Lü Fei

Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction. Results of a two-year follow-up study.

OBJECTIVES The aim of this study was to compare the predictive value of mean RR interval assessed from predischarge Holter recordings with that of heart rate variability and left ventricular ejection fraction for risk stratification after myocardial infarction. BACKGROUND Heart rate variability is a powerful tool for risk stratification after myocardial infarction. Although heart rate variability is related to heart rate, little is known of the prognostic value of 24-h mean heart rate. METHODS A total of 579 patients surviving the acute phase of myocardial infarction were followed up for at least 2 years. Predischarge heart rate variability, 24-h mean RR interval and left ventricular ejection fraction were analyzed. RESULTS During the first 2 years of follow-up, there were 54 deaths, 42 of which were cardiac (26 sudden). Shorter mean RR interval was a better predictor of all-cause mortality as well as cardiac and sudden death than depressed left ventricular ejection fraction. Depressed heart rate variability predicted the risk of death better than mean RR interval for sensitivities < 40%. For sensitivities > or = 40%, mean RR interval was as powerful as heart rate variability. All three variables performed equally well in predicting nonsudden cardiac death. For cardiac death prediction, a left ventricular ejection fraction < 35% had a 40% sensitivity, 78% specificity and 14% positive predictive accuracy; a mean RR interval < 700 ms had a 45% sensitivity, 85% specificity and 20% positive predictive accuracy; and a heart rate variability < 17 U had a 40% sensitivity, 86% specificity and 20% positive predictive accuracy. CONCLUSIONS Predischarge 24-h mean heart rate is a strong predictor of mortality after myocardial infarction that can compete with left ventricular ejection fraction and heart rate variability.

Short- and long-term assessment of heart rate variability for risk stratification after acute myocardial infarction

Depressed heart rate variability (HRV) has been shown to be a powerful and independent risk factor in patients following acute myocardial infarction (AMI). A detailed comparison of the predictive values between short- and long-term HRV has not been made. The predictive value of short-term HRV for 1-year total cardiac mortality was studied in 700 consecutive patients after AMI. All patients underwent 24-hour Holter monitoring before discharge from the hospital (5 to 8 days after AMI) and were followed up for 1 year. Short-term HRV was computed as the standard deviation of all normal RR intervals (SDNN) from a 5-minute stationary period selected from 24-hour Holter electrocardiographic recordings. Long-term HRV was computed as an HRV index over the entire 24 hours. There was a significant but relatively poor correlation between SDNN and HRV index (r = 0.51, p <0.001). The positive predictive accuracy of SDNN for 1-year mortality (13% to 18%) was lower than the HRV index (17% to 43%) over a range of sensitivity of 25% to 75%. Assessment of HRV index in > or = 35% of the patients preselected by the lowest SDNN was able to achieve predictive power similar to that of HRV index assessed in all the patients. These data suggest that lower predischarge short-term HRV is associated with increased 1-year total cardiac mortality in patients after AMI. Analysis of long-term HRV for postinfarction risk stratification can safely be limited to patients preselected by depressed short-term HRV measures.

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.

Change of autonomie influence on the heart immediately before the onset of spontaneous idiopathic ventricular tachycardia

OBJECTIVES This study aimed to assess heart rate variability immediately before the onset of episodes of spontaneous ventricular tachycardia. BACKGROUND It has been shown that decreased heart rate variability may be associated with a propensity to ventricular tachyarrhythmias. However, it is still disputed whether there is an abrupt change in heart rate variability immediately before the onset of these arrhythmias. METHODS Twenty-three patients with idiopathic ventricular tachycardia underwent two-channel 24-h Holter monitoring in a drug-free state. Spectral heart rate variability was computed as low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components at 2-min intervals over a 1-h period immediately before the onset of ventricular tachycardia. Average values of heart rate variability were also computed for the entire 24-h recordings. The low/high frequency component ratio was calculated as an index of the autonomic balance of the heart. RESULTS Seventy-one episodes of ventricular tachycardia from the 23 recordings formed this study. There was an increased low/high ratio during 6- to 8-min periods immediately before the onset of ventricular tachycardia episodes compared with the average values for the entire 24 h. This increase in the low/high ratio resulted largely from a decrease in the high frequency component value (4.70 +/- 1.15 vs. 5.10 +/- 1.06 ln[ms2] [mean +/- SD], p = 0.001) because there was no significant change in the low frequency component value (6.37 +/- 1.20 vs. 6.34 +/- 0.91 ln[ms2], p = 0.786, 95% confidence interval -0.25 to 0.19 ln[ms2], type II error < 0.0001 for change of 7.8%). In contrast, there were no significant differences in the low or high frequency components or low/high ratio between 6-min salvo-free periods 40 min before the onset of ventricular tachycardia and the average 24-h values (type II error < 0.0001, < 0.038 and < 0.1841, respectively, for change of 7.8%). The low/high ratio was also significantly higher during the 6 min immediately before the onset of ventricular tachycardia compared with that during the 6-min salvo-free periods 40 min before the onset of ventricular tachycardia. A significant increase in mean heart rate immediately before the onset of ventricular tachycardia was also noted. CONCLUSIONS There is a significant change in autonomic influence on the heart during the last few minutes preceding the onset of episodes of idiopathic ventricular tachycardia. This seems to result mainly from decreased vagal activity rather than enhanced sympathetic input to the heart.

Decreased Heart Rate Variability in Patients with Congestive Heart Failure and Chronotropic Incompetence

Heart rate variability was studied in 41 patients (aged 48 ± 12 years) with congestive heart failure secondary to idiopathic dilated cardiomyopathy. All patients underwent a treadmill exercise test and 24‐hour Holter ECC monitoring. Chronotropic incompetence was defined as the failure to achieve > 80% of the predicted maximal heart rate response given by 220 – age (years) at peak exercise. Spectral heart rate variability was analyzed from 24‐hour Holter ECCs and was expressed as total (0.01–1.00 Hz), low (0.04–0.15 Hz), and high (0.15–0.40 Hz) frequency components. The standard deviation of all normal RR intervals (SDNN) was also computed. Chronotropic incompetence was observed in ten patients. Peak oxygen consumption was significantly lower in patients witb chronotropic incompetence compared with those without chronotropic incompetence. The total (5.11 ± 1.26 In [ms2] vs 6.41 ± 0.92 In [ms2]; P = 0.009) and low (3.38 ± 1.65 In [ms2] vs 5.45 ± 1.34 In [ms2];P = 0.003), but not the high (3.42 ± 1.04 In [ms2] vs 4.00 ± 1.12 in [ms2]; P = 0.249) frequency components of heart rate variability were significantly lower in patients with chronotropic incompetence, although there was no significant difference in mean heart rate (88 ± 20 beats/min vs 86 ± 15 beats/min; P = 0.831) or left ventricular ejection fraction (22%± 10% vs 24%± 10%; P = 0.619). SDNN was also significantly lower in patients with chronotropic incompetence compared witb those without chronotropic incompetence (64 ± 34 ms vs 102 ± 37 ms; P = 0.030). Conclusions: The observation that heart rate variability is significantly decreased in patients with congestive heart failure who have chronotropic incompetence suggests that chronotropic incompetence may relate to an abnormal autonomic influence on the heart in these patients.

Is there increased sympathetic activity in patients with hypertrophic cardiomyopathy

OBJECTIVES This study aimed to assess autonomic nervous system activity in patients with hypertrophic cardiomyopathy. BACKGROUND Patients with hypertrophic cardiomyopathy are traditionally thought to have increased sympathetic activity. However, convincing evidence is lacking. METHODS Heart rate variability was assessed from 24-h ambulatory electrocardiographic (Holter) recordings in 31 patients with hypertrophic cardiomyopathy and 31 age- and gender-matched normal control subjects in a drug-free state. Spectral heart rate variability was calculated as total (0.01 to 1.00 Hz), low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components using fast Fourier transformation analysis. RESULTS There was a nonsignificant decrease in the total frequency component of heart rate variability in patients with hypertrophic cardiomyopathy compared with that of normal subjects (mean +/- SD 7.24 +/- 0.88 versus 7.59 +/- 0.57 ln[ms2], p = 0.072). Although there was no significant difference in the high frequency component (5.31 +/- 1.14 versus 5.40 +/- 0.91 ln[ms2], p = 0.730), the low frequency component was significantly lower in patients than in normal subjects (6.25 +/- 1.00 versus 6.72 +/- 0.61 ln[ms2], p = 0.026). After normalization (i.e., division by the total frequency component values), the low frequency component was significantly decreased (38 +/- 8% versus 43 +/- 8%, p = 0.018) and the high frequency component significantly increased (16 +/- 6% versus 12 +/- 6%, p = 0.030) in patients with hypertrophic cardiomyopathy. The low/high frequency component ratio was significantly lower in these patients (0.94 +/- 0.64 versus 1.33 +/- 0.55, p = 0.013). In patients with hypertrophic cardiomyopathy, heart rate variability was significantly related to left ventricular end-systolic dimension and left atrial dimension but not to maximal left ventricular wall thickness. No significant difference in heart rate variability was found between 14 victims of sudden cardiac death and 10 age- and gender-matched low risk patients. CONCLUSIONS Our observations suggest that during normal daily activities, patients with hypertrophic cardiomyopathy experience a significant autonomic alteration with decreased sympathetic tone.

Ambulatory Assessment of the QT Interval in Patients with Hypertrophic Cardiomyopathy: Risk Stratification and Effect of Low Dose Amiodarone

This study aims to assess the dynamics of the QT interval in patients with hypertrophic cardiomyopathy (HCM). Three consecutive QT intervals and the preceding RR intervals were measured on 24‐hour ambulatory electrocardiograms at 30‐minute intervals in ten high risk patients with HCM (sudden cardiac death [SCD] and/or documented ventricular fibrillation), aged 29 ± 17 years, compared with ten age and sex matched low risk patients with HCM (no syncope, no adverse family history, and no ventricular tachycardia on Holter monitoring), and ten normal subjects. Another ten patients who were on amiodarone therapy (200‐mg daily) were also studied. Patients witb intraventricular conduction defects were excluded. There were 4,424 pairs of QT intervals and their preceding RR intervals were measured in this study. A nonsignificant prolongation in the QT interval and a significant prolongation in QTc values (Bazetts and Fridericias formulas) were demonstrated in patients with HCM compared with normals. There were no significant differences in the QT and QTc between high and low risk patients. The slope of regression line for the QT against RR interval was significantly different between normals and HCM (0.1583 ± 0.040 vs 0.2017 ± 0.043. P < 0.05), but not between high and low risk patients. Amiodarone significantly prolonged the QT and QTc without significantly altering the slope of the regression line (0.2017 ± 0.043 vs 0.2099 ± 0.037, NS). Our findings support the observations that there is a prolonged QT interval in patients with HCM and that there is no significant use dependent effect of amiodarone on ventricular repolarization. In conclusion, ambulatory assessment of the QT interval provides an alternative method for the assessment of ventricular repolarization and for the assessment of use dependent effects of anti arrhythmic drugs on ventricular repolarization during normal daily activities. However, this method does not help in the identification of patients at high risk of SCD in HCM.

Is there an abnormal QT interval in sudden cardiac death survivors with a “normal” QTc?

Correcting the QT interval for heart rate may mask ventricular repolarization abnormalities and may lead to a misinterpretation of the physiologic and pathophysiologic findings. In this study the QT/R-R relationship was studied in eight sudden cardiac death (SCD) survivors without overt structural heart disease and compared with eight age- and sex-matched normal subjects. All patients were in a drug-free state. The QT intervals and their preceding R-R intervals were measured on electrocardiogram (ECG) strips from 24-hour Holter recordings at hourly intervals. The differences in mean heart rate, mean QT intervals, and QTc values between SCD survivors and normal subjects were not statistically significant. There was a significant correlation between the QT and R-R intervals in normal subjects (tau = 0.71 +/- 0.13, p < 0.05) and in SCD survivors (tau = 0.79 +/- 0.07, p < 0.05). However, the regression line of the QT interval against the R-R interval was significantly (p < 0.01) altered in SCD survivors compared with normal subjects. These observations suggest that there is abnormal ventricular repolarization (QT interval) despite an apparently normal QTc using Bazetts formula in these patients. Evaluation of the QT/R-R relationship by means of 24-hour ambulatory Holter ECG monitoring may provide a useful clinical tool for the assessment of ventricular repolarization abnormalities.

Effects of passive tilt and submaximal exercise on spectral heart rate variability in ventricular fibrillation patients without significant structural heart disease

It has been shown that tilt and exercise elicit significant changes in autonomic activity in normal subjects and that submaximal exercise causes a greater reduction in heart rate variability (HRV) in animals susceptible to ventricular fibrillation (VF). Whether there is an abnormal HRV response to tilt and exercise in patients at risk of sudden cardiac death (SCD) remains unknown. Short-term HRV before and during passive tilt and exercise was studied in 12 survivors of out-of-hospital cardiac arrest with documented VF and compared with 12 age- and sex-matched normal controls. No patient had significant structural heart disease or left ventricular dysfunction. HRV was computed as total-frequency (TF, 0.01 to 1.00 Hz), low-frequency (LF, 0.04 to 0.15 Hz) and high-frequency (HF, 0.15 to 0.40 Hz) components. There was no significant difference between normal controls and SCD survivors in HRV before or during tilt or submaximal exercise testing. The HF component was significantly decreased during tilt compared with that in the supine position in both normal controls (5.85 +/- 0.61 vs 5.08 +/- 0.95 In(msec2), p = 0.005) and patients (5.58 +/- 1.49 versus 4.74 +/- 1.18 In(msec2), p = 0.003). There was again no significant change in the TF or LF components during tilt in either patients or controls. All frequency components were significantly decreased during submaximal exercise testing in both patients and controls. However, there was no significant difference in any of these tilt- and exercise-induced changes in HRV between normal controls and SCD survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration of the QT/RR Relationship in Patients with Idiopathic Ventricular Tachycardia

It has been shown that alterations in QT/RR relationship may be associated with arrhythmogenesis in several clinical settings. In the present study the QT/RR relationship was studied in 20 patients with idiopathic ventricular tachycardia (12 men and 8 women, aged 41±14 years) compared to 20 normal subjects (9 men and 11 women, aged 39 ± 13 years). All the patients were off any antiarrhythmic drugs and had no evidence of intraventricular conduction defects. The QT intervals and their preceding RR intervals were measured on electrocardiogram strips from 24‐hour Holter tapes at hourly intervals. The differences in the maximum, minimum, and mean of either the QT interval or its corrected values between patients with idiopathic ventricular tachycardia and normal subjects were not statistically significant. There was a significant correlation between the QT and RR intervals in normal subjects (γ= 0.73 ± 0.12, P < 0.05) and in patients with idiopathic ventricular tachycardia (γ= 0.80 ± 0.10, P < 0.05). However, the linear regression line of the QT interval against the RR interval were significantly (P < 0.001) altered in patients with idiopathic ventricular tachycardia (QT = 0.24 + 0.18 RR) compared to normal subjects (QT = 0.27 ± 0.12 RR). We conclude that although there is no significant change in the QT interval and its corrected values, the QT/RR relationship is significantly altered in patients with idiopathic ventricular tachycardia as compared to normal subjects. This may be of importance in the pathogenesis of idiopathic ventricular tachycardia in these patients.