Prevention of ventricular extrasystole by mexiletine in patients with normal QT intervals is associated with a reduction of transmural dispersion of repolarization

BACKGROUNDS: Antiarrhythmic potential of mexiletine in patients with congenital and acquired long-QT syndrome (LQTS) has been attributed to a reduction of transmural dispersion of repolarization (TDR). A similar mechanism could be involved in the antiarrhythmic activity of the drug in patients with normal QT intervals, but the issue remains to be investigated. METHODS AND RESULTS: We analyzed 24-h Holter ECG recordings from 17 patients in sinus rhythm showing premature ventricular complexes (PVCs) with normal QT intervals (age, 62+/-10 years, mean+/-S.D.). Treatment of the patients with oral mexiletine (300 mg/day for 21-40 days) resulted in a significant reduction of PVCs (from 13899+/-18887 to 6949+/-12822 beats/24 h, p<0.01). Rate-dependent behavior of ventricular repolarization was analyzed by plotting QT intervals (QT(peak), QT(end)), and the interval from T-wave peak to T-wave end (TPE) against preceding respective RR intervals of sinus beats. Both the QT(peak) and QT(end) tended to be shortened by mexiletine at RR intervals from 600 ms to 1000 ms, although the changes did not reach statistical significances. TPE, which reflects TDR, was shortened significantly at relatively long RR intervals (by 14+/-9% at RR of 900 ms, p<0.05). There was a linear relationship between the percentage shortening of TPE and the percentage reduction of PVCs (r=0.86, p<0.04). TPE> or =70 ms was significantly associated with PVC suppression >75% with an odds ratio of 0.60 (95% confidence interval 0.36-0.98, per 1 ms increment). CONCLUSION: Inhibitory effect of mexiletine against PVCs in patients with normal QT intervals is mediated at least in part by a reduction of TDR. Mexiletine may be effective in patients exhibiting longer baseline TPE.     

Effects of β-Blocker Therapy on the Dynamic QT/RR Relation in Patients with Long QT Syndrome During 24-Hour Holter ECG Monitoring

Objective: Patients with long QT syndrome (LQTS) have an abnormality in the dynamic relationship between the QT and RR intervals (QT/RR relation) assessed by 24-hour Holter ECG monitoring. The clinical efficacy of β-blocker therapy in LQTS patients has been established, but its antiarrhythmic mechanism has not been fully elucidated. In the present study, the influences of β-blocker therapy on the QT/RR relation were investigated in LQTS patients with no arrhythmic event during β-blocker therapy. Methods: Holter ECG recordings before and after the therapy were obtained from seven LQTS patients (all female, age range 10–45 years). The QT/RR relation was analyzed by our original computer algorithm with automatic measurement of the Q-aT interval (time interval from the QRS onset to the T wave apex. The correlation coefficient (r), and the slope of the best fit linear regression line between the Q-aT and RR intervals (Q-aT/RR slope) after β-blocker therapy were compared with those before the therapy. To determine whether the dose of β-blockers was sufficient for suppression of the sympathetic nervous activity, a frequency-domain analysis of the heart rate variability was performed (low frequency power [LF]: 0.04–0.15 Hz, high frequency power [HF]: 0.15–0.40 Hz). Results: The LF component of the heart rate variability decreased and the HF component increased during the daytime after β-blocker therapy. However, the Q-aT/RR relation after β-blocker therapy was the same as that before the therapy (mean slope before = 0.20 ± 0.07, mean slope after = 0.19 ± 0.08; P = not significant; mean r before = 0.82 ± 0.17; mean r after = 0.76 ± 0.15; P = not significant). Conclusion: β-Blocker therapy did not affect the unique Q-aT/RR relation, which reflects an intrinsic abnormality of the ventricular repolarization in LQTS patients.     

Repolarization dynamics in patients with long QT syndrome

INTRODUCTION: Dynamics of ventricular repolarization may contribute to cardiac arrhythmias in subjects with the long QT syndrome (LQTS). The aim of the present study was to assess the dynamics of repolarization duration and the dynamics of repolarization complexity in LQTS patients and their unaffected family members. METHODS AND RESULTS: Twelve-lead 24-hour ambulatory ECG recordings were obtained from LQTS patients (n = 38) and unaffected family members (n = 20). The 24-hour dynamics of the QT interval, T wave complexity (TWC) index measured by principal component analysis, and the RR interval were analyzed using standard deviation (SD) and square root of the mean squared differences of successive values of the parameters (RMSSD). QT variability, mean TWC, and TWC variability were increased in the LQTS patients compared with unaffected family members (QT-SD: 38 +/- 20 msec vs 19 +/- 7 msec, P = 0.0001; QT-RMSSD: 36 +/- 20 msec vs 14 +/- 8 msec, P = 0.0001; TWC: 27.7% +/- 11.1% vs 20.4% +/- 6.7%, P = 0.003; TWC-SD: 6.7% +/- 2.8% vs 4.6% +/- 1.8%, P = 0.003; TWC-RMSSD: 5.3% +/- 2.8% vs 3.7% +/- 1.2%, P = 0.004, respectively). At the same time, the measures of heart rate variability were similar between the affected and unaffected LQTS subjects (SD of normal-to-normal RR intervals [SDNN]: 94 +/- 25 msec vs 89 +/- 37 ms, P = 0.56; RMSSD: 49 +/- 26 msec vs 49 +/- 34 ms, P = 0.97, respectively). CONCLUSION: Despite similar heart rate variability, QT variability and the variability of TWC are significantly increased in LQTS patients compared with unaffected family members, suggesting that disturbances in temporal dynamics of repolarization and repolarization complexity in LQTS patients possibly increase vulnerability to arrhythmias.     

Relation between QT and RR intervals in patients with bradyarrhythmias.

OBJECTIVE--To investigate the relation between QT and RR intervals in the sick sinus syndrome or high degree atrioventricular block. PATIENTS--32 patients with episodes of prolonged RR intervals (> or = 2.6 s) on Holter electrocardiographic recordings. DESIGN--QT and RR intervals were measured manually every 100 to 150 beats on electrocardiographic strips reprinted from the Holter tape over 24 hours. The slope of the QT/RR relation was determined by the linear regression equation for RR intervals < or = 1.4 s (slope 1) and > 1.4 s (slope 2). RESULTS--Slope 2 (0.0068 (0.0030)) was significantly lower than slope 1 (0.0824 (0.0059), P < 0.0001) in the overall patient population. Slopes 1 and 2 were significantly lower (P < 0.001) in the 23 patients with QT intervals at the preceding RR interval of 1 s (QT1s) of < 0.44 s (0.0692 (0.0053) and 0.0019 (0.0030), respectively) than in the nine patients with QT1s intervals > or = 0.44 s (0.1159 (0.0091) and 0.0194 (0.0055), respectively). Slopes 1 and 2 correlated positively with QT1s interval in all patients. CONCLUSIONS--The QT/RR relation was comparatively flat when the RR interval was prolonged. Patients with prolonged QT intervals showed exaggerated prolongation of the QT interval with prolonged cycle lengths when compared with patients with normal QT intervals.     

Spontaneous sequences of onset of torsade de pointes in patients with acquired prolonged repolarization: Quantitative analysis of Holter recordings

Objectives. This study investigated the cycle length changes preceding the spontaneous onset of torsade de pointes in patients with acquired prolonged ventricular repolarization.

Background. Torsade de pointes is a polymorphic ventricular tachycardia generally associated with prolonged ventricular repolarization. Because torsade de pointes is not inducible by programmed electrical stimulation, quantitative analysis of Holter recordings of spontaneous episodes may clarify the mechanisms favoring the onset of torsade de pointes in actual clinical conditions.

Methods. The digitized Holter recordings of 12 patients were analyzed by a computerized Holter system (ATREC). All arrhythmias were grouped according to three classes: 1) isolated premature ventricular beats (n = 47,147, mean/patient [±SD] 3,929 ± 11,571); 2) salvos of 2 to 4 consecutive beats (n = 2,003, mean/patient 167 ± 359); 3) torsade de pointes ≥5 beats (n = 105, mean/patient 9 ± 11). For each patient and class of arrhythmias, six variables were computed from the 10 min and the 10 cycles preceding the event onset.

Results. A significant heart rate increase in the last minute (p < 0.01) and typical oscillatory short-long-short cycle length sequences preceded the onset of arrhythmias, with greater oscillation preceding torsade de pointes than salvos and premature ventricular beats. The cycle lengths preceding the onset were highly correlated with the class of arrhythmias (r = 0.65, p < 0.005) and allowed the correct classification of 69% of events by discriminant analysis (p < 0.0001). A significant negative correlation was observed between the duration of torsade de pointes and the mean length of the initial cycles (r = −0.62, p < 0.001), indicating that longer torsade de pointes had a faster rate than that at onset.

Conclusions. In patients with acquired prolonged repolarization, the spontaneous onset of ventricular arrhythmias was preceded by an increasing heart rate in the last minute and escalating oscillatory “short-long-short” cycle length patterns, with greater oscillations preceding torsade de pointes than salvos and isolated ventricular beats. These findings suggest that adrenergic- and pause-dependent mechanisms (possibly inducing afterdepolarizations and triggered activity) may have a synergetic role in the genesis of complex ventricular arrhythmias associated with delayed ventricular repolarization.     

Comparison of QT/RR Relationship Using Two Algorithms of QT Interval Analysis for Identification of High Risk Patients for Life-Threatening Ventricular Arrhythmias

Objective: The purpose of this study was to evaluate the dynamic relationship between QT and RR intervals considering either the QTe interval (i.e., time between the onset of QRS and the end of the T wave) or the QTa interval (i.e., time between the onset of QRS and the apex of the T wave) from 30-second modules. Method: The Holter recordings in three groups of adult subjects (30 patients with malignant ventricular tachyarrhythmias [VT/VF patients], 40 patients with coronary artery disease [CAD], and 44 normal subjects) were analyzed using the ELATEC System. Results: In normal subjects the correlation coefficient between QTa and RR (QTa/RR) was significantly higher (0.87 ± 0.12) than those between QTe and RR (QTe/RR) (0.79 ± 0.17). In the other groups there was no significant difference between QTa/RR and QTe/RR: QTa/RR (CAD: 0.71 ± 0.3; VT/VF: 0.73 ± 0.19); and QTe/RR (CAD: 0.63 ± 0.33; VT/VF: 0.69 ± 0.21). The slope of QTe/ RR over 24 hours was significantly larger in VT/VF patients (0.23 ± 0.11) than in the other groups (control: 0.18 ± 0.08; CAD: 0.17 ± 0.1). Measuring the QTa/RR relation there was no difference between the three groups (VT/VF: 0.19 ± 0.09; CAD: 0.15 ± 0.09; normal: 0.19 ± 0.06). Conclusion: QTe/RR as well as QTa/RR analyses are methods of detecting a deranged rate dependence of QT intervals in high risk patients. An increased QTe/RR slope indicates a higher risk of life-threatening ventricular arrhythmias. Because there was no difference in QTa/RR we conclude that the end of the T wave gives important information about disorders in repolarization.     

Initiation of monomorphic ventricular tachycardia: electrophysiological,clinical features,and drug therapy in patients with implantable defibrillators

At least 2 distinct patterns of sustained monomorphic ventricular tachycardia (MVT) have been ascribed during analysis of stored intracardiac electrograms retrieved from implantable cardioverter defibrillators and Holter recordings in patients with ventricular arrhythmia. We aimed to investigate the electrophysiological features of MVT with different initiation patterns in patients with implantable cardioverter defibrillators and to assess whether there is a relationship of the initiation patterns of sustained MVT with clinical characteristics and efficacy of antiarrhythmic therapy. Seventy-four stored intracardiac electrograms in 21 patients (mean age of 68.2 +/- 4.2 years) with MVT were evaluated. Cardiovascular diagnosis included coronary artery disease in 85.7% of the patients. All MVT episodes were classified as those initiating with ventricular premature beats (nonsudden onset MVT) and those without ventricular ectopy preceding tachycardia (sudden onset MVT). There was significant difference in left ventricular ejection fraction between MVTs with different initiation pattern, being the lower in those with nonsudden onset (33.6% +/- 38.4% vs. 38.4 +/- 7.0%, P <.04). Ventricular tachycardia cycle length was shorter in group of MVT with nonsudden onset as compared with sudden onset (338.5% +/- 48.1% vs. 376.8% +/- 57.0%, P <.02). Tachycardia with sudden onset was associated with shorter preceding RR interval than tachycardia with nonsudden onset (821.8 +/- 136.2% vs. 748.7 +/- 107.7%, P <.01). There were no significant differences in the type of antiarrhythmic drug therapy used between groups (P >.05). Monomorphic ventricular tachycardias with nonsudden onset occurred more frequently than with sudden onset, without precipitating RR cycles shortening, are faster in rate, associating with lower ejection fraction. Monomorphic ventricular tachycardias with sudden onset are characterized by preceding shortening of RR intervals, slower cycle length, and less worsening of ejection fraction.     

Differences in heart rate turbulence between patients with coronary artery disease and patients with ventricular arrhythmias but structurally normal hearts

The term "heart rate turbulence" (HRT) indicates the physiologic changes in the sinus cycle that follow a ventricular premature complex; impaired HRT denotes abnormalities in cardiac autonomic function. To investigate whether HRT is impaired in patients with stable coronary artery disease (CAD), we studied 29 patients with documented CAD and frequent (>/=30/hour) ventricular premature complexes on Holter monitoring and 31 patients with frequent ventricular arrhythmias but normal hearts (NH-VA). HRT and heart rate variability analyses were analyzed on 24-hour Holter recordings. HRT variables differed significantly between the 2 groups (turbulence onset -0.20 +/- 1.7% vs -0.67 +/- 2.2%, p = 0.00001; turbulence slope 2.83 +/- 1.9 vs 10.83 +/- 7.4 ms/RR, p = 0.0001 in patients with CAD and NH-VA, respectively). The difference was independent of a history of previous myocardial infarction, left ventricular function, and age. Top quartile turbulence onset values (>-0.26%) and bottom quartile turbulence slope values (<2.12 ms/RR) had similar predictive power in discriminating between patients with CAD and NH-VA (positive predictive value 86.7%, negative predictive value 64.4% for both). Among heart rate variables, bottom quartile SD of all RR intervals values (<96.3 ms) only had the same power of HRT variables in discriminating between patients with CAD and NH-VA. Thus, our data show that HRT variables are impaired in patients with CAD patients versus those with NH-VA, indicating abnormalities in the control of short-term cardiac autonomic mechanisms resulting in decreased vagal activity with likely predominant sympathetic activity.     

Idiopathic Long QT Syndrome Exacerbated by Beta-Adrenergic Blockade and Responsive to Left Cardiac Sympathetic Denervation: Implications Regarding Electrophysiologic Substrate and Adrenergic Modulation

Electrophysiologic Substrate of Long QT Syndrome. Introduction: The mechanisms of T wave abnormalities and arrhythmias in patients affected by the long QT syndrome (LQTS) are unclear, as are the reasons why a high-risk subgroup (20%) continues to have syncope during therapy with beta blockers but is protected after left cardiac sympathetic denervation (LCSD). Afterdepolarizations, both early (EAD) or delayed (DAD), have been implicated as likely electrophysiologic substrates for the ECG abnormalities and arrhythmias in LQTS. To test this hypothesis, we analyzed nine Hotter recordings of a LQTS patient typical of the high-risk subgroup. Methods and Results: We applied to the ECG rules derived from previous in vitro and in vivo studies, which relate the coupling intervals of the dysrhythmic beats to the preceding cycle lengths, to discriminate among arrhythmia mechanisms. In the absence of therapy, the patient's ECG showed peaked T waves, with a notched second component accentuated by sinus pauses. The amplitude of the notches increased directly with the preceding RR interval (r = 0.58, P < 0.05), as it is observed with EAD. Therapy with the beta blocker propranolol did not modify the notches, which maintained their amplitude and their relationship with the preceding RR (r = 0.62, P < 0.05). Moreover, during beta-blocker therapy, ventricular premature beats, couplets, and runs of ventricular tachycardia (VT) occurred. The coupling intervals of ventricular premature beats and couplets were not influenced by the preceding RR intervals. By contrast, the coupling interval of the first beat of VT decreased as the preceding RR shortened, as it occurs with DAD-induced triggered activity. After LCSD, T wave notch amplitude was reduced (P < 0.05) and was no longer influenced by the preceding RR (r = 0.31, P = 0.22). The same was true when the calcium entry blocker verapamil was administered. Conclusion: In this patient, T wave abnormalities and some ventricular arrhythmias had the behavior observed in vitro for EAD and the consequent triggered activity. However, the cycle length dependence of VT manifested the behavior observed in vitro for DAD and the related triggered activity. The fact that these phenomena were accentuated by beta blockade and disappeared after LCSD suggests that the alpha-adrenergic receptor-effector system may be a modulator of T wave abnormalities and arrhythmias in some patients unresponsive to beta blockade and protected by LCSD. (J Cardiovasc Electrophysiol, Vol. 3, pp. 295–305, August 1992)     

Characteristics of non-sustained ventricular tachycardia found during dynamic ECG in patients with recent myocardial infarction

The characteristics of ventricular tachycardia found during Holter ECG monitoring before discharge in patients hospitalized because of acute myocardial infarction were analyzed. One or more ventricular tachycardia episodes were found in 29 of 251 patients (11.5%). On the whole, there were 233 episodes of ventricular tachycardia: 18 patients (62%) had only one episode of ventricular tachycardia, 9 (31%) 2-5 episodes and 2, respectively, 68 and 118 episodes. Episodes of ventricular tachycardia were more numerous in patients with frequent or polymorphic premature ventricular complexes than in patients with sporadic or monomorphic premature ventricular complexes. Fifty-seven ventricular tachycardia episodes were analyzed: 30 of 3 beats, 25 of 4-9 beats and 2 of 15 beats. Forty-seven episodes were monomorphic and 10 (17.5%) were polymorphic. The ventricular tachycardia rate was 136.4 +/- 25 b/m' (range 104-200). The RR'/QT ratio (where RR' = coupling interval of the first beat of ventricular tachycardia) was 1.67 +/- 0.42 and was not correlated either with the rate or the number of beats of ventricular tachycardia. Heart rate at the moment of ventricular tachycardia was 82 +/- 15 b/m' and QT interval 0.36 +/- 0.05 sec; there was no difference when compared to their values of 1 and 5 minutes before ventricular tachycardia. Furthermore, the heart rate showed no difference when compared to the mean value of the hours in which ventricular tachycardia episodes occurred. In addition, heart rate was not correlated with ventricular tachycardia rate, whereas a good correlation was found between the last RR interval preceding ventricular tachycardia and RR' interval (r = 0.61, P less than 0.01).     

The effects of antimalarial drugs on ventricular repolarization

Cardiotoxicity has become a major concern during treatment with antimalarial drugs. Lengthening of the QTc and severe cardiac arrhythmia have been observed, particularly after treatment with halofantrine for chloroquine-resistant Plasmodium falciparum malaria. The purpose of this prospective study was to evaluate whether antimalarial agents alter dispersion of the QTc and ventricular repolarization dynamicity. Sixty patients with uncomplicated falciparum malaria were randomly allocated in four groups of 15 patients and treated with quinine, mefloquine, artemether, or halofantrine at recommended doses. Patients in treatment groups were compared with a group including 15 healthy controls with no history of malaria and/or febrile illness within the last month. QTc dispersion was measured on surface electrocardiograms. Repolarization dynamicity was analyzed from Holter recordings, which allow automatic beat-to-beat measurement of QT and RR intervals. Plasma drug concentration was determined by reversed-phase high-performance liquid chromatography. No change in QTc dispersion was observed after treatment with quinine, mefloquine, or artemether. Treatment with halofantrine was followed by a significant increase in QTc dispersion at 9 hours (P < 0.0001) and 24 hours (P < 0.01). Assessment of QT heart rate variability by QT/RR nychtohemeral regression slope demonstrated no significant difference between the artemether (mean +/- SEM = 0.170 +/- 0.048), mefloquine (0.145 +/- 0.044), and the control groups (0.172 +/- 0.039). A significant decrease in the Q-eT/RR slope was observed in the quinine group compared with the control and artemether groups (0.135 +/- 0.057; P < 0.04). With halofantrine, a significant increase in the QT/RR regression slope (0.289 +/- 0.118) was observed (P < 0.0002). QTc interval, QT dispersion, and QT regression slope were significantly correlated with halofantrine and quinine plasma concentration. Mefloquine and artemether did not alter ventricular repolarization. Quinine induced a significant decrease in QT/RR slope of the same order of magnitude as those previously observed with quinidine. Both QTc dispersion and QT/RR slope were significantly modified by halofantrine. These repolarization changes were related to a class-III antiarrhythmic drug effect and may explain the occurrence of ventricular arrhythmia and/or sudden deaths reported after halofantrine intake.     

Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome

Introduction:  The QTc interval prolongation is not a perfect surrogate marker of the presence of an increased risk for arrhythmic events. In the search for alternative markers, we investigated the T-amplitude and QT interval adaptation to heart rate (HR) in patients with the congenital long QT syndrome (LQTS) and individuals with sotalol-induced QT prolongation.
Methods and Results:  Our investigation is based on the analysis of continuous 12-lead digital Holter recordings in: 49 LQT1 carriers, 25 LQT2 carriers, 37 healthy individuals off drugs and on 160 mg of sotalol, and 21 of them also on 320 mg of sotalol. The Holter recordings were used to investigate repolarization parameters and their HR dependency. A loss of HR dependency of the T-amplitude was found as a common feature in individuals with impaired I_kr kinetics: LQT2 carriers and subjects on sotalol. The T-amplitude/RR slope was significantly (P < 0.05) flatter in LQT2 (0.31 ± 0.27 μV/ms) than in both LQT1 (0.62 ± 0.40 μV/ms) and healthy individuals (0.55 ± 0.29 μV/ms). A dose-dependent reduction of the T-amplitude/RR slope was also observed in subjects on sotalol (160 mg dose: 0.26 ± 0.19 μV/ms; 320 mg dose: 0.21 ± 0.14 μV/ms). The QT/RR slope was less effective than T-amplitude/RR slope in differentiating between congenital and drug-induced repolarization delay.
Conclusions:  Impaired adaptation of T-amplitude to changing HR is a common electrocardiographic feature associated with KCNH2 mutation and I_kr blockade by sotalol. This ECG marker may play an important role in the future of the assessment of the penetrance of KCNH2 mutation and the identification of a drug effect on the I_kr kinetics.     

QT dynamics in risk stratification after myocardial infarction

OBJECTIVES: The purpose of this study was to compare measures of repolarization dynamics (QT dynamics) with other Holter risk predictors, left ventricular systolic function, and demographic characteristics to establish whether QT dynamics add independent information on risk stratification after myocardial infarction (MI). A novel QT dynamics parameter, the QT/RR variability ratio (VR), was introduced in this study. BACKGROUND: Abnormal repolarization contributes to arrhythmogenesis, and quantification of QT dynamics may have prognostic value after MI. METHODS: A 24-hour Holter recording was performed in 481 consecutive MI patients. Recordings from 311 patients were included in the analysis. QT/RR slope and intercept, mean and standard deviation of all QT, QTc, and RR intervals, and VR (defined as the ratio between the standard deviation of all QT intervals and the standard deviation of all RR interval) were calculated. Ventricular premature beats and ventricular tachycardia were counted. RESULTS: During 3-year follow-up, 70 deaths from all causes occurred. All parameters except mean of all QT intervals and standard deviation of all QTc intervals univariately predicted all-cause mortality. In multivariate Cox analysis, only VR per 0.1 (hazard ratio [HR]: 1.9 [1.5-2.4]), left ventricular ejection fraction per 5% (HR: 1.2 [1.1-1.3]), ventricular premature beats per 10 beats/hour (HR: 1.03 [1.002-1.06]), and age per 10 years (HR: 1.6 [1.3-2.0]) independently predicted all-cause mortality. CONCLUSIONS: Measures of QT dynamics univariately predicted total mortality. VR, left ventricular ejection fraction, ventricular premature beats, and age made up the optimal Cox model for risk stratification after MI. VR seems to be a promising risk factor for identifying sudden arrhythmic death.     

Short-term fluctuations in sinus cycle length after premature ventricular beats in patients with hypertrophic cardiomyopathy and myocardial infarction

BACKGROUND: Sinus cycle length has been reported to fluctuate after a ventricular premature beat (VPB). The purpose of this study was to assess the short-term fluctuations of sinus cycle length in patients with hypertrophic cardiomyopathy (HCM) and prior myocardial infarction (MI). METHODS: The relative deviation of RR intervals from the mean of the last two RR intervals preceding a VPB were calculated during the 20 subsequent beats following the VPB from Holter recordings in 92 patients with non-obstructive HCM, 57 patients with prior MI and 54 healthy controls. RESULTS: In controls, the deviations of the RR intervals were negative for several beats after a VPB and subsequently changed to positive before returning to the baseline. Similar changes in RR intervals following a VPB were exhibited in HCM patients; however, the late positive deviations of RR intervals were more marked than in controls. By contrast, in patients with prior MI, the early negative deviations of RR intervals were smaller compared with controls, and the deviations returned to the baseline without incidence of the positive changes. CONCLUSIONS: Short-term fluctuations in sinus cycle length after a VPB differed exclusively among HCM patients, prior MI patients, and healthy controls.     

Rate-dependence of QT dispersion and the QT interval: comparison of atrial pacing and exercise testing

OBJECTIVES: The study was done to determine whether variables of QT dispersion from the 12-lead electrocardiogram (ECG) are dependent on heart rate. BACKGROUND: The dispersion of the QT interval is under evaluation as a risk marker in patients at risk for ventricular arrhythmias. Assuming that a similar rate correction is necessary as for the QT interval itself, investigators have frequently reported QTc-dispersion values utilizing the Bazett formula. It is not known whether there is a physiologic basis for such a rate correction in the human heart. METHODS: In 35 patients referred for evaluation of ventricular arrhythmias, digital 12-lead ECGs recorded at various heart rates during submaximal exercise testing and again during atrial pacing upon electrophysiologic testing were submitted to computerized interactive analysis of several ECG dispersion variables. RESULTS: Data from 11 patients were excluded due to incomplete high-quality analysis possible at all heart rates. From the remaining 24 patients, a total of 193 ECG recordings at various heart rates (ranging from 76 +/- 17 beats/min to 117 +/- 14 beats/min during atrial pacing and from 78 +/- 18 beats/min to 110 +/- 14 beats/min during exercise testing) were available. A highly significant linear relationship with heart rate was found for both the QT interval and the Q-to-T-peak interval. By contrast, standard QT interval dispersion (QTmax - QTmin), the T-peak-to-T-end interval, and the average area under the T wave did not change with increasing heart rates. CONCLUSIONS: Dispersion of the QT interval and other ECG variables of dispersion of ventricular repolarization are independent of heart rate. Therefore, it is not necessary to rate-correct these measurements.     

Refeeding normalizes the QT rate dependence of female anorexic patients

We postulated that dynamic alterations in QT interval adaptation could characterize patients with anorexia nervosa (AN) and could be restored after weight gain. To assess ventricular repolarization features, we evaluated the QT dynamicity along RR intervals from 24-hour electrocardiographic data of patients with AN before and after refeeding. Ten young women with AN (19 +/- 3 years) were included in the study. The QT/RR slope was found significantly enhanced compared with normals (-1.82 +/- 0.62 vs -1.40 +/- 0.30; p < 0.05). This slope returned to normal range values after refeeding. The QT/RR slope was significantly correlated with the body mass index (r = 0.59; p < 0.007) in the patient group.     

Relation of ventricular repolarization to cardiac cycle length in normal subjects, hypertrophic cardiomyopathy, and patients with myocardial infarction.

BACKGROUND: Prolonged QT interval and QT dispersion have been reported to reflect an increased inhomogeneity of ventricular repolarization, which is believed to be responsible for the development of arrhythmic events in patients with long QT syndrome, coronary heart disease, and myocardial infarction, congestive heart failure, and hypertrophic cardiomyopathy (HC). HYPOTHESIS: This study was undertaken to determine whether an abnormal QT/RR dynamicity may reflect autonomic imbalance and may contribute to arrhythmogenesis in patients with heart disease. METHODS: The relation between QT, QTpeak (QTp), Tpeak-Tend (TpTe) intervals and cardiac cycle length was assessed in 70 normal subjects, 37 patients with HC, and 48 survivors of myocardial infarction (MI). A set of 10 consecutive electrocardiograms was evaluated automatically in each subject using QT Guard software (Marquette Medical Systems, Milwaukee, Wisc.). RESULTS: In patients with HC, all intervals were significantly prolonged compared with normals (p < 0.001 for QT and QTp; p < 0.04 for TpTc); in survivors of MI, this was true for the maximum QT and QTp intervals (p < 0.05). A strong linear correlation between QT, QTp, and RR intervals was observed in normals and in patients with MI and HC (r = 0.65-0.59, 0.82-0.77, 0.79-0.74, respectively, p < 0.0001). TpTe interval only showed a weak correlation with heart rate in normals (r = 0.24, p < 0.05) and was rate-independent in both patient groups (p = NS). Compared with normals, the slopes of QT/RR and QTp/RR regression lines were significantly steeper in patients with MI and HC (0.0990-0.0883, 0.1597-0.1551, 0.1653-0.1486, respectively). Regression lines were neither parallel nor identical between normals and patients (T > 1.96, Z > 3.07). There was no difference in steepness for TpTeR/RR lines between groups (0.0110, 0.0076, 0.0163, respectively). TpTe/QTp ratio was similar in normals and in patients with MI and HC (0.30 +/- 0.03, 0.31 +/- 0.07, 0.30 +/- 0.04, respectively), in the absence of any correlation between QTp and TpTe intervals, suggesting disproportional prolongation of both components of QT interval. CONCLUSION: Compared with normals, a progressive increase in QT and QTp intervals at slower heart rates in patients with MI and HC may indicate an enhanced variability of the early ventricular repolarization and may be one of the mechanisms of arrhythmogenesis.     

Effects of acute alcohol infusion on duration and dispersion of QT interval in male patients with coronary artery disease and in healthy controls.

BACKGROUND AND HYPOTHESIS: Alcohol consumption may have advantageous epidemiologic effects but ethanol also increases the risk of sudden coronary death. Prolongation of QT interval has been reported in chronic alcoholics. Long QT period predisposes to serious arrhythmias, and therefore we studied whether acute alcohol intoxication prolongs repolarization in patients with stable coronary artery disease (CAD). METHODS: The effects of acute ethanol steady-state intravenous infusion (0.72 g/kg body weight within 60 min) on QT interval and QT dispersion, assessed by 12-lead electrocardiograms (ECG), were studied in 22 men with stable CAD and in 10 controls. Heart rate variability was measured by Holter recordings. RESULTS: Mean blood alcohol rose to 26.1 +/- 4.3 mmol/l(1.2 +/- 0.2/1000), and was maintained for 2 h. Heart rate was 56 +/- 7 beats/min before and 54 +/- 8 beats/min during ethanol infusion (NS). The heart rate-adjusted QT interval increased on the average 13-23 ms over the 12-lead ECG (p < 0.005). The QT dispersion remained unaltered. The was no difference in the repolarization response in the patients with CAD compared with the controls. The high- and low-frequency components of heart rate variability remained unaltered. CONCLUSIONS: In middle aged men, regardless of the presence of CAD, moderate amounts of alcohol cause prolongation of ventricular repolarization. Changes in the activity of the autonomic nervous system do not seem to explain the observed phenomenon.     

Heart rate response during exercise testing and ambulatory ECG monitoring in patients with syndrome X.

The response of the heart rate during exercise testing and 24-hour ambulatory electrocardiographic (ECG) monitoring performed with patients not receiving antianginal treatment was assessed in 26 patients (9 men and 17 women; mean age 51 +/- 8 years) with syndrome X (angina pectoris with normal coronary arteries), in 27 patients with coronary artery disease (10 men and 17 women; mean age 55 +/- 9 years), and in 21 healthy subjects (8 men and 13 women; mean age 47 +/- 11 years). In patients with syndrome X the slope of the regression line of heart rate versus time (heart rate/time slope) during exercise testing was similar to that of patients with coronary artery disease (3.3 +/- 0.8 versus 3.1 +/- 1.2 beats/min), but significantly lower than that in healthy subjects (4.2 +/- 1.1 beats/min; p less than 0.003). In patients with syndrome X the intercept of the heart rate/time slope was significantly higher than that in coronary artery disease patients and healthy subjects (102 +/- 15, 86 +/- 18, and 90 +/- 16 beats/min, respectively; p less than 0.015). Resting preexercise heart rate was also significantly higher in syndrome X, compared with coronary artery disease patients and healthy subjects (91 +/- 16, 79 +/- 16, and 80 +/- 14 beats/min, respectively). During ambulatory ECG monitoring, mean diurnal heart rate (from 6 AM to 6 PM) was higher in patients with syndrome X (83 +/- 8 beats/min) than in patients with coronary artery disease (75 +/- 8 beats/min) and healthy subjects (74 +/- 11 beats/min) (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

QT rate dependence in norm and myocardial infarction

AIM: To assess QT/RR relationship in healthy subjects and in patients with acute myocardial infarction (AMI) using long term 12-lead ECG monitoring. MATERIAL AND METHODS: We studied separately diurnal and nocturnal QT interval rate-dependence using a linear model "QT=beta+alphaxRR" in 42 patients with AMI on 2-nd week of the disease and in 14 healthy volunteers. All necessary parameters were automatically calculated from 24-hour 12 lead ECG recordings using special programs. Myocardial perfusion and infarct size were assessed using 99mTc-MIBI gated SPECT. RESULTS: Long-term ECG monitoring permitted: 1) to detect the ECG lead with most pronounced QT/RR relationship delineated by alpha(max); 2) to determine value of "deltaalpha=alpha(max)-alpha(min)", that characterized spatial heterogeneity of QT/RR relationship. In norm diurnal values of alpha(max) were significantly higher than nocturnal ones (0.207+/-0.037 vs. 0.151+/-0.035, respectively; p<0.01). The alpha(max) values correlated with the size of MI (r=0.42-0.43, p<0.01). Therefore in patients with anterior AMI who demonstrated significantly larger defects of 99mTc-MIBI uptake than patients with inferior AMI, diurnal mean value of amax remained high despite therapy with b-blockers (0.225+/-0.037), and nocturnal alpha(max) value significantly exceeded respective amax value in healthy subjects (0.216+/-0.097 vs 0.151+/-0.035, respectively; p<0.01). Patients with AMI demonstrated an increased mean Da value when compared to normal subjects (in anterior AMI 0.098+/-0.057 vs. 0.039+/-0.014, respectively; p<0.001--diurnal period; 0.104+/-0,042 vs. 0.039+/-0.022, respectively; p<0.001--nocturnal period). In anterior AMI Da values correlated with infarct size (r=0.62, p=0.001). CONCLUSIONS: A new approach to the assessment of QT rate dependence with the use of 12-lead Holter monitoring widens possibilities of the method, firstly, because of selection of most informative ECG lead that shows maximal QT/RR relationship dynamic, and, secondly due, to discovery of the new field of ventricular repolarization research by assessment of space dispersion of QT/RR relationship. In patients with AMI when compared with healthy subjects we observed a decrease of QT/RR circadian modulation, increase of the slope and space dispersion of QT/RR rate dependence.