Evidences of the gender-related differences in cardiac repolarization and the underlying mechanisms in different animal species and human

Clinical and experimental studies have shown that gender differences exist in cardiac repolarization in various animal species and human, as is evidenced by significantly longer QT, JT intervals and action potential duration in females than in males due to a reduced repolarization reserve in females. The latter is shown by the relatively greater increase in ventricular repolarization and higher incidence of torsades de pointes (TdP) in preparations from females by drugs blocking repolarizing K(+) currents. These results can be modulated by gonadectomy, suggesting that gonadal steroids are important determinants of gender difference in repolarization. In human subjects, QT and JT intervals are longer in women, whereas QT dispersion and Tp-e interval (the interval from the peak to the end of T wave) are longer in men. At slow heart rates greater prolongation in QT and increase in transmural repolarization heterogeneity (i.e. increase in Tp-e) may predispose to TdP tachycardias in women. In healthy postmenopausal women, hormone replacement therapy with estrogen alone usually produced a prolongation of QT interval, while estrogen plus progesterone had no significant effects on QT interval but reduced QT dispersion. Along with these, there are still conflicting data reported. Further work is needed before the elucidation of the basis of gender differences in ventricular repolarization.     

Dispersion in ventricular repolarization in patients with severe intraventricular conduction disturbances

Increased dispersion of repolarization, measured invasively or by QT interval measurements, is associated with an increased risk for ventricular arrhythmias and sudden death. Most studies on this issue have included patients with normal intraventricular conduction, and it is not known if this finding has a predictive value also in patients with intraventricular conduction disorders. An invasive electrophysiological study, including programmed ventricular stimulation and assessment of effective refractory periods at two RV sites, was performed in 103 patients with bifascicular block (mean age 67 +/- 12 years). QT dispersion was measured from standard 12-lead ECGs. In patients with inducible sustained polymorphic VT or VF the dispersion in refractoriness between the two RV sites was significantly greater (46 +/- 11 ms, n = 13) than in noninducible patients (14 +/- 14 ms, n = 84) and in patients with inducible sustained monomorphic VT (16 +/- 5 ms, n = 6) (P < 0.01). Similarly, QT dispersion was 104 +/- 46 ms, 66 +/- 31 ms, and 77 +/- 33 ms, respectively, in the three groups (P < 0.05). Dispersion in repolarization, neither measured invasively nor by QT interval measurements, predicted sudden death, all cause mortality, or ventricular arrhythmia during a mean follow-up period of 3 years. In patients with bifascicular block, there is a relation between the degree of dispersion of ventricular repolarization and the inducibility of polymorphic ventricular arrhythmia, but this outcome did not occur during follow-up.     

Magnetocardiographic QT Interval Dispersion in Postmyocardial Infarction Patients with Sustained Ventricular Tachycardia: Validation of Automated QT Measurements

T dispersion is a measure of heterogeneity in ventricular repolarization. Increased ECG QT dispersion is associated with life-threatening ventricular arrhythmias. We studied if magnetocardiographic (MCG) measures of QT dispersion can separate postmyocardial infarction patients with and without susceptibility to sustained VT. Manual dispersion measurements were compared to a newly adapted automatic QT interval analysis method. Ten patients with a history of sustained VT (VT group) and eight patients without ventricular arrhythmias (Controls) were studied after a remote myocardial infarction. Single-channel MCGs were recorded from 42 locations over the frontal chest area and the signals were averaged. QT dispersion was defined as maximum — minimum or standard deviation of measured QT intervals. VT group showed significantly more QT and JT dispersion than Controls. QT_apex dispersions were 127 ± 26 versus 83 ± 21 ms (P = 0.004) and QT_end dispersions 130 ± 37 versus 82 ± 37 ms (P = 0.013), respectively. Automatic method gave comparable values. Their relative differences were 9% for QT_apex and 27% for QT_end dispersion on average. In conclusion, increased MCG QT interval dispersion seems to be associated with a susceptibility to VT in postmyocardial infarction patients. MCG mapping with automated QT interval analysis may provide a user independent method to detect nonhomogeneity in ventricular repolarization.     

QT dispersion from body surface ECG does not reflect the spatial dispersion of ventricular repolarization in sheep

The correlation between the QT dispersion on body surface ECG and the dispersion in ventricular repolarization from the cardiac surface was studied in six sheep anesthetized with pentobarbital. The standard 12-lead body surface ECG and multiple ventricular epicardial ECGs were simultaneously recorded. The activation-recovery interval (ARI) was measured from the unipolar epicardial ECGs. The pooled QT dispersion from the six animals was significantly smaller than the pooled ARI dispersion (22.7 +/- 2.6 vs 33.0 +/- 6.9 ms, P < 0.01). There was no correlation between the QT and ARI dispersion. The unipolar epicardial ECGs were then converted into bipolar ECGs and epicardial QT intervals were subsequently acquired from these ECGs. The average value of epicardial QT dispersion from the six animals was similar to that of body surface ECG, but was less than the ARI dispersion (27.5 +/- 6.8 vs 33.0 +/- 6.9, P < 0.01). A good correlation between the epicardial QT dispersion and ARI dispersion was identified (r = 0.84, P < 0.05). In addition, a prolongation in ventricular repolarization, induced by an increase in coronary flow, elicited a pooled ARI dispersion of 62.3 +/- 6.2 ms (n = 6), which was larger than the simultaneously recorded body surface QT dispersion (28.3 +/- 9.8 ms, n = 6, P < 0.01). No correlation between the ARI and QT dispersion was found in the presence of the prolonged ventricular repolarization. In conclusion, QT dispersion from a 12-lead body surface ECG seems to underestimate the spatial dispersion of ventricular repolarization acquired from sheep epicardium.     

Assessment of QT interval duration and dispersion in athlete's heart

An athlete's heart is characterized by morphological and functional changes occurring as a consequence of regular physical exercise. We sought to determine if these physiological changes lead to ventricular repolarization abnormalities in trained athletes. Forty-four trained athletes and 35 sex- and age-matched healthy sedentary controls were included in the study. A 12-lead surface electrocardiogram (ECG) was obtained from all participants. Maximum QT (QTmax) and minimum QT (QTmin) interval durations, QT dispersion (QTd) and corrected QT dispersion (QTcd) were calculated for each ECG record. Heart rate, systolic and diastolic blood pressure values were found to be identical in both groups. QTmax and QTmin interval durations were not statistically different between the athletic and control groups. Similarly, QTd and QTcd did not differ significantly between the two groups. No association was observed between an athlete's heart and ventricular heterogeneity compared with healthy sedentary controls, despite physiological and structural changes.     

CRT治疗患者心室复极异质性指标的变化及不同起搏部位的影响

目的探讨心脏再同步化治疗患者心室复极异质性指标的变化以及不同部位起搏对心室复极异质性指标的影响。方法22例难治性心力衰竭患者,纽约心功能协会(NYHA)心功能分级Ⅲ~Ⅳ级,左心室射血分数(LVEF)≤35%,左心室舒张末内径(LVEDD)>55 mm,QRS波时限>120 ms,组织多普勒显像(TDI)证实心脏机械活动不同步,且经最优化药物治疗无效,行心脏再同步化治疗(CRT)后定期随访。以常规体表12导联心电图QT离散度及Tpeak-end间期以及Tpeak-end离散度作为心室复极异质性的指标。于CRT术前、术后1、3、6、12个月,分别在右室起搏、左室起搏、双室起搏三种不同起搏模式下测量心室复极异质性指标。结果QT离散度及Tpeak-end、Tpeak-end离散度在双室起搏时最小,左室起搏时最大,双室起搏与右室起搏之间没有统计学差异;CRT治疗后心室复极异质性指标明显改善,并且随着时间延长,心室复极异质性指标逐渐变小。结论CRT治疗可以明显改善心室复极异质性,右室起搏下心室复极异质性指标与双室起搏相似,但左室起搏则明显增加心室复极异质性指标。     

QT Interval Dispersion and its Clinical Utility

QT dispersion as a measure ofin-terlead variations of QT interval duration in the surface 12-lead ECG is believed to reflect regional differences in repolarization heterogeneity and thus, may provide an indirect marker of arrhythmogenicity. Methodology for determining QT dispersion and reproducibility of this parameter vary significantly between studies and, together with some other unresolved problems witb QT dispersion assessment, often lead to contradictory suggestions about potential clinical utility of this parameter. The results of our own study in 213 survivors of myocardial infarction, together with a comprehensive review of the literature, suggest that most of these inconsistencies reflect incomplete understanding of electrocardiographic correlates of both normal and abnormal ventricular repolarization. The application of more objective techniques, such as spectral analysis or combined assessment of different parameters (e.g., area beneath the T wave and its symmetricity) may add a new dimension to the noninvasive assessment of ventricular repolarization.     

New Insight into Repolarization Abnormalities in Patients with Congenital Long QT Syndrome: the Increased Transmural Dispersion of Repoiarization

There is evidence from experimental studies that the time interval from the peak to the end of T-wave reflects the transmural dispersion in repolarization (electrical gradient) between myocardial "layers" (epicardial, M-cells, endocardial). Since Congenital Long QT Syndrome (LQTS) is considered to be classical disease or repolarisation abnormalities, we performed the present study to assess the transmtiral dispersion of repolarization in LQTS patients. The study group consisted of 17 patients: 7 LQTS pts and 10 pts from the control group. In each patient the 24-hour ECG recording was performed on magnetic tape. The interval from the peak to the end of the T-wave (TpTo) was automatically measured by Holter system during every hour as a measure of transmural dispersion of repolarisation. Thereafter the mean TpTo from 24-hours was calculated. In addition the spatial QT dispersion was measured from 12 lead ECG and 3 channel Holter tape as a difference between the shortest and the longest QT interval between leads. The values were compared between groups using the Anova test.
TpTo was 79,6±9,6 ms (72–92 ms) in LQTS group and 62,4±7,5 ms (51–70) in the control group (p< 0.001). In LQTS group TpTo was significantly longer at night hours 72,5±2 when compared to day hours 87,4±8 (p<0.01). The spatial QT dispersion was significantly higher in LQTS patients when compared to control, both in 12-lead standard and Holter ECG.
Congenital long QT syndrome is associated with increase in both transmural and spatial dispersion of repolarization. The extent of prolongation of the terminal portion of QT in patients with congenital long QT syndrome is greater at night sleep hours compared to daily activity.     

QT 离散度与冠心病关系的研究进展

QT离散度（QTd）对冠心病预测心肌缺血程度、范围及预后具有重要参考价值,近年来受到广泛关注。QTd[体表心电图12导联中最大QT间期（QTmax）与最小QT间期（QTmin）之间的差值]反映心室肌细胞复极过程不均一性与冠心病心肌缺血有关系。QT离散度可用于评价冠状动脉病变特点,从而指导冠心病患者血运重建,对评估介入治疗术前及术后预后具有重要的临床意义。     

Dispersion of QT Intervals: A Measure of Dispersion of Repolarization or Simply a Projection Effect?

QT interval dispersion may provide little information about repolarization dispersion. Some clinical measurements demonstrate an association between high QT interval dispersion and high morbidity and mortality, but what is being measured is not clear. This study was designed to help resolve this dilemma. We compared the association between different clinical measures of QT interval dispersion and the ECG lead amplitudes derived from a heart vector model of repolarization with no repolarization dispersion whatsoever. We compared our clinical QT interval dispersion data obtained from 25 subjects without cardiac disease with similar data from published studies, and correlated these QT dispersion results with the distribution of lead amplitudes derived from the projection of the heart vector onto the body surface during repolarization. Published results were available for mean relative QT intervals and mean differences from the maximum QT interval. The leads were derived from Uijen and Dower lead vector data. Using the Uijen lead vector data, the correlation between measurements of dispersion and derived lead amplitudes ranged from 0.78 to 0.99 for limb leads, and using the Dower values ranged from 0.81 to 0.94 for the precordial leads. These results show a clear association between the measured QT interval dispersion and the variation in ECG lead amplitudes derived from a simple heart vector model of repolarization with no regional information. Therefore, measured QT dispersion is related mostly to a projection effect and is not a true measure of repolarization dispersion. Our existing interpretation of QT dispersion must be reexamined, and other measurements that provide true repolarization dispersion data investigated.     

Spatial Distribution of QT Intervals: An Alternative Approach to QT Dispersion

QT dispersion (QTd) describes the heterogeneity of ventricular repolarization on the basis of the temporal range of QT intervals as measured in the 12-lead ECG. We examined the spatial distribution of QTd using multichannel magnetocardiograms (MCGs), which noninvasivety register changes in magnetic field strength at 37 sites over the heart. As in ECG, the MCG signal in each channel may be used to measure QT interval. By calculating QT deviation from QT_min at each site, one can reconstruct the spatial distribution of QTd. Analysis of spatial QTd in ten healthy subjects and ten patients after acute myocardial infarction (MI) showed clear differences in spatial distribution. The healthy subjects generally displayed shorter QT intervals along a line corresponding to the approximate position of the septum with longer intervals in plateaus in the upper right and lower left. Spatial QTd of the post-MI patients deviated from this pattern, often displaying a sharp rise in QT duration over specific areas, which could be related to functional and morphological disturbances. The quantification of local irregularities as well as the overall pattern on the basis of a smoothness index allowed better discrimination between healthy subjects and post- MI patients than QTd. Distribution patterns of QTd which reflect local repolarization alterations may thus represent a more differentiated marker for pathology and risk.     

Gender Effects on Novel Time Domain Parameters of Ventricular Repolarization Inhomogeneity

Introduction: Parameters of ventricular repolarization variability are increasingly being used in an attempt to understand better and predict the occurrence of ventricular tachycardia. Nevertheless, some of the measures used have thus far not been analyzed regarding gender differences in a large group of healthy subjects. Furthermore, new parameters might give further insight.
Methods and Results: We investigated 139 healthy volunteers (mean age 41.6 ± 15.3 years, range 20–77, median 40.0 years, 76 women) without evidence of organic cardiac disease. Mean RR interval and established time domain parameters of heart rate variability (rMSSD; SDNN) were measured for each subject. Beat-to-beat QT interval and time-domain QT interval variability were analyzed. Characteristics of the QT interval and QT interval variability were determined as hourly mean values. The standard deviation of all QT intervals/hour (SDQT) and the standard deviation of all QTc intervals/hour (SDQTc) were used to measure QT interval variability. Four novel ratios of repolarization inhomogeneity (VRI: SDQT/SDNN; VR II: SDQT/rMSSD; VR III: SDQTc/SDNN; VR IV: SDQTc/rMSSD) were introduced. Female subjects exhibited significantly higher values in all four ratios of variability.
Conclusion: The obvious gender differences in repolarization inhomogeneity found in this study might be valuable in better understanding differences between men and women in the genesis of ventricular tachycardia.     

Dynamics of the QT interval

Spatial and temporal inhomogeneity of ventricular repolarization has been associated with the susceptibility to development of malignant ventricular arrhythmias. QT interval and QT dispersion dynamically change depending on not only heart rate but also other various factors such as autonomic tone, gender, aging, electrolytes or some drugs. Several studies have demonstrated that the dynamic behavior in the QT interval and QT dispersion such as the beat-to-beat fluctuations or the diurnal variation were altered in the setting of the abnormal pathophysiological conditions. Although the assessment of QT dynamicity remains a challenging issue from a technical point of view, it may provide the important information for identifying patients at potential risk of ventricular arrhythmias.     

Different Effects of Amiodarone and Quinidine on the Homogeneity of Myocardial Refractoriness in Patients With Intraventricular Conduction Delay

BACKGROUND: Increases in QT and JT dispersion have been suggested as indicative of a proarrhythmic potential as a result of heterogeneity in myocardial refractoriness, the reduction of which by antiarrhythmic agents might be associated with a beneficial effect on the development of serious ventricular arrhythmias. METHODS: To test the hypothesis that amiodarone reduces the heter-ogeneity of ventricular refractoriness to a significantly greater extent than quinidine in patients with intraventricular conduction defects under treatment for ventricular arrhythmias, the corrected and uncorrected QT and JT intervals and dispersions from 12-lead surface electrocardiograms were determined in 120 patients with intraventricular conduction defects with cardiac arrhythmias before and during treatment with amiodarone (n = 60) and quinidine (n = 60). RESULTS: Amiodarone increased QT from 403 +/- 50 ms to 459 +/- 47 ms (P <.001), with a similar increase in the corrected QT interval (QTc) (P <.001). Amiodarone reduced QT dispersion by 40% (P <.001), whereas quinidine increased by 18% (P <.001). The net effects of both drugs were similar for OTc. Amiodarone, but not quinidine, reduced heart rate significantly; amiodarone had no effect on the QRS; but quinidine increased if (P <.001). Quinidine as well as amiodarone increased the JT and JTc intervals significantly, but the effect of quinidine was qualitatively less striking. Amiodarone decreased the JT dispersion by 33% (P <.001) and JTc dispersion by 37% (P <.001). On the other hand, quinidine increased the corresponding values for JT and JTc by 18% (P <.001) and 21% (P <.001), respectively. The overall data on QT and JT dispersion indicate an improvement in the homogeneity of myocardial refractoriness with amiodarone treatment and the converse with quinidine treatment; this observation is consistent with a lower proarrhythmic propensity and mortality with amiodarone than with quinidine. Quinidine increased the QRS interval more than amiodarone, and the data indicate that in patients with intraventricular conduction defects, the monitoring of the JT interval might more accurately reflect changes in myocardial repolarization. CONCLUSIONS: Amiodarone and quinidine both increased the corrected and uncorrected QT and JT intervals; amiodarone decreased and quinidine increased the dispersion of these intervals, and these results suggested an improvement in the homogeneity of myocardial refractoriness as a result of amiodarone treatment and the converse as a result of quinidine treatment. Quinidine increased the QTS interval more than amiodarone, and the data indicate that in patients with intraventricular conduction defects, the monitoring of the JT interval might more accurately reflect changes in myocardial repolarization.     

Influence of cardiac autonomic neuropathy on heart rate dependence of ventricular repolarization in diabetic patients

OBJECTIVE: Prolongation of the QT interval and increased QT dispersion are associated with a poor cardiac prognosis. The goal of this study was to assess the long-term influence of the autonomic nervous system on the heart rate dependence of ventricular repolarization in patients with diabetic autonomic neuropathy (DAN). RESEARCH DESIGN AND METHODS: We studied 27 subjects (mean age 51.8 years) divided into three age- and sex-matched groups: nine control subjects, nine diabetic subjects with DAN (mostly at a mild stage; DAN+), and nine diabetic subjects without DAN (DAN-). DAN was assessed on heart rate variations during standard maneuvers (Valsalva, deep-breathing, and lying-to-standing maneuvers). No subject had coronary artery disease or left ventricular dysfunction or hypertrophy, and no subject was taking any drugs known to prolong the QT interval. All subjects underwent electrocardiogram and 24-h Holter recordings for heart rate variations (time and frequency domain) and QT analysis (selective beat averaging QT/RR relation, nocturnal QT lengthening). RESULTS: Rate-corrected QT intervals (Bazett formula) did not differ significantly between the three groups. The diurnal and nocturnal levels of low frequency/high frequency, an index of sympathovagal balance, were significantly reduced in DAN+ subjects. Using the selective beat-averaging technique, a day-night modulation of the QT/RR relation was evidenced in control and DAN- subjects. This long-term modulation was significantly different in DAN+ subjects, with a reversed day-night pattern and an increased nocturnal QT rate dependence. CONCLUSIONS: In diabetic patients with mild parasympathetic denervation, QT heart rate dependence was found to be impaired, as determined by noninvasive assessment using Holter data. Analysis of ventricular repolarization could represent a sensitive index of the progression of neuropathy. The potential prognostic impact of a reversed day-night pattern with steep nocturnal QT/RR relation still remains to be defined.     

QT-interval variability and autonomic control in hypertensive subjects with left ventricular hypertrophy

Left ventricular hypertrophy is a risk factor for sudden death. Malignant ventricular arrhythmias originate from altered cardiac repolarization. Ample data have described spatial abnormalities in cardiac repolarization [QT interval (QT) dispersion] in subjects with hypertension; more data are needed on temporal changes. This study was designed to assess the QT variability index (QTVI), the slope between QT and the RR interval (QT-RR(slope)) and spectral QT variability in subjects with arterial hypertension. The results were compared with those from a population at high risk of sudden death, i.e. patients with hypertrophic cardiomyopathy (HCM) who had received an implantable cardioverter/defibrillator (ICD), and those from normotensive control subjects. A total of 44 hypertensive subjects, six patients with HCM and an ICD and 33 control subjects underwent simultaneous short-term recording (256 beats) of QT, RR and systolic blood pressure variability, in the supine position, during controlled breathing. QTVI and spectral components of QT variability in the hypertensive group were significantly higher than in normotensive control subjects (P<0.001), but significantly lower than in patients with HCM and an ICD (P<0.001). The severity of left ventricular hypertrophy correlated significantly with QTVI and the ratio of low-frequency (LF) to high-frequency (HF) power obtained from the RR variability spectra (RR(LF/HF), slope=0.24, P<0.05; QTVI, slope=4.06, P<0.0001; intercept, slope=2.40, P<0.05; chi(2)=38.8; P<0.0001). The QT--RR slope was significantly higher only in patients with HCM and an ICD (P<0.001). In conclusion, the increased QTVI and the correlation of this index with left ventricular hypertrophy indicates that hypertension increases temporal cardiac repolarization abnormalities. At the level of the cardiac sinus node, this alteration is associated with increased sympathetic and reduced vagal modulation. As already noted in patients with HCM, the increased QTVI could be a factor responsible for triggering malignant ventricular arrhythmias in subjects with hypertension.     

Autonomic Effects of Dipyridamole Stress Testing on Frequency Distribution of RR and QT Interval Variability

Transient myocardial ischemia and associated changes in the autonomic nervous system may influence heart rate and ventricular repolarization to variable degrees. This study evaluated the effect of dipyridamole (DIP) induced ischemia on the autonomic balance by spectral analysis of RR and QT intervals variability. Patients with coronary artery disease undergoing DIP stress echocardiography were studied. From high resolution ECG recordings, RR and QT interval measurements were performed by a dynamic template-matching algorithm. A time-variant analysis was used to estimate power in the LF (0.05–0,15 Hz) and in the HF (0.15–0.4 Hz) band of RR and QT interval spectra. Patients were grouped in ischemic and nonischemic subgroups based on the echocardiographic detection of wall-motion abnormalities. In patients without ischemia (n = 28), DIP caused a decrease in LF power and an increase in HF power of the RR and QT interval variability, indicating concordant changes of both intervals. In contrast, patients with inducible ischemia (n = 11) showed a decrease in HF power of the RR interval spectra and an increase of HF power of QT interval spectra. Furthermore, LF power was increased for RR but decreased for QT interval spectra. Our study suggests that DIP induced ischemia causes a loss of autonomic coupling between heart rate and ventricular repolarization for sympathetic and parasympathetic activities. This lability in ventricular repolarization may constitute an arrhythmogenic substrate during acute ischemia in patients with coronary artery disease.     

Heart rate variability and QT dispersion in patients with subclinical hypothyroidism.

The effect of subclinical hypothyroidism (SH) on cardiovascular autonomic function and ventricular repolarization has not been yet elucidated. The aim of the present study was to evaluate the dispersion of QT interval, i.e. an index of inhomogeneity of repolarization, and heart rate variability (HRV), i.e. a measure of cardiac autonomic modulation, in SH patients. METHODS: The study included 42 patients (29 women and 13 men; mean age 53.2+/-14.2 years; body surface area 1.76+/-0.14 m2) with SH, as judged by elevated serum TSH levels (>3.6 mIU/l; range, 3.8-12.0) and normal free thyroid hormones (FT4 and FT3) and 30 euthyroid volunteer. Subjects with cardiac, metabolic, neurological disease or any other systemic disease that could affect autonomic activity were excluded from the study. Patients with SH and control subjects underwent a full history, physical examination, standard 12-lead ECG, and 24-h ambulatory ECG monitoring. To evaluate the effect of treatment with L-thyroxine on QT dispersion and HRV, 15 patients with SH were randomly assigned to receive therapy with L-thyroxine. All the subjects were evaluated at enrolment and after 6 months. RESULTS: Patients with SH showed higher QT dispersion and lower HRV measures than healthy controls (P<0.01 for all). In SH patients, the standard deviation of N-Ns (SDNN) was negatively related to TSH (r=-0.42, P=0.006), while low frequency (LF)/high frequency (HF) ratio was positively related to TSH (r=0.42, P=0.006). Moreover, in SH patients both QT dispersion and QTc dispersion were positively related to TSH (r=0.64 and r=0.63, P<0.001 for both). After 6 months, the patients treated with L-tiroxine exhibited a reduction of QT dispersion and an increase of HRV parameters. CONCLUSION: The results of the present study demonstrated that SH can alter autonomic modulation of heart rate and cause increased inhomogeneity of ventricular recovery times. Accordingly, early L-thyroxine treatment may be advised not only to prevent progression to overt hypothyroidism but also to improve abnormal cardiac autonomic function and ventricular repolarization inhomogeneity.     

Circadian variation of beat-to-beat QT interval variability in patients with prior myocardial infarction and the effect of beta-blocker therapy

BACKGROUND: Recent studies have demonstrated that increased QT interval variability (QTV) is associated with a greater susceptibility to ventricular arrhythmias and that patients with prior myocardial infarction (MI) were prone to ventricular arrhythmias during the daytime. The goal of the present study was to investigate the circadian variation of the QTV and to determine whether beta-blocker therapy improves the temporal fluctuation of the ventricular repolarization in patients with MI. METHODS: The study population consisted of 15 MI patients who had not received beta-blocker therapy, 11 MI patients who had received beta-blocker therapy, and 12 healthy subjects. Twenty-four hour Holter monitoring was obtained, and the RR and QT intervals were calculated automatically from 512 consecutive sinus beats for every 2 hours. RESULTS: In the daytime, the QT-SD was significantly greater in the MI group than in the healthy subjects (P<0.01), but there was no difference in the QT-SD when comparing the beta-blocker group to the control group. Moreover, the QT variability index and the QT variance normalized for the mean QT were similar pattern with QT-SD. The heart rate variability did not significantly differ when compared between the three study groups. CONCLUSION: These data indicate that the QTV increases during the daytime in patients with MI and that this circadian effect is prevented by beta-blocker therapy. Thus, beta-blocker therapy may reverse the maladaptation of the ventricular repolarization to the change in the heart rate and may thereby reduce the ventricular arrhythmias and decrease the mortality in patients with MI.