Yaver Bashir

Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability, ambulatory electrocardiographic variables and the signal-averaged electrocardiogram

The value of heart rate variability, ambulatory electrocardiographic (ECG) variables and the signal-averaged ECG in the prediction of arrhythmic events (sudden death or life-threatening ventricular arrhythmias) was assessed before hospital discharge in 416 consecutive survivors of acute myocardial infarction. During the follow-up period (range 1 to 1,112 days), there were 24 arrhythmic events and 47 deaths. The initial relation between several prognostic factors and arrhythmic events was explored with use of the Kaplan-Meier product limit estimates of survival function. Impaired heart rate variability less than 20 ms (p less than 0.0000), late potentials (p less than 0.0000), ventricular ectopic beat frequency (p less than 0.0000), repetitive ventricular forms (p less than 0.0000), left ventricular ejection fraction less than 40% (p less than 0.02) and Killip class (p less than 0.02) were identified as significant univariate predictors of arrhythmic events. When these variables were analyzed by using a stepwise Cox regression model, only impaired heart rate variability, followed by late potentials and repetitive ventricular forms remained independent predictors of arrhythmic events. The combination of impaired heart rate variability and late potentials had a sensitivity of 58%, a positive predictive accuracy of 33% and a relative risk of 18.5 for arrhythmic events and was superior to other combinations including those incorporating left ventricular function, exercise ECG, ventricular ectopic beat frequency and repetitive ventricular forms. These results suggest that a simple method of assessment based on heart rate variability and the signal-averaged ECG can select a small subgroup of survivors of myocardial infarction at high risk of future life-threatening arrhythmias and sudden death.

Comparison of the predictive characteristics of heart rate variability index and left ventricular ejection fraction for all-cause mortality, arrhythmic events and sudden death after acute myocardial infarction.

Heart rate (HR) variability index and left ventricular ejection fraction (EF) were compared for the prediction of all-cause mortality, arrhythmic events and sudden death in 385 survivors of acute myocardial infarction. For arrhythmic events, where, for a sensitivity of 75%, HR variability index had a specificity of 76%, EF had a specificity of only 45%. An EF of less than or equal to 40% had a sensitivity of 42% and a specificity of 75% for arrhythmic events; for the same sensitivity an HR variability index of 20 U had a specificity of 92%. An EF less than or equal to 40% had a sensitivity of 40% and a specificity of 73% for sudden death; HR variability index had a specificity of 83% for the same sensitivity. For all cause mortality, where, for a sensitivity of 75%, HR variability index had a specificity of 52%, EF had a specificity of 40%. It is concluded that HR variability index appears a better predictor of important postinfarction arrhythmic complications than left ventricular EF, but both indexes perform equally well in predicting all-cause mortality.

Assessment of heart rate variability in hypertrophic cardiomyopathy. Association with clinical and prognostic features.

BackgroundAltered vascular responses during exercise and disturbed responses to autonomic function testing have been documented in hypertrophic cardiomyopathy (HCM) and are associated with markers of an adverse prognosis. Reduced heart rate variability (HRV) and baroreflex sensitivity are predictors of increased risk of sudden death after myocardial infarction, but the value of these parameters in 11CM is unknown. Methods and ResultsTo determine the clinical significance of HRV and its relation to markers of electrical and hemodynamic instability in 1CM, the 24-hour Holter recordings of 104 patients in sinus rhythm and off medication were analyzed. Five nonspectral measures of HRV were computed. The frequency components ofHRVwere calculated by fast Fourier transformation of the RR time intervals; the areas under the low (0.04 to 0.15 Hz) and high (0.15 to 0.4 Hz) frequency portions of the spectrum were measured as indices of autonomic and specific vagal influences on HRV, respectively. Spectral and nonspectral measures were compared with clinical, echo/Doppler, and Holter variables. ANCOVA was performed to allow for the effect of age on differences between variables. Spectral and nonspectral measures of HRV were correlated (r>.65; Ps.001), indicating that the different time-domain and frequency parameters reflected similar measures ofHRY. Global measures ofHRV including the standard deviation of the mean ofRR intervals (SDRR) and the standard deviation of 5-minute mean RR intervals (SDANN) were increased in patients with an adverse family history of 1CM (173±67 vs 131±38 milliseconds, P=.001, and 158±66 vs 116+36 milliseconds, P=.004, respectively). In patients with exertional chest pain, global nonspectral measures were reduced compared with asymptomatic patients (118±31 vs 152±53 milliseconds, P=.006, and 105±30 vs 136±52 milliseconds, P=.014, respectively). Specific vagal influences on HRV including the proportion of RR intervals more than 50 milliseconds different (PNN5O) and the high frequency peak on spectral analysis were less in patients with supraventricular arrhythmias on Holter monitoring (7.2±8 vs 16±13%, P=.012, and 21±+10 vs 28±+13 milliseconds, P=.048, respectively). Similarly, both global and specific vagal measures of HRV were less in the 27 patients with nonsustained ventricular tachycardia on Holter (PNN5O, 7.7±9 vs 15±_13 milliseconds, P=.048, and high frequency component, 19±9 vs 28±+13 milliseconds, P=.05. During follow-up, 10 patients, 9 of whom were aged less than 33 years, experienced catastrophic events; 6 were resuscitated from ventricular fibrillation and 4 died suddenly. Indices of HRV were similar in these 10 patients to indices in the 94 survivors. ConclusionsTime-domain and spectral measures of BRV yield similar information about the specific autonomic influences on the heart. Global and specific vagal influences on HRV were reduced in patients with symptoms and arrhythmias and global HRV is increased in patients with an adverse family history of HCM, but these indices do not add to the predictive accuracy of established risk factors.

Impaired immediate vasoconstrictor responses in patients with recurrent neurally mediated syncope

Immediate responses to head-up tilt were determined in 78 consecutive patients with unexplained syncope undergoing 45-minute tilt tests at 60 degrees. Thirty-four patients developed neurally mediated syncope (mean time to syncope 18 minutes), 40 tolerated the full duration of tilt, and 4 were unable to complete the study but did not develop syncope. Blood pressure, heart rate, forearm blood flow and forearm vascular resistance were measured at baseline and after 2 and 5 minutes of tilt. Syncopal and nonsyncopal patients were well-matched for age and baseline hemodynamic parameters. There was no difference between the groups in heart rate or blood pressure at 2 minutes, but there was a small but significant difference in percent reduction in mean arterial pressure at 5 minutes. After 2 and 5 minutes of tilt, mean forearm blood flow was 2.4 and 2.6 ml/min/100 ml, respectively, in syncopal patients compared with 1.6 (p < 0.05) and 1.7 ml/min/100 ml (p < 0.01), respectively, in patients who tolerated 45 minutes of tilt. In syncopal patients, forearm vascular resistance was 51.0 and 44.0 at 2 and 5 minutes, respectively, whereas in nonsyncopal patients, it was 82.4 (p < 0.02) and 73.1 (p < 0.001), respectively. These differences remained consistent when only data for patients developing syncope after > 15 minutes were included in the analysis. Patients with neurally mediated syncope have clearly demonstrable abnormalities in vascular control immediately after assumption of the upright posture. The results shed new light on the pathophysiology of neurally mediated syncope.

Assessment of autonomic function in patients with neurally mediated syncope: Augmented cardiopulmonary baroreceptor responses to graded orthostatic stress

OBJECTIVESnThe purpose of this study was to assess vagal tone and cardiopulmonary baroreceptor activity in patients with tilt-induced neurally mediated syncope.nnnBACKGROUNDnThe causes of individual susceptibility to orthostatic stress leading to recurrent neurally mediated syncope remain obscure. The trigger for sympathetic withdrawal and increased vagal activity is believed to be stimulation of ventricular mechanoreceptors.nnnMETHODSnSeventeen patients (mean age 50.6 years) with recurrent syncope and a positive response on a 45-min 60 degrees head-up tilt test were compared with a control group of 17 patients (mean age 47.5 years) with unexplained syncope and negative tilt test findings. Vagal activity was assessed by high pressure baroreceptor testing and by temporal and spectral analysis of heart rate variability during Holter ambulatory electrocardiographic monitoring. Cardiopulmonary baroreceptor sensitivity was assessed by measurement of forearm vascular responses to lower body negative pressure.nnnRESULTSnMean high pressure baroreceptor sensitivity was 16.4 +/- 12.2 ms/mm Hg in the group with a positive tilt test response compared with 15.1 +/- 13.0 ms/mm Hg in the control group (p = NS). There were no significant differences between the groups in any of the temporal or spectral measures of heart rate variability. The increase in forearm vascular resistance in response to lower body negative pressure was 11.5 +/- 14.2 U in patients with tilt-induced syncope and 3.5 +/- 3.2 U in the control group at -5 mm Hg, 16.8 +/- 18.6 U and 4.8 +/- 5.3 U, respectively, at -10 mm Hg and 26.4 +/- 24.3 U and 10.2 +/- 7.8 U, respectively, at -20 mm Hg (p < 0.001).nnnCONCLUSIONSnPatients with tilt-induced neurally mediated syncope have augmented cardiopulmonary baroreceptor responses to orthostatic stress. This finding sheds new light on the etiology of neurally mediated syncope.

Localization of accessory pathways from the 12-lead electrocardiogram using a new algorithm

A new algorithm (St. Georges algorithm), based on the polarity and morphology of QRS complexes rather than delta waves, was developed for localizing accessory pathways to 1 of 9 sites on the atrioventricular annuli. This was compared with algorithms previously proposed by Skeberis et al (localizing to 1 of 7 sites) and Milstein et al (localizing to 1 of 4 sites). The preexcited 12-lead electrocardiograms recorded during sinus rhythm in 106 consecutive patients (including 60 retrospectively analyzed patients and 46 prospectively analyzed patients) who underwent successful radiofrequency catheter ablation of a single accessory pathway were analyzed by 3 blinded observers using all 3 algorithms. The results were compared with the actual localization of accessory pathways as derived from endocardial mapping during catheter ablation. In all 106 patients, the accuracy of the 3 algorithms for 4 sites on the atrioventricular annuli (as considered by Milsteins method) was 72%, 79%, and 92% for Milsteins, Skeberis, and St. Georges algorithms, respectively. For 7 sites (as considered by Skeberis method), the accuracy was 65% (Skeberis algorithm) and 88% (St. Georges algorithm), and for 9 sites (as considered by our method) the accuracy was 86% (St. Georges algorithm). In 46 prospectively analyzed patients, the accuracy of the 3 algorithms for 4 sites was 70% (Milsteins), 67% (Skeberis), and 87% (St. Georges); for 7 sites the accuracy was 61% (Skeberis) and 85% (St. Georges), and for 9 sites the accuracy was 85% (St. Georges). The reproducibility of St. Georges and Skeberis methods was better than that of Milsteins method.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of long-term oral magnesium chloride replacement in congestive heart failure secondary to coronary artery disease.

Magnesium deficiency frequently develops in patients with congestive heart failure and may increase susceptibility to lethal arrhythmias and sudden death via multiple pathophysiologic mechanisms. The effects of peroral magnesium supplementation were investigated in a randomized, double-blind, crossover trial involving 21 patients with stable congestive heart failure secondary to coronary artery disease. All were receiving long-term loop diuretics, and had normal renal function, and low or normal serum magnesium concentrations. Subjects alternately received enteric-coated magnesium chloride (15.8 mmol magnesium per day) and placebo for 6 weeks. Magnesium therapy increased serum magnesium from 0.87 +/- 0.07 to 0.92 +/- 0.05 mmol/liter (p < 0.05), serum potassium from 4.0 +/- 0.3 to 4.3 +/- 0.4 mmol/liter (p < 0.01) and urinary magnesium excretion from 2.82 +/- 0.96 to 4.74 +/- 2.38 mmol/24 hours (p = 0.001). There was no significant change in heart rate or Doppler cardiac index, but mean arterial pressure decreased from 91 +/- 10 to 87 +/- 10 mm Hg (p < 0.05) and systemic vascular resistance from 1,698 +/- 367 to 1,613 +/- 331 dynes s cm-5 (p = 0.047). The frequency of isolated ventricular premature complexes was reduced by 23% (95% confidence interval [CI] 6 to 37%; p < 0.02), couplets by 52% (95% CI 30 to 65%; p < 0.001) and nonsustained ventricular tachycardia episodes by 24% (95% CI 15 to 49%; p < 0.01). Plasma epinephrine decreased from 447 +/- 535 to 184 +/- 106 pg/ml (p = 0.02), but there was no corresponding change in plasma norepinephrine or heart rate variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine infusion for the reversal of pulmonary vasoconstriction in biventricular failure. A good test but a poor therapy.

BackgroundElevation of pulmonary vascular resistance is an important determinant of right ventricular function in patients with end-stage biventricular heart failure. Vasodilator drug therapy directed at the pulmonary vasculature is used in the hemodynamic assessment of patients for orthotopic heart transplantation, and therapy aimed at decreasing pulmonary vascular resistance and transpulmonary pressure gradient has been advocated in patients awaiting heart transplantation. Adenosine infusion has been shown to cause selective pulmonary vasodilatation in normal subjects and in patients with primary pulmonary hypertension but has not been assessed in patients with biventricular heart failure. Methods and ResultsUsing two infusion doses, we studied the pulmonary and renal hemodynamic effects of adenosine on patients referred for heart transplantation (n=21) and compared it with sodium nitroprusside (n= 18). Patients received 30percnt; oxygen via face mask throughout the study. Adenosine at 100 μg/kg/min achieved the same percentage fall in pulmonary vascular resistance as nitroprusside (41±6% versus 42±4%) and a greater and more consistent fall in transpulmonary pressure gradient (35±6% versus 9±30%, p<0.02). The mean arterial blood pressure fell by 16 mm Hg with nitroprusside but was unchanged by adenosine, indicating that in contrast to nitroprusside, adenosine acted as a selective pulmonary vasodilator. Despite this, cardiac index showed only a modest increase with adenosine (1.73 ±0.09 to 1.89±0.161. m −2, p<0.05), and there was a rise in pulmonary capillary wedge pressure from baseline at the higher dose (29.7±2.5 to 33.4±3.4 mm Hg, p<0.05). Renal blood flow was unchanged during adenosine infusion. ConclusionsAdenosine is a potent selective pulmonary vasodilator in patients with biventricular heart failure and is preferable to sodium nitroprusside as a test for the reversibility of pulmonary vasoconstriction. However, its deleterious effects on left atrial pressure make it unsuitable as a therapeutic agent in patients awaiting heart transplantation.

Do patients with neurally mediated syncope have augmented vagal tone

Abstract Head-up tilt testing is now recognized as a valuable diagnostic tool for identifying patients with neurally mediated syncope. However, the causes of individual susceptibility to such orthostatic stress have not been well characterized in this patient population. At the time of syncope, there is evidence to suggest both withdrawal of sympathetic tone as well as increased vagal activity. The latter is manifest by bradycardia, increased high-frequency spectral power of heart rate variability and release of pancreatic polypeptide. 1,2 The purpose of this study was to assess the importance of resting autonomic tone assessed by temporal and spectral measures of heart rate variability and vagal reserve assessed by baroreceptor sensitivity in patients with neurally mediated syncope and in control subjects.

Frequency versus time domain analysis of signal-averaged electrocardiograms. II. Identification of patients with ventricular tachycardia after myocardial infarction.

Late potentials detected by the time domain signal-averaged electrocardiogram (ECG) are a well established marker for ventricular tachycardia in patients after a myocardial infarction, but the value of frequency domain analysis of the signal-averaged ECG in identifying these patients remains controversial. This study compared the results of time domain, frequency domain and spectral temporal mapping analyses of the signal-averaged ECG in 30 postinfarction patients with spontaneous sustained ventricular tachycardia and in 30 postinfarction patients without ventricular tachycardia matched for age, gender and infarct site. No patient with bundle branch block was included. Time domain signal-averaged ECG indexes were significantly different in patients with and without ventricular tachycardia (p less than 0.001). Frequency domain results were not consistently different between these groups. The values of the normality factor of spectral temporal mapping were significantly lower in patients with ventricular tachycardia (p less than 0.04). Results of the time domain signal-averaged ECG were abnormal in 22 patients with ventricular tachycardia (73%) but in only 3 control patients (10%) (p less than 0.001). Spectral temporal mapping results were abnormal in 21 patients with ventricular tachycardia (70%) compared with 12 control patients (40%) (p less than 0.04). When the optimal numeric values of dichotomy points were computed for patient stratification at different sensitivity levels, time domain analysis identified patients with ventricular tachycardia with significantly fewer false positive results than were obtained with either frequency analysis or spectral temporal mapping. It is concluded that frequency domain analysis and spectral temporal mapping of the signal-averaged ECG did not improve the identification of postinfarction patients with ventricular tachycardia and without bundle branch block.