QT Adaptation Research Articles

The role of β-adrenergic stimulation in QT interval adaptation to heart rate during stress test.

The adaptation lag of the QT interval after heart rate (HR) has been proposed as an arrhythmic risk marker. Most studies have quantified the QT adaptation lag in response to abrupt, step-like changes in HR induced by atrial pacing, in response to tilt test or during ambulatory recordings. Recent studies have introduced novel methods to quantify the QT adaptation lag to gradual, ramp-like HR changes in stress tests by evaluating the differences between the measured QT series and an estimated, memoryless QT series obtained from the instantaneous HR. These studies have observed the QT adaptation lag to progressively reduce when approaching the stress peak, with the underlying mechanisms being still unclear. This study analyzes the contribution of β-adrenergic stimulation to QT interval rate adaptation in response to gradual, ramp-like HR changes. We first quantify the QT adaptation lag in Coronary Artery Disease (CAD) patients undergoing stress test. To uncover the involved mechanisms, we use biophysically detailed computational models coupling descriptions of human ventricular electrophysiology and β-adrenergic signaling, from which we simulate ventricular action potentials and ECG signals. We characterize the adaptation of the simulated QT interval in response to the HR time series measured from each of the analyzed CAD patients. We show that, when the simulated ventricular tissue is subjected to a time-varying β-adrenergic stimulation pattern, with higher stimulation levels close to the stress peak, the simulated QT interval presents adaptation lags during exercise that are more similar to those measured from the patients than when subjected to constant β-adrenergic stimulation. During stress test recovery, constant and time-varying β-adrenergic stimulation patterns render similar adaptation lags, which are generally shorter than during exercise, in agreement with results from the patients. In conclusion, our findings support the role of time-varying β-adrenergic stimulation in contributing to QT interval adaptation to gradually increasing HR changes as those seen during the exercise phase of a stress test.

Accelerated QT adaptation following atropine-induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis.

Hysteresis, a ubiquitous regulatory phenomenon, is a salient feature of the adaptation of ventricular repolarization duration to heart rate (HR) change. We therefore compared the QT interval adaptation to rapid HR increase in patients with the long QT syndrome type 1 (LQT1) versus healthy controls because LQT1 is caused by loss-of-function mutations affecting the repolarizing potassium channel current IKs , presumably an important player in QT hysteresis. The study was performed in an outpatient hospital setting. HR was increased in LQT1 patients and controls by administering an intravenous bolus of atropine (0.04 mg/kg body weight) for 30 s. RR and QT intervals were recorded by continuous Frank vectorcardiography. Atropine induced transient expected side effects but no adverse arrhythmias. There was no difference in HR response (RR intervals) to atropine between the groups. Although atropine-induced ΔQT was 48% greater in 18 LQT1 patients than in 28 controls (p < 0.001), QT adaptation was on average 25% faster in LQT1 patients (measured as the time constant τ for the mono-exponential function and the time for 90% of ΔQT; p < 0.01); however, there was some overlap between the groups, possibly a beta-blocker effect. The shorter QT adaptation time to atropine-induced HR increase in LQT1 patients on the group level corroborates the importance of IKs in QT adaptation hysteresis in humans and shows that LQT1 patients have a disturbed ultra-rapid cardiac memory. On the individual level, the QT adaptation time possibly reflects the effect-size of the loss-of-function mutation, but its clinical implications need to be shown.

QT Interval Adaptation to Heart Rate Changes in Atrial Fibrillation as a Predictor of Sudden Cardiac Death.

The clinical significance of QT interval adaptation to heart rate changes has been poorly investigated in atrial fibrillation (AF), since QT delineation in the presence of f-waves is challenging. The objective of the present study is to investigate new techniques for QT adaptation estimation in permanent AF. A multilead strategy based on periodic component analysis, to emphasize T-wave periodicity, is proposed for QT delineation. QT adaptation is modeled by a linear, time-invariant filter, which describes the dependence between the current QT interval and the preceding RR intervals, followed by a memoryless, nonlinear, function. The QT adaptation time lag is determined from the estimated impulse response. Using simulated ECGs in permanent AF, the transformed lead was found to offer more accurate QT delineation and time lag estimation than did the original ECG leads for a wide range of f-wave amplitudes. In a population with chronic heart failure and permanent AF, the time lag estimated from the transformed lead was found to have the strongest, statistically significant association with sudden cardiac death (SCD) (hazard ratio = 3.49). Periodic component analysis provides more accurate QT delineation and improves time lag estimation in AF. A prolonged QT adaptation time lag is associated with a high risk for SCD. SCD risk markers originally developed for sinus rhythm can also be used in AF, provided that T-wave periodicity is emphasized. The time lag is a potentially useful biomarker for identifying patients at risk for SCD, guiding clinicians in adopting effective therapeutic decisions.

Sex and Rate Change Differences in QT/RR Hysteresis in Healthy Subjects

While it is now well-understood that the extent of QT interval changes due to underlying heart rate differences (i.e., the QT/RR adaptation) needs to be distinguished from the speed with which the QT interval reacts to heart rate changes (i.e., the so-called QT/RR hysteresis), gaps still exist in the physiologic understanding of QT/RR hysteresis processes. This study was designed to address the questions of whether the speed of QT adaptation to heart rate changes is driven by time or by number of cardiac cycles; whether QT interval adaptation speed is the same when heart rate accelerates and decelerates; and whether the characteristics of QT/RR hysteresis are related to age and sex. The study evaluated 897,570 measurements of QT intervals together with their 5-min histories of preceding RR intervals, all recorded in 751 healthy volunteers (336 females) aged 34.3 ± 9.5 years. Three different QT/RR adaptation models were combined with exponential decay models that distinguished time-based and interval-based QT/RR hysteresis. In each subject and for each modelling combination, a best-fit combination of modelling parameters was obtained by seeking minimal regression residuals. The results showed that the response of QT/RR hysteresis appears to be driven by absolute time rather than by the number of cardiac cycles. The speed of QT/RR hysteresis was found decreasing with increasing age whilst the duration of individually rate corrected QTc interval was found increasing with increasing age. Contrary to the longer QTc intervals, QT/RR hysteresis speed was faster in females. QT/RR hysteresis differences between heart rate acceleration and deceleration were not found to be physiologically systematic (i.e., they differed among different healthy subjects), but on average, QT/RR hysteresis speed was found slower after heart rate acceleration than after rate deceleration.

Adaptation of ventricular repolarization dispersion during heart rate increase in humans: A roller coaster process

BackgroundRegional differences in ventricular activation sequence and action potential duration and morphology result in dispersion in ventricular repolarization (VR). VR dispersion is a key factor in arrhythmogenesis. We studied the adaptation of global VR dispersion in humans during normal and abnormal ventricular activation, and the relation to the QT adaptation (hysteresis). MethodsWe measured global VR dispersion as T amplitude, T area, and ventricular gradient (VG), using continuous Frank vectorcardiography, in response to abrupt and sustained atrial (AP) or ventricular pacing (VP) aiming at 120 bpm, in 21 subjects with permanent pacemakers. ResultsFollowing pacing start, VR adaptation showed an initially rapid and complex tri-phasic pattern, most pronounced for T amplitude. There were major differences in the patterns of VR dispersion adaptation following abrupt AP vs VP, confirming that the adaptation pattern is activation dependent. In response to AP, an instantaneous decrease in VR dispersion occurred, followed by an increase and then a slow decrease, all at a lower level than baseline. In contrast, following VP there was an immediate increase to ~4× baseline in T amplitude and T area (but not in VG), with a subsequent biphasic adaptation lasting longer during VP than AP. The initial rapid changes occurred within the time for QT adaptation to reach steady-state. ConclusionsOur results corroborate and expand data from animal and invasive human studies, showing similarities of the adaptation pattern on different scales. The initial rapidly changing VR adaptation phase presumably reflects a window of increased vulnerability to arrhythmias.

Haloperidol affects coupling between QT and RR intervals in guinea pig isolated heart

Prolonged QT interval is an independent risk factor for development of ventricular arrhythmias. Haloperidol is one of the drugs inducing QT prolongation. Previous studies showed that haloperidol affects not only QT duration but also heart rate (RR interval). The present work focused on relationship between QT and RR and its changes under acute and chronic haloperidol administration. The study included 14 male guinea pigs divided into control and haloperidol-treated group. After 21-days administration of haloperidol or vehiculum, electrograms in isolated hearts were recorded. QT/RR and dQT/dRR coupling were calculated. Chronic haloperidol administration significantly decreases the coupling between QT and RR. Acute haloperidol exposure significantly decreases the dQT/dRR coupling in both treated and untreated guinea pig hearts. Flatter QT/RR relationship reveals a lack of QT adaptation to increased heart rate. It should be emphasized that in such situation ECG recording will not show significant QT prolongation evaluated according to clinical rules. However, if QT interval does not adapt to increased heart rate sufficiently, the risk of ventricular arrhythmias may be increased despite practically normal QT interval length. The results are supported by findings in biochemical analyses, which proved eligibility of the used model.

QT Adaptation during Exercise in Cirrhosis

AIM: QT-interval prolongation is frequently seen in cirrhosis; whether it is simply a marker of disease severity is debated. Analysis of QT-interval behavior during physical exercise may disclose more specific abnormalities of cardiac repolarization of cirrhotic cardiomyopathy. MATERIALS AND METHODS: Thirty-eight out-patients with non-alcoholic liver cirrhosis and portal hypertension (32 males, aged 62 ± 9 years) and 36 sex- and age-matched healthy volunteers (32 males; aged 59 ± 7 years) underwent bicycle exercise test with QT-interval measurement, echocardiographic and Doppler analysis of systolic and diastolic left ventricular function, determinations of systemic hemodynamic and pro-brain natriuretic peptide concentration. RESULTS: Patients had longer Fridericia-corrected QT-interval than healthy subjects at baseline and peak-exercise, and reduced chronotropic index, despite similar predicted workload. Corrected-QT shortening extent at peak-exercise was the same; however, in early-exercise, corrected-QT increased in 6 healthy subjects versus 25 patients, and in patients the increase was greater and significantly delayed. QT hysteresis was greater in patients. Abnormal repolarization during exercise and recovery in patients with normal baseline corrected-QT did not correlate to Child-Pugh class and hemodynamic alterations, whereas patients with > 440 ms corrected-QT (n = 16) showed diastolic dysfunction and increased pro-brain natriuretic peptide. CONCLUSIONS: QT behavior during physical exercise supports the hypothesis of anomalous modulation of potassium currents in cirrhosis; only long rest corrected-QT correlates to clinical signs of cirrhotic cardiomyopathy.

Population-based beat-to-beat QT analysis from Holter recordings in the long QT syndrome

The increasing dissemination of wearable ECG recorders (e.g. Holter, patches, and strap sensors) enables the acquisition of large amounts of data during long periods of time. However, the clinical value of these long-term continuous recordings is hindered by the lack of automatic tools to extract clinically relevant information (other than non-sinus and life-threatening rhythms) from such long-term data, particularly when targeting population-based research. In this work, we propose and test a new tool for analyzing beat-to-beat interval measurements and extracting features from Holter ECGs. Specifically, we assess the adaptation of the QT interval following sudden changes in heart rate in the primary long QT types (1 & 2). We find that in long QT syndrome type 2, certain QT adaptation patterns can indicate a higher risk for cardiac events.

Valor del «test de bipedestación» en el diagnóstico y la evaluación de la respuesta al tratamiento con bloqueadores beta en el síndrome de QT largo

Introduction and objectivesPatients with congenital long QT syndrome (LQTS) have an abnormal QT adaptation to sudden changes in heart rate provoked by standing. The present study sought to evaluate the standing test in a cohort of LQTS patients and to assess if this QT maladaptation phenomenon is ameliorated by beta-blocker therapy. MethodsElectrographic assessments were performed at baseline and immediately after standing in 36 LQTS patients (6 LQT1 [17%], 20 LQT2 [56%], 3 LQT7 [8%], 7 unidentified-genotype patients [19%]) and 41 controls. The corrected QT interval (QTc) was measured at baseline (QTcsupine) and immediately after standing (QTcstanding); the QTc change from baseline (ΔQTc) was calculated as QTcstanding – QTcsupine. The test was repeated in 26 patients receiving beta-blocker therapy. ResultsBoth QTcstanding and ΔQTc were significantly higher in the LQTS group than in controls (QTcstanding, 528 ± 46ms vs 420 ± 15ms, P < .0001; ΔQTc, 78 ± 40ms vs 8 ± 13ms, P < .0001). No significant differences were noted between LQT1 and LQT2 patients. Typical ST-T wave patterns appeared after standing in LQTS patients. Receiver operating characteristic curves of QTcstanding and ΔQTc showed a significant increase in diagnostic value compared with the QTcsupine (area under the curve for both, 0.99 vs 0.85; P < .001). Beta-blockers attenuated the response to standing in LQTS patients (QTcstanding, 440 ± 32ms, P < .0001; ΔQTc, 14 ± 16ms, P < .0001). ConclusionsEvaluation of the QTc after the simple maneuver of standing shows a high diagnostic performance and could be important for monitoring the effects of beta-blocker therapy in LQTS patients.Full English text available from: www.revespcardiol.org/en

Value of the “Standing Test” in the Diagnosis and Evaluation of Beta-blocker Therapy Response in Long QT Syndrome

Introduction and objectivesPatients with congenital long QT syndrome (LQTS) have an abnormal QT adaptation to sudden changes in heart rate provoked by standing. The present study sought to evaluate the standing test in a cohort of LQTS patients and to assess if this QT maladaptation phenomenon is ameliorated by beta-blocker therapy. MethodsElectrographic assessments were performed at baseline and immediately after standing in 36 LQTS patients (6 LQT1 [17%], 20 LQT2 [56%], 3 LQT7 [8%], 7 unidentified-genotype patients [19%]) and 41 controls. The corrected QT interval (QTc) was measured at baseline (QTcsupine) and immediately after standing (QTcstanding); the QTc change from baseline (ΔQTc) was calculated as QTcstanding – QTcsupine. The test was repeated in 26 patients receiving beta-blocker therapy. ResultsBoth QTcstanding and ΔQTc were significantly higher in the LQTS group than in controls (QTcstanding, 528 ± 46ms vs 420 ± 15ms, P < .0001; ΔQTc, 78 ± 40ms vs 8 ± 13ms, P < .0001). No significant differences were noted between LQT1 and LQT2 patients. Typical ST-T wave patterns appeared after standing in LQTS patients. Receiver operating characteristic curves of QTcstanding and ΔQTc showed a significant increase in diagnostic value compared with the QTcsupine (area under the curve for both, 0.99 vs 0.85; P < .001). Beta-blockers attenuated the response to standing in LQTS patients (QTcstanding, 440 ± 32ms, P < .0001; ΔQTc, 14 ± 16ms, P < .0001). ConclusionsEvaluation of the QTc after the simple maneuver of standing shows a high diagnostic performance and could be important for monitoring the effects of beta-blocker therapy in LQTS patients.

Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa.

Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; P<0.001) and lower peak heart rates (159±20 versus 184±9 beats/min; P<0.001). The mean QTc intervals were longer at peak exercise in patients (442±29 versus 422±19 ms; P<0.001). During submaximal exertion at comparable heart rates (114±6 versus 115±11 beats/min; P=0.54), the QTc interval had prolonged significantly more in patients than controls (37±28 versus 24±25 ms; P<0.016). The RR/QT slope, best described by a curvilinear relationship, was more gradual in patients than in controls (13.4; 95% confidence interval, 12.8-13.9 versus 15.8; 95% confidence interval, 15.3-16.4 ms QT change per 10% change in RR interval; P<0.001) and steepest in patients within the highest body mass index tertile versus the lowest (13.9; 95% confidence interval, 12.9-14.9 versus 12.3; 95% confidence interval, 11.3-13.3; P=0.026). Despite the absence of manifest QT prolongation, adolescent anorexic females have impaired repolarization reserve in comparison with healthy controls. Further study may identify impaired QT dynamics as a risk factor for arrhythmias in anorexia nervosa.

P0100 : QT adaptation during exercise in liver cirrhosis: Adjunctive signs of cirrhotic cardiomyopathy

P0100 : QT adaptation during exercise in liver cirrhosis: Adjunctive signs of cirrhotic cardiomyopathy

Parathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidism, as evaluated by exercise test

To investigate whether parathyroidectomy (PTx) reverses risk factors for arrhythmias related to the QT dynamic changes evaluated during bicycle ergometry exercise test (ET). Twenty-four postmenopausal women with primary hyperparathyroidism (PHPT) (mean age 60.08.4 years) and 30 sex- and age-matched controls underwent ET, echocardiography, and biochemical evaluation. The following stages were considered during ET: rest, peak exercise, and recovery. The patients were randomized to two groups: 12 underwent PTx (group A) and 12 were followed-up conservatively (group B). After 6 months, the patients were studied again. Groups A and B showed no differences in mean baseline biochemical values, echocardiographic parameters, and QTC interval. PHPT patients showed an increased occurrence of ventricular premature beats (VPBS) during ET compared with controls (37.0 vs 6.6%, P=0.03). Serum calcium level was a predictor of VPBS (P=0.05). Mean value of QTC was in the normal range at baseline (Group A: 401±16.9; group B: 402.25±13.5 ms) but significantly lower than controls (417.8±25.1 ms, P<0.01). A negative correlation was found between QTc and calcium values (P=0.03). Physiological reduction of QTc interval from rest to peak exercise was not observed in PHPT patients before surgery. After PTx, group A had a significant reduction in VPBs compared with baseline (at baseline, 5 of 12 vs none of 12 patients after PTx, P=0.03) and a restored normal QT adaptation during ET. Group B showed no significant changes after a 6-month period. PTx reduces the occurrence of VPBs and restored the QTc adaptation during ET.

Potassium dynamics are attenuated in hyperkalemia and a determinant of QT adaptation in exercising hemodialysis patients

Disturbances in plasma potassium concentration (pK) are well known risk factors for the development of cardiac arrhythmia. The aims of the present study were to evaluate the effect of hemodialysis on exercise pK dynamics and QT hysteresis, and whether QT hysteresis is associated with the pK decrease following exercise. Twenty-two end-stage renal disease patients exercised on a cycle ergometer with incremental work load before and after hemodialysis. ECG was recorded and pK was measured during exercise and recovery. During exercise, pK increased from 5.1 ± 0.2 to 6.1 ± 0.2 mM (mean ± SE; P < 0.0001) before hemodialysis and from 3.8 ± 0.1 to 5.1 ± 0.1 mM (P < 0.0001) after hemodialysis. After 2 min of recovery, pK had decreased to 5.0 ± 0.2 mM and 4.1 ± 0.1 mM (P < 0.0001) before and after hemodialysis, respectively. pK increase during exercise was accentuated after hemodialysis. The pK increase was negatively linearly correlated with pK before exercise (β = -0.21, R(2) = 0.23, P = 0.001). QT hysteresis was negatively linearly correlated with the decrease in pK during recovery (β = -28 ms/mM, R(2) = 0.36, P = 0.006). Thus, during recovery, low pK was associated with relatively longer QT interval. In conclusion, new major findings are an accentuated increase in pK during exercise after hemodialysis, an attenuated increase in pK in hyperkalemia, and an association between pK and QT interval adaptation during recovery. The acute pK shift after exercise may modulate QT interval adaptation and trigger cardiac arrhythmias.

Estimation and Modeling of QT-Interval Adaptation to Heart Rate Changes

This paper introduces a new method for QT-interval estimation. It consists in a batch processing mode of the improved Woody's method. Performance of this methodology is evaluated using synthetic data. In parallel, a new model of QT-interval dynamics behavior related to heart rate changes is presented. Since two kinds of QT response have been pointed out, the main idea is to split the modeling process into two steps: 1) the modeling of the fast adaptation, which is inspired by the electrical behavior at the cellular level relative to the electrical restitution curve, and 2) the modeling of the slow adaptation, inspired by experimental works at the cellular level. Both approaches are based on a low-complexity autoregressive process whose parameters are estimated using an unbiased estimator. This new modeling of QT adaptation, combined with the presented QT-estimation process, is applied to several ECG recordings with various heart rate variability dynamics. Its potential is then illustrated on ECG recorded during rest, atrial fibrillation episodes, and exercise. Meaningful results in agreement with physiological knowledge at the cellular level are obtained.

Utility of treadmill testing and DCG in diagnosis of long QT syndrome

BackgroundThe hereditary long QT syndrome (LQTS) is a genetic channalopathy that is characterised by a prolonged QT interval, syncope, ventricular arrhythmias, and sudden death. The clinical diagnosis of LQTS remains...

Genotype- and Mutation Site–Specific QT Adaptation During Exercise, Recovery, and Postural Changes in Children With Long-QT Syndrome

Exercise stress testing has shown diagnostic utility in adult patients with long-QT syndrome (LQTS); however, the QT interval adaptation in response to exercise in pediatric patients with LQTS has received little attention. One-hundred fifty-eight patients were divided into 3 groups: Those with LQTS type 1 (LQT1) or LQTS type 2 (LQT2) and normal control subjects without cardiovascular disease. Each patient underwent a uniform exercise protocol with a cycle ergometer followed by a 9-minute recovery phase with continuous 12-lead ECG monitoring. Each patient underwent a baseline ECG while resting in the supine position and in a standstill position during continuous ECG recording to determine changes in the QT and RR intervals. Fifty patients were gene-positive for LQTS (n=29 for LQT1 and n=21 for LQT2), and the control group consisted of 108 patients. QT interval adaptation was abnormal in the LQT1 patients compared with LQT2 and control patients (P<0.001). A corrected QT interval (QTc) >460 ms in the late recovery phase at 7 minutes predicted LQT1 or LQT2 versus control subjects with 96% specificity, 86% sensitivity, and a 91% positive predictive value. A recovery ΔQTc((7 min-1 min)) >30 ms predicted LQT2 versus LQT1 with 75% sensitivity, 82% specificity, and a 75% positive predictive value. The postural ΔQT was significantly different between LQTS and control groups (P=0.005). Genotype-specific changes in repolarization response to exercise and recovery exist in the pediatric population and are of diagnostic utility in LQTS. An extended recovery phase is preferable to assess the repolarization response after exercise in the pediatric population.

Slow QT Interval Adaptation to Heart Rate Changes in Normal Ambulatory Subjects

Clinical formulas for QT correction utilize instantaneous HR. We showed previously that longer-term HR affects QT duration. We extend these findings, identifying more accurate models of QT behavior. Multiple models of QT dependence on HR were tested in 2 independent populations. Holter recordings were analyzed in population A (healthy volunteers, n = 14, 6 males, age 26.9 ± 12.3 yr). The hypotheses generated in population A were tested in an independent group population B, healthy volunteers, n = 15, 9 males, age 52.9 ± 15.6 yr). Linear models of QT interval dependence on a weighted average of RR intervals in the preceding 3 minutes were compared to models based on the immediately preceding RR interval (instantaneous HR). In population A, linear models based on RR intervals over the preceding minute performed better than the best nonlinear model based on the single RR interval immediately preceding the QT interval. Linear models including HR values preceding the QT interval by more than 60 s further improved model fit. This model hierarchy was confirmed in population B. Linear formula for QT correction based on exponential decay of HR effect with 60 s time constant outperformed Bazett and Fridericia formulas in both populations. QT duration in normal ambulatory subjects is affected by noninstantaneous HR, including HR history dating back more than 60 s. Exponential decay of this "memory effect" with time constant of 1 minute provides an accurate description of QT adaptation. This may be of clinical importance when HR is not steady.

A Novel Method for Patient-Specific QTc-Modeling QT-RR Hysteresis

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. 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. 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.

Effect of β-adrenergic stimulation on QT interval accommodation

QT interval correction formulas are based on instantaneous heart rate (HR), but QT interval adaptation to sudden HR change occurs gradually. In humans, the QT interval has been reported to reach a new steady-state value in about 2 minutes. This study sought to assess β-adrenergic stimulation effects on QT interval response to HR change. Ten subjects (42.1 ± 15.3 years, 3 men) undergoing radiofrequency ablation of supraventricular tachycardia were studied. Atrial pacing for 5 minutes at an HR ranging from 60 to 140 beats/min was performed before and during dobutamine infusion (10 μg/kg/min). The QT response to sudden HR change was evaluated. The QT response to sudden HR change consists of an immediate response (IR), followed by a gradual monoexponential course to the new steady-state value. Linear function results in inferior fit of QT adaptation course (P < .05 compared with exponential). The time constant of the exponential is approximately 1 minute (50.9 ± 11.4 seconds). The IR magnitude is approximately 3% of the RR interval change (2.97% ± 2.01%). Dobutamine shortens steady-state QT at given HR (from 301.8 ± 11.2 ms to 290.6 ± 13.2 ms at 120 beats/min; P < .001) and increases IR magnitude (to 13.28% ± 8.99% of RR change; P < .01). During sinus rhythm, QT variability and QT variability index were significantly increased by dobutamine. QT adaptation has 2 distinct phases, which might have different mechanisms. The effect of β-adrenergic stimulation on IR may increase QT variability by increasing the immediate response to HR variability. These results may be important in the assessment of drug effects on repolarization and for understanding of QT variability.