Morphological algebraic models of the TU-wave patterns/in idiopathic long QT syndrome.

A computer-assisted analysis of the TU-complex morphology was employed to characterize repolarization abnormalities in LQTS and to assess arrhythmic risk. Electrocardiograms (ECGs) were collected from 14 idiopathic LQTS patients (seven without symptoms and seven with a history of syncope or cardiac arrest) and from 14 sex- and age-matched normal subjects. Digitized TU-wave patterns from V2-V6 precordial leads were analyzed. The morphologies of the T and U waves were modeled by an algebraic sum of differences between two pairs of action potential-like curves of different shape and duration so that the whole TU complex was approximated by (S1-S2)+(L1-L2). By finding the best fit model of the digitized TU-wave signal, the amplitude and duration of each decomposition curve were determined for each lead. The following 'secondary' parameters were then derived: (a) the ratio between the sum of the amplitudes of the two long (L1 and L2) and the two short (S1 and S2) decomposition curves (A-ratio), (b) the highest A-ratio found in V2 to V6 (A-ratio(max)), and (c) the model-derived durations of the T-wave, U-wave and TU-complex. Conventional measures of RR and QTc intervals and of QT dispersion did not differ between symptomatic and asymptomatic LQTS patients. Modeled QT interval was significantly longer in the symptomatic than in the asymptomatic LQTS patients and in asymptomatic LQTS patients than in the controls. In addition, symptomatic LQTS patients had a longer S2 and T-wave duration in most leads than normal subjects. Conversely, modeled QU interval and U-wave duration did not significantly differ between the three groups. Compared to normal subjects, the amplitudes of S1, S2, L1 and L2 in the LQTS patients were not significantly different in most leads. A-ratio and A-ratio(max) were greater in symptomatic than asymptomatic LQTS patients and in the latter than in controls. A cut-off value of 0.90 of A-ratio(max) separated all symptomatic (1.34+/-0.38) from all asymptomatic patients (0.60+/-0.21). Although the correlation between model parameters and cellular substrate is at present unclear, it is possible that the morphological alterations described by the model are related to the arrhythmogenic mechanism(s) of the idiopathic LQTS.

Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training.

BACKGROUND: The absence (deletion allele [D]) of a 287-base pair marker in the ACE gene is associated with higher ACE levels than its presence (insertion allele [I]). If renin-angiotensin systems regulate left ventricular (LV) growth, then individuals of DD genotype might show a greater hypertrophic response than those of II genotype. We tested this hypothesis by studying exercise-induced LV hypertrophy. METHODS AND RESULTS: Echocardiographically determined LV dimensions and mass (n=140), electrocardiographically determined LV mass and frequency of LV hypertrophy (LVH) (n=121), and plasma brain natriuretic peptide (BNP) levels (n=49) were compared at the start and end of a 10-week physical training period in male Caucasian military recruits. Septal and posterior wall thicknesses increased with training, and LV mass increased by 18% (all P<.0001). Response magnitude was strongly associated with ACE genotype: mean LV mass altered by +2.0, +38.5, and +42.3 g in II, ID and DD, respectively (P<.0001). The prevalence of electrocardiographically defined LVH rose significantly only among those of DD genotype (from 6 of 24 before training to 11 of 24 after training, P<.01). Plasma brain natriuretic peptide levels rose by 56.0 and 11.5 pg/mL for DD and II, respectively (P<.001). CONCLUSIONS: Exercise-induced LV growth in young males is strongly associated with the ACE I/D polymorphism.

Use of ventricular premature complexes for risk stratification after acute myocardial infarction in the thrombolytic era.

The independent predictive role of ventricular premature complex (VPC) frequency in the stratification of mortality risk after acute myocardial infarction (AMI) was established in the prethrombolytic era by extensive multicenter trials. Thrombolysis has lead to important changes in the natural history of patients after AMI, so that reassessment of established risk factors is now required. The prognostic significance of VPCs was assessed in 680 patients, of whom 379 received early thrombolytic therapy. All patients underwent 24-hour Holter monitoring in a drug-free state between 6 and 10 days after AMI. Patients were followed up for 1 to 8 years. During the first year of follow-up, cardiac death occurred in 33 patients, sudden death in 24, and sustained ventricular tachycardia in 20. Mean VPC frequency was significantly higher in patients who died of cardiac causes, in those who died suddenly, and in those with arrhythmic events during the first year of follow-up. This was also true when patients who did and did not undergo thrombolysis were considered separately. The positive predictive accuracy of VPC frequency in predicting adverse cardiac events was greater in patients who did than did not undergo thrombolysis. At a sensitivity level of 40%, the positive predictive accuracy for cardiac mortality and arrhythmic events for the group with thrombolysis was 19.4% and 25.8%, respectively, compared with 16% and 16% for those without thrombolysis. Moreover, the highest VPC frequency for the dichotomy of patients into high-and low-risk groups was 25 VPCs/hour for patients without thrombolysis. VPC frequency appears to be more highly predictive of prognosis after AMI in patients who have undergone thrombolysis than in those who have not, but the optimal frequency for dichotomy is higher in the former.

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)

Change of autonomic 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.

Relationship between short- and long-term measurements of heart rate variability in patients at risk of sudden cardiac death.

Because of technical difficulties in analyzing heart rate variability (HRV) from ambulatory Holter recordings over 24-hour periods, short-term recordings are more practical for the clinical application of HRV. However, the relationship between short- and long-term recordings is unclear. In this study, short-term (10 min) electrocardiograms were assessed in the supine position, during passive head-up tilt and on standing in 15 patients (aged 39 +/- 14 years) with ventricular tachycardia/fibrillation not associated with coronary artery disease. Spectral HRV was computed as total frequency (TF: 0.01-1.00 Hz), low frequency (LF: 0.04-0.15 Hz), and high frequency (HF: 0.15-0.40 Hz) components. The short-term HRV parameters were compared with those obtained from long-term (24 hour) recordings from the same patients. There was a significant decrease in the HF component of HRV and a significant increase in LF/HF ratio during passive tilt or active standing compared with supine recordings, but no significant changes were observed in the TF or LF components. All frequency components of HRV for the 24-hour periods showed significant correlation with the values from short-term recordings (tau ranged from 0.67-0.87). Stepwise multivariate regression analysis showed that both the TF and HF components of HRV over 24 hours were predominantly related to the corresponding frequency components of HRV in the supine position, while the LF component of HRV over 24 hours was predominantly related to that on standing. Our observations suggest that the short-term HRV is related to the long-term value, but global HRV over 24 hours cannot completely be replaced by the short-term recordings.(ABSTRACT TRUNCATED AT 250 WORDS)

QT dispersion: problems of methodology and clinical significance.

QT dispersion is defined as the difference in QT interval between the different leads of the surface 12-lead ECG. This may provide an indirect measure of the underlying inhomogeneity of myocardial repolarization, which is believed to be important in arrhythmogenesis. Methodology for determining QT dispersion varies significantly between studies, and the results of these studies need to be interpreted in light of the methodology used. Although QT dispersion is developing into an important research tool, as yet it has no established role in clinical practice. Once standardization of methodology is achieved a clinical role may emerge, particularly in the assessment of patients before and after intervention aimed at reduction of arrhythmia risk.

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 Bazett's 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.

Heart rate variability and its relation to ventricular arrhythmias in congestive heart failure.

BACKGROUND: It has been shown that heart rate variability is decreased in patients with congestive heart failure and that depressed heart rate variability is associated with a propensity to ventricular arrhythmias. Little is known, however, about heart rate variability in patients with both congestive heart failure and ventricular arrhythmias. METHODS: Spectral heart rate variability was analysed from 24 hour ambulatory electrocardiograms in 15 controls, 15 patients with non-sustained ventricular tachycardia associated with clinically normal hearts (NHVT group), and 40 patients with congestive heart failure (CHF group) secondary to either ischaemic heart disease (n = 15) or idiopathic dilated cardiomyopathy (n = 25). Of the 40 patients with congestive heart failure 15 had no appreciable ventricular arrhythmias (ventricular extrasystoles < 10 beats/h and no salvos) and formed the CHF-VA- group. Another 15 patients with congestive heart failure and non-sustained ventricular tachycardia formed the CHF-NSVT group. RESULTS: Heart rate variability was significantly lower in the CHF group than in controls (mean (SD) total frequency 23 (12) v 43 (13) ms; low frequency 12 (8) v 28 (9) ms; high frequency 8 (5) v 14 (7) ms; p < 0.001). The differences in heart rate variability between controls and the NHVT group, between ischaemic heart disease and dilated cardiomyopathy, and between the CHF-VA- and CHF-NSVT groups were not significant. In the CHF group heart rate variability was significantly related to left ventricular ejection fraction but not associated with ventricular arrhythmias. The frequency of ventricular extrasystoles was significantly related to the high frequency component of heart rate variability (r = 0.54, p < 0.05) in the NHVT group. Stepwise multiple regression analysis showed that in the CHF group, heart rate variability was predominantly related to left ventricular ejection fraction (p < 0.05). There was no significant difference in heart rate variability between survivors (n = 34) and those who died suddenly (n = 6) at one year of follow up in the CHF group. CONCLUSION: In patients with congestive heart failure, heart rate variability is significantly decreased. The depressed heart rate variability is principally related to the degree of left ventricular impairment and is independent of aetiology and the presence of ventricular arrhythmias. The data suggest that analysis of heart rate variability does not help the identification of patients with congestive heart failure at increased risk of sudden death.

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 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 (gamma = 0.73 +/- 0.12, P < 0.05) and in patients with idiopathic ventricular tachycardia (gamma = 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.

Decreased heart rate variability in survivors of sudden cardiac death not associated with coronary artery disease.

BACKGROUND: Although heart rate variability has already been studied in survivors of sudden cardiac death secondary to coronary artery disease, an assessment of heart rate variability in survivors of sudden cardiac death not associated with coronary artery disease has not been made. METHODS: 10 patients with aborted sudden cardiac death not associated with coronary artery disease (seven patients with primary ventricular fibrillation and three with unclassified mild cardiomyopathy) underwent two channel 24 hour Holter monitoring in a drug free state. All subjects were in sinus rhythm and had normal atrioventricular conduction and normal cardiac function. Spectral heart rate variability was analysed on a Holter analysis system 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 for each hour. Heart rate variability index was calculated for the 24 hour periods. 10 age and sex matched healthy subjects were taken as a control group. RESULTS: The spectral heart rate variability over 24 hours was significantly lower in survivors of sudden cardiac death than in controls (total 38(15) v 48(14) ms; low, 25(11) v 32(13) ms; and high, 13(8) v 18(8) ms; p < 0.05 for all comparisons). The differences in the ratio of low/high (2.19(0.76) v 1.98(0.50), p = 0.132), mean heart rate (77(12) v 69(12) beats/min, p = 0.070), and heart rate variability index (38(12) v 44(16), p = 0.287) over 24 hours between survivors of sudden cardiac death and controls did not reach significance. Comparisons of the hourly heart rate variability over the 24 hour period between the two groups showed that the differences in all components of heart rate variability, low/high ratio and mean heart rate were highly significant. Furthermore, there was no significant difference in the maximum hourly heart rate variability over the 24 hour period. The minimum hourly heart rate variability was, however, significantly lower in survivors of sudden cardiac death than in controls (total, 20(8) v 28(4) ms; low, 12(6) v 17(3) ms; high, 6(2) v 8(2) ms; p < 0.05 for all comparisons). CONCLUSIONS: These findings suggest that there is abnormal autonomic influence on the heart in patients without coronary artery disease at risk of sudden cardiac death. Hourly analysis of heart rate variability throughout the 24 hour period may provide additional information important in the identification of high risk patients.

Carcinoma of the caecum in a scorbutic patient.

The clinical findings of scurvy have been known for well over 3,000 years. In 1753, Sir James Lynd demonstrated the efficiency of citrus fruit in the prevention of this condition. Scurvy still occurs from time to time in this country, notably in the elderly, particularly in bachelors who live alone and eat a poor diet. Scurvy has been associated with gastrointestinal malignancy, but, as far as we know, it has not been reported in association with carcinoma of the caecum. We report the case of an elderly female patient who presented with features of scurvy and was also found to have carcinoma of the caecum.