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

Background: 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.
Methods: 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 (RR₀), the RR interval preceding RR₀ (RR_-1), or the average RR interval in the 60-second period before QT interval (mRR).
Results: 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 RR₀ and RR_-1. It also provided better fit than any nonlinear model based on RR₀. This was also true for LQT1 patients. For non-LQT1 patients, all models provided poor prediction of QT interval.
Conclusions: 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.     

Heart Rate‐Dependence of QTc Intervals Assessed by Different Correction Methods in Patients with Normal or Prolonged Repolarization

Background: There is a continuing debate about the optimal method for QT interval adjustment to heart rate changes. We evaluated the heart rate dependence of QTc intervals derived from five different QT correction methods. Methods: Study patients (n = 123, age 68 ± 11 years) were dual‐chamber device recipients with baseline normal or prolonged QT interval who had preserved intrinsic ventricular activation with narrow QRS complexes. Patients were classified to either Normal‐QT (n = 69) or Prolonged‐QT (n = 54) groups. Serial QT intervals were recorded at baseline (52 ± 3 beats per minute) and following atrial pacing stages at 60, 80, and 100 beats per minute. The QTc formulae of Bazett, Fridericia, Sagie‐Framingham, Hodges, and Karjalainen‐Nomogram were applied to assess the effect of heart rate on the derived QTc values by using linear mixed‐effects models. Results: Heart rate had a significant effect on QTc regardless of the formula used (P < 0.05 for all formulae). The Bazett's formula demonstrated the highest QTc variability across heart rate stages (highest F values) in both patient groups (in the total cohort, F = 175.9). In the following rank order, the formulae Hodges, Karjalainen‐Nomogram, Sagie‐Framingham, and Fridericia showed similar QTc heart rate dependence at both slower and faster heart rates in both patient groups (F = 21.8, 25.6, 28.8, 36.9, in the total cohort, respectively). Conclusions: Of the studied QTc formulae, the Bazett appeared the most heart rate dependent. Our results suggest the use of Hodges and the Karjalainen‐Nomogram secondly to ensure least heart rate dependence of QTc intervals in patients with either normal or prolonged repolarization. (PACE 2010; 553–560)     

QT Sensing Rate Responsive Pacing and Myocardial Infarction:

A 65-year-old man, treated with the QT sensing rate responsive pacemaker required to manage high degree AV block, sustained a transmural inferior wall myocardial infarction 6 months after the pacemaker implant. The rate response of the pacemaker during the acute phase of the infarction was physiological as evidenced by increased pacing rate during pain and with the gradual decrease in rate during the first postinfarction days. The underlying mechanisms are discussed.     

QT Interval in Children with Sensory Neural Hearing Loss

EL HABBAL, M.H., et al. : QT Interval in Children with Sensory Neural Hearing Loss. Long QT syndrome was first described in children with congenital sensory neural hearing loss (SNHL). The deafness was attributed to abnormalities in potassium ion channels of the inner ear. Similar channels are present in the heart and its dysfunction causes long QT syndrome. Whether congenital SNHL is associated with prolonged QT is unknown. This study examined 52 patients (median age 8.35 years, range 0.21–17.42 years) with SNHL and compared them to 63 healthy children (median age 10.2 years; range 0.67–19 years). An observer, who was blinded from the presence or absence of SNHL, measured QT, QTc intervals and dispersions from a standard 12‐lead electrocardiogram. To assess the cardiac autonomic enervation, power spectral analysis of heart rate variability was determined using a 24‐hour ambulatory heart rate monitor and was expressed as high (HF) to low frequency (LF) ratio. Left ventricular size and functions were evaluated by using two‐dimensional echocardiography. The medians (and ranges) of QT intervals were 340 ms (230–420 ms) in patients and 320 ms (240–386 ms) in the control group (P < 0.01 ). The QTc was longer in patients with SNHL (median 417 ms, range 384–490 ms) than in controls (median 388 ms, range 325–432 ms, P < 0.001 ). QT dispersions in SNHL were higher (median .038 ms, range 00–11 ms) than controls (median 27 ms, range 00–52 ms, P < 0.001 ). T wave inversion (n = 16 ) and alternans (n = 3 ) occurred in patients with SNHL. Heart rates were similar in both groups. Some deaf patients (n = 8 ) had dizzy episodes with a QTc > 440 ms. The HF:LF ratio was 1.32 (0.516–2.33) in deaf patients and 1.428 (0.67–2.3) in the control group (P > 0.1 ). Left ventricular size and functions were similar and normal in deaf patients and controls. In children, congenital SNHL is associated with a prolonged QT interval.     

Malfunction of the automatic slope adjustment of the QT sensor in patients with normal QT intervals

DDDR pacemakers with QT driven sensor algorithms may be susceptible to inappropriate pacemaker tachycardia when implanted into patients who have a relatively extended cardiac repolarization. The inability to detect and measure the QT interval at near maximum sensor rate, results in an inappropriate adjustment of the automatic QT slope. Triggering pacemaker induced tachycardia.     

Comparative Evaluation of Chronotropic Responses of QT Sensing and Activity Sensing Rate Responsive Pacemakers

The rate responses of activity sensing (ATS) and QT sensing (QTS) rate responsive pacemakers to different forms and durations of exercises were compared. Nine patients with ATS and five with QTS were studied. All had complete heart block and atrial arrhythmias. At the onset, the pacemakers were programmed to achieve a pacing rate of 100-110 bpm by the end of stage 1 of the Bruce protocol, and to a pacing rate range of 70-150 bpm. With progressive exercise, using a treadmill (Bruce protocol), the maximum pacing rates in the two groups were not significantly different (mean +/- SD: 123 +/- 18 vs 129 +/- 23 bpm, ATS vs QTS). The time taken to return to the baseline pacing rate during recovery was significantly longer with QTS (178 +/- 70 vs 264 +/- 68 s, p less than 0.05). Brief exercise tests on a treadmill were performed for 3 min each with different combinations of treadmill speeds (1.2 and 2.5 mph) and gradients (0, 5, 10 and 15%). In both groups of patients, faster walking speed was associated with a faster pacing rate at each gradient. However, with increasing gradients, at each speed, there was a rise in the maximum pacing rate only in patients with QTS. During brief exercise tests, the maximum rate was achieved by the end of exercise in patients with ATS, but was delayed by 33 +/- 20 s after exercise in patients with QTS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of epinephrine on right ventricular monophasic action potentials in the LQT1 versus LQT2 form of long QT syndrome: preferential enhancement of "triangulation" in LQT1

AIMS: To explore effects of epinephrine and phenylephrine on the behavior of right ventricular monophasic action potentials (MAPs) in symptomatic LQT1 and LQT2 patients. METHODS AND RESULTS: We recorded endocardial MAPs from right interventricular septum at baseline and during epinephrine and phenylephrine infusions in six symptomatic DNA-verified LQT1 (QTc 528 +/- 83) and five LQT2 patients (QTc 527 +/- 72) and in five control patients (QTc 381 +/- 22). We measured MAP durations at 90% and at 50% levels of repolarization and their difference (MAP50 to MAP90, a measure of MAP morphologic "triangulation"), during atrial pacing to characterize rate dependence of MAPs and repolarization phase 3 durations, respectively. Restitution kinetics were determined during atrioventricular sequential pacing, using the approach of empirical restitution rate. Epinephrine prolonged MAP50-to-MAP90 duration and increased the rate dependence of MAP90 duration and increased restitution rate in type LQT1, but not in LQT2 patients nor in control subjects. Phenylephrine did not change MAP behavior. During epinephrine administration, both LQT1 and LQT2 patients had a ratio of the restitution rate of MAP to diastolic interval >1.0 at short diastolic intervals. CONCLUSION: Symptomatic LQT1 patients with prolonged baseline QTc intervals showed beta-adrenergic-induced changes in MAPs (triangulation) known to be arrhythmogenic, thus giving insight to the difference in clinical triggers of life-threatening arrhythmias between LQT1- and LQT2-affected individuals.     

Comparative Evaluation of Rate Modulation in New Generation Evoked QT and Activity Sensing Pacemakers

Two new generation rate adaptive pacemakers, the Rhythmyx (Vitatron) using the evoked QT interval and the Legend (Medtronic) using vibration as indicators of metabolic demand, were compared for rate adaptive characteristics during different forms of exercise. While both showed improvements over previous generation pacemakers, they still show deficiencies in some aspects of rate modulation. Rhythmyx was slow to respond to changes in metabolic need and showed an "over-shoot" with increasing pacing rate on cessation of exercise. Legend was quick to adapt rate at beginning and end of exercise but showed a plateaus of rate modulation during the period of slowly increasing workload. Legend also showed only modest rate adaptation to changes in treadmill gradient and to bicycle ergometer exercise. Further developments in pacemaker technology are required if physiological rate adaptation to exercise is required.     

Cardiac repolarization properties during standardized exercise test as studied by QT,QT peak and terminated T-wave intervals

Summary. Changes in QT, QT peak (QT_p) and terminal T-wave, T_p–T_e (QT–QT_p) were studied in 11 apparently healthy subjects during and after a standardized exercise test. ECG was recorded at scalar lead positions. Averaged complexes were later analysed by computer for the different time intervals. QT and QT_p decreased in parallel with increasing heart rate with a ratio QT_p/QT of 0·80 ± 0.02 at rest and 0·74 ± 0·02 at maximal heart rate around 170. After exercise QT and QT_p prolonged disproportionately slower than heart rate, reaching the relation observed during exercise only 9·5 min post exercise. T_p–T_e was 75 ± 10 ms at rest and 65 ± 8 ms at maximal heart rate. The decrease was significant (P<0·001). The main part of the rate-associated shortening of the QT interval occurred in the QT_p interval where it was about six to seven times larger than in the T_p–T_e interval. In conclusion, QT and QT_p decreased similarly with heart rate during exercise. Post exercise there was an initial slower return of these intervals to the resting state than for heart rate. T_p–T_e changes were minimal.     

Transient proarrhythmic state following atrioventricular junctional radiofrequency ablation

This study was designed to prospectively assess ventricular de- and repolarization by the QRS, QT, and JT intervals, and their dispersion in the 12-lead ECG during right ventricular pacing at 60, 70, and 80 beats/min during the first month after AV junctional RF ablation. Previous reports have found early polymorphic ventricular arrhythmia after RF AV junctional ablation. Our hypothesis was that there is a proarrhythmic state following this procedure, which depends on the paced rate and time after ablation. The analysis of the immediate changes was based on 17 patients (10 men) with a mean age of 64 years (SD 14) (range 38-82 years). A 12-lead ECG was recorded during right ventricular pacing at 60, 70, and 80 beats/min within 24 hours (day 1), between 24 and 48 hours (day 2), and 1 week after ablation (day 7). For analysis of changes beyond 1 week, 13 additional patients with a mean age of 73 years (SD 8) (range 62-90 years) were analyzed on days 1, 7, and 30. All intervals were measured with a digitizing table. The mean QRS duration shortened by 2.4% at 60 beats/min (P <0.01), and the mean QT and JT intervals shortened by 5-7% between days 1 and 7 (P < 0.001). The mean QT was 9% shorter and the mean JT interval was 13% shorter at 80 compared to 60 beats/min on day 1 (P < 0.001). QT dispersion was reduced by 13% when the stimulation rate was increasedfrom 60 to 80 beats/min on day 1 (P < 0.05). There were no significant changes beyond the first week. The study results point to the induction of a proarrhythmic state immediately after AV junctional RF ablation resolving during the first week. Repolarization shortened gradually between 80 and 60 beats/min to an extent that is suggestive of a clinically important antiarrhythmic effect at the higher rate, which was supported also by clinical experience.     

Temporal Relationship Between Exercise and QT Shortening in Patients with QT Pacemakers

The present study was undertaken to examine the temporal relationship between exercise and QT interval shortening as one of the principal determinants for the functioning of QT pacemakers. Ten patients (mean age of 72.6 years) with implanted QT pacemakers were subjected to supine bicycle exercise with two different slopes, 90% and 80%. The QT interval as seen by the pacemaker was monitored by telemetry and stored on magnetic tape. After the beginning of exercise QT prolongation of a few msec occurred up to 40 sec in most patients. The earliest QT shortening of 4 msec was noted after 63.4 sec with 90% slope and 75.7 sec with 80% slope. The difference was not significant. The further time course was dependent on slope and pacemaker algorithm. Maximal QT shortening was 65.9 msec with 90% and 69.8 msec with 80% slope. It was seen 29.2 sec after termination of exercise with 90% slope and 69.5 sec with 80% slope (P < 0.05). There was no correlation of the measured delays with age. Earliest rate response in QT driven pacemakers is determined by earliest QT shortening on one hand and by the slope setting of the pacemaker on the other, where the limiting parameter appears to be QT shortening, which occurs after the first minute of exercise.     

A Randomized Double-Blind, Cross-Over Study of the Linear and Nonlinear Algorithms for the QT Sensing Rate Adaptive Pacemaker

BAIG, M.W., ET AL.: A Randomized Double-Blind, Cross-Over Study of the Linear and Nonlinear Algorithms for the QT Sensing Rate Adaptive Pacemaker. We have compared the pacing rate responses during cardiopulmonary exercise testing in 11 patients (mean 59 years, six female) with implanted QT sensing rate adaptive pacemakers who were randomly programmed to 1-month periods in the linear and nonlinear algorithms using a double-blind, cross-over design. Exercise testing was performed at the end of each month block and symptoms were scored with the MacMaster questionnaire. With exercise, the time to a 10 beats/min increment in rate was significantly less with the nonlinear compared to the linear algorithm (126 sec vs 255 sec, P = 0.02) but there were no significant differences in exercise duration, the peak pacing rate, the peak VO₂, the VO₂ at the anaerobic threshold or the mean correlation coefficients of the pacing rate VO₂ relationship. Rate oscillation occurred in seven patients in the linear algorithm and in two patients in the nonlinear setting. Initial deceleration of the pacing rate at the onset of exercise occurred in seven patients in the linear algorithm and in four patients in the nonlinear setting. The nonlinear algorithm is associated with a faster response time during exercise and fewer instances of rate instability. However, it has not overcome the problem of a dip in the pacing rate at the beginning of exercise. The major difference in the function of the two algorithms is faster initial acceleration with the nonlinear algorithm. This is explained by the significantly higher values of the slope setting at the lower rate limit for the nonlinear versus the linear algorithm (6.3 ms/ms vs 5.1 ms/ms).     

Assessment of ventricular repolarization in a large group of children with early onset deafness

This study examined the ECG traces of 397 deaf children (age 12.5 +/- 2.9 years, range 6-19 years), after exclusion of cases with Jervell and Lange-Nielsen syndrome (JLNS), and compared them to those of 361 normal hearing counterparts (age 12.5 +/- 2.7 years; range 7-18 years). An observer, who was unaware of the hearing status of the subjects, measured QT and QTc intervals and calculated dispersions of QT and QTc from standard 12-lead ECGs recorded at a speed of 25 mm/s at rest. Although the mean QT was found to be longer in deaf children than that observed in the control group (P < 0.0001), the mean QTc was significantly shorter (P < 0.0001). The mean heart rate was significantly lower in deaf children. When QT and QTc data were recompared after the children were grouped according to the heart rate, the observed difference became less significant or disappeared. In conclusion, there are no major abnormalities for repolarization parameters in children with congenital sensorineural deafness, when compared to hearing counterparts, if heart rates are similar. Based on these results, routine ECG screening of deaf children for repolarization abnormalities may be unnecessary unless they have a history of syncope or positive family history of syncope and/or early sudden death.     

QT interval prolongation

The QT interval is a function of ventricular repolarization time and is measured from the onset of the QRS complex to the end of the T wave. The length of this interval is inversely related to heart rate. A prolonged QT interval is most often secondary to the use of Type I antidysrhythmic medications (quinidine, procainamide). It is also associated with phenothiazines, organophosphates, hypocalcemia, liquid protein diets and the congenital long QT syndromes. QT prolongation is associated with a variety of ventricular dysrhythmias, most characteristically Torsades des pointes. Treatment consists of correction of the underlying metabolic disorder or discontinuation of the offending medication.     

One-Year Follow-Up of Automatic Adaptation of the Rate Response Algorithm of the QT Sensing, Rate Adaptive Pacemaker

Optimal functioning of a rate adaptive pacemaker depends upon reliable sensing of the sensor and appropriate programming of the rate response algorithm. QT sensing pacemakers use data derived from the endocardial electrogram in the programming of the rate response algorithm. In the latest versions of these pacemakers, programming of the rate response algorithm may be performed using either a semiautomatic Fast Learn (FLJ procedure or by using the newly developed, fully Automatic Slope Adaptation (ASA) mechanism. We report our experience in a prospective study of 17 patients in the first year postimplantation. ASA was characterized by significant changes only in the values of the slope settings at the lower rate limit (3.7 msec/msec at time 0 to 5.77 msec/msec at 2 weeks, P < 0.001) during the first 2 weeks after its enablement. Further adaptation between weeks 2 to 4 was observed (5.77 msec/msec to 6.4 msec/msec, P = 0.2) but this was not significant. The slope settings derived using the FL procedure were also checked at 2 and 4 weeks and were reproducible. They were closest in value to the values attained by the automated mechanism at 4 weeks. This suggests that the final value of the slope setting at the lower rate limit using ASA is reached between weeks 2 to 4. Both methods of slope determination result in satisfactory and similar rate response profiles but the time to achieve slope stability will necessarily be slower with ASA.     

Stability of ventricular repolarization in conscious dogs with chronic atrioventricular dissociation and his-bundle pacing

Following AVN ablation, eight dogs were surgically instrumented for chronic (continuous) HIS-bundle pacing. For data collection, implanted pacemakers were transiently programmed to pace in stepwise ascending ramps at rates from 50 to 200 beats/min in 30-beat/min steps. Each rate was held for 60 seconds. At each rate, ECG signals were collected from conscious dogs for measurements of QT intervals during the last 10 seconds of each paced rate to construct a QT-HR ramp. This QT-HR ramp was repeated twice on each day of study 10 minutes apart. Dogs were randomly assigned to two groups and studied weekly for a minimum of 6 weeks. Group 1 dogs had pacemakers programmed to a rate of 80 beats/min for the duration of the study. Group 2 dogs were paced at 80 beats/min for weeks 1-3, then increased to 140 beats/min for weeks 4-6. The difference between paired QT-HR ramps within 1 day was <3 ms. QT-HR ramps were statistically indistinguishable over the 6-week study for group 1 dogs. Group 2 dogs experienced a slight flattening in the slope of the QT-HR ramps from week 3 to week 6 due to a reduction in QT interval at low HRs (50 and 80 beats/min) only. This conscious HIS-pacing model in dogs is a sensitive, stable, and reproducible method to define ventricular repolarization characteristics over a range of programmable HRs and experimental conditions.     

Improved Pattern of Rate Responsiveness with Dynamic Slope Setting for the QT Sensing Pacemaker

We have recently described the electrophysiological basis of a new algorithm for the QT (TX) sensing rate responsive pacemaker. By using the new software program running on the standard programmer it has been possible to simulate the new algorithm in ten patients with complete heart block (seven patients had implanted TX units and three were paced with an external TX pacemaker) during routine exercise testing. In this way a single-blind, intra-patient comparison of the pattern of pacing rate change using both the existing and new algorithms was possible. In nine out of the ten cases the time taken to increase the pacing rate from 70 to 80 bpm was reduced significantly when the new algorithm was used (P = 0.037). Additionally, the correlation between the atrial and ventricular rates in those patients with normal sinus node function (seven patients) was determined. In all cases we have observed a significantly improved correlation between the atrial and ventricular paced rates during exercise with the new algorithm (P less than 0.001).     

Usefulness of 1-Hour and 24-Hour Heart Rate Holter Inbuilt in New TX* Rate Adaptive Pacemakers

SERMASI S., ET AL.: Usefulness of 1-Hour and 24-Hour Heart Rate Holter Inbuilt in New TX* Rate Adaptive Pacemakers. The rate adaptive TX* pacemaker uses the evoked QT interval as an indicator of physiological demand. In order to obtain a rate adaptation close to physiological patterns we used in the past, in each patient, on the slope value and/or the T wave sensing window, controlling via exercise stress testing and Holter the results achieved. It was an expensive method, but the system produced effective rate responsive pacing. The new series of TX* pacemakers (Quintech 919 and Rhythmyx), beside the dynamic slope feature, are equipped with a 1-hour heart rate Holter (HRH) that can be used during effort without the need for manually recording the heart rate. In this mode TX* pacemakers calculate the average heart rate over 20-second periods and stores the values continuously for 1 hour. In addition, a 24-hour HRH is available, which calculates the average heart rate over 7.5-minute periods, showing heart rate trend during the last day prior to interrogation. Each HRH can be accessed by the programmer and printed out. Using four Quintech 919* and five Rhythmyx units, the inbuilt HRH proved its utility by making the heart rate adaptation checking procedure easier, faster, and more economic.     

Beat-To-Beat Behavior of QT Interval During Conducted Supraventricular Rhythm in the Normal Heart

To assess beat-to-beat behavior of QT interval under different conditions, high resolution recordings and computerized beat-to-beat analysis of the electrocardiogram were performed at rest, during recovery after short exercise, and during atrial pacing. Beat-to-beat variations of QT interval during sinus rhythm at rest and after short exercise were measured in ten healthy men. In an additional three patients with supraventricular tachycardia, beat-to-beat QT changes were studied after abrupt sustained acceleration and deceleration of heart rate by atrial pacing. Beat-to-beat changes in RH interval at rest are followed by minimal changes of the QT interval. The measured proportional change of the QT interval compared with the change in HR interval (Δ QT/A BR) was 0.02. This value represents 10% of the value expected for QT changes from Bazett's formula. Following short exercise QT interval did not change for 15 seconds and reached a maximal value 30 seconds later as compared to the RR interval (192 vs 115 sees, P < 0.001). The steady state of the QT interval during sustained atrial pacing was achieved after 132, 135, and 133 seconds for pacing intervals of 600, 500, and 600 msec, respectively. Our data indicate a relatively slow adaptation of the QT interval to changes in heart rate.