短QT综合征的研究近况

短QT综合征是近来被认识的一种遗传综合征,以持续短QT间期、高的家族性心悸、晕厥、猝死和心房颤动发生率,缩短的有效不应期和电生理研究中诱发的心室颤动为特征。本文结合了近年来的临床研究,综述了短QT综合征的诊断标准、电生理特点、发病机制、临床表现、治疗方法以及有待于研究的问题。     

QT interval prolongation in type 2 (non-insulin-dependent) diabetic patients with cardiac autonomic neuropathy

Summary QT interval alterations were measured in 41 non-insulin-dependent (type 2) diabetic patients and 14 age- and sex-matched control subjects. Cardiac autonomic neuropathy (CAN) was assessed by noninvasive tests (deep breathing, Valsalva maneuver and lying-to-standing) and diabetics were divided into three groups according to the results of these tests: diabetics with definitive (n=14), early (n=13) and without (n=14) CAN. The corrected values of QT intervals (QT_c) at rest were significantly longer in diabetics with definitive (447±5 ms; p<0.001), early (426±5 ms; p<0.05) and without (424±5 ms; p<0.05) CAN than in controls (407±5 ms). Moreover, QT_c intervals at rest were significantly (p<0.01) longer in diabetics with definitive CAN than in diabetics with early and without CAN. QT_c intervals at maximum tachycardia, induced by Valsalva maneuver, were considerably longer in diabetics with definitive CAN (451±6 ms) than in controls (407±6 ms; p<0.001) and in diabetics with early (434±6 ms; p<0.05) or without (422±6 ms; p<0.01) CAN. Furthermore, QT_c intervals at maximum tachycardia were significantly (p<0.01) longer in diabetics with early CAN than in controls. QT_c intervals at maximum bradycardia after Valsalva maneuver were significantly longer in diabetics with definitive (446±5 ms; p<0.001), early (434±5 ms; p<0.001) and without (424±5 ms; p<0.01) CAN than in controls (403±5 ms). Moreover, QT_c intervals at maximum bradycardia were considerably (p<0.01) longer in diabetics with definitive than without CAN. At least one abnormal (>440 ms) QT_c period was found in 19 out of 27 patients with early or definitive CAN, but 4 of 14 diabetics without any signs of CAN and none of the controls exibited abnormal QT_c period. It was concluded that QT_c interval prolongation due to imbalance of autonomic nervous tone could be observed in type 2 diabetic patients with CAN, suggesting a possible role in sudden cardiac death.     

Prognostic significance of circadian variability of RR and QT intervals and QT dynamicity in patients with chronic heart failure

BACKGROUND: In patients with chronic heart failure (CHF), circadian variability of RR and QT intervals may be altered because of neurohumoral activation and functional and structural remodeling of the heart. OBJECTIVE: The aim of this study was to evaluate the prognostic significance of circadian variability of the RR and QT intervals and QT dynamicity (QT/RR slope) in CHF patients. METHODS: We prospectively enrolled 121 patients with stable CHF in sinus rhythm (age 67 +/- 14 years, mean +/- SD; range 34 to 87 years). The RR, QT, and rate-corrected QT (QTc) intervals and the QT/RR slope measured from 24-hour Holter electrocardiogram were fitted by cosine curves. RESULTS: During the follow-up period of 34 +/- 17 months, 40 (33%) patients died of cardiac causes, 10 of which were sudden. All patients showed significant circadian rhythms in the RR, QT, and QTc intervals and the QT/RR slope by cosine-curve fitting. In addition to the expected higher heart rate, longer QT interval, and steeper QT/RR slope, we found that patient who died of cardiac causes had reduced circadian variability of QT interval (10 +/- 10 ms vs 21 +/- 13 ms) and a later maximum RR interval (4.1 +/- 0.9 AM vs 2.3 +/- 2.1 AM) compared with survivors, among many other statistically significant circadian parameter differences. These 2 parameters were independent predictors of cardiac death in multivariate Cox proportional hazards regression analysis. CONCLUSION: Circadian variability analyses of Holter-derived RR and QT intervals may provide prognostic information beyond that provided by 24-hour averages of these parameters.     

肺动脉高压患者心率校正QT间期和QT离散度的研究

目的:检测肺动脉高压(pulmonary hypertension,PH)患者的心率校正的QT间期(heartrate-corrected QT interval,QTc)和QTc离散度(QTc dispersion,QTcd),并评价其与肺动脉压力的关系。方法:入选2003年12月至2008年7月因初步诊断为PH而进行右心导管术的患者。记录静息12导联心电图,手工测量QT间期并用Bazett公式进行校正。根据平均肺动脉压,将患者分为对照组,轻-中度PH组和重度PH组。结果:共入选201例患者。男性患者的QTc和QTcd在3组间差异无统计学意义。女性患者中,重度PH组的QTc比对照组高〔(436.1±39.4)msvs.(407.6±24.8)ms,P=0.037〕,重度PH组的QTcd(68.5±20.9)ms高于对照组(45.1±12.6)ms和轻-中度组(58.6±14.7)ms(P=0.002;P=0.003)。此外,女性患者的QTc和QTcd与平均肺动脉压正相关(r=0.207,P=0.03;r=0.236,P=0.012)。结论:本组资料中女性PH患者的QTc和QTcd与平均肺动脉压正相关,且在重度PH患者中显著增高,有待于进一步探讨。     

Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes

Aims/hypothesis Hypoglycaemia is associated with heart rate-corrected QT (QTc) interval lengthening on the ECG; this may be important in the pathogenesis of sudden overnight death in young people with diabetes. Since hypoglycaemic QTc lengthening appears to be mediated through the sympathoadrenal response, we tested the hypothesis that beta₁-blockade will prevent these changes in type 1 diabetic patients and so provide a potential therapeutic intervention.Methods We studied eight type 1 diabetic adults without cardiovascular or renal complications. Similar hypoglycaemic clamp studies were performed on two occasions, at least 4 weeks apart, but immediately before one visit subjects received atenolol 100 mg daily for 7 days. Following a 60-min euglycaemic (5 mmol/l) period, blood glucose was lowered over 30 min to 2.5 mmol/l, and held for 60 min. High-resolution ECG was recorded at baseline and at 0, 30 and 60 min during each glycaemic plateau. QT interval was measured using a semiautomated tangent method and QTc was derived from QT using the Fridericia formula.Results Mean (SD) baseline QTc was similar at both visits: control 391 (30) ms, post-atenolol 386 (34) ms; (p=0.33). Without atenolol pretreatment, QTc lengthened during hypoglycaemia to a maximum of 448 (34) ms (p<0.001). On atenolol, QTc lengthening was significantly reduced (peak QTc 413 (27) ms; p=0.004 vs control visit).Conclusions/interpretation Hypoglycaemic QTc lengthening is blunted by atenolol in patients with type 1 diabetes. Selective beta₁-blockade may help prevent sudden death, if we can identify those at high risk.     

Circadian rhythm of the QT interval dispersion in healthy subjects. Correlation with heart rate variability circadian pattern

Circadian variation of QT interval dispersion (QTd) and heart rate variability spectral indices was evaluated in healthy persons in 24-hour 3-lead electrocardiogram. Mean values, SD, and SD/mean were evaluated for 24 hours, each hour separately and in night, day, and morning periods. Table Curve 2D and multiple regression were applied to find correlations between parameters. In 50% of subjects, a significant negative correlation was revealed between QTd and HF. Also, in 50% of persons, a significant positive correlation was found between QTd and low frequency/high frequency. After adjustment for periods, correlations were only observed during morning hours. With Table Curve 2D, 2 models of correlations between QTd and HF were found. Multiple regression analysis revealed relations between mean QTd and R-R as well as mean QTd and HF. It is possible that it is sympathovagal balance, as reflected in heart rate variability, and not the tone of both autonomic components that affects QTd variability.     

Association between C-reactive protein,corrected QT interval and presence of QT prolongation in hypertensive patients

C-reactive protein (CRP) and corrected QT (QTc) interval are predictors of cardiovascular disease. Whether CRP is associated with QTc interval and QT prolongation is unknown in hypertensive patients. We recruited hypertensive patients from a cardiovascular clinic in a tertiary medical center in Taiwan. All received standard 12-lead electrocardiogram examination. QT prolongation was defined as QTc interval ≥440 ms in men or ≥450 ms in women. High-sensitive CRP kits were used for the measurement of the CRP levels. A total of 466 consecutive patients were finally enrolled. Mean age was 60.6 ± 12.0 years. CRP level was correlated with QTc interval (p < 0.001) and presence of QT prolongation (p = 0.014). Multivariate regression analysis showed that CRP level (p = 0.001), age (p = 0.004), sex (p < 0.001), height (p = 0.001), low-density lipoprotein (p = 0.041), and QRS interval (p < 0.001) were associated with QTc interval. Furthermore, CRP level [odds ratio (OR) = 1.203, 95% confidence interval (CI) = 1.027–1.410, p = 0.022], age (OR = 1.040, 95% CI = 1.010–1.071, p = 0.009), waist (OR = 1.033, 95% CI = 1.000–1.066, p = 0.047), triglyceride (OR = 0.993, 95% CI = 0.987–0.999, p = 0.021) and QRS interval (OR = 1.046, 95% CI = 1.028–1.065, p < 0.001) independently predicted the presence of QT prolongation. Because CRP is an independent predictor of QTc interval and presence of QT prolongation, it could be considered in the risk assessment for hypertensive patients.     

Beat‐to‐Beat QT Interval Variability Is Primarily Affected by the Autonomic Nervous System

Background : Beat‐to‐beat QT interval variability is associated with life‐threatening arrhythmias and sudden death, however, its precious mechanism and the autonomic modulation on it remains unclear. The purpose of this study was to determine the effect of drugs that modulate the autonomic nervous system on beat‐to‐beat QT interval. Method : RR and QT intervals were determined for 512 consecutive beats during fixed atrial pacing with and without propranolol and automatic blockade (propranolol plus atropine) in 11 patients without structural heart disease. Studied parameters included: RR, QTpeak (QRS onset to the peak of T wave), QTend (QRS onset to the end of T wave) interval, standard deviation (SD) of the RR, QTpeak, and QTend (RR‐SD, QTpeak‐SD, and QTend‐SD), coefficients of variation (RR‐ CV, QTpeak‐CV, and QTend‐CV) from time domain analysis, total power (TP; RR‐TP, QTpeak‐TP, and QTend‐TP), and power spectral density of the low‐frequency band (LF; RR‐LF, QTpeak‐LF, and QTend‐LF) and the high‐frequency band (HF; RR‐HF, QTpeak‐HF and QTend‐HF). Results : Administration of propranolol and infusion of atropine resulted in the reduction of SD, CV, TP, and HF of the QTend interval when compared to controlled atrial pacing (3.7 ± 0.6 and 3.5 ± 0.5 vs 4.8 ± 1.4 ms, 0.9 ± 0.1 and 0.9 ± 0.1 vs 1.2 ± 0.3%, 7.0 ± 2.2 and 7.0 ± 2.2 vs 13.4 ± 8.1 ms², 4.2 ± 1.4 and 4.2 ± 1.2 vs 8.4 ± 4.9 ms², respectively). Administration of propranolol and atropine did not affect RR interval or QTpeak interval indices during controlled atrial pacing. Conclusions : Beat‐to‐beat QT interval variability is affected by drugs that modulate the autonomic nervous system.     

QT interval in cardiac amyloidosis

The aim of the study was to investigate whether cardiac amyloidosis is associated with QT interval abnormalities and ventricular arrhythmias. A controlled study of 30 patients was undertaken at a university cardiology department in a large referral hospital. Thirty patients (18 men, 12 women, mean age 56 ± 12 years) with systemic amyloidosis verified by biopsy and strong indications of cardiac amyloidosis comprised the study group, with 30 healthy age- and sex-matched individuals serving as controls. Complete M-mode and two-dimensional echocardiographic study was undertaken and QT interval and QT_c were calculated. All patients and controls underwent 24-h Holter monitoring for arrhythmias. Left ventricular (LV) wall thickening was found in all patients with cardiac amyloidosis. The LV mass in the patients with cardiac amyloidosis was significantly greater than that of the control group, as was the ratio LVmass/body surface area (p < 0.001). There was no significant difference in the max QT interval or in QT_c dispersion between the two groups, although the max QT_c was greater in the patients with cardiac amyloidosis. Patients with cardiac amyloidosis did not have a higher incidence of arrhythmias than the controls. Although patients with thickened cardiac walls due to cardiac amyloidosis have a prolonged QT_c in comparison with controls, they do not show an increase in interlead QT_c dispersion which might suggest the possibility of regional disturbances of the uniformity of repolarization. Patients with cardiac amyloidosis do not have a higher incidence of arrhythmias than controls.     

美托洛尔对充血性心力衰竭患者QT离散度的影响及临床意义

目的探讨美托洛尔对充血性心力衰竭（CHF）患者QT离散度的影响及临床意义。方法将56例CHF患者随机分为治疗组（28例）和对照组（28例）,对照组采用常规治疗,治疗组在常规治疗的基础上加用美托洛尔,并作治疗前后的QTd测量及比较。结果QTd与心功能受损的程度呈正相关;CHF伴室性心律失常者QTd大于不伴室性心律失常者（P〈0.05）;给予美托洛尔治疗后CHF患者QTd明显缩短（P〈0.05）。结论CHF患者QTd明显增大。美托洛尔可使QTd缩小,对防治室性心律失常和猝死有重要意义。     

Heart rate‐corrected QT interval: A novel diagnostic biomarker for diabetic peripheral neuropathy

Aims/IntroductionTo explore the relationship between heart rate‐corrected QT (QTc) interval and diabetic peripheral neuropathy (DPN), and whether QTc interval has diagnostic utility for DPN beyond nerve conduction velocity.Materials and MethodsA total of 965 patients with diabetes, including 473 patients with DPN and 492 patients without DPN, underwent standard 12‐lead electrocardiography and detailed assessments of peripheral neuropathy.ResultsPatients with DPN had longer QTc intervals than those without. Among participants, from the first to fourth quartile of QTc interval, the proportion of patients with DPN appreciably increased and the nerve conduction velocity obviously decreased (P for trend <0.001). The univariate and multivariate analyses showed that prolonged QTc interval was closely associated with increased risk of DPN (univariable odds ratio 1.112, 95% confidence interval 1.097–1.127, P < 0.001; multivariable odds ratio 1.118, 95% confidence interval 1.099–1.137, P < 0.001). Receiver operating characteristic analysis for the diagnosis of DPN showed a greater area under the curve for QTc interval of 0.894 than the median nerve motor conduction velocity of 0.691, median nerve sensory conduction velocity of 0.664 and peroneal nerve motor conduction velocity of 0.692. The optimal cut‐off point of QTc interval for DPN was 428.5 ms with sensitivity of 0.715 and specificity of 0.920 (P < 0.001). The combination of QTc interval and nerve conduction testing increased the area under the curve for the diagnosis of DPN (from 0.736 to 0.916; P < 0.001).ConclusionsQTc interval with 428.5 ms has more reliable diagnostic utility for DPN than nerve conduction velocity, and prolonged QTc interval is closely associated with an increased risk of DPN.     

慢性心力衰竭患者QT间期频率依赖性与室性心律失常的关系

目的探索慢性心力衰竭患者QT问期频率依赖性与室性心律失常的关系。方法选31例慢性心力衰竭患者有效病例资料。检测左心室舒张末期内径（LVEDD）、左心室射血分数（LVEF）、QT间期离散度（QTd）、心率变异性（HRV）、QT／RR相关直线的斜率、24h室性早搏（VPB）和非持续性室性心动过速（NSVT）的次数。比较有NSVT和无NSVT患者上述指标的差别,研究上述指标与NSVT的相关性。结果31例心力衰竭患者中,有17例动态心电图记录到NSVT。有NSVT与无NS—VT的患者比较,VPB次数[（5631．2±7218．0）对（285．9±371．7）,P〈0．05],QTe／RR斜率[（0．210±0．049）对（0．161±0．058）,P〈0．05]和QTp／RR斜率[（0．195±0．046）对（0．151±0．041）,P〈0．05]的差异有统计学意义。在全部31例患者中,QTd（r=0．414）、VPB次数（r=0．768）、QTe／RR斜率（r=0．380）、QTp／RR斜率（r=0．433）和NSVT有显著的相关性（P〈0．05）。结论QT间期频率依赖性是反映QT间期动态变化的指标,慢性心力衰竭患者的QT／RR斜率与室性心律失常有较好的相关性,在心脏性猝死的风险评估中有一定价值。     

QT Interval and Long‐Term Mortality Risk in the Framingham Heart Study

Background : The association between QT interval and mortality has been demonstrated in large, prospective population‐based studies, but the strength of the association varies considerably based on the method of heart rate correction. We examined the QT‐mortality relationship in the Framingham Heart Study (FHS). Methods : Participants in the first (original cohort, n = 2,365) and second generation (offspring cohort, n = 4,530) cohorts were included in this study with a mean follow up of 27.5 years. QT interval measurements were obtained manually using a reproducible digital caliper technique. Results : Using Cox proportional hazards regression adjusting for age and sex, a 20 millisecond increase in QTc (using Bazett's correction; QT/RR^1/2 interval) was associated with a modest increase in risk of all‐cause mortality (HR 1.14, 95% CI 1.10–1.18, P < 0.0001), coronary heart disease (CHD) mortality (HR 1.15, 95% CI 1.05–1.26, P = 0.003), and sudden cardiac death (SCD, HR 1.19, 95% CI 1.03–1.37, P = 0.02). However, adjustment for heart rate using RR interval in linear regression attenuated this association. The association of QT interval with all‐cause mortality persisted after adjustment for cardiovascular risk factors, but associations with CHD mortality and SCD were no longer significant. Conclusion : In FHS, there is evidence of a graded relation between QTc and all‐cause mortality, CHD death, and SCD; however, this association is attenuated by adjustment for RR interval. These data confirm that using Bazett's heart rate correction, QTc, overestimates the association with mortality. An association with all‐cause mortality persists despite a more complete adjustment for heart rate and known cardiovascular risk factors.     

室性期前收缩频率在阻塞性睡眠呼吸暂停的冠心病者中的临床意义

目的 评价室性期前收缩(VPC)频率及交感活性在惠有阻塞性睡眠呼吸暂停综合征(OSAS)的冠心病患者中的意义.方法 125例中有OSAS的冠心病患者,均行多导睡眠图检查,将患者按AHI值进行分组.睡眠阶段分为清醒组、S1、S2、S34及REM.并对患者心率震荡(HRT)参数进行测量对比.结果 VPC频率受睡眠阶段(清醒期、S2及REM,F=5.8,P<0.005)及AHI(F=8.7,P<0.005)影响;在严重OSAS患者,REM期VPC频率较清醒期为高(P=0.011),相反,中等OSAS患者VPC频率较低,且没有睡眠阶段依赖性(P=0.19).氧失饱和持续间期与AHI成正相关(r2=0.71,P<0.001),且在REM期较非REM期为长(P<0.0001),在REM期HRT参数TS与氧失饱和持续间期成负相关(r2=0.06,P=0.014).结论 REM期高VPC频率可能是阻塞性睡眠呼吸暂停综合症患者夜间高死亡率的原因之一.     

Heart rate and catecholamine contribution to QT interval shortening on exercise.

BACKGROUND: QT interval shortens with exercise. Some of this shortening is due to an increase in heart rate, and some is due to other effects of exercise, probably mostly neuroendocrine effects. Data from subjects with cardiac transplants have suggested that non-heart rate-related changes in QT interval on exercise are due to the effects of circulating catecholamines. HYPOTHESIS: We sought to determine whether changes in plasma catecholamine levels with exercise are an important contributor to non-heart rate-related QT interval shortening. METHODS: Subjects with DDD pacemakers were recruited. Subjects had QT intervals measured at rest, during a low fixed level exercise test designed to increase heart rate to about 110 beats/min, and, after resting, during pacing at a heart rate of 110 beats/min. Catecholamine levels were measured at each stage of the study. RESULTS: QT interval at rest was 420 +/- 12 ms, during pacing 366 +/- 16 ms, and on exercise 325 +/- 14 ms. This then gave the proportion of QT interval shortening due to heart rate as 68.6 +/- 9.3% of total QT shortening, with the range between 35 and 95.6%. There was no proportionality between the degree of QT interval shortening on exercise that was not due to increases in heart rate and changes in plasma catecholamine levels. CONCLUSION: Two-thirds of exercise-induced QT interval shortening are due to an increase in heart rate, and one-third to other effects. Changes in plasma catecholamine levels on exercise were not closely related to changes in the QT interval on exercise.