QT Adaptation Research Articles

QT Interval Variability and Adaptation to Heart Rate Changes in Patients with Long QT Syndrome

Increased QT variability (QTV) has been reported in conditions associated with ventricular arrhythmias. Data on QTV in patients with congenital long QT syndrome (LQTS) are limited. Ambulatory electrocardiogram recordings were analyzed in 23 genotyped LQTS patients and in 16 healthy subjects (C). Short-term QTV was compared between C and LQTS. The dependence of QT duration on heart rate was evaluated with three different linear models, based either on the RR interval preceding the QT interval (RR(0)), the RR interval preceding RR(0) (RR(-1)), or the average RR interval in the 60-second period before QT interval (mRR). Short-term QTV was significantly higher in LQTS than in C subjects (14.94 +/- 9.33 vs 7.31 +/- 1.29 ms; P < 0.001). It was also higher in the non-LQT1 than in LQT1 patients (23.00 +/- 9.05 vs 8.74 +/- 1.56 ms; P < 0.001) and correlated positively with QTc in LQTS (r = 0.623, P < 0.002). In the C subjects, the linear model based on mRR predicted QT duration significantly better than models based on RR(0) and RR(-1). It also provided better fit than any nonlinear model based on RR(0). This was also true for LQT1 patients. For non-LQT1 patients, all models provided poor prediction of QT interval. QTV is elevated in LQTS patients and is correlated with QTc in LQTS. Significant differences with respect to QTV exist among different genotypes. QT interval duration is strongly affected by noninstantaneous heart rate in both C and LQT1 subjects. These findings could improve formulas for QT interval correction and provide insight on cellular mechanisms of QT adaptation.

Rate‐Independent QT Shortening During Exercise in Healthy Subjects: Terminal Repolarization Does Not Shorten with Exercise

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. 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. 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.

QT/RR Relationship in Patients after Remote Anterior Myocardial Infarction with Left Ventricular Dysfunction and Different Types of Ventricular Arrhythmias

QT/RR relationship was found to be both rate-dependent and rate-independent, what suggests the influence of autonomic drive and other not-autonomic related factors on it. The steeper QT/RR slope in patients after acute myocardial infarction (MI) was described, but the relationship to ventricular arrhythmias is unknown. The purpose of this study was to calculate differences in QT/RR relationship in patients after remote anterior MI with left ventricular dysfunction and different types of ventricular arrhythmias. The cohort of 95 patients (age: 63 +/- 11 years, LVEF: 35 +/- 9%) with previous anterior MI (mean 1.1 years) was divided into two well-matched groups-50 patients without episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) (NoVT/VF: 39 males, 64 +/- 12 years, LVEF 37 +/- 8%) and 45 patients with VT and/or VF (all with ICD implanted) (VT/VF: 35 males, 62 +/- 10 years, LVEF 34 +/- 10%). No true antiarrhythmics were used. QT/RR slope was calculated from 24-hour Holter ECG for the entire recording (E), daytime (D) and nighttime (N) periods. Groups did not differ in basic clinical data (age, LVEF, treatment). QT/RR slopes were steeper in VT/VF than in NoVT/VF group in all analyzed periods: E - 0.195 +/- 0.03 versus 0.15 +/- 0.03 (P < 0.001), N - 0.190 +/- 0.03 versus 0.138 +/- 0.03 (P < 0.001) and D - 0.200 +/- 0.04 versus 0.152 +/- 0.03 (P < 0.001). No significant day-to-night differences were found in both groups. Steeper QT/RR slope and complete lack of day-to-night differences in VT/VF patients show inappropriate QT adaptation to the heart rate changes. The prognostic significance of this parameter needs prospective studies.

QT hysteresis in long-QT syndrome children with exercise testing

Congenital long QT syndrome (LQTS) is an inherited ion channel disorder resulting in abnormal cardiac repolarization that can cause syncope and sudden death associated with a prolonged rate-corrected QT interval and polymorphic ventricular tachycardia. Several studies in adults showed that LQTS patients have altered QT adaptation to heart rate changes compared with normal subjects which forming a "hysteresis loop" in the QT-circle length plot. This study was to observe the QT interval changing during exercise testing in children long QT syndrome (LQTS) patients, explore the new diagnosis methods of LQTS. The subjects were divided into 3 groups according to 1993 LQTS diagnostic criteria. Group 1: LQTS group (n = 17) who scored > or = 4 points indicating definite LQTS. Group 2: Middle group (n = 16), patients who have prolonged QT interval but scored 1.5 to 3.5. Group 3: Normal control group (n = 18). The average age of all study population is (12.3 +/- 5.8) years. No case had beta-adrenergic antagonists administration before exercise testing. All subjects were underwent tread mill exercise testing and electrocardiograph in whole exercise testing and recovery were recorded. QT and heart rate changing during whole exercise testing period were recorded. DeltaQT, the QT interval at 1, 2, 4, 6 minutes into recovery subtract from the QT interval at a similar heart rate during exercise, were calculated. In all three groups, QT intervals were shortening with the increasing of heart rate, but QTc had no significant change. DeltaQT at 1 minute ((45 +/- 11) ms), 2 minutes ((37 +/- 15) ms), 4 minutes ((23 +/- 12) ms) into recovery in LQTS group were significantly greater than that of the other two groups (P < 0.05, P < 0.01, P < 0.01, respectively). There was no DeltaQT significant difference between middle group and normal control group at recovery time. During the recovery phase in LQTS group, the QT interval remained shortened despite a decelerating heart rate, forming a hysteresis "loop" in the curve relating the QT interval to the cycle length. In children LQTS patients, there is significant QT hysteresis loop in the relation of QT interval with heart rate during recovery of exercise testing, which could be useful to the early diagnosis for LQTS.

Beat-to-beat QT dynamics in paroxysmal atrial fibrillation

QT dynamics parameters are used only in sinus rhythm. However, because many patients with paroxysmal atrial fibrillation undergo antiarrhythmic treatment that changes QT, developing methods for measuring QT dynamics during atrial fibrillation is important. The purpose of this study was to evaluate whether QT dynamics in atrial fibrillation can be measured more reliably if additional RR intervals are included in the QT calculation. QT and RR intervals were measured in 15 patients with atrial fibrillation and sinus rhythm on the same 24-hour Holter recording. Full QT adaptation is not instantaneous but lags behind over several beats. To correct for this lag, we adapted a weighted average method using five successive RR intervals. Linear regression was performed on (QT, RR) and (QT, RR(modified)) pairs. Variability ratio (standard deviation of all QT intervals/standard deviation of all RR intervals) and modified variability ratio (standard deviation of all QT intervals/modified standard deviation of all RR intervals) were calculated. QT-RR slope was reduced in atrial fibrillation compared with sinus rhythm (0.076 +/- 0.009 vs 0.113 +/- 0.0013, P = .0005). When correcting for lag, using the QT-RR(modified) slope, the slope in atrial fibrillation became similar to the slope in sinus rhythm (0.126 +/- 0.013 vs 0.126 +/- 0.013, P = .9547). The variability ratio was reduced in atrial fibrillation compared with sinus rhythm (0.175 +/- 0.017 vs 0.240 +/- 0.031, P = .009), but when correcting for the lag, the modified variability ratio was similar in atrial fibrillation and sinus rhythm (0.262 +/- 0.029 vs 0.267 +/- 0.038, P = .80). The results of this study demonstrate that QT dynamics can be measured reliably in atrial fibrillation using 24-hour Holter recordings.

Hysteresis of electrocardiographic depolarization–repolarization intervals during dynamic physical exercise and subsequent recovery

The post-exercise electrocardiographic QT interval is shortened relative to that at similar heart rates during exercise or pre-exercise rest. This lag in QT adaptation to the recovering heart rate is described as ‘hysteresis’. No previous studies have quantified the influence of ECG electrode placement on hysteresis following physical exercise. Six males and six females of similar age, mass and aerobic fitness undertook progressive sub-maximal bicycle exercise. A three-channel ECG was recorded continuously during pre-exercise, exercise and recovery. Beat-to-beat NN (cardiac interval) and QTa interval (Q wave onset to T wave apex) data were measured for each sinus heart beat. QTa–NN hysteresis was calculated as the difference in QTa magnitude at identical heart rates during the rest/exercise and post-exercise recovery periods. There were some significant (p < 0.05) between-channel and between-gender differences in calculated hysteresis values. Hysteresis was generally greatest during the second or third minute post-exercise; ranges of means for all channels were 10.9 ± 11.7 ms to 25.5 ± 16.8 ms (males) and 19.1 ± 10.3 ms to 28.4 ± 3.0 ms (females). For males only, hysteresis values calculated using channel 1 between 1 and 3 min post-exercise were generally significantly (p < 0.05) different to those between 4 and 10 min. Similar trends were observed in females. QTa–NN hysteresis is significantly affected by the locations of the ECG electrodes used to record the surface ECG. These results emphasize the need for standardization of ECG electrode placement in future investigations.

Control of rapid heart rate changes for electrocardiographic analysis: implications for thorough QT studies

Following an abrupt change in heart rate (HR), QT adaptation is achieved within a delayed time frame. The exclusion of electrocardiograms (ECGs) showing rapid HR changes influences the level of a drug-induced QT prolongation. Continuous 12-lead ECG-Holter monitoring was performed in 31 healthy subjects. Using the "bin" method, we evaluated moxifloxacin effects on (1) QT interval duration at different RR intervals and (2) on the rate dependence of QT interval. These endpoints were calculated separately for five types of ECG analysis: classification of cardiac complexes based on (a) the single preceding RR interval (RR-1) and (b) RR filters excluding rapid HR changes according to the formula RR-1 = RR[time-window] +/- threshold, where the time-window could be 30 or 60 s (R30 and R60) and the threshold 15 or 30 ms (th15 or th30). Moxifloxacin-induced QT prolongation was consistently higher using the stable models when compared with the RR-1 model. Moxifloxacin-induced QT prolongation at RR = 1000 ms was 8.2 +/- 11.2 vs. 10.9 +/- 10.4 ms using the RR-1 and R60th15 stable models, respectively (p < 0.05). Moxifloxacin-induced QT prolongation was more pronounced at slow than at fast HR. This so-called "reverse rate-dependent" effect was more pronounced when assessed using stable HR models (0.023 IC95% [0.019;0.027] vs. 0.015 IC95% [0.012;0.017] using the RR-1 model). The exclusion of ECGs with rapid HR changes influences the magnitude of drug-induced QT changes. The hysteresis phenomenon should not be neglected when dedicated QT studies are performed.

733 Vasovagal syncope: prognostic factors for syncope recurrences

value from Mann-Whitney test. Standard deviation of the normal-to-normal beat interval averages calculated over 5 minutes (SDANN) and lowfrequency power (LF% n.u.) were significantly lower in ARVD patients than in healthy controls; there were no differences in measures of parasympathetic activity. There were no significant differences in QTc duration between groups. However, QT variability was increased and QT/RR slopes were steeper in ARVD patients than in controls. Conclusions: Young ARVD patients show decreased heart rate variability, increased QT variability, and signs of abnormal QT adaptation that might contribute to an increased risk of arrhythmic events.

QT dynamics and variability.

Repolarization dynamics and variability are of increasing interest as Holter-derived parameters reflecting changes in myocardial vulnerability and contributing to increased risk of arrhythmic events and sudden death. Repolarization dynamics is usually defined as phenomenon describing and quantifying QT adaptation to changing heart rate. The analysis of QT-R-R slopes in long ECG recordings is one of the ways to evaluate repolarization dynamics. Increased QT-R-R slopes are frequently observed in patients at risk for cardiac death and arrhythmic events: postinfarction patients, long QT syndrome patients, patients with nonischemic cardiomyopathy as well as in patients taking drugs affecting repolarization. QT variability reflects beat-to-beat changes in repolarization duration and morphology and such changes can be quantified using a number of algorithms currently in various phases of development and validation. Increased QT variability is observed in several conditions with increased risk of arrhythmias. Recent data from MADIT II indicate that increased QT variability is a powerful predictor of arrhythmic events in postinfarction patients with left ventricular dysfunction. More studies are needed to determine further the potential clinical usefulness for diagnosing patients and for risk stratification purposes using both QT dynamics and QT variability methods, and compare these methods with exercise-induced T wave alternans.

Abnormalities of the repolarization characteristics of patients with heart failure progress with symptom severity.

Congestive heart failure is a common condition with high mortality. Many of these deaths are sudden and unexpected. Ventricular action potential, surface repolarization (QT interval), and dispersion of repolarization are prolonged in the failing heart, contributing to arrhythmogenesis and sudden death. We studied the relationship between QT and heart rate (RR interval) from ambulatory recordings using a novel method in patients with ischemic heart disease and varying degrees of left-ventricular impairment (IHD) and compared them to healthy subjects (HS). We compare the degree of abnormality with the functional impairment and ejection fraction. Using a previously described automated method for continuous estimation of the QT/RR characteristic that incorporates a correction formula for compensation of QT adaptation lag (VERDA, Del Mar Reynolds Medical Ltd., Hertford, UK), we compared recordings from 41 IHD patients with age-matched HS. IHD Patients have prolonged 24-hour mean QTo (461 ms vs 426 ms, P < 0.01), and abnormal rate dependence relative to controls (24-hour mean slope: 0.20 vs 0.14, P < 0.001; J: 0.38 vs 0.28, P < 0.001). There is increased temporal variation in J with respect to HS. These abnormalities of repolarization increase with worsening NYHA class, but do not correlate with ejection fraction. The use of a universal correction formula to compare dynamic QT data in IHD patients is inappropriate. The observed progressive abnormalities may be responsible for the high incidence of sudden death through promotion of arrhythmias.

Estimation of the QT/RR hysteresis lag

The process of QT interval adaptation to heart rate (HR) changes was evaluated by considering weighted averages of RR intervals to characterize the influence of previous cardiac cycles. An optimum adaptation pattern was individually derived for each patient and several descriptors of the QT/RR hysteresis were subsequently calculated. The values of these parameters showed that the QT adaptation to HR changes is highly individual and, consequently, any generalized approach may lead to inappropriate conclusions.

Repolarization analysis in children with the long QT syndrome

QT duration changes were analysed in 26 children with long QT syndrome (median age 9 years). With 12-lead Holter recordings, we found that macroscopically QT adaptation to heart rate changes was slow and only 3 of 26 patients showed abrupt changes in QT interval duration. These changes in the time domain were always accompanied by changes of STT morphology in the 3 of 26 patients. Application of Bazett′s heart rate correction algorithm was inappropriate to show true QT changes in this young patient group due to temporary typical large cycle length variations, where moreover an overcorrection of the heart rate impact resulted in reflection of RR interval changes rather than true QT duration changes.

Autonomic nervous system influences on qt interval in normal subjects

ObjectivesWe sought to determine whether the relationship between heart rate (HR) and QT interval (QT) differs as HR increases in response to exercise, atropine and isoproterenol. BackgroundAutonomic nervous system influences on repolarization are poorly understood and may complicate the interpretation of QT measurements. MethodsTwenty-five normal subjects sequentially underwent graded-intensity bicycle exercise, atropine injection and isoproterenol infusion. Serial 12-lead electrocardiograms were recorded at steady state during each condition and analyzed using interactive computer software. The HR-QT data were modeled linearly and the slopes (quantifying QT adaptation to HR) as well as the QT intervals at 100 beats/min for each intervention were compared by repeated-measures analysis of variance. ResultsAs HR increased, QT was longer for isoproterenol in comparison to exercise or atropine, which were similar. The HR-QT slope (ms/beats/min) was less steep for isoproterenol (−0.83 ± 0.53) than for atropine (−1.45 ± 0.21) or exercise (−1.37 ± 0.23) (p < 0.0001). In comparison to men, women had more negative HR-QT slopes during all interventions. At 100 beats/min, the QT was 364 ms during isoproterenol, which was significantly longer than that during exercise (330 ms) or atropine (339 ms) (p < 0.0001). Isoproterenol produced a dose-dependent increase in U-wave amplitude that was not observed during exercise or atropine. ConclusionsIn comparison to exercise and atropine, isoproterenol is associated with much less QT shortening for a given increase in HR and, therefore, greater absolute QT intervals. Our findings demonstrate that autonomic conditions directly affect the ventricular myocardium of healthy subjects, causing differences in QT that are independent of HR.

Beta blockers normalize QT hysteresis in long QT syndrome

Objectives This study was performed to evaluate the impact of beta blockers on QT adaptation to heart rate during the exercise and recovery phases of exercise testing in long QT syndrome. Background Long QT syndrome is characterized by familial syncope and sudden death in the context of sudden heart rate changes. QT hysteresis has been proposed as a phenotypic marker of long QT syndrome, suggesting altered QT adaptation to changes in heart rate. Methods Fourteen patients with long QT syndrome (aged 26 ± 16 years, 6 male) and 10 healthy volunteers (aged 37 ± 11 years, 9 male) underwent graded exercise testing with continuous lead II electrocardiographic monitoring. Long QT patients underwent repeat assessment after 1 month of beta blockade. QT intervals at matching heart rates were compared during exercise and recovery to determine the effect of beta blockade on QT hysteresis, defined as the recovery QT peak interval subtracted from the exercise QT peak interval. Results In the 14 long QT syndrome patients, beta blockers slowed the resting heart rate without affecting the corrected QT interval (502 ± 52 ms baseline vs 481 ± 40 ms beta blocker, P =.17). The increase in heart rate with exercise was similar in the 3 groups (P =.73). Exaggerated hysteresis of the QT interval was seen in the patients with long QT syndrome at baseline compared with controls (46 ± 19 ms vs 19 ± 11 ms 1 minute into recovery, P =.006). Beta blockers had minimal effect on the QT interval but markedly reduced hysteresis with minimal separation of the exercise and recovery QT/RR curves (25 ± 35 ms 1 minute into recovery, P =.027). The combined curve separation at all 6 time points analyzed was 165 ± 95 ms in patients with long QT syndrome at baseline, 40 ± 131 ms after beta blockade, and 29 ± 30 ms in control subjects (P =.002). Comparison of the beta blocker effect on hysteresis in the 2 genotypes suggested a greater reduction in hysteresis in the 3 patients with long QT syndrome 1 compared with the 11 patients with long QT syndrome 2. Conclusions Beta blockers reduce QT hysteresis in patients with long QT syndrome to values seen in normal patients. This improved QT adaptation to changes in heart rate may explain the clinical benefit of beta blockers in long QT syndrome. (Am Heart J 2002;143:528-34.)

Response of the QT interval to mental and physical stress in types LQT1 and LQT2 of the long QT syndrome

OBJECTIVETo study and compare the effects of mental and physical stress on long QT syndrome (LQTS) patients.DESIGNCase–control study.MAIN OUTCOME MEASURESQT intervals were measured from lead V3. Serum potassium and plasma catecholamine concentrations were also monitored.PATIENTS16 patients with type 1 LQTS (LQT1), 14 with type 2 LQTS (LQT2), both groups asymptomatic, and 14 healthy control subjects.INTERVENTIONSThree types of mental stress tests and a submaximal exercise stress test.RESULTSHeart rate responses to mental stress and exercise were similar in all groups. During mental stress, the mean QT interval shortened to a similar extent in controls (–29 ms), LQT1 patients (–34 ms), and LQT2 patients (–30 ms). During exercise, the corresponding QT adaptation to exercise stress was more pronounced (p &lt; 0.01) in healthy controls (–47 ms) than in LQT1 (–38 ms) or LQT2 patients (–38 ms). During exercise changes in serum potassium concentrations were correlated to changes in QT intervals in controls, but not in LQTS patients. LQT1 and LQT2 patients did not differ in serum potassium, catecholamine or heart rate responses to mental or physical stress.CONCLUSIONSQT adaptation to mental and exercise stress in healthy people and in patients with LQTS is different. In healthy people QT adaptation is more sensitive to physical than to mental stress while no such diverging pattern was seen in asymptomatic LQTS patients.

The impact of QT lag compensation on dynamic assessment of ventricular repolarization: reproducibility and the impact of lead selection.

In cardiac disease, abnormalities exist in the rate-corrected QT interval and the relationship between QT and heart rate. The QT/RR relationship is known to be dynamic and show circadian variation. The availability of automated methods for measurement of QT and RR intervals allows monitoring of the QT/RR relationship and may provide insights into arrhythmia onset. Using a method for analyzing 24-hour recordings that incorporates beat-by-beat QT and RR measurement and an automated mechanism for compensating for lag in adaptation of QT to changes in RR, the authors evaluated the impact of lag compensation on assessment of the QT/RR relationship, reproducibility, and the effect of lead selection in 15 normal subjects. The QT/RR relationship is continuously estimated from the lag compensated data over a 5-minute scrolling time frame. The relationship is expressed as an exponential formula, QT = QTo.RRJ where QTo is the QT interval at a standardized RR interval of 1 second and J is a variable exponent. We found that the use of lag compensation significantly improves the mean 24-hour correlation between QT and RR data (r = 0.87 vs 0.65). The 24-hour mean of QTo and J were highly reproducible (coefficients of variation 2% and 8%, respectively). The mean 24-hour QT/RR relationship for the population was QT = 0.415.(RR)0.32. There was a small difference between leads in QTo and J. Compensating for QT adaptation lag provides a means of assessing the QT/RR relationship over long and short periods. This method allows investigation of the effect of acute interventions on the dynamic QT/RR relationship, which has previously been restricted by the presence of QT hysteresis.

Involvement of IsK-associated K+ channel in heart rate control of repolarization in a murine engineered model of Jervell and Lange-Nielsen syndrome.

The Jervell and Lange-Nielsen (JLN) syndrome affects the human cardioauditory system, associating a profound bilateral deafness with an abnormally long QT interval on the ECG. It results from mutations in KVLQT1 and ISK genes that encode the 2 subunits forming the K+ channel responsible for the cardiac and inner ear slowly activating component of the delayed rectifier K+ current (IKs). A JLN mouse model that presents typical inner ear defects has been created by knocking out the isk gene (isk-/-). This study specifically reports on the cardiac phenotype counterpart, determined in the whole animal and at mRNAs and cellular levels. Surface ECG recordings of isk-/- mice showed a longer QT interval at slow heart rates, a paradoxical shorter QT interval at fast heart rates, and an overall exacerbated QT-heart rate adaptation compared with wild-type (WT) mice. A 300-ms increase in the heart rate cycle length induces a 309+/-21% increase in the QT duration of the WT mice versus a 500+/-50% in isk-/- mice (P<0.001). It is concluded that the isk gene product and/or IKs, when present, blunts the QT adaptation to heart rate variations and that steeper QT-RR relationships reflect a greater susceptibility to arrhythmias in patients lacking IKs.

ADAPTATION OF THE QT INTERVAL TO HEART RATE CHANGES IN ISOLATED PERFUSED GUINEA PIG HEART: INFLUENCE OF AMIODARONE ANDD-SOTALOL

The inadequacy of the QT interval to shorten following heart rate increase is a feature of the inherited long QT syndrome and may have a role in the genesis of the typical arrhythmias associated with this syndrome (torsade des pointes). The aim of our study was to evaluate whether drugs that prolong the QT interval, such as amiodarone andd-sotalol, may also impair the ability of the QT interval to adapt to sudden heart rate changes. Experiments were carried out on isolated perfused guinea pig hearts (Langendorff preparation). Driving frequency was changed, in steps, every two minutes (Hz: 2·5–3–2·5–3·75–2·5–5–2·5), while epicardial ECG was continuously recorded on magnetic tape. QT interval was automatically measured by means of a beat-by-beat analysis program.d-sotalol was added to the perfusion medium at a concentration of 4 μg ml−1, while amiodarone was administered, before in vitro evaluation, for seven days (50 mg kg−1per day, intraperitoneally). In control experiments two phases of QT adaptation were identified: an abrupt QT shortening at the first beat after frequency change (QT1), followed by a gradual, exponential QT shortening that reached a new steady state in about 1 min (half life: 13 sec). The electrical restitution curve (the relation between QT1and the corresponding diastolic interval) had a rate constant of 57±8 ms. Neither drug changed the slow component of QT adaptation. However, both drugs increased the ability of QT to shorten upon premature stimulation:d-sotalol by increasing the rate constant of the restitution curve and amiodarone by decreasing the y-intercept. Our results indicate thatd-sotalol and amiodarone do not impair QT shortening during tachycardia but, on the contrary, they may favour QT adaptation, thus reducing the likelihood of the potentially lethal ‘R on T phenomenon’. This may be an additional mechanism by which these drugs can exert their antifibrillatory action.

Dynamics of the QT interval in patients with exercise-induced ventricular tachycardia in normal and abnormal hearts

Inhomogeneity of ventricular repolarization reflected in prolongation of the QT interval of the surface electrocardiogram can predispose patients to ventricular arrhythmia. This study examines whether an abnormality of QT adaptation to changes in heart rate is likely to be of importance in the pathogenesis of ventricular tachycardia (VT) in patients with and without underlying structural heart disease. The QT-R-R relationship during exercise was studied in 52 patients. Forty-two patients had VT associated with a “clinically normal” heart (idiopathic VT), of which 23 had no VT on exercise and 19 had exercise-induced VT. These patients were compared to 10 subjects with exercise-induced VT related to ischemic heart disease. The QT interval was measured manually from computer-averaged QRS complexes recorded at 1- to 3-minute intervals during treadmill exercise tests. An approximately linear association existed between the QT and R-R intervals within the range of heart rates observed. The slope of the QT-R-R relation was lower in patients with structural heart disease (0.23 ± 0.06) than in patients with normal hearts with (0.29 ± 0.12) and without (0.29 ± 0.12) exercise-induced VT ( p < 0.05). The intercept of the regression line was higher in patients with structurally abnormal hearts (209.2 ± 55.3 msec) than in patients with idiopathic VT with (155.6 ± 49.7 msec) and without (157.7 ± 69.0 msec) exercise-induced VT ( p < 0.02). The corrected QT (Bazett's formula) was similar in all three groups at rest, but was higher in patients with structurally abnormal hearts at peak exercise, 449.6 ± 28.0 versus 425.8 ± 27.4 msec (idiopathic VT, exercise induced) versus 427.3 ± 26.6 msec (idiopathic VT, not exercise induced) ( p < 0.05). There was no statistically significant difference in any of these parameters between patients with and without exercise-induced VT in structurally normal hearts. The results suggest that rate adaptation of the QT interval is abnormal in patients with structural heart disease and may be involved in the pathogenesis of the VT. QT adaptation is normal in patients with idiopathic VT and exercise-induced arrhythmia in which the mechanism is less likely to be dependent on an abnormality of repolarization dynamics.

Hysteresis of the ventricular paced QT interval in response to abrupt changes in pacing rate

The rate of QT adaptation to abrupt changes in pacing rate was studied in seven patients with newly diagnosed complete heart block with a ventricular escape rate of less than 40 beats.min-1. Their median age was 70 (range 36-84) years, and none was taking any cardioactive medication known to affect the QT interval. From a baseline pacing rate of 50 or 110 beats.min-1 the ventricular rate was increased or decreased to a new level. The time taken for the ventricular paced QT interval to complete 90% of the change secondary to the change in rate was found to be 136(16) s (mean(SEM] when the rate was increasing and 189(25) s when the rate was decreasing (p less than 0.01). This time interval was independent of the magnitude of the rate change and the baseline heart rate from which the change occurred. Furthermore, the time course of QT adaptation was found to be exponential and was characterised by a time constant of 49.1(2.2) s when the rate was increasing and 60.4(2.0) s when the rate was decreasing (p less than 0.01). It is concluded that QT measurements in response to a change in pacing rate should take into account the time dependent nature of QT changes.