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.

• Keywords
• QT/RR adaptation, QT/RR hysteresis, age influence, best-fit models, healthy subjects, non-linear regression modelling, sex differences,
• Publication type
• Journal Article MeSH

BACKGROUND: The patients with the long QT syndrome type-1 (LQT-1) have an impaired adaptation of the QT interval to heart rate changes. Yet, the description of the dynamic QT-RR coupling in genotyped LQT-1 has never been thoroughly investigated. METHOD: We propose a method to model the dynamic QT-RR coupling by defining a transfer function characterizing the relationship between a QT interval and its previous RR intervals measured from ambulatory Holter recordings. Three parameters are used to characterize the QT-RR coupling: a fast gain (Gain(F) ), a slow gain (Gain(L) ), and a time constant (τ). We investigated the values of these parameters across genders, and in genotyped LQT-1 patients with normal QTc interval duration (QTc < 470 ms). RESULTS: The QT-RR dynamic profiles are significantly different between LQT-1 patients (97) and controls (154): LQT-1 have longer QTc interval (453 ± 35 vs. 384 ± 26 ms, P < 0.0001), and an increased dependency of the QT interval to previous RR changes revealed by a larger Gain(L) (0.22 ± 0.06 vs. 0.18 ± 0.07, P < 0.0001) and Gain(F) (0.05 ± 0.02 vs. 0.03 ± 0.01, P < 0.0001). Importantly, LQT-1 patients have a faster QT dynamic response to previous RR changes described by τ: 122 ± 44 vs. 172 ± 92 beats (P < 0.0001). This faster QT dynamic response of the QT-RR dynamic coupling remained in LQT-1 patients with QTc in a normal range (<430 ms). CONCLUSIONS: The measurement of QT-RR dynamic coupling could be used in patients suspected to carry a concealed form of the LQT-1 syndrome, or to provide insights into the types of arrhythmogenic triggers a patient may be prone to.

• MeSH
• Circadian Rhythm MeSH
• Adult MeSH
• Electrocardiography, Ambulatory methods   statistics & numerical data   MeSH
• Adaptation, Physiological MeSH
• Cohort Studies MeSH
• Humans MeSH
• Young Adult MeSH
• Reference Values MeSH
• Heart Rate MeSH
• Long QT Syndrome diagnosis   physiopathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

Data provided by THEW was used to test QT gender differences. Three QT/RR models were used during analysis: a transfer function model (TRF), a model based on exponential weighting of RR intervals (EXP), and an EXP model with additive direct coupling with RR intervals (EXPDC). Data from 81 men and 73 women was analyzed.Women have a significantly higher QTc (p<10(-6)), steeper Gain(L) (QT/RR slope, gain for slow RR variability, p<0.01), faster τ (QT adaptation, p<0.05), higher Gain(F) (gain for fast RR variability, immediate change of QT, p<0.05) and higher QT random variability (p<0.05).The higher prevalence of arrhythmias in women, given by longer QTc, is compensated to some extent by a higher level of Gain(F) and faster τ. The proarrhythmic influence of drugs may originate in a change of Gain(L), Gain(F) or τ without any change in QTc.

• Publication type
• Journal Article MeSH

BACKGROUND: Cardiac repolarization is assessed by the QT interval on the surface electrocardiogram and varies with the heart rate. Standard QT corrections (QTc) do not account for the lag in QT change following a change in heart rate (QT hysteresis). Our group has developed and tested a transfer function (TRF) model to assess the effectiveness of a dynamic model of QT/RR coupling in eliminating hysteresis. METHODS: We studied three groups: group I, healthy volunteers (n = 23, 41 ± 17 years); group II, hypertensive patients (n = 25, 45 ± 11 years); and group III, patients in a predominately paced rhythm (n = 5, 75 ± 6 years). To vary the heart rate, either exercise bicycling in the supine position (groups I and II) or manipulation of the pacemaker parameters (group III) was done. We then compared a dynamic TRF model with a model based on weighted averages of previous RR intervals. Two parameters were tested: root mean square (RMS) of the error signal between measured and computed QT and the elimination of hysteretic loops. RESULTS: TRF-based measurements eliminated hysteresis in 22/23 (95%) group I patients, 21/25 (84%) group II patients, and 4/5 (80%) group III patients. When hysteresis elimination was not complete, the QT drift that followed RR intervals was different before and after bicycling (100 ms). In these patients, the corresponding QT interval did not significantly change during this period. The TRF model was found superior to the other tested models with respect to both analyzed parameters (RMS and hysteresis elimination). CONCLUSION: The TRF model limited QT hysteresis in healthy, hypertensive, and pacemaker-dependent patients. In addition, an important finding of QT drift in patients with hypertension was identified. With further study in these and other diseased states, the TRF model may improve our ability to measure accurately cardiac repolarization and to determine arrhythmia risk.

• MeSH
• Adult MeSH
• Electrocardiography * MeSH
• Risk Assessment MeSH
• Hypertension diagnosis   physiopathology   MeSH
• Cardiac Pacing, Artificial methods   MeSH
• Pacemaker, Artificial * MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Models, Cardiovascular MeSH
• Follow-Up Studies MeSH
• Heart Conduction System physiopathology   MeSH
• Reference Values MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Heart Rate physiology   MeSH
• Long QT Syndrome diagnosis   therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH