Dynamic changes in the QT interval during the head-up tilt test in patients with vasovagal syncope

Dynamic changes of the QT and QTc interval as well as QT dispersion and QTc dispersion during the head-up tilt test were investigated in 15 patients (8 men, mean age 32 years) with vasovagal syncope (VVS) and a positive head-up tilt test and in a control group of 15 patients with syncope in the case-history and a negative head-up tilt test (9 men, mean age 33 years). The value at rest of the QT interval did not differ in patients with VVS and controls. In controls at the beginning of HUT shortening of QT occurred (0.447 sec. vs. 0.419 sec. p = 0.0002), subsequently the QT did not change significantly. In patients with VVS during the beginning of the test only an insignificant shortening of QT occurred, while during the development of the syncope QT was prolonged (0.394 sec. vs. 0.420 sec. p < 0.0001). QT corrected for the pulse rate (QTc) did not change significantly during HUT. QTc dispersion was in patients with VVS significantly lower 3 minutes before the development of the syncope (0.067 sec. vs. 0.085 sec. p = 0.03), which may indicate the decline of the sympathetic and increase of the parasympathetic tonus which subsequently leads to the development of vasovagal syncope. QTc dispersion before the test was higher in patients with VVS as compared with controls (0.087 sec. vs. 0.063 sec., p = 0.03), which suggests an increase in the baseline sympathetic tonus in patients with VVS.     

Preferred QT Correction Formula for the Assessment of Drug‐Induced QT Interval Prolongation

Drug‐Induced QTc Interval Assessment. Introduction: There is debate on the optimal QT correction method to determine the degree of the drug‐induced QT interval prolongation in relation to heart rate (ΔQTc). Methods: Forty‐one patients (71 ± 10 years) without significant heart disease who had baseline normal QT interval with narrow QRS complexes and had been implanted with dual‐chamber pacemakers were subsequently started on antiarrhythmic drug therapy. The QTc formulas of Bazett, Fridericia, Framingham, Hodges, and Nomogram were applied to assess the effect of heart rate (baseline, atrial pacing at 60 beats/min, 80 beats/min, and 100 beats/min) on the derived ΔQTc (QTc before and during antiarrhythmic therapy). Results: Drug treatment reduced the heart rate (P < 0.001) and increased the QT interval (P < 0.001). The heart rate increase shortened the QT interval (P < 0.001) and prolonged the QTc interval (P < 0.001) by the use of all correction formulas before and during antiarrhythmic therapy. All formulas gave at 60 beats/min similar ΔQTc of 43 ± 28 ms. At heart rates slower than 60 beats/min, the Bazett and Framingham methods provided the most underestimated ΔQTc values (14 ± 32 ms and 18 ± 34 ms, respectively). At heart rates faster than 60 beats/min, the Bazett and Fridericia methods yielded the most overestimated ΔQTc values, whereas the other 3 formulas gave similar ΔQTc increases of 32 ± 28 ms. Conclusions: Bazett's formula should be avoided to assess ΔQTc at heart rates distant from 60 beats/min. The Hodges formula followed by the Nomogram method seem most appropriate in assessing ΔQTc. (J Cardiovasc Electrophysiol, Vol. 21, pp. 905‐913, August 2010)     

A Novel Method for Patient‐Specific QTc—Modeling QT‐RR Hysteresis

Background: Cardiac repolarization adaptation to cycle length change is patient dependent and results in complex QT‐RR hysteresis. We hypothesize that accurate patient‐specific QT‐RR curves and rate corrected QT values (QTc) can be derived through patient‐specific modeling of hysteresis. Method and Results: Model development was supported by QT‐RR observations from 1959 treadmill tests, allowing extensive exploration of the influences of autonomic function on QT adaptation to rate changes. The methodology quantifies and then removes patient‐specific repolarization adaptation rates. The estimated average 95% QT confidence limit was approximately 1 msec for the studied population. The model was validated by comparing QT‐RR curves derived from a submaximal exercise protocol with rapid exercise and recovery phases, characterized by high hysteresis, with QT‐RR values derived from an incremental stepped protocol that held heart rate constant for 5 minutes at each stage of exercise and recovery. Conclusions: The underlying physiologic changes affecting QT dynamics during the transitions from rest to exercise to recovery are quite complex. Nevertheless, a simple patient‐specific model, comprising only three parameters and based solely on the preceding history of RR intervals and trend, is sufficient to accurately model QT hysteresis over an entire exercise test for a diverse population. A brief recording of a resting ECG, combined with a short period of submaximal exercise and recovery, provides sufficient information to derive an accurate patient‐specific QT‐RR curve, eliminating QTc bias inherent in population‐based correction formulas. Ann Noninvasive Electrocardiol 2011;16(1):3–12     

Correlation of QT interval with disease activity in newly detected SLE patients at baseline and during flare

AimTo study correlation between QT interval parameters (QTc interval & QT dispersion) and disease activity (SLEDAI) in patients with systemic lupus erythematosus (SLE).MethodsThe study was done on 100 newly diagnosed patients with SLE and 100 age matched controls from January 2012 to December 2013. A standard 12 lead Electrocardiogram was obtained. QT interval was calculated from beginning of ‘q’ wave to end of T wave in lead II or lateral leads (V5, V6). QT dispersion was measured as the difference between maximum and minimum QT intervals. SLE disease activity was measured SLEDAI.ResultsEighty four patients had high disease activity. QTc was >440 msec in 51 patients and 6 controls. QTd was prolonged in 6 patients and 6 controls. The mean QTc interval among patients (463.30 ± 27.43 msec) was higher than in controls (397.24 ± 31.85 msec; p < 0.001). However the mean QTd among patients (44.40 + 20.61 msec) was similar to that in controls (39.2 + 17.7 msec). Difference of QTc values during severe flare from baseline QTc values was statistically significant (r = 0.863; Pearson's correlation coefficient).ConclusionsPatients with high disease activity have higher prevalence of QTc prolongation, QTc interval may be used as a surrogate marker for assessing disease activity in SLE.     

Beat‐to‐Beat QT Interval Variability Is Primarily Affected by the Autonomic Nervous System

Background : Beat‐to‐beat QT interval variability is associated with life‐threatening arrhythmias and sudden death, however, its precious mechanism and the autonomic modulation on it remains unclear. The purpose of this study was to determine the effect of drugs that modulate the autonomic nervous system on beat‐to‐beat QT interval. Method : RR and QT intervals were determined for 512 consecutive beats during fixed atrial pacing with and without propranolol and automatic blockade (propranolol plus atropine) in 11 patients without structural heart disease. Studied parameters included: RR, QTpeak (QRS onset to the peak of T wave), QTend (QRS onset to the end of T wave) interval, standard deviation (SD) of the RR, QTpeak, and QTend (RR‐SD, QTpeak‐SD, and QTend‐SD), coefficients of variation (RR‐ CV, QTpeak‐CV, and QTend‐CV) from time domain analysis, total power (TP; RR‐TP, QTpeak‐TP, and QTend‐TP), and power spectral density of the low‐frequency band (LF; RR‐LF, QTpeak‐LF, and QTend‐LF) and the high‐frequency band (HF; RR‐HF, QTpeak‐HF and QTend‐HF). Results : Administration of propranolol and infusion of atropine resulted in the reduction of SD, CV, TP, and HF of the QTend interval when compared to controlled atrial pacing (3.7 ± 0.6 and 3.5 ± 0.5 vs 4.8 ± 1.4 ms, 0.9 ± 0.1 and 0.9 ± 0.1 vs 1.2 ± 0.3%, 7.0 ± 2.2 and 7.0 ± 2.2 vs 13.4 ± 8.1 ms², 4.2 ± 1.4 and 4.2 ± 1.2 vs 8.4 ± 4.9 ms², respectively). Administration of propranolol and atropine did not affect RR interval or QTpeak interval indices during controlled atrial pacing. Conclusions : Beat‐to‐beat QT interval variability is affected by drugs that modulate the autonomic nervous system.     

Dynamic Changes in the QT–R‐R Relationship during Head‐Up Tilt Test in Patients with Vasovagal Syncope

Background: QT interval is influenced by preceding R‐R intervals and autonomic nervous tone. Changes in QT intervals during vasovagal reflex might reflect autonomic modulation of ventricular repolarization; however, this issue has not been fully elucidated. This study aimed to evaluate dynamic response of QT interval to transient changes in R‐R interval during vasovagal syncope (VVS) induced by head‐up tilt test. Methods: Eighteen patients with VVS and 18 age‐and sex‐matched controls were studied. All patients with VVS had a positive mixed‐type response to head‐up tilt and all controls had a negative response. CM5‐lead digital electrocardiogram (ECG) was recorded and QT intervals were analyzed using Holter ECG analyzer. Using scatter plots of consecutive QT and the preceding R‐R intervals, QT–R‐R relations during tilt‐up and tilt‐back or during vasovagal reflex were independently fitted to an exponential curve: QT (second) = A + B × exp[k × R‐R (second)]. Results: During the tilt‐up, A, B, and k did not differ between patients with VVS and controls. During the tilt back, k showed equivalent positive value compared to the tilt‐up (4.1 ± 1.3 vs ?4.6 ± 0.9) in controls. However, k remained negative (?1.3 ± 1.5) during vasovagal reflex in patients with VVS. In six patients, in whom metoprolol was effective in eliminating VVS, QT–R‐R relationship during the tilt‐back became similar to that in controls. Conclusions: In patients with VVS, hysteresis of the QT–R‐R relation is similarly shown during tilt‐up as in controls, whereas this hysteresis is no longer evident and failure of QT prolongation is observed during VVS.     

Modulation of Ventricular Repolarization and R‐R Interval Is Altered in Patients with Globally Impaired Cardiac 123I‐MIBG Uptake

Background: Cardiac ¹²³l‐metaiodobenzylguanidine (MIBG) imaging is widely used to assess cardiac sympathetic neuronal function. However, physiologic significance of impaired cardiac MIBG uptake is not fully elucidated. The purpose of the present study was to determine influences of abnormal cardiac sympathetic neuronal function on heart rate variability (HRV) and ventricular repolarization process. Methods: Twenty‐nine patients with prior myocardial infarction were divided into two groups by a heart‐to‐mediastinum ratio (H/M) of MIBG scintigraphy. Ten patients with globally decreased MIBG uptake (group I: H/M < 1.5), 19 patients with partially decreased MIBG uptake (group II: H/M < 1.5), and 17 control subjects with normal MIBG uptake (group III) were studied. Holler recording and a standard 12‐lead electrocardiography were used for evaluation of HRV, QT‐RR relation, and QT dispersion. Results. Low, high, and total frequency components decreased in groups I and II, as compared to that of group III. The reduction of these frequency domain measures was more severe in group I than in group II, but the differences did not reach statistical significance. Circadian variation of frequency domain measures disappeared in group I. The slope of QT‐RR relation was significantly greater in group I than in groups II and III. QT dispersion was also greater in group I (64 ± 25 msec) than in group 11(43 ± 19 msec) and group III (28 ± 9 msec). Conclusion. These results suggest that patients with sympathetic neuronal dysfunction inferred from globally impaired cardiac MIBG uptake have an altered modulation of ventricular repolarization process as well as decreased HRV.     

Paradoxical effects of exercise on the QT interval in patients with polymorphic ventricular tachycardia receiving type Ia antiarrhythmic agents

We analyzed the results of exercise testing performed in the absence of all antiarrhythmic drugs in 11 case patients with newly documented polymorphic ventricular tachycardia in response to type Ia antiarrhythmic agents. These results were compared with those found in 11 control patients matched for age, sex, and heart disease to determine whether the response of the QT interval to exercise testing was abnormal in patients who developed worsening of arrhythmia while taking antiarrhythmic drugs. QT, RR, and QTc intervals (by Bazett's method) were evaluated at rest and at 3 minutes of exercise in both groups. At rest, there was no significant difference in the QT interval (410 +/- 13 vs. 386 +/- 11 msec), RR interval (890 +/- 56 vs. 781 +/- 43 msec), or corrected QT interval (438 +/- 10 vs. 438 +/- 4 msec) in the case patients and the control patients. Both groups demonstrated a similar chronotropic response to exercise. The QT interval shortened in both groups with exercise (p less than 0.001), but the degree of shortening tended to be greater in the control patients (to 310 +/- 9 msec) than in the case patients (to 357 +/- 11 msec) (p = 0.06). Thus, there was a paradoxical increase in the QTc interval in the patients who experienced a proarrhythmic effect of type Ia drugs but not in the control patients (to 482 +/- 8 vs. 431 +/- 5 msec; p less than 0.001). Ten of 11 case patients but only one of 11 control patients had an increase in QTc interval of more than 10 msec with exercise (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

T‐Wave Morphology in Short QT Syndrome

Background: Short QT syndrome (SQTS) is an inherited disorder characterized by a short QT interval and vulnerability to ventricular tachyarrhythmias. The diagnostic criteria for this syndrome are not well defined, since there is uncertainty about the lowest normal limits for the corrected QT (QTc) interval. Objective: The aim of this study was to determine whether T‐wave morphology parameters are abnormal in short QT subjects and whether those parameters can help in the diagnosis of SQTS. Methods and Results: We describe three families (10 patients) with short QT intervals (QTc 310 ± 32 ms). Seven subjects had suffered serious arrhythmic events and three were asymptomatic. T‐wave morphology was assessed using the principal component analysis (PCA). QTc was significantly shorter and T‐wave amplitude in lead V₂ higher in the short QT subjects compared to healthy controls (n = 149), (P < 0.001 for both). The total cosine of the angle between the main vectors of the QRS and T‐wave loops (TCRT) was markedly abnormal among the symptomatic patients with short QT syndrome (n = 7) (TCRT –0.14 ± 0.55 vs 0.36 ± 0.51, P = 0.019). None of the three asymptomatic patients with short QT but without a history of arrhythmic events had an abnormally low TCRT. Conclusion: Our observations suggest that patients with a short QT interval and a history of arrhythmic events have abnormal T‐wave loop parameters. These electrocardiogram (ECG) features may help in the diagnosis of SQTS in addition to the measurement of the duration of QT interval from the 12‐lead ECG.     

Effect of obesity and weight loss on ventricular repolarization: a systematic review and meta‐analysis

We performed a systematic review and meta‐analysis of the effects of obesity ± overweight and weight loss on the corrected QT interval (QTc) and QT or QTc dispersion (indices of ventricular repolarization). Mean difference for both QTc and QT or QTc dispersion with 95% confidence intervals (CIs) was calculated comparing obese ± overweight subjects and normal weight controls and QTc and QT or QTc dispersion before and after weight loss from diet ± exercise or bariatric surgery. A total of 22 studies fulfilled the selection criteria. Compared with normal weight controls, there was a significantly longer QTc in obese ± overweight subjects (mean difference of 21.74 msec, 95% CI: 18.76 to 22.32) and significantly longer QT or QTc dispersion (mean difference of 15.17 msec, 95% CI: 13.59 to 16.74). Weight loss was associated with a significant decrease in QTc (mean difference ?25.77 msec, 95% CI: ?28.33–23.21) and QT or QTc dispersion (mean difference of ?13.46 msec, 95% CI: ?15.60 to ?11.32 in obese ± overweight subjects. Thus, obesity ± overweight is associated with significant prolongation of QTc and QT or QTC dispersion. Weight loss in obese ± overweight subjects produces significant decreases in these variables. © 2016 World Obesity     

QT Dispersion and Mortality in the Elderly

Background: The prognostic value of QT interval dispersion measured from a standard 12‐lead electrocardiogram (ECG) in the general population is not well established. The purpose of the present study was primarily to assess the value of QT interval dispersion obtained from 12‐lead ECG in the prediction of total, cardiac, stroke, and cancer mortality in the elderly. Methods: A random population sample of community‐living elderly people (n = 330, age ≧; 65 years, mean 74 ±; 6 years) underwent a comprehensive clinical evaluation, laboratory tests, and 12‐lead ECG recordings. Results: By the end of the 10‐year follow‐up, 180 subjects (55%) had died and 150 (45%) were still alive. Heart rate corrected QT (QTc) dispersion had been longer in those who had died than in the survivors (75 ±; 32 ms vs 63 ±; 35 ms, P = 0.01). After adjustment for age and sex in the Cox proportional hazards model, prolonged QTc dispersion (≧; 70 msec) predicted all‐cause mortality (relative risk [RR] 1.38, 95% confidence interval [Cl] 1.02–1.86) and particularly stroke mortality (RR 2.7, 95% Cl 1.29–5.73), but not cardiac (RR 1.38, 95% Cl 0.87–2.18) or cancer (RR 1.51, 95% Cl 0.91–2.50) mortality. After adjustment for age, sex, body mass index, blood pressure, blood glucose and cholesterol concentrations, functional class, history of cerebrovascular disease, diabetes, smoking, previous myocardial infarction, angina pectoris, congestive heart failure, medication, left ventricular hypertrophy on ECG, presence of atrial fibrillation and R‐R interval, increased QTc dispersion still predicted stroke mortality (RR 3.21, 95% Cl 1.09–9.47), but not total mortality or mortality from other causes. The combination of increased QTc dispersion and left ventricular hypertrophy on ECG was a powerful independent predictor of stroke mortality in the present elderly population (RR 16.52, 95% Cl 3.37–80.89). QTcmin (the shortest QTc interval among the 12 leads of ECG) independently predicted total mortality (RR 1.0082, 95% Cl 1.0028–1.0136, P = 0.003), cardiac mortality (RR 1.0191, 95% Cl 1.0102–1.0281, P < 0.0001) and cancer mortality (RR 1.0162, 95% Cl 1.0049–1.0277, P = 0.005). Conclusions: Increased QTc dispersion yields independent information on the risk of dying from stroke among the elderly and its component, QTcmin, from the other causes of death. A.N.E. 2001; 6(3):183–192     

Normalization of Ventricular Repolarization with Flecainide in Long QT Syndrome Patients with SCN5A:ΔKPQ Mutation

Background: The Long QT Syndrome (LQTS) is a genetic channelopathy with life‐threatening implications. The LQT3 form of this disease is caused by mutations of the SCN5A sodium‐channel gene. A specific mutation, SCN5A:ΔKPQ, is associated with repetitive reopenings of the sodium channel and prolonged inward current. This dominant inward current is manifest on the electrocardiogram as QT prolongation. Flecainide is a potent blocker of the open sodium channel. Methods and Results: The effect of flecainide on the duration of the QT‐interval and the T‐wave morphology was systematically evaluated in five male patients age 2–64 years having the SCN5A:ΔKPQ mutation. After baseline electrocardiograms were obtained, low‐dose oral flecainide was administered for 48 hours. Serial electrocardiograms and blood flecainide levels were obtained during flecainide therapy. The QTc interval decreased on average by 104 ms, from a baseline value of 565 ± 60 ms to 461 ± 23 ms (P < 0.04) at a mean flecainide level of 0.28 ± 0.08 mg/L, with shortening of the QTonset interval (P < 0.003) and normalization of T‐wave morphology. The effects of flecainide were compared with oral mexiletine in two patients, with flecainide showing greater QTc shortening and more complete normalization of repolarization. No adverse side effects or proarrhythmia were observed with flecainide in this study. Conclusion: Low‐dose, oral flecainide consistently shortened the QTc interval and normalized the repolarization T‐wave pattern in five LQT3 patients with SCN5A:ΔKPQ mutation. This preliminary study indicates that low‐dose flecainide is a promising therapeutic agent for LQTS patients with the SCN5A:ΔKPQ sodium channel mutation. A.N.E. 2001;6(2):153–158     

Autonomic Effects on the QT Interval

Background: This study was designed to evaluate the effects of autonomic tone on the QT interval, using conventional and heart rate independent analysis. Effects of autonomic tone on the QT interval have been studied either using rate correction formulae or during fixed rate atrial pacing, both of which have been associated with problems. Since most autonomic interventions are associated with heart rate changes, separation of “true” autonomic effects from rate related effects on the QT interval is essential. Methods: Electrocardiographic recordings were performed in 14 healthy volunteers during: (1) sympathetic stimulation (tilt, epinephrine infusion, isoproterenol infusion, and exercise); (2) β-adrenergic blockade; (3) parasympathetic blockade; (4) autonomic blockade; (5) tilt following autonomic blockade; (6) parasympathetic stimulation (phenylephrine infusion); and (7) isolated α-adrenergic stimulation (phenylephrine infusion following atropine). The QT interval was adjusted for heart rate using Bazett's formula. Heart rate independent analysis was performed between conditions with similar cycle lengths. Results: QT interval measurements were reproducible and exhibited the typical QT-RR relationship. Sympathetic stimulation decreased the RR interval and prolonged the QT_c interval. Parasympathetic blockade also increased the QT_c. Heart rate independent analysis of the effects of β-blockade showed a shortening of the QT (from 368.5 ± 20.5 ms to 355.9 ± 17.9 ms; n = 8). Alpha-adrenergic stimulation also decreased the QT interval from 302.4 ± 16.8 ms to 294.3 ± 17.7 ms (n = 7). Conclusion: Sympathetic stimulation prolongs the QT interval, while β-blockade shortens it. Alpha-adrenergic stimulation also shortens the QT interval. Autonomic effects on the QT interval as assessed by heart rate independent analysis may help separate the true autonomic effects from rate related effects.     

Problems of heart rate correction in assessment of drug-induced QT interval prolongation

INTRODUCTION: Estimation of QT interval prolongation belongs to safety assessment of every drug. Among unresolved issues, heart rate correction of the QT interval may be problematic. This article proposes a strategy for heart rate correction in drug safety studies and demonstrates the strategy using a study of ebastine, a nonsedating antihistamine. METHODS AND RESULTS: Four-way cross-over Phase I study investigated 32 subjects on placebo, ebastine 60 mg once a day, 100 mg once a day, and terfenadine 180 mg twice a day. Repeated ECGs were obtained before each arm and after 7 days of treatment. The changes in heart rate-corrected QTc interval were investigated using (A) 20 published heart rate correction formulas, (B) a correction formula optimized by QT/RR regression modeling in all baseline data, and (C) individual corrections optimized for each subject by drug-free QT/RR regression modeling. (A) Previously published correction formulas found QTc interval increases on terfenadine. The results with ebastine were inconsistent. For instance, Bazett's and Lecocq's correction found significant QTc increase and decrease on ebastine, respectively. The results were related (absolute value(r) > 0.95) to the success of each formula (independence of drug-free QTc and RR intervals). (B) The pooled drug-free QT/RR regression found an optimized correction QTc = QT/RR(0.314). QTc interval changes on placebo, ebastine 60 mg, ebastine 100 mg, and terfenadine were -1.95 +/- 6.87 msec (P = 0.18), -3.91 +/- 9.38 msec (P = 0.053), 0.75 +/- 8.23 msec (P = 0.66), and 12.95 +/- 14.64 msec (P = 0.00025), respectively. (C) Individual QT/RR regressions were significantly different between subjects and found optimized corrections QTc = QT/RR(alpha) with alpha = 0.161 to 0.417. Individualized QTc interval changes on placebo, ebastine 60 mg, ebastine 100 mg, and terfenadine were -2.76 +/- 5.51 msec (P = 0.022), -3.15 +/- 9.17 msec (P = 0.11), -2.61 +/- 9.55 msec (P = 0.19), and 12.43 +/- 15.25 msec (P = 0.00057, respectively. Drug-unrelated QTc changes up to 4.70 +/- 8.92 msec reflected measurement variability. CONCLUSION: Use of published heart rate correction formulas in the assessment of drug-induced QTc prolongation is inappropriate, especially when the drug might induce heart rate changes. Correction formulas optimized for pooled drug-free data are inferior to the formulas individualized for each subject. Measurement imprecision and natural variability can lead to mean QTc interval changes of 4 to 5 msec in the absence of drug treatment.     

QT Interval Length and Diabetic Autonomic Neuropathy

QT interval length was measured in ECG recordings from three groups of age-matched male subjects: 36 normal subjects, 41 diabetic patients without (DAN-ve), and 34 with (DAN+ve) autonomic neuropathy. ECG samples were selected from previously recorded 24-h ECGs on the basis of a clearly defined T wave and a steady RR interval over 2 min of around 750 ms (80 beats min^?1). There were no significant differences in RR interval between the groups. The two diabetic groups had slightly longer QT measurements (normal 365 ± 14 (±SD) ms, DAN-ve 373 ± 18 ms, DAN+ve 375 ± 23 ms, p = 0.05), and corrected QT (QTc) values (normal 423 ± 15 ms, DAN-ve 430 ± 20 ms, DAN+ve 435 ± 24 ms, p = 0.05). Ten diabetic patients fell above our defined upper limit of normal for QTc (>mean + 2SD). There was a significant correlation in the DAN-ve group between the QT indices and 24-h RR counts (QT r = ?0.38, p < 0.01; QTc r = ?0.40, p < 0.01). We conclude that there are some small alterations in QT interval length in the steady state in diabetic autonomic neuropathy. The changes appear to be due to autonomic impairment, rather than diabetes per se.     

Effect of acute unloading via head-up tilt on QTc prolongation in patients with ischemic or non-ischemic cardiomyopathy

Patients with advanced cardiomyopathy develop prolongations in ventricular myocyte action potential duration that are reflected by prolongations of QT intervals on surface electrocardiograms. Recent studies demonstrate that the placement of a left ventricular (LV) assist device, which induces profound cardiac decompression, acutely increases QT intervals within hours. The goal of this study was to use head-up tilt (HUT) to examine electrocardiographic responses to cardiac unloading in patients with cardiomyopathy. Surface electrocardiograms were analyzed during HUT in 21 patients with cardiomyopathy (ejection fraction <30%) and in 33 age-matched controls. Four to 6 different QT and RR intervals were measured at baseline (supine), at 5 and 25 minutes after HUT. The heart-rate-adjusted QT interval (QTc) was calculated using Bazett's formula. The mean QTc in control patients decreased at 5 minutes (426 +/- 31 vs 418 +/- 28 ms, p < 0.05, vs supine) and was unchanged at 25 minutes (426 +/- 31 vs 423 +/- 25 ms, p = NS, vs supine). However, in patients with cardiomyopathy, there was a significant increase in QTc during HUT (455 +/- 45 vs 473 +/- 42 and 479 +/- 42 ms, p < 0.001, vs supine). The change in heart rate during HUT did not differ between patients with cardiomyopathy and controls. In conclusion, HUT is associated with the immediate prolongation of myocardial repolarization in patients with cardiomyopathy. This response was not seen in age-matched controls. These results suggest that adaptations to chronic cardiac distention may include processes that help accelerate repolarization. Conversely, the prolongation of repolarization after unloading may modulate myocardial relaxation and arrhythmogenic risk.     

Correction for Heart Rate Is Not Necessary for QT Dispersion in Individuals without Structural Heart Disease and Patients with Ventricular Tachycardia

Background: It remains controversial whether QT dispersion should be corrected for heart rate, especially when the limitations of rate correction formulae are considered. We investigated whether incremental atrial pacing affects QT dispersion and the rate‐corrected values according to Bazett's formula in individuals without structural heart disease and in patients with history of sustained ventricular tachycardia. Methods: We studied 32 individuals without structural heart disease (group A), and 16 patients with a history of sustained ventricular tachycardia (group B). QT dispersion and corrected for heart rate QT dispersion using Bazett's formula (QTc dispersion) were calculated in sinus rhythm, and during continuous right atrial pacing for one minute at 100 and 120 beats/min. Results: Interobserver variability was not significant (P ≧ 0.10). QT dispersion did not differ at rest between groups A and B and did not change significantly from baseline at any heart rate in both groups. However, QTc dispersion increased significantly with atrial pacing in a similar manner in group A and group B (42 ± 19 ms at rest vs 53 ± 23 ms at 120 beats/min, P < 0.001 for group A, 39 ± 16 ms at rest vs 60 ± 19 ms at 120 beats/min, P < 0.001 for group B). Conclusions: We conclude that QT dispersion remains unchanged during atrial pacing at heart rates up to 120 beats/min in both individuals without structural heart disease and in patients with a history of sustained ventricular tachycardia. Correction by Bazett's formula results in prolongation of QTc dispersion, yielding values which may be misleading. A.N.E. 2002;7(1):47–52     

Rate-independent QT shortening during exercise in healthy subjects: terminal repolarization does not shorten with exercise

Introduction: QT interval for a given heart rate differs between exercise and recovery (QT hysteresis) due to slow QT adaptation to changes in heart rate. We hypothesized that QT hysteresis is evident within stages of exercise and investigated which component of the QT contributes to hysteresis. Methods and Results: Nineteen healthy volunteers performed a staged exercise test (four stages, 3 min each). Continuous telemetry was analyzed with software to compare QT intervals in a rate‐independent fashion. QRST complexes during each minute were sorted by RR interval, and complexes in bins of 20 ms width were signal‐averaged. QT and QTp (onset of QRS to peak T wave) were measured, and terminal QT calculated (peak to end of T wave, Tpe = QT – QTp). QT, QTp, and Tpe at the same heart rate were compared between the first and last minute of each stage. QT shortened from the first to last minute of exercise in each stage (Stage I: 358 ± 30 to 346 ± 25 ms, P < 0.001; Stage II: 342 ± 27 to 331 ± 24 ms, P = 0.003; Stage III: 329 ± 21 to 322 ± 18 ms, P = 0.03; Stage IV: 313 ± 22 to 303 ± 23 ms, P = 0.005). QTp also shortened in each stage, while Tpe was unchanged. Conclusion: QT hysteresis occurs during exercise in normals, and the major determinant is shortening of the first component of the T wave. Terminal repolarization (peak to end of T wave), a surrogate for transmural dispersion of repolarization, does not shorten significantly with exercise.     

Circadian Variation and Waking Hour Dynamics of the QT Interval

Background: The incidence of sudden cardiac death is maximal in the morning hours. Although ventricular arrhythmias have been implicated as a potential mechanism, and several neurohumoral factors affecting myocardial excitability have been shown to be raised in the early morning hours, it is not known if there is any circadian variation in the dynamics of ventricular repolarization when studied on a beat-to-beat basis. The objective of this study was to examine the range, diurnal variations, and circadian distribution of the variability of the QT interval in healthy subjects. Method: We developed and validated a new method for continuous measurement of QT intervals from 24-hour Holter recordings. The QT intervals measured semi-automatically were corrected by a linear regression formula derived independently for each patient from his own QT and RR values in 32 healthy males (20 ± 0.4 years). QT variability was assessed by the mean standard deviation of the average of consecutive uncorrected QT intervals (SDA-QT Index) and corrected QT intervals (SDA-QTc index) over 5-minute segments. The rate-dependent changes of the QT interval were studied as a function of the slope of the regression line between the QT and RR values. Results: The average QTc range was mean (SD) 79 (± 28) ms; the average maximal QTc interval was 481 (± 24) ms. The 95% upper confidence limit for the mean 24-hour QTc interval was 443 ms. The RR, QT, and QTc intervals were longer, while the SDA-QT and SDA-QTc indices were shorter during sleep. Hourly averages of the SDA-QT and SDA- QTc index revealed a sudden increase in QT variability in the first hour of waking (P < 0.0001 and P = 0.006). Conclusion: The dynamic behavior of the QT interval shows significant diurnal variations. The maximal QTc interval over 24 hours is longer than previously assumed. The period shortly following awakening is characterized by a peak in the variability of the QT interval. These changes may be indicative of autonomic instability during the early waking hours and correspond with the peak incidence of sudden arrhythmic death.