Beat‐to‐Beat QT Dynamics in Healthy Subjects

Background: Measures of QT dynamics express repolarization abnormalities that carry prognostic information, but the reproducibility of beat‐to‐beat QT dynamics has never been established. The QT interval is prolonged at night, but how the circadian rhythm and heart rate influence the dynamic QT measurements is still unsettled. The aims of the present study were: (1) to describe the reproducibility of beat‐to‐beat QT dynamics with respect to intrasubject, between‐subject, and between‐observer variability and (2) to describe the normal range, circadian variation, and heart rate dependence of QT dynamics. Methods: Ambulatory Holter recordings were performed three times on 20 healthy volunteers and were analyzed by two experienced cardiologists. Slope and intercept of the QT/RR regression, the variability of QT and R‐R intervals expressed as the standard deviation, and the relation between QT and RR variability expressed as a variability ratio were measured among other QT dynamics. Results: The reproducibility of all QT dynamics was good. All QT dynamics showed circadian variation when calculated on an hourly basis. The day/night variation in slope could be explained by the differences in heart rate, whereas the day/night variation in intercept was heart rate independent. Conclusion: The present study shows that reliable automatic QT measurements could be performed, encouraging further evaluation of the clinical value of QT dynamics in risk stratification of cardiac patients.     

Weighing the QT Intervals with the Slope or the Amplitude of the T Wave

Objective: The reproducibility of QT interval measurements is low, even for the mean QT interval based on the standard ECG. In this study we analyzed whether the reproducibility of the mean weighed QT interval was better than the simple mean QT interval. The weighing was based on the amplitude of the T wave or the slope of the steepest tangent on the terminal part of the T wave. Material and methods: 12‐lead ECGs of 130 postmyocardial infarction patients were obtained. The QT intervals were measured by the tangent‐method on two occasions by the same observer Mismatch QT intervals were defined as QT intervals that were measured at only one occasion. Sixteen ECGs were rejected. The data were split into 34 and 80 ECGs for optimization and validation of the weighing, respectively. The weighed QT dispersion was calculated as the weighed mean of the three longest minus the weighed mean of the three shortest QT intervals. Results: Weighing with the slope increased the reproducibility by 41% (P = 3 10^‐6), but weighing with the amplitude reduced it by 20% (P = 0.02). However, if measurements with errors above 75 ms were rejected, weighing with the slope or the amplitude increased the reproducibility with 26% and 20% (P = 0.02), respectively. Weighing did not change the reproducibility of the weighed QT dispersion. Conclusion: Weighing with the slope improved the reproducibility of the mean weighed QT interval. However, if measurements with errors above 75 ms were rejected, weighing with the amplitude also increased the reproducibility. Weighing did not change the reproducibility of the weighed QT dispersion. Weighing is particularly efficient at reducing the negative impact of mismatch QT intervals on the reproducibility. A.N.E. 2002;7(1):4–9     

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

Background: 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. Methods: 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. Results: 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. Conclusions: 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.     

Comparing Methods of Measurement for Detecting Drug‐Induced Changes in the QT Interval: Implications for Thoroughly Conducted ECG Studies

Background: The aim of this study was to compare the reproducibility and sensitivity of four commonly used methods for QT interval assessment when applied to ECG data obtained after infusion of ibutilide. Methods: Four methods were compared: (1) 12‐lead simultaneous ECG (12‐SIM), (2) lead II ECG (LEAD II), both measured on a digitizing board, (3) 3‐LEAD ECG using a manual tangential method, and (4) a computer‐based, proprietary algorithm, 12SL? ECG Analysis software (AUT). QT intervals were measured in 10 healthy volunteers at multiple time points during 24 hours at baseline and after single intravenous doses of ibutilide 0.25 and 0.5 mg. Changes in QT interval from baseline were calculated and compared across ECG methods, using Bland–Altman plots. Variability was studied using a mixed linear model. Results: Baseline QT values differed between methods (range 376–395 ms), mainly based on the number of leads incorporated into the measurement, with LEAD II and 3‐LEAD providing the shortest intervals. The 3‐LEAD generated the largest QT change from baseline, whereas LEAD II and 12‐SIM generated essentially identical result within narrow limits of agreement (0.4 ms mean difference, 95% confidence interval ± 20.5 ms). Variability with AUT (standard deviation 15.8 ms for within‐subject values) was clearly larger than with 3‐LEAD, LEAD II, and 12‐SIM (9.6, 10.0, and 11.3 ms). Conclusion: This study demonstrated significant differences among four commonly used methods for QT interval measurement after pharmacological prolongation of cardiac repolarization. Observed large differences in variability of measurements will have a substantial impact on the sample size required to detect QT prolongation in the range that is currently advised in regulatory guidance.     

Interobserver Reproducibility of QT Interval Measurement and QT Dispersion in Patients After Acute Myocardial Infarction

Background: The study evaluated interobserver differences in the classification of the T-U wave repolarization pattern, and their influence on the numerical values of manual measurements of QT interval duration and dispersion in standard predischarge 12-lead ECGs recorded in survivors after acute myocardial infarction. Methods: Thirty ECGs recorded at 25 mm/s were measured by six independent observers. The observers used an adopted scheme to classify the repolarization pattern into 1 of 7 categories, based on the appearance of the T wave, and/or the presence of the U wave, and the various extent of fusion between these. In each lead with measurable QRST(U) pattern, the RR, QJ, QT-end, QT-nadir (i.e., interval between Q onset and the nadir or transition between T and U wave) and QU interval were measured, when applicable. Based on these measurements, the mean RR interval, the maximum, minimum, and mean QJ interval, QT-end and/or QT-nadir interval, and QU interval, the difference between the maximum and minimum QT interval (QT dispersion [QTD]), and the coefficient of variation of QT intervals was derived for each recording. The agreement of an individual observer with other observers in the selection of a given repolarization pattern were investigated by an agreement index, and the general reproducibility of repolarization pattern classification was evaluated by the reproducibility index. The interobserver agreement of numerical measurements was assessed by relative errors. To assess the general interobserver reproducibility of a given numerical measurement, the coefficient of variance of the values provided by all observers was computed for each ECG. Statistical comparison of these coefficients was performed using a standard sign test. Results: The results demonstrated the existence of remarkable differences in the selection of classification patterns of repolarization among the observers. More importantly, these differences were mainly related to the presence of more complex patterns of repolarization and contributed to poor interobserver reproducibility of QTD parameters in all 12 leads and in the precordial leads (relative error of 31%–35% and 34%–43%, respectively) as compared with the interobserver reproducibility of both QT and QU interval duration measurements (relative error of 3%–6%, P < 0.01). This observation was not explained by differences in the numerical order between QT interval duration and QTD, as the reproducibility of the QJ interval (i.e., interval of the same numerical order as QTD was significantly better (relative error of 7.5%–13%, P < 0.01) than that of QTD. Conclusions: Poor interobserver reproducibility of QT dispersion related to the presence of complex repolarization patterns may explain, to some extent, a spectrum of QT dispersion values reported in different clinical studies and may limit the clinical utility in this parameter.     

Prognostic value of QT/RR slope in predicting mortality in patients with congestive heart failure

Introduction: Repolarization dynamics, reflecting adaptation of QT to changing heart rate, is considered a marker of unfavorable prognosis in patients with heart diseases. We aimed to evaluate the prognostic value of QT/RR slope in predicting total mortality (TM) and sudden death (SD) in patients with congestive heart failure (CHF). Methods and Results: In 651 sinus rhythm patients with CHF in NYHA class II–III enrolled in the MUSIC study, 24‐hour Holter monitoring was performed at enrollment to assess slope of the QTa/RR (QT apex) and QTe/RR (QTend) during the entire 24‐hour Holter recording and separately during day and night periods. Patients were followed for a median of 44 months, with the primary endpoint defined as TM and the secondary as SD. Analysis of repolarization dynamics was feasible in 542 patients (407M), mean age 63 years, 83% in NYHA class II, 49% with ischemic cardiomyopathy, with mean LVEF 37%. Mean value of QTa/RR slope was 0.172 and QTe/RR was 0.193. During the 44‐month follow‐up there were 119 deaths including 47 SD. Nonsurvivors were characterized by steeper QT/RR slopes. Increased QT/RR slopes during the daytime (>0.20 for QTa and >0.22 for QTe) were independently associated with increased TM in multivariate analysis after adjustment for clinical covariates with respective hazard ratios 1.57 and 1.58, P = 0.002. None of the dynamic repolarization parameters was associated with increased risk of SD in the entire population. Conclusions: Abnormal repolarization dynamics reflected as increased daytime QT/RR slopes is an independent risk stratifier of all‐cause mortality in patients with chronic heart failure     

Changes in the QT interval and its adaptation to rate, assessed with continuous electrocardiographic recordings in patients with ventricular fibrillation, as compared to normal individuals without arrhythmias

Various QT interval variables and heart rate variability parameterswere studied in six patients with ventricular fibrillation butwithout heart disease and compared with findings in 21 normalpersons. QT and QT dispersion (QTd) were measured from conventional12 lead ECGs; for dynamic QT analysis, QT intervals were automaticallymeasured to the end of the T wave (QTe) on a 24 h ECG recording.The adaptation of the QT interval to changes in heart rate wasexpressed as the slope of the linear regression lines relatingQTe to the RR interval (Se). The complete 24 h ECG recordingand four 6 h segments were studied (morning, day, evening, andnight). Ventricular fibrillation patients had slightly prolongedQT_max intervals on the 12 lead ECG, QT dispersion was longerin ventricular fibrillation patients than in normal persons(88±29 ms vs 59±26 ms, p<0·05), andon the 24 h ECG recording, normal persons and ventricular fibrillationpatients had a comparable RR. In addition, parameters for long-term (SD, standard deviationof normal RR intervals) and short-term (RMSSD, the root-mean-squaresuccessive differences of normal RR intervals) heart rate variabilitywere not different. Automatic measurement of the QT intervaland the QTe/RR slopes was possible over 24 h and in the 6 hintervals in a large majority of patients (25/27 and 88/108readings). The mean 24 h QT and the mean 6 h QT interval werecomparable in normal subjects and ventricular fibrillation patientsexcept for the day segment. The 24 h Se was significantly lowerin ventricular fibrillation patients, compared to normal individuals.Furthermore, Se in the morning and night segment was also significantlylower in ventricular fibrillation patients (both p<0·05). In conclusion, patients with ventricular fibrillation but withoutunderlying structural heart disease have normal heart rate variabilityparameters. However, abnormal re-polarization behaviour, characterizedby an increased QTd and a depressed adaptation of QT to variationsin RR (especially during the night and the morning), is present.These findings may help to understand and treat arrhythmiasin this patient group.     

QTc interval measurement in patients with right bundle branch block: A practical method

Background and Aim

Prolonging the QT interval in the right bundle branch block (RBBB) can create challenges for electrophysiologists in estimating repolarization time and eliminating the effect of depolarization changes on QT interval. In this study, we aimed to develop a practice formula to eliminate the effect of depolarization changes on QT interval in patients with RBBB.

Methods

This prospective study evaluated accidentally induced RBBB in patients undergoing electrophysiological study. Two expert electrophysiologists recorded the ECG parameters, including QRS duration, QT interval, and cycle length, in the patients. The formula was developed based on QT interval differences (with and without RBBB) and its proportion to QRS. Additionally, the Bazzet, Rautaharju, and Hodge formulas were used to evaluate QTc.

Results

We evaluated 96 patients in this study. The mean QT interval without RBBB was 369.39 ± 37.38, reaching 404.22 ± 39.23 after inducing RBBB. ΔQT was calculated as 34.83 ± 17.61, and the ratio of ΔQT/QRS with RBBB was almost 23%. Our formula is: (QT_{with RBBB} − 23% × QRS). Subtraction of 25% instead of 23% seems more straightforward and practical. Our formula could also predict the QTc interval in RBBB based on the Bazzet, Rautaharju, and Hodge formulas.

Conclusion

Previous formulas for QT correction were hard to apply in the clinical setting or were not specified for RBBB. Our new formula allows a rapid and practical method for QT correction in RBBB in clinical practice.     

Diagnostic Performance of Various QTc Interval Formulas in a Large Family with Long QT Syndrome Type 3: Bazett's Formula Not So Bad After All …

Background: Recently, we identified a novel mutation of SCN5A (1795insD) in a large family with LQTS₃. The aim of this study was to assess whether the various proposed corrections of the QT interval to heart rate help to improve the identification of carriers of the mutant gene. Methods: The study group consisted of 101 adult family members: 57 carriers and 44 noncarriers (mean age 44.6 ± 14.6 and 40.3 ± 12.8 years, respectively). In all individuals a 12‐lead ECG, exercise ECG, and 24‐hour Holter ECG were obtained. Results: Correction for heart rate significantly improved the diagnostic performance of the QT interval. Diagnostic performance of the Bazett formula was similar to that of the newer formulas (Fridericia, Hodges, Framingham, and a logarithmic formula). At a cut‐off value of 440 ms, the Bazett corrected QT interval was associated with a sensitivity and specificity of 90% and 91%, respectively. Using the 24‐hour Holter ECG, a prolonged QTc at heart rates less than 60 beats/min was almost pathognomonic for genetic mutation (sensitivity and specificity both 99%), whereas the QTc calculated at the lowest heart rate using Bazett's formula provided full discrimination. Conclusion: In the present family, the resting ECG gave a good indication about the presence or absence of genetic mutation but a 24‐hour Holter recording was mandatory to ascertain the diagnosis. In the diagnosis of this form of LQTS₃, Bazett's formula was at least as good as other proposed corrections of the QT interval to heart rate.     

Circadian Pattern of QT/RR Adaptation in Patients with and Without Sudden Cardiac Death after Myocardial Infarction

Background: Abnormalities in the adaptation of the QT interval to changes in the RR interval may facilitate the development of ventricular arrhythmias. Methods: This study sought to evaluate the dynamic relation between the QT and RR intervals in patients after acute myocardial infarction. The study population consisted of 14 patients after myocardial infarction (age 60 ± 7 years, 12 men) who died suddenly (SCD victims) within 1 year after the myocardial infarction and 14 pair-matched age, sex, left ventricular ejection fraction, infarct site, thrombolytic therapy) patients who remained event-free after myocardial infarction (Ml survivors) for at least 3 years. Fourteen normal subjects were studied as controls (age 55 ± 9 years, 11 men). QT and RR intervals were measured on a beat-to-beat basis automatically with a visual control from 24-hour ambulatory ECGs using Reynolds Pathfinder 700. Mean hourly values of the QT/RR slope (QT =α+βRR) and corrected QT interval at 1000 ms of RR interval (QT_1s) were derived for each subject using an inhouse program (QT_1s=α+1000β). The dynamics of the QT/RR slope and QT_1s were assessed on the basis of hourly mean values. The circadian rhythm of ventricular repolarization (QT_1s and QT/RR slope) was examined by harmonic regression analysis. Results: There was a trend towards a significant difference in 24-hour mean value of QT_1s between study groups (408 ± 26 ms vs 381 ± 43 ms and 386 ± 22 ms, P = 0.06), and a significant difference was found between SCD victims and normal subjects (408 ± 26 vs 386 ± 22 ms, P = 0.02). The QT_1s differed significantly between study groups (P = 0.038) only during the day time (09:00–19:00 hour), when QT_1s was significantly longer in SCD victims than in normal subjects (409 ± 33 vs 380 ± 27 ms, P = 0.02) and tended to be longer than in Ml survivors (409 ± 33 vs 379 ± 42 ms, P = 0.08). The 24-hour mean value of QT/RR slope was significantly different between study groups (P = 0.04), with a significantly steeper slope in SCD victims than in normal subjects (0.15 ± 0.07 vs 0.09 ± 0.02, P = 0.008). During day time, the QT/RR slope differed significantly between study groups (P = 0.04), while the difference was less marked at night (P = 0.08). The slope was significantly steeper in SCD victims than in normal subjects during both day and night (P < 0.05). A marked circadian variation of QT_1s was observed in normal subjects, which was blunted in Ml survivors and SCD victims. Conclusions: Abnormal repolarization behaviors, characterized by longer QT_1s and impaired adaptation of QT to variations in RR intervals, were found in SCD victims. Hence, lethal ventricular tachyarrhythmias might be provoked by the altered repolarization dynamics in patients after myocardial infarction. A.N.E. 1999;4(3):286–294     

Reproducibility of Computerized Measurements of QT Interval from Multiple Leads at Rest and During Exercise

Background: Accurate measurement of the QT interval is important for diagnosing long QT syndrome (LQTS), and in research on determinants of ventricular repolarization time. We tested automatic analysis of QT intervals from multiple ECG leads on chest. Methods: Eleven healthy volunteers and 10 genotyped LQTS patients were tested at rest and during exercise with a bicycle ergometer twice 1–31 months apart. Electrocardiograms were recorded with the body surface potential mapping system, and 12 precordial channels were selected for analysis. Averaged QT peak and QT end intervals were determined with an automated algorithm, and the difference QT end minus QT peak (Tp‐e) was calculated. Repeatability was assessed by coefficient of variation (CV) between measurements. Results: Within one test at rest the QT end intervals were highly repeatable with CV 0.6%. In repeated tests CV was 4.4% for QT end interval and 3.5% when the QT interval was corrected for heart rate. In exercise test at specified heart rates, mean CV was 3.0% for QT end and 2.9% for QT peak interval. The CV of Tp‐e interval was 10.2% at rest, and 9.3% in exercise test. Reproducibility was comparable between healthy subjects and LQTS patients. Conclusions: The BSPM system with automated analysis produced accurate and highly repeatable QT interval measurements. Reproducibility was adequate also over prolonged time periods both at rest and in exercise stress test. The method can be applied in studying duration of ventricular repolarization time in different physiologic and pharmacologic interventions.     

Impact of Left Ventricular Remodeling on Ventricular Repolarization and Heart Rate Variability in Patients after Myocardial Infarction Treated with Primary PCI: Prospective 6 Months Follow‐up

Background: The relation between postinfarction left ventricle remodeling (LVR), autonomic nervous system and repolarization process is unclear. Purpose of the study was to assess the influence of LVR on the early (QTpeak) and late (TpeakTend) repolarization periods in patients after myocardial infarction (MI) treated with primary PCI. The day‐to‐night differences of repolarization parameters and the relation between QT and heart rate variability (HRV) indices, as well left ventricle function were also assessed. Methods: The study cohort of 104 pts was examined 6 months after acute MI. HRV and QT indices (corrected to the heart rate) were obtained from the entire 24‐hour Holter recording, daytime and nighttime periods. Results: LVR was found in 33 patients (31.7%). The study groups (LVR+ vs LVR?) did not differ in age, the extent of coronary artery lesions and treatment. Left ventricle ejection fraction (LVEF) was lower (38%± 11% vs 55%± 11%, P < 0.001), both QTc (443 ± 26 ms vs 420 ± 20 ms, P < 0.001) and TpeakTendc (98 ± 11 ms vs 84 ± 12 ms, P < 0.005) were longer in LVR + patients, with no differences for QTpeakc. Trends toward lower values of time‐domain (SDRR, rMSSD) HRV parameters were found in LVR+ pts. Day‐to‐night difference was observed only for SDRR, more marked in LVR‐group. Remarkable relations between delta LVEF (6 months minus baseline), delta LVEDV and TpeakTendc were found, with no such relationships for QTpeakc. Conclusions: The patients with LVR have longer repolarization time, especially the late phase‐ TpeakTend, which represents transmural dispersion of repolarization. Its prolongation seems to be related to local attributes of myocardium and global function of the left ventricle but unrelated to the autonomic nervous influences. Remodeling with moderate LV systolic dysfunction is associated with insignificant decrease in HRV indices and preserved circadian variability.     

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

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

Ventricular repolarization and Holter monitoring. Effect of sympathetic blockage on the QT/RR ratio

Circadian variations of the QT interval and its heart rate dependency have been established. However, the respective roles of the sympathetic and parasympathetic nervous systems in their regulation are still undetermined. Eighteen healthy volunteers (average age 39 +/- 7 years, 10 men) were recruited and selected randomly to receive either placebo or atenolol (100 mg/day). The treatments were crossed after 7 days. The rate dependency of the QT was assessed by day and by night by 24 hour Holter ECG monitoring. The effects of atenolol on the rate dependency of the QT interval depend on the time of day. During the daytime, the QT rate dependency was reduced by atenolol (0.180 (0.162:0.198) versus 0.216 (0.195:0.236) with placebo, p < 0.01) whereas during the night, the QT rate dependency was the same in both groups. Therefore, the betablocker is associated with an inversion of the daily modulation of the QT rate dependency. The daytime rate-dependency of the QT interval in decreased with betablocker therapy. This result suggests a direct or indirect influence of the sympathetic nervous system on the rate dependency of ventricular repolarisation.     

Dynamicity of Early and Late Phases of Repolarization in Patients with Remote Anterior Myocardial Infarction: The Interlead Differences

Background: Repolarization dynamicity (QT/RR) is supposed to be a prognostic marker in post‐MI patients. However, data on the relationships between early and late phases of QT and RR intervals (QT peak/RR and T peak–T end/RR) are insufficient, and which ECG lead should be used for the analysis is unclear. We analyzed repolarization dynamicity in patients after anterior MI with and without VT/VF history using two leads of Holter recordings‐ modified V₅ and V₃. The daytime and nighttime periods were also analyzed. Methods: Cohort of 88 patients after anterior MI (>6 months) consisted of 43 patients without VT/VF (33 males; 59 ± 12 years; LVEF: 41 ± 7%; NoVT/VF), and 45 patients with VT/VF history‐ ICD implanted as secondary prevention (40 males; 64 ± 10 years; LVEF: 32 ± 8%; VT/VF). QT/RR, QT peak/RR and T peak–T end/RR were calculated from 24‐hour ECG for the entire recording, daytime and nighttime periods, from V₅ and V₃ leads, respectively. Results: VT/VF patients had lower LVEF (P = 0.001). There were no differences in age and gender. VT/VF group had steeper QT/RR, QT peak/RR, and T peak–T end/RR in V₅: 0.233 ± 0.04 versus 0.150 ± 0.05, P = 0.0001, 0.181 ± 0.04 versus 0.120 ± 0.04, P = 0.0001, 0.052 ± 0.02 versus 0.030 ± 0.02, P = 0.0001, and in V₃: 0.201 ± 0.04 versus 0.149 ± 0.05, P = 0.0001, 0.159 ± 0.03 versus 0.118 ± 0.04, P = 0.0001, and 0.042 ± 0.02 versus 0.031 ± 0.02, P = 0.004; respectively. VT/VF patients had higher indices in V₅ than in V₃ lead (P = 0.001). QT/RR and QT peak/RR were steeper at daytime period in both leads. It was not found for T peak–T end/RR. Conclusions : Patients with VT/VF history are characterized by steeper relationships between repolarization duration and RR intervals. These findings are more evident in modified V₅ lead.     

Diagnostic performance of QT interval variables from 24-h electrocardiography in the long QT syndrome

Aims The long QT syndrome is mainly defined by QT interval prolongation(QTc >0·44s). However, data obtained in genotyped patientsshowed that resting QTc measurement alone may be inaccuratefor ascertaining the phenotype. The aim of this study was toevaluate the diagnostic performance of QT interval rate-dependencein untreated chromosome 11-linked patients. Methods The study population consisted of 25 untreated longQT patients linked to chromosome 11 and 25 age- and gender-matchedcontrols. QTc intervals were measured on 12-lead resting ECGrecordings. From 24-h Holter recordings, the slope of the relationshipbetween ventricular repolarization and heart rate was studiedseparately day and night to assess neural modulation. Mean heartrates and rate-dependences of QT and Q-maximum of T (QTm) intervalswere compared between long QT patients and controls for bothtime periods. Results In both groups, the rate-dependences were modulatedby day–night influences. When compared to controls, longQT patients showed a significant increase at night in QT/RRslopes (0·158±0·05 vs 0·117±0·03,P=0·002)and QTm/RR slopes (0·163±0·05 vs 0·116±0·04,P=0·0006).Multivariate analysis, adjusting QTc interval on age and gender,discriminated between long QT patients and controls with a 76%sensitivity and a 84% specificity. A 96% sensitivity and a 96%specificity were reached by taking into account the QTm/RR slopeat night, the QTc interval and the mean heart rate during theday. Conclusion QT interval variables obtained from 24-h ECG recordingsimprove long QT syndrome diagnosis by showing an increased nocturnalventricular repolarization rate-dependence in genotyped chromosome11-linked patients.     

Electrocardiographic Identification of Drug‐Induced QT Prolongation: Assessment by Different Recording and Measurement Methods

Background: Careful assessment of QT interval prolongation is required before novel drugs are approved by regulatory authorities. The choice of the most appropriate method of electrocardiogram (ECG) acquisition and QT/RR interval measurement in clinical trials requires better understanding of the differences among currently available approaches. This study compared standard and Holter‐derived 12‐lead ECGs for utility in detecting sotalol‐induced QT/QTc and RR changes. Manual methods (digitizing pad and digital on‐screen calipers) were compared for precision of QT and RR interval measurement. Methods and Results: Sixteen hundred pairs of serial 12‐lead digital ECGs were recorded simultaneously by standard resting ECG device and by continuous 12‐lead digital Holter over 3 days in 39 healthy male and female volunteers. No therapy was given on the 1st day followed by 160 mg and 320 mg of sotalol on the 2nd and 3rd day, respectively. Holter‐derived and standard ECGs produced nearly identical sotalol‐induced QT/QTc and RR changes from baseline, as did the manual digipad and on‐screen caliper measurements. The variability of on‐screen QT measurement in this study was greater than that of digipad. Conclusions: Digital 12‐lead Holter and standard 12‐lead ECG recorders, as well as the manual digitizing pad and digital on‐screen calipers, are of equal utility for the assessment of drug‐induced change from baseline in QT and RR interval, although the variability of the on‐screen method in this study was greater than of the digipad.     

Diurnal variation of ventricular repolarization in a large family with LQT3-Brugada syndrome characterized by nocturnal sudden death.

BACKGROUND: In patients with long-QT syndrome type 3 (LQT3), symptoms occur particularly at rest or during sleep. As to the underlying mechanism, excessive prolongation of the QT interval at slow heart rates probably plays a role. OBJECTIVES: The purpose of the present study was to investigate QT interval prolongation unrelated to heart rate comparing nighttime and daytime in a family with features of both LQT3 and Brugada syndrome. METHODS: The study group consisted of 38 carriers of the mutant gene (SCN5A, 1795insD) and 30 noncarrier family members, who served as controls. Holter monitoring was performed with beat-to-beat QT interval measurement. In addition, in a subset of subjects, an exercise test and a pacing test (carriers only) with measurement of the RT interval were performed. RESULTS: In carriers, the slope between heart rate and QT interval was significantly steeper during nighttime (0:00 a.m. to 6:00 a.m.) than during daytime (8:00 a.m. to 22:00 p.m.) (regression coefficient -6.18 and -2.80, respectively), (p=0.03),no such effect being observed in the noncarriers. Further, the RT interval was markedly shorter during recovery than during exercise in carriers but not in noncarriers. In contrast, during AAI pacing in the carriers, RT interval shortening along with increasing heart rate was followed by a comparable prolongation of the RT interval along with subsequent decreasing heart rate. CONCLUSIONS: In this large LQT3-Brugada syndrome family, carriers of the mutant gene (SCN5A, 1795insD) are characterized by diurnal variation of ventricular repolarization by exhibiting QT interval prolongation, which is more pronounced during nighttime compared with daytime, even when taking into account differences in heart rate. The autonomic nervous system appears to play a role in mediating this effect. This observation may be of relevance for explaining the high incidence of nocturnal sudden death in this family, but this remains to be proven. In addition, whether our findings also apply to other families with LQT3 is uncertain.     

Knowledge Deficits Related to the QT Interval Could Affect Patient Safety

Background: Recently, some QT‐prolonging, noncardiac medications were withdrawn from the U.S. drug market because of continued inappropriate use by health care practitioners despite warnings and label changes from both the drug manufacturers and the U.S. Food and Drug Administration. This led us to assess the health care practitioners' knowledge of the QT interval and medications that may prolong it. Methods: We surveyed health care practitioners, primarily specialists in cardiology, to identify knowledge deficits related to the QT interval. Results: From a total of 334 survey respondents, 157 (47%) were physicians; 271 (81%) stated that cardiology was their area of specialization. Most of the respondents (86%) said that they would check an ECG before and after starting QT‐prolonging medications, but less than half (42%) of all respondents and only 60% of physician respondents were able to accurately measure a sample QT interval on the survey. Less than two‐thirds (63%) of respondents were able to accurately identify possible QT‐prolonging medications, while only about half (51%) could accurately identify medication combinations that might prolong the QT interval. Conclusions: We identified significant knowledge deficits regarding the QT interval and QT‐prolonging medications. Additional research is needed to determine the extent to which these knowledge deficits may negatively affect patient safety. We must also develop effective strategies to eliminate these deficits.     

Physiological significance and normative parameters of rate adaptation of QT-interval during holter monitoring in healthy persons of young age

Aim of the investigation consisted in to study parameters of " QT-dynamics " in healthy children and adolescents. We examined 26 children aged 7 - 17 years (mean 11,6 +/- 7 years) - 7 girls (9,3 +/- 2,3 years) and 19 boys (12,5 +/- 3,6 years). Holter monitoring with manual and automatic estimation of QT and QTc intervals. Dynamics of magnitude of QT interval was determined with the use of equation of linear regression Y = aX+b, where aX - coefficient of linear regression QT/RR (slope QT/RR), b - shear coefficient (intercept QT/RR). Values of QT interval at automatic analysis were 368,8 +/- 18,04 (340 - 410) ms for absolute QT and 424 +/- 14,99 (390 - 450) ms - for QTc, 289,4 +/- 14,6 (260 - 320). Mean values of " QT dynamics " were for slope QT/RR: 0,18 +/- 0,03 (0,13 - 0,24) for 24 hours, 0,16 +/- 0,03 (0,10 - 0,22) for daytime period, and 0,11 +/- 0,13 (0,05 - 0,18) for night time period; for intercept: QT/RR - 230,4 +/- 20,7 (192 - 282) for 24 hours, 299 +/- 25,5 (258 - 364) for day time period, and 242,7 +/- 21,8 (204 - 295) for night time period. Coefficient of correlation of intervals QT and RR (r QT/RR) was 0,79 +/- 0,05 (0,69 - 0,89) for 24 hours; 0,68 +/- 0,07 (0,52 - 0,82) for day time period, and 0,52 +/- 0,13 (0,19 - 0,74) for night time period. All values of " QT-dynamics " significantly differed from each other during various periods of day (p < 0,05). Negative relation was noted between 24 hour slope and intercept QT/RR (r= -0,88, p < 0,05), diurnal (r= -0,87, p < 0,05) and nocturnal slope and intercept QT/RR (r= -0,72, p < 0,05), positive relation was noted between 24 hour values of slope QT/RR and QT (r=0,49, p < 0,05), and intercept QT/RR with absolute QT (r=0,41, p < 0,05). Significantly higher values (p < 0,01) of slope QT/RR were in girls. Thus, increase of slope QT/RR is noted during augmentation of tone of sympathetic part of vegetative nervous system, lowering - when vagal influences are also enhanced. Intercept QT/RR appears to be combination parameter, increase of which reflects both lengthening of absolute mean value of QT interval and reciprocal nocturnal lowering of the slope parameter. It is necessary to assesses clinical and diagnostic significance of changes of novel parameters of " QT-dynamics " on the basis of normative sexual-aging values and physiological mechanisms, determining their variability.