QT Interval In ECG Research Articles

A multiscale model linking ion-channel molecular dynamics and electrostatics to the cardiac action potential

Ion-channel function is determined by its gating movement. Yet, molecular dynamics and electrophysiological simulations were never combined to link molecular structure to function. We performed multiscale molecular dynamics and continuum electrostatics calculations to simulate a cardiac K(+) channel (I(Ks)) gating and its alteration by mutations that cause arrhythmias and sudden death. An all-atom model of the I(Ks) alpha-subunit KCNQ1, based on the recent Kv1.2 structure, is used to calculate electrostatic energies during gating. Simulations are compared with experiments where varying degrees of positive charge-added via point mutation-progressively reduce current. Whole-cell simulations show that mutations cause action potential and ECG QT interval prolongation, consistent with clinical phenotypes. This framework allows integration of multiscale observations to study the molecular basis of excitation and its alteration by disease.

Predictive value of electrocardiographic QT interval and T-wave morphology parameters for all-cause and cardiovascular mortality in a general population sample

The predictive value of ECG QT interval for mortality in the general population has been weak. Only a few population studies on the predictive value of ECG T-wave morphology parameters for mortality have been reported. The purpose of this study was to examine the predictive value of ECG QT interval and T-wave morphology parameters for all-cause and cardiovascular mortality in the general population. The prognostic values of ECG QT interval and four T-wave morphology parameters (principal component analysis ratio, T-wave morphology dispersion, total cosine R-to-T, T-wave residuum) were assessed in 5,917 adults (45% men; age 52 +/- 14 years) participating in the Finnish population-based Health 2000 Study. After a mean follow-up of 5.9 +/- 0.8 years, 335 deaths had occurred, including 131 cardiovascular deaths. QT interval and, with a few exceptions, all T-wave morphology parameters were significant univariate mortality predictors. In men, in Cox multivariate analyses, principal component analysis ratio and T-wave morphology dispersion remained as independent predictors of all-cause and cardiovascular mortality, with the above-median T-wave morphology dispersion group showing the highest risk of cardiovascular death (hazard ratio [HR] 4.4, 95% confidence interval [CI] 2.1-9.4). In women, independent mortality predictors were total cosine R-to-T (cardiovascular mortality) and T-wave residuum (all-cause and cardiovascular mortality), with the above-median T-wave residuum group showing the highest risk of cardiovascular death (HR 2.2, 95% CI 1.1-4.2). In the general population, T-wave morphology parameters, but not heart rate-corrected QT interval, provide independent prognostic information on mortality. The prognostic value of T-wave morphology parameters is specifically related to cardiovascular mortality and seems to be gender specific.

Genetic Variations in Nitric Oxide Synthase 1 Adaptor Protein Are Associated With Sudden Cardiac Death in US White Community-Based Populations

The ECG QT interval is associated with risk of sudden cardiac death (SCD). A previous genome-wide association study demonstrated that allelic variants (rs10494366 and rs4657139) in the nitric oxide synthase 1 adaptor protein (NOS1AP), which encodes a carboxy-terminal PDZ ligand of neuronal nitric oxide synthase, are associated with the QT interval in white adults. The present analysis was conducted to validate the association between NOS1AP variants and the QT interval and to examine the association with SCD in a combined population of 19 295 black and white adults from the Atherosclerosis Risk In Communities Study and the Cardiovascular Health Study. We examined 19 tagging single-nucleotide polymorphisms in the genomic blocks containing rs10494366 and rs4657139 in NOS1AP. SCD was defined as a sudden pulseless condition of cardiac origin in a previously stable individual. General linear models and Cox proportional hazards regression models were used. Multiple single-nucleotide polymorphisms in NOS1AP, including rs10494366, rs4657139, and rs16847548, were significantly associated with adjusted QT interval in whites (P<0.0001). In whites, after adjustment for age, sex, and study, the relative hazard of SCD associated with each C allele at rs16847548 was 1.31 (95% confidence interval 1.10 to 1.56, P=0.002), assuming an additive model. In addition, a downstream neighboring single-nucleotide polymorphism, rs12567209, which was not correlated with rs16847548 or QT interval, was also independently associated with SCD in whites (relative hazard 0.57, 95% confidence interval 0.39 to 0.83, P=0.003). Adjustment for QT interval and coronary heart disease risk factors attenuated but did not eliminate the association between rs16847548 and SCD, and such adjustment had no effect on the association between rs12567209 and SCD. No significant associations between tagging single-nucleotide polymorphisms in NOS1AP and either QT interval or SCD were observed in blacks. In a combined analysis of 2 population-based prospective cohort studies, sequence variations in NOS1AP were associated with baseline QT interval and the risk of SCD in white US adults.

A Simple ECG Marker for the Detection of Coronary Restenosis after Successful Coronary Angioplasty

The dynamic nature of QT dispersion (QTd) and the absence of an acceptable normal value suggest that the relative change not the absolute value of QTd would be a better predicator of coronary restenosis. We sought to examine the usefulness of the relative change in QTd, compared to the absolute value, as a predictor for coronary restenosis after previously successful percutaneous transluminal coronary angioplasty (PTCA). Ninety-two patients with a history of successful PTCA who were referred for coronary angiography (CA) for exclusion of coronary restenosis were included in this analysis. QTd was calculated as the difference in milliseconds between the maximum and minimum QT interval in the 12-lead ECG. Relative change in QTd was measured as [QTd at the time of angiography (current) - QTd after the successful PTCA (baseline)]/QTd (baseline) %. Receiver operating characteristics (ROC) analysis was used to detect the best cut-off point and also to compare the diagnostic accuracy of the relative change in QTd vs. the absolute QTd for prediction of coronary restenosis. The relative change in QTd showed a significantly larger ROC area under curve (AUC) compared to the absolute QTd [AUC (95% CI): 0.79 (0.698, 0.872) and 0.61 (0.498, 0.703) respectively; p=0.011 for AUCs comparison]. The best cut-off point for the relative QTd was 40%, and for the absolute QTd this was 50 ms. The sensitivity and specificity of > or =40% increase in QTd to detect coronary restenosis was 71% and 83%, with positive and negative predictive values of 90% and 57%, respectively. The diagnostic accuracy of the absolute value of QTd was much less than this; the sensitivity and specificity of QTd > or =50 ms were 48% and 58%, with positive and negative predictive values of 71% and 34%, respectively. Compared to the absolute value, the relative change in QTd is a better predictor of coronary restenosis after a previously successful PTCA. These findings may open the door for rethinking the use of QTd as a simple ECG predictor for cardiovascular outcomes.

The 5‐HT2 antagonist ketanserin is an open channel blocker of human cardiac ether‐à‐go‐go‐related gene (hERG) potassium channels

Ketanserin, a selective 5-HT receptor antagonist, prolongs the QT interval of ECG in patients. The purpose of the present study was to determine whether ketanserin would block human cardiac ether-à-go-go-related gene (hERG) potassium channels. Whole-cell patch voltage-clamp technique was used to record membrane currents in HEK 293 cells expressing wild type or mutant hERG channel genes. Ketanserin blocked hERG current (I(hERG)) in a concentration-dependent manner (IC50=0.11 microM). The drug showed an open channel blocking property, the block increasing significantly at depolarizing voltages between +10 to +60 mV. Voltage-dependence for inactivation of hERG channels was negatively shifted by 0.3 microM ketanserin. A 2.8 fold attenuation of inhibition by elevation of external K+ concentration (from 5.0 to 20 mM) was observed, whereas the inactivation-deficient mutants S620T and S631A had the IC50s of 0.84 +/- 0.2 and 1.7 +/-0.4 microM (7.6 and 15.4 fold attenuation of block). In addition, the hERG mutants in pore helix and S6 also significantly reduced the channel block (2-59 fold) by ketanserin. These results suggest that ketanserin binds to and blocks the open hERG channels in the pore helix and the S6 domain; channel inactivation is also involved in the blockade of hERG channels. Blockade of hERG channels most likely contributes to the prolongation of QT intervals in ECG observed clinically at therapeutic concentrations of ketanserin.

Effect of Aldehyde Dehydrogenase‐2 Genotype on Cardiac Autonomic Nervous Responses to Moderate Alcohol Ingestion

Asian people are divided into the individuals who can ingest alcohol and cannot because of the difference of aldehyde dehydrogenase-2 (ALDH2) genotype. The purpose of the present study was to investigate the effect of ALDH2 genotype on cardiac autonomic nervous responses to moderate alcohol ingestion. Subjects were 17 healthy male students at Kyoto University. According to the difference of ALDH2 genotype, they were divided into two groups: the STRONG (n = 10) and WEAK (n = 7) group. The subjects ingested 10 (the LITTLE trial) or 30 g (the MUCH trial) of pure alcohol on a separate day randomly. We collected ECG data and analyzed QT interval. ECG QT interval, the important marker for sudden cardiac death in cardiac patients as well as healthy people, of the STRONG group were not prolonged after alcohol ingestion, but that of the WEAK group were significantly prolonged, compared to control. Moreover, with respect to the comparison of the change of QT interval between the LITTLE and MUCH trials, there were also no significant differences in the STRONG group. In the WEAK group, however, the change was more marked at MUCH trial. It is concluded that the cardiovascular response to alcohol ingestion is influenced by ALDH2 genotype and that the drinking assumed to be in moderation puts a strain on the hearts for the ALDH2-deficient individuals. The results of this investigation show that moderate drinking does not have a good effect on everybody with respect to QT interval. This study also shows that moderate alcohol intake does not have a bad effect on the immune system regardless of ALDH2 genotype.

Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome

Long QT syndrome (LQTS) is a heritable disease associated with ECG QT interval prolongation, ventricular tachycardia, and sudden cardiac death in young patients. Among genotyped individuals, mutations in genes encoding repolarizing K+ channels (LQT1:KCNQ1; LQT2:KCNH2) are present in approximately 90% of affected individuals. Expression of pore mutants of the human genes KCNQ1 (KvLQT1-Y315S) and KCNH2 (HERG-G628S) in the rabbit heart produced transgenic rabbits with a long QT phenotype. Prolongations of QT intervals and action potential durations were due to the elimination of IKs and IKr currents in cardiomyocytes. LQT2 rabbits showed a high incidence of spontaneous sudden cardiac death (>50% at 1 year) due to polymorphic ventricular tachycardia. Optical mapping revealed increased spatial dispersion of repolarization underlying the arrhythmias. Both transgenes caused downregulation of the remaining complementary IKr and IKs without affecting the steady state levels of the native polypeptides. Thus, the elimination of 1 repolarizing current was associated with downregulation of the reciprocal repolarizing current rather than with the compensatory upregulation observed previously in LQTS mouse models. This suggests that mutant KvLQT1 and HERG interacted with the reciprocal wild-type alpha subunits of rabbit ERG and KvLQT1, respectively. These results have implications for understanding the nature and heterogeneity of cardiac arrhythmias and sudden cardiac death.

Effect of the Combination of Ginseng, Oriental Bezoar and Glycyrrhiza on Autonomic Nervous Activity as Evaluated by Power Spectral Analysis of HRV and Cardiac Depolarization-Repolarization Process

Ginseng, oriental bezoar and glycyrrhiza are the most widespread herbs often used in Kampo. These three herbs have been used for a Kampo for a thousand years and a number of pharmacological and clinical studies have reported about their effects. However, it has not been previously described how the combination of these most commonly used herbs affects the autonomic nervous system (ANS). This is a randomized, double-blind, placebo-controlled experiment to examine the acute effects of Kampo on autonomic nervous activity by using power spectral analysis of heart rate variability (HRV) and cardiac depolarization-repolarization time intervals in humans. Ten healthy men volunteered to participate in this study. The Kampo at a dose of two capsules contained the following ingredients: powdered ginseng 250 mg, powdered oriental bezoar 50 mg, and powdered glycyrrhiza 50 mg. The placebo capsules contained corn starch. A CM5 lead ECG was recorded before, and 30 min and 60 min after the oral administration of Kampo or a placebo on different days. HF power (high frequency component in the HRV) was significantly increased and HR (heart rate) was significantly decreased after taking Kampo at 60 min (p<0.05) compared with the placebo. TP (total power) and LF power (low frequency component in the HRV) did not change significantly between the Kampo and placebo, and there were also no statistically significant differences in heart-rate-corrected ECG QT interval (QTc) or recovery time (RTc) between the Kampo and placebo. However, we observed that there was a tendency of decreased QTc interval and RTc after taking Kampo at 60 min compared with response of the placebo (p<0.1). These results indicated that the Kampo mainly potentiated parasympathetic nervous activity and may be useful for cardiovascular health.

Identification of a Potent hERG Channel Activator with a Novel Mechanism of Action

hERG potassium channels are an important component of cardiac action potential repolarization, and loss of function mutations of hERG channels prolong the cardiac ECG QT interval. Long QT Syndrome is associated with cardiac rhythm disorders, including torsades de pointes, which can degenerate into lethal ventricular fibrillation. In this study, we report the discovery of a potent hERG activator (Compound 1). Using whole cell patch-clamp studies of recombinant hERG expressed in HEK293 cells, we found that 3 μM Compound 1 increased hERG current amplitude more than 10-fold. This increase was reversed by the hERG blocker E4031(1 μM). Enhancement of hERG was steeply concentration dependent (EC50 0.5 ± 0.1 μM, Hill slope 3.3 ± 0.2). The observed increase in amplitude was primarily due to removal of channel inactivation. The compound also produced a hyperpolarizing shift in the voltage dependence of channel activation at high concentrations and a modest slowing of deactivation. In isolated guinea pig ventricular myocytes, Compound 1 produced a concentration-dependent shortening of action potential duration (>70%, 3 μM) that was prevented by pre-incubation with E4031. In conclusion, we have identified a novel activator of hERG potassium channels. This compound may provide a useful tool for further biophysical characterization of hERG channels and investigation of cardiac electrophysiology.

20: QT dispersion for detection of cardiac allograft vasculopathy in heart transplant patients

Purpose: After heart transplantation, cardiac allograft vasculopathy (CAV) may result in ventricular repolarization abnormalities, which can be detected by an increase in QTc and QT dispersion. Thus, we hypothesize that sequential ECG QT dispersion assessment can serve as a noninvasive marker of CAV. Methods and Materials: We analyzed 24 patients with angiographically confirmed and 22 control transplant patients without CAV. Using the program NIH Image, we analyzed early after heart transplantation (11 20 days), at time of diagnosis (1919 714 days), and at two intermediate time (646 306 days) and (1274 500 days). ECGs from control heart patients were analyzed at similar intervals. Sampling times are similar in both groups. ECG QT intervals were measured for each lead. Between-lead, QT dispersion (QTmax QTmin) and corrected dispersion (QTc QT(ms)/[1000(ms-1) RR(ms)]1/) were measured for spatial irregularity of myocardial electrical conduction. Results: CAV and control groups were similar in age (49 12 v 53 11 years; p NS), sex (all males), ethnicity (Caucasian 75 v 77 %, African American 20 v 22%), pre transplant diagnosis (ischemic 45 v 50 %, idiopathic 37 v 45 %, and viral 4 v 4 %). QTc dispersion (graph) was similar between no CAV (n) and CAV (y) at the first and second time interval, but the CAV (y) is significantly greater than CAV (n) at the third (* p 0.0001) and fourth time intervals (* p .0001). Conclusions: Dispersion of QTc was significantly increased in the heart transplant group with CAV. These data suggest that development of CAV is associated with an increase in QT dispersion, a parameter reflective of repolarization and may serve as a noninvasive predictor for cardiac allograft vasculopathy.

Alterations of Autonomic Nervous Activity and Energy Metabolism by Capsaicin Ingestion during Aerobic Exercise in Healthy Men

We investigated whether capsaicin ingestion (150 mg) enhances substrate oxidation associated with thermogenic sympathetic activity as an energy metabolic modulator without causing prolongation of the cardiac OT interval during aerobic exercise in humans. Ten healthy males [24.4 (4.3) y] volunteered for this study. The cardiac autonomic nervous activities evaluated by means of heart rate variability of power spectral analysis, energy metabolism, and ECG QT interval were continuously measured during 5-min rest and 30-min exercise at 50% of maximal ventilatory threshold (50% VT(max)) on a stationary ergometer with placebo or capsaicin oral administration chosen at random. The results indicated that there were no significant differences in heart rate during rest or exercise between the two trials. Autonomic nervous activity increased in the capsaicin tablet trial during exercise, but the difference did not reach statistical significance. Capsaicin, however, significantly induced a lower respiratory gas exchange ratio [0.92 (0.02) vs. 0.94 (0.02), means (SE), p < 0.05] and higher fat oxidation [0.17 (0.04) vs. 0.12 (0.04) g/min, means (SE), p < 0.05] during exercise. On the other hand, the data on the cardiac OT interval showed no significant difference, indicating that oral administration of capsaicin did not cause any adverse effect on cardiac depolarization-repolarization. In conclusion, it may be considered that capsaicin consumption 1 h before low intensity exercise (50% VT(max)) is a valuable supplement for the treatment of individuals with hyperlipidemia and/or obesity because it improves lipolysis without any adverse effects on the cardiac depolarization and repolarization process.

Evaluation of Exercise‐Induced T Wave Changes in Patients with Idiopathic Dilated Cardiomyopathy Before and After Beta‐Blocker Therapy

Ventricular repolarization abnormalities are thought to contribute to lethal ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy (DCM). The purpose of this study was to evaluate exercise-induced T wave changes in DCM patients before and after beta-blocker therapy to investigate repolarization abnormalities. Treadmill exercise testing was performed in 20 DCM patients and 50 normal subjects. T wave amplitude (TA: baseline to T wave apex; mV) and recovery time (RT: QRS onset to the maximum dV/dt point of the T wave; msec) were measured before and 1 minute after peak exercise. TA was averaged in the right and left precordial leads (TA(V1-3), TA(V4-6)). RT was normalized to the maximum QT interval in the 12-lead ECG and expressed as the %RT (%RT). %RT was also averaged in the precordial leads (%RT(V1-3), %RT(V4-6)). After exercise, TA increased and %RT decreased in both groups. In DCM patients, TA(V1-3) was greater and TA(V4-6) was less than in normal subjects before and after exercise. There was no difference in %RT(V1-3) between the groups, but %RT(V4-6) was greater in DCM patients both before and after exercise. DCM patients repeated the same evaluation after 6 months of oral beta-blocker therapy. Compared with measurements before beta-blocker therapy, TA(V1-3) and %RT(V1-3) did not change. However, TA(V4-6) increased and %RT(V4-6) decreased significantly both before and after exercise. DCM patients showed small TA and large %RT in the left precordial leads at rest as well as after exercise. Chronic beta-blocker therapy in DCM patients normalized these ventricular repolarization abnormalities.

Electrocardiographic risk stratification in families with congenital long QT syndrome

The QT interval in the surface ECG is one of the most often used risk stratifiers in families with congenital long QT syndrome (LQTS). The best ECG lead for clinical management of LQTS families remains unclear. The predictive power of the QTc interval in all ECG leads was studied in 200 consecutive genotyped LQTS family members to identify mutation carriers (n = 103; age: 35+/-19 years) and high-risk LQTS patients (n = 16 with survived sudden cardiac arrest) using receiver operating curve (ROC) analysis (ROC = area under curve). Additionally, the risk for events (syncope and sudden cardiac arrest) was calculated for QTc decile in all individuals. The predictive power was highest in lead II and lead V5 for identifying carriers in LQTS families. These ECG leads were optimal for risk stratification (ROC range 0.83-0.87). In these leads, positive predictive value (PPV) and negative predictive value (NPV) were highest for suggested QTc cut-offs (440 and 500 ms) for identification of LQTS mutation carriers and high-risk patients (PPV between 78-81 and 73-80%, respectively). The risk for events in QTc deciles increased exponentially from 10 to 80% and was 40% for QTc > 500 ms. On the basis of these data, QTc is the best diagnostic and prognostic ECG parameter in LQTS families. A single measurement should be obtained in lead II if measurable and then in left precordial leads (preferably V5) as a second choice.

Block of hERG channel by ziprasidone: Biophysical properties and molecular determinants

Ziprasidone, an antipsychotic agent, delays cardiac repolarization and, thus, prolongs the QT interval of the cardiac ECG. In this study, we examined the biophysical properties and the molecular determinants of the ziprasidone block of wild-type hERG potassium channels stably expressed in HEK-293 cells or wild-type and mutant hERG channels expressed in Xenopus oocytes. In stably transfected HEK-293 cells, ziprasidone blocked wild-type hERG current in a voltage- and concentration-dependent manner (IC 50 = 120 nM, 0 mV, 37 °C). Ziprasidone showed minimal tonic block of hERG current estimated during a depolarizing voltage (−20 or +30 mV) or evaluated by the envelope of tails test (+30 mV). Rate of the block onset was rapid, but not significantly affected by test potentials ranging from −20 to +30 mV (time constant ( τ) = 114 ± 14 ms at +30 mV). The time constant of the slow component of hERG current deactivation (at −50 mV) was significantly increased by ziprasidone ( τ = 1776 ± 90 versus 1008 ± 71 ms, P < 0.01). Time course of channel inactivation was slowed by ziprasidone in a voltage-dependent manner. The V 1/2 values for steady-state activation and inactivation of hERG channel in HEK-293 cells were not significantly altered by ziprasidone. In Xenopus oocytes, ziprasidone exhibited less potent block of wild-type hERG current (IC 50 = 2.8 μM, 0 mV, 23 °C). Mutation of the aromatic residues (Tyr-652 or Phe-656) located in the S6 domain of hERG dramatically reduced the potency of channel block by ziprasidone (IC 50 > 0.4 and 1 mM at 0 mV for Y652A and F656A, respectively). In conclusion, ziprasidone preferentially binds to and blocks open hERG channels. Tyr-652 and Phe-656 are two critical residues in the ziprasidone-binding site.

Ventricular rate determines early bradycardic electrical remodeling

The purpose of this study was to isolate chronic ventricular rate as the primary determinant of early bradycardic ventricular electrical remodeling. Ventricular repolarization delay predisposing to potentially lethal tachydysrhythmias occurs during chronic bradycardia. Prolonged QT intervals and torsades de pointes are associated with down-regulated ventricular myocyte delayed rectifier potassium (K(+)) currents. Transcatheter AV node ablation in rabbits was followed by chronic right ventricular pacing at either 140 bpm (n = 16) or the near-physiologic rate of 280 bpm (n = 9). ECG QT intervals were assessed in vivo at days 0 and 8 of paced AV block. Repolarizing currents in isolated left and right ventricular myocytes were assessed using whole-cell patch clamp technique. Bradycardic rabbits had increased steady-state QT intervals (230 +/- 6 ms vs 206 +/- 7 ms [mean +/- SE], day 8 vs day 0; P < .001). Biventricular myocyte expression of the delayed rectifier K(+) currents I(Kr) and I(Ks) was down-regulated in bradycardic rabbits, with no change in the transient outward current I(to) or inwardly rectifying current I(K1). None of these changes were observed in rabbits paced at 280 bpm. Pause-dependent torsades de pointes was documented in one bradycardic animal on day 8. No heart failure or ventricular hypertrophy was apparent. Bradycardic ventricular electrical remodeling proceeds independently of structural remodeling, heart failure, or AV synchrony and is prevented by maintenance of near-physiologic ventricular rate.

Long QT syndrome. Why does sex matter?

There is increased awareness of the extent to which cardiac function is influenced by gender. One of the most dramatic and potentially lethal differences is that seen in cardiac repolarization reflected in the QT interval of the surface ECG. Gender differences in QT and QTc intervals have been observed to change during the lifetime in the general population. These differences can be explained to a large extent by sex hormone driven differences in gene expression of myocardial ion channels. Numerous studies have shown that women's risk to suffer arrhythmias in the context of QT prolonging drugs is doubled compared to men. For familial long QT syndrome there is no conclusive evidence for gender effects with respect to disease onset or mortality. Only subgroup analysis by genotype demonstrated a higher risk in female patients carrying mutations in the LQT2 locus. Special attention should be given to drug-induced QT prolongation in women.

A16-5 Automatic measurement of corrected qt interval in holter ECG as a marker of life-threatening arrhythmias in postmyocardial infarction patients

A16-5 Automatic measurement of corrected qt interval in holter ECG as a marker of life-threatening arrhythmias in postmyocardial infarction patients

A16-5 Automatic measurement of corrected qt interval in holter ECG as a marker of life-threatening arrhythmias in postmyocardial infarction patients

A16-5 Automatic measurement of corrected qt interval in holter ECG as a marker of life-threatening arrhythmias in postmyocardial infarction patients

Reduction of QT Dispersion by Losartan in Patients with Mild to Moderate Hypertension

Background: QT dispersion (QTd) is the difference between the longest and the shortest QT interval in the standard 12-lead ECG. QTd may be a measure of spatial dispersion of repolarization in the myocardium, and may be influenced by antihypertensive treatment. Objective: To study the effects of losartan in comparison to amlodipine on QTd in mildly to moderately hypertensive patients, and to assess correlations of reduced QTd with echocardiographic left ventricular mass (LVM). Methods: Twenty-eight adult patients with mild to moderate hypertension were randomly assigned to a double-blind treatment either with losartan 50 mg titrated to losartan 50 mg-hydrochlorothiazide 12.5 mg or amlodipine 5 mg titrated to amlodipine 10 mg. Blood pressure and echocardiographic LVM were measured before and after 16 weeks of treatment. QTd was measured by two independent examiners blinded to patient data, study phase and treatment. Results: Systolic and diastolic blood pressure were significantly reduced in the losartan and amlodipine groups. Treatment with losartan significantly reduced LVM (from 311 ± 31 to 252 ± 16 g, mean ± SE; p < 0.01), cardiac mass index and QTd (from 42.3 ± 5.4 to 27.8 ± 2.2 ms, mean ± SE; p < 0.05). Conclusion: Losartan significantly reduced QTd after 16 weeks of treatment in patients with mild to moderate hypertension. This reduction was not significantly correlated with the reduction in LVM.

Reproducibility of Minimum, Maximum and Median QT Intervals in the 12‐Lead Resting ECG

Background: Heterogeneity in the recovery of ventricular refractory periods is an important factor in the development of ventricular arrhythmia. The QT dispersion (QTD) is increasingly used to measure this heterogeneity but its clinical value is limited due to methodological problems. QTD is defined as the maximum minus the minimum QT intervals that are suspected to be the least reproducible of the QT measurements.Objective: To analyze the reproducibility of the minimum, maximum and median QT intervals.Material: One database consisted of 356 subjects: 169 with diabetes and 187 nondiabetic control persons. The other database consisted of 110 subjects with remote myocardial infarction: 55 with no history of arrhythmia, and 55 with a recent history of ventricular tachycardia or fibrillation.Methods: 12‐lead surface ECGs were recorded with an amplification of 10 millimeters per millivolt at a paper speed of 50 mm/s. QT was measured manually by the tangent‐method. The reproducibility was calculated from measurements of QT in successive beats.Results: The standard deviation (SD) of QTs reproducibility was 9 ms for the arrhythmia data and 8 ms for the diabetes data. The reproducibility of QTmax and QTmin were on average 30% and 15% worse than for QTmedian. The SD of QTmax was significantly higher than for QTmedian in both database (P &lt; 0.001), whereas SD of QTmin was only significantly higher than for QTmedian for the diabetes data (P &lt; 0.001).Conclusions: The reproducibility of QTmin and in particular QTmax was significantly lower than for QTmedian. This indicates that the QT dispersion is based on the least reproducible of the QT measurements. A.N.E. 2000;5(4):354–357