocardial blood flow ratio were similar in patients with and without syncope and with and without non-sustained ventricular tachycardia on Holter. However, patients with non-sustained ventricular tachycardia had larger left ventricular end-diastolic (47 +/- 6 vs 44 +/- 5 mm, P < 0.05) and end-systolic diameters (30 +/- 6 vs 27 +/- 4 mm, P < 0.05). CONCLUSIONS: (1) Coronary vasodilation is not more severely impaired in patients with hypertrophic cardiomyopathy and syncope or non-sustained ventricular tachycardia. (2) The left ventricle is more dilated in hypertrophic cardiomyopathy with non-sustained ventricular tachycardia.     

Catheter ablation of incessant ventricular tachycardia: acute and long-term results

SUBJECTS: Seventeen patients with incessant ventricular tachycardia refractory to anti-arrhythmic therapy underwent catheter ablation between 1987 and 1993. Fifteen patients had coronary heart disease and two had dilated cardiomyopathy. The mean age of the patients was 65 +/- 8 and the mean left ventricular ejection fraction was 31 +/- 9%. METHODS: Ablation sites were selected on the basis of endocardial activation mapping, concealed entrainment or bundle branch mapping. Catheter ablation was performed with direct current in nine patients and with radiofrequency energy in eight patients. Incessant ventricular tachycardia was terminated by catheter ablation in all 17 patients. RESULTS: One patient died after the ablation procedure due to pericardial tamponade. During electrophysiological testing 5-14 days later, 7 of 16 patients (44%) had inducible sustained or non-sustained ventricular tachycardia. Five of them underwent implantation of an automatic cardioverter/defibrillator, and three of these experienced discharges of the device during a mean follow-up of 30 +/- 12 months. another patient underwent implantation of a cardioverter/defibrillator after spontaneous recurrence of ventricular tachycardia. Out of the nine patients without inducible ventricular tachycardia, one died as a result of sudden cardiac death, and another had spontaneous ventricular tachycardia. Thus, ventricular tachycardia recurred clinically in 6 of 16 patients (38%), in whom ventricular tachycardia with the same morphology as that of the ablated ventricular tachycardia could be determined only in one patient. CONCLUSION: Catheter ablation is the method of choice for the emergency treatment of patients with incessant ventricular tachycardia. Due to the high risk of recurrence, additional anti-arrhythmic management, such as the implantation of a cardioverter/defibrillator, has to be considered.     

Survival and incidence of myocardial infarction in men with ambulatory ECG-detected frequent and complex ventricular arrhythmias. 10 year follow-up of the 'Men born 1914' study in Malm?, Sweden

AIM: To assess to what extent do frequent or complex ventricular arrhythmias, detected during 24 h ambulatory electrocardiographic recording (ECG), influence prognosis with regard to survival and incidence of ischaemic heart disease. METHODS AND RESULTS: The study subjects were the 456 randomly selected men born in 1914, the population-based cohort study of 1982-83, in Malm?, Sweden. The main outcome measures were total mortality and incidence of cardiac event (myocardial infarction and death from ischaemic heart disease). Frequent or complex ventricular arrhythmias (Lown classes 2-5) were detected in 49% of the men with (n = 77), and in 35% of those without, a history of myocardial infarction or angina pectoris at baseline, P = 0.019. Independent of clinically evident coronary artery disease at baseline, and after adjustment for traditional atherosclerotic risk factors and use of digitalis or beta-blocker therapy, frequent or complex ventricular arrhythmias were associated with an increased mortality from ischaemic heart disease (relative risk (RR), 2.1; 95% confidence interval (CI), 1.2-3.9) and an increased cardiac event rate (RR, 1.6; 95% CI, 1.0-2.5)). Men free from both ischaemic-type ST depression and frequent or complex ventricular arrhythmias (used as the control group) had the lowest ischaemic heart disease death rate, 5.9 per 1000 person-years. The combination of ST depression and frequent or complex ventricular arrhythmias was associated with an ischaemic heart disease death rate of 20.9 per 1000 person-years. The cardiac event rate in these two groups was 15.6 and 76.1 per 1000 person-years, respectively (adjusted RR, 2.3; CI, 1.1-4.6). CONCLUSIONS: In elderly men without a history of myocardial infarction and angina pectoris, frequent or complex ventricular arrhythmias during ambulatory ECG recording is associated with an increased incidence of myocardial infarction and mortality. Men who, during ambulatory ECG recording, also demonstrate ST-segment depression have an even less favourable prognosis.     

Left ventricular geometric patterns and QT dispersion in untreated essential hypertension

The spectrum of left ventricular adaptation to hypertension, different types of hypertrophy patterns, and QT dispersion in different types of hypertrophy was investigated in 107 patients with untreated essential hypertension and 30 age- and gender-matched normal adults studied by 12-derivation electrocardiogram (ECG), two-dimensional, and M-mode echocardiography. Left ventricular mass (LVM), body mass index, total peripheral resistance (TPR), relative wall thickness (RWT), and QT dispersion were found to be statistically significantly higher in the hypertension group (P < .001 for all). Among hypertensive patients, 41.1% had both normal LVM and RWT, here called normal left ventricle in hypertension; 10.3% had concentric hypertrophy with increased LVM and RWT; 14.95% had eccentric hypertrophy with increased LVM and normal RWT; and 32.7% had concentric remodeling with normal LVM and increased RWT. Echocardiographically derived cardiac index was higher in the concentric hypertrophy and eccentric hypertrophy patterns (P = .002 and P < .0001, respectively), whereas TPR was higher in the concentric hypertrophy and concentric remodeling patterns (P = .017 and .02, respectively). QT dispersion values were found to be increased in the hypertensive group (P = .001), whereas similar values were calculated for different types of hypertrophy patterns. We conclude that the more common types of ventricular adaptation to essential hypertension are eccentric hypertrophy and concentric remodeling. Concentric hypertrophy is found to be associated with both volume and pressure overload, whereas eccentric hypertrophy is associated with volume overload only and concentric remodeling is associated with pressure overload. But different left ventricular geometric patterns seem to have similar effects on QT dispersion.     

The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens

AIMS: To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population. METHODS AND RESULTS: The QT interval was measured in all leads from a standard 12-lead ECG in a random sample of 1658 women and 1797 men aged 30-60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2.9 for the QT interval (95% confidence interval 1.1-7.8) and 4.4 for QT interval dispersion (95% confidence interval 1.0-19-1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2.7 (95% confidence interval 1.4-5.5) for the QT interval and 2.2 (95% confidence interval 1.1-4.0) for QT interval dispersion. CONCLUSION: Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.     

Evaluation of antiarrhythmic efficacy of sotalol in various doses in patients with ventricular tachyarrhythmias

Antiarrhythmic efficacy of sotalol--noncardioselective beta-adrenergic blocking agent with class III antiarrhythmic action was evaluated in 34 patients [pts] (mean age 55 +/- 11) with chronic ventricular arrhythmias and coronary artery disease, 38% with previous myocardial infarction. Two schedules of dosing were tested: 3 x 80 mg and 2 x 160 mg during 28 days of therapy. Pts with Lown class II and IV arrhythmia derived from 24-hours Holter recording were assigned. Ventricular premature complexes [VPCs] and couplets reduction by 80% and total elimination of runs defined antiarrhythmic efficacy. Proarrhythmia was defined by four times increase in VPCs, ten times increase in couplets and runs or sustained VT episodes. RESULTS: Antiarrhythmic efficacy of two doses of sotalol according to study criterion was: 31% for lower dose (3 x 80 mg) and 24% for higher dose (2 x 160 mg). Overall efficacy for both doses was 55%. According to Morganroth criterion, lower dose was effective in 29% pts and both doses, lower and higher, in 41% pts. According to other commonly used criterion: 70% VPCs reduction, 90% couplets reduction and total elimination of runs, lower dose of sotalol was effective in 32% pts and both doses in 47% pts. Significant reduction of heart rate and prolongation of QT and QTc were observed. In 3 pts QT was prolonged over 500 ms. Proarrhythmia according to Velebit criterion was suspected in one patient after one week of 3 x 80 mg teratment which caused premature cessation of therapy. No significant abnormalities in laboratory values were observed. CONCLUSIONS: Antiarrhythmic efficacy of sotalol was comparable to other studies. Its value in pts with malignant ventricular tachyarrhythmias: sustained ventricular tachycardia and ventricular fibrillation requires further studies with higher number of patients.     

Regression of left ventricular hypertrophy results in improvement of QT dispersion in patients with hypertension

OBJECTIVES: Increased QT dispersion has been considered as predisposing to ventricular arrhythmias in hypertrophic cardiomyopathy, congestive heart failure, and coronary artery disease. An increased QT dispersion has also been found in hypertensive patients with left ventricular hypertrophy (LVH). The data on the effect of LVH regression on QT dispersion are limited. METHODS AND RESULTS: To assess the relation of LVH regression and QT dispersion decrease, 68 patients (42 men and 26 women, mean age 56.3+/-9.5 years) with uncomplicated essential hypertension were studied. All underwent full electrocardiographic and echocardiographic studies at baseline and after 6 months of monotherapy, 29 with angiotensin-converting enzyme inhibitors and 39 with calcium antagonists. QT dispersion was calculated by subtracting the shortest QT from the longest QT, in absolute value (QTmax - QTmin). It was also corrected with Bazett's formula (QTc dispersion). Left ventricular mass index was assessed according to the Devereux formula. After treatment, LVH decreased with both angiotensin-converting enzyme inhibitors (from 155 to 130 g/m2, P < .001) and calcium antagonists (156 to 133/92/m2, P < .001). QT dispersion decreased both after angiotensin-converting enzyme inhibitor treatment (from 82 to 63 ms) and calcium antagonist treatment (from 77 to 63 ms, both P < .001 ). There was a significant correlation of QT dispersion and left ventricular mass after therapy (r = 0.36, P < .005). There was a correlation of the degree of LVH and QT dispersion decrease (r = 0.27, P < .05). CONCLUSIONS: It is concluded that LVH regression influences AQT favorably. Its prognostic value has yet to be determined.     

Sudden death in hypertrophic myocardiopathy]

Hypertrophic cardiomyopathy is the most common cause of sudden death in young individuals who are otherwise healthy. Risk of sudden death is highest in patients who are between 14 and 35 years old. Several mechanisms are involved in sudden death: ventricular arrhythmias, supraventricular arrhythmias leading to cardiac collapse, bradycardias and severe ischemia. Many studies have analyzed how to identify high risk patients. The factors that best identify high risk patients are: previous history of sudden death or syncope, induction in adults of sustained ventricular arrhythmias, the presence of non-sustained ventricular tachycardia in symptomatic patients, the presence of ischemia associated with hypotension in children, the presence of mutations in the beta-myosin heavy chain together with a family history of sudden death and a poor left ventricular ejection fraction. Risk stratification should be done on an individualized basis. In those patients in whom a high risk for sudden arrhythmic death is suspected, the only current effective treatment is the implantable defibrillator.     

Comparison of ECG variables of dispersion of ventricular repolarization with direct myocardial repolarization measurements in the human heart

INTRODUCTION: QT dispersion (QTD) from the 12-lead ECG has been widely adopted as a noninvasive index of dispersion of ventricular repolarization (DVR). QTD, however, has never been validated by direct comparison with myocardial DVR in the human heart. METHODS AND RESULTS: Monophasic action potential (MAP) recordings obtained in an earlier study were retrospectively matched with 12-lead ECGs available from within 24 hours of the invasive procedure. MAPs were available from an average of 8+/-3 left endocardial sites in 4 patients with left ventricular hypertrophy (LVH) and 7 patients with normal ECGs, and 6+/-2 epicardial sites in 3 patients of each group during normal ventricular activation. Local repolarization time (RT) was determined as MAP duration at 90% repolarization plus the local activation time. Dispersion of RT was calculated as the difference between the earliest and latest RT. ECGs were digitized and analyzed with recently described interactive QTD analysis software. In addition to standard QTD (defined as QTmax-QTmin), all currently proposed ECG dispersion variables were compared and correlated with the invasive measurements of DVR. QTD exhibited a reasonable correlation with dispersion of RT (R = 0.67; P < 0.01). Several other variables designed to measure DVR exhibited a similar, but not better, correlation. Among them, the QT peak/QT end ratio in V3 (R = -0.72; P < 0.01) and averaged over all analyzable leads (R = -0.59; P < 0.01) exhibited a good correlation with dispersion of RT, which was further improved when endocardial measurements were considered alone. T area measures did not correlate with dispersion of RT, but discriminated LVH. CONCLUSION: DVR can be assessed by means of a 12-lead surface ECG. Several of the variables under study exhibit a similar accuracy in determination of true myocardial dispersion of repolarization. Variables involving the terminal part of repolarization, such as the QT peak/QT ratio, even from a single lead, may add to the determination of DVR from the human heart.     

Prognostic role of heart rate variability in patients with a recent acute myocardial infarction

A low heart rate variability (HRV) has been shown to be a powerful predictor of cardiac events in patients surviving an acute myocardial infarction (MI), but it is not clear yet which among the HRV parameters has the best predictive value. Time domain and frequency domain HRV was assessed on 24-hour predischarge Holter recording of 239 patients with a recent MI. Patients were followed up for 6 to 54 months (median 28), during which 26 deaths (11%) occurred, 19 of which were cardiac in origin and 12 were sudden. Most HRVs did not show any difference between patients with or without mortality end points, but the average low-frequency and low-frequency/high-frequency ratio was lower in patients with events. However, when dichotomized according to cut points that maximized the risk of sudden death, several HRVs were significantly predictive of clinical end points. Overall, the mean of the standard deviations of all RR intervals for all 5-minute segments and the standard deviation of the mean RR intervals for all 5-minute segments were the time domain variables most significantly associated with mortality end points, whereas very low frequency was the most predictive frequency domain variable. Compared with the best time domain variables, very low frequency showed a better sensitivity (0.27 to 0.42 vs 0.19 to 0.33) for end points with only a small loss in specificity (0.92 vs 0.96). On multivariate Cox proportional analysis, a left ventricular ejection fraction <40% and a number of ventricular premature beats > or = 10/hour were the most powerful independent predictors for all end points, whereas no HRV was independently associated with the events. A low frequency/high frequency ratio < 1.05 only had a borderline association with sudden death (RR = 2.86, p = 0.076). Our data show a strong association between HRV and mortality in patients surviving a recent MI, with a slight better sensitivity of frequency domain analysis. In our study, however, HRV did not add independent prognostic information to more classic prognostic variables (e.g., left ventricular function and ventricular arrhythmias).     

An activator/repressor dual system allows tight tetracycline-regulated gene expression in budding yeast

OBJECTIVES: This study sought to determine the prevalence and significance of nonsustained ventricular tachycardia (NSVT) in patients with premature ventricular contractions (PVCs) and heart failure treated with vasodilator therapy. BACKGROUND: Heart failure patients with ventricular arrhythmia and NSVT have a significantly increased risk of premature cardiac death. Recently there has been the question of whether these arrhythmias are expressions of a severely compromised ventricle or are they independent risk factors. We, therefore, determined the prevalence and significance of NSVT in patients with PVCs and heart failure and on vasodilator therapy. METHODS: Twenty-four hour ambulatory recordings were done at randomization, at 2 weeks, at months 1, 3, 6, 9 and 12 and then every 6 months in 674 patients with heart failure and on vasodilator therapy. The median period of follow-up was 45 months (range 0 to 54). RESULTS: Nonsustained ventricular tachycardia was present in 80% of all patients. Patients without (group 1) and with (group 2) NSVT were balanced for variables: age, etiology of heart disease, New York Heart Association (NYHA) functional class, use of amiodarone and diuretics and left ventricular diameter by echocardiogram. However, group 1 patients had significantly less beta-adrenergic blocking agent use and higher ejection fraction (EF) (p < 0.002 and p < 0.001, respectively). Survival analysis for all deaths showed a greater risk of death among group 2 patients (p=0.01). Similarly, sudden death was increased in group 2 patients (p=0.02, risk ratio 1.8). After adjusting for the above variables, only EF (p=0.001) and NYHA class (p=0.01) were shown to be independent predictors of survival. Nonsustained ventricular tachycardia showed a trend (p=0.07) as an independent predictor for all-cause mortality but not for sudden death. Only EF was an independent predictor for sudden death. CONCLUSIONS: Nonsustained ventricular tachycardia is frequently seen in patients with heart failure and may be associated with worsened survival by univariate analysis. However, after adjusting other variables, especially for EF, NSVT was not an independent predictor of all-cause mortality or sudden death. These results have serious implications in that suppression of these arrhythmias may not improve survival.     

Precordial QT dispersion and inducible ventricular tachycardia

We compared the performance of precordial QT dispersion, late potentials on the signal-averaged electrocardiogram (ECG), and reduced left ventricular ejection fraction for identification of inducible ventricular tachycardia (VT) in 162 patients undergoing electrophysiologic study (EPS). QT(apex) dispersion in 56 patients with inducible VT (72 +/- 55 msec) was greater than that in 106 patients without inducible VT (55 +/- 36 msec, p < 0.01); dispersion was greater in both groups than in 144 normal subjects (33 +/- 19 msec). A QT(apex) dispersion partition of more than 68 msec, the upper ninety-fifth percentile in normal subjects, identified inducible VT with a specificity of 75% and a sensitivity of 45%. Although the performances of late potentials (specificity 82%, sensitivity 59%) and reduced ejection fraction (specificity 86%, sensitivity 54%) were each stronger than QT dispersion alone for identification of inducible VT, abnormal QT(apex) dispersion remained a significant additional predictor of inducible VT in a logistic regression model that included the three variables (specificity 78%, sensitivity 75%).     

Okadaic acid-stimulated degradation of p35, an activator of CDK5, by proteasome in cultured neurons

BACKGROUND: Implantable cardioverter-defibrillators have been infrequently used in children as therapy for resuscitated sudden death and syncope due to ventricular arrhythmias unresponsive to antiarrhythmics. METHODS: The medical records of 5 children with implantable cardioverter-defibrillators were retrospectively reviewed. All patients had experienced syncope and 3 (60%) an out-of-hospital cardiac arrest. Underlying pathology included hypertrophic cardiomyopathy in 2, long QT syndrome in 2, and ventricular arrhythmia after remote repair of congenital heart disease in 1. Open thoracotomy with epicardial lead placement and transvenous endocardial approaches were used. RESULTS: There was no early or late mortality in the 5 pediatric patients undergoing implantable cardioverter-defibrillator placement. Postoperative complications occurred more frequently when open thoracotomy was used for placement. At mean follow-up of 34 months, 4 of the 5 (80%) have received shocks. CONCLUSIONS: Implantable cardioverter-defibrillator is a safe and reliable therapy for children with resuscitated sudden death and syncope due to ventricular tachycardia unresponsive to antiarrhythmics. Transvenous lead placement lowers morbidity and hospital length of stay.