Differential diagnosis between LQT1 and LQT2 by QT/RR relationships using 24‐hour Holter monitoring: A multicenter cross‐sectional study

BackgroundThe clinical course and therapeutic strategies in the congenital long QT syndrome (LQTS) are genotype‐specific. However, accurate estimation of LQTS genotype is often difficult from the standard 12‐lead ECG.ObjectivesThis study aims to evaluate the utility of QT/RR slope analysis by the 24‐hour Holter monitoring for differential diagnosis of LQTS genotype between LQT1 and LQT2.MethodsThis cross‐sectional study enrolled 54 genetically identified LQTS patients (29 LQT1 and 25 LQT2) recruited from three medical institutions. The QT‐apex (QTa) interval and the QT‐end (QTe) interval at each 15‐second were plotted against the RR intervals, and the linear regression (QTa/RR and QTe/RR slopes, respectively) was calculated from the entire 24‐hour and separately during the day or night‐time periods of the Holter recordings.ResultsThe QTe/RR and QTa/RR slopes at the entire 24‐hour were significantly steeper in LQT2 compared to those in LQT1 patients (0.262 ± 0.063 vs. 0.204 ± 0.055, p = .0007; 0.233 ± 0.052 vs. 0.181 ± 0.040, p = .0002, respectively). The QTe interval was significantly longer, and QTe/RR and QTa/RR slopes at daytime were significantly steeper in LQT2 than in LQT1 patients. The receiver operating curve analysis revealed that the QTa/RR slope of 0.211 at the entire 24‐hour Holter was the best cutoff value for differential diagnosis between LQT1 and LQT2 (sensitivity: 80.0%, specificity: 75.0%, and area under curve: 0.804 [95%CI = 0.68–0.93]).ConclusionThe continuous 24‐hour QT/RR analysis using the Holter monitoring may be useful to predict the genotype of congenital LQTS, particularly for LQT1 and LQT2.     

Effect of Phenylephrine Provocation on Dispersion of Repolarization in Congenital Long QT Syndrome

Introduction: Syncope and sudden death are associated with sympathetic stimulation in LQT1 while LQT2 patients are more susceptible to arrhythmias during nonexertional states. Abnormal spatial (QTd)‐ and transmural (TDR)‐dispersion of repolarization may indicate increased arrhythmogenicity. This study compares the effect of phenylephrine on QTd and TDR in genotyped LQTS to control (C). Methods and Results: Seventeen LQT1, 12 LQT2, and 18 age‐ and sex‐matched normal controls received 2 mcg/kg of phenylephrine intravenously. At baseline and peak phenylephrine effect, BP, QT, RR, Bazett's QTc, precordial QTd (QTmax?QTmin), and T‐peak to T‐end (Tp‐e) intervals were determined blinded to the patient's clinical and genotype status. Baseline QT intervals and QTc were significantly longer in LQT1 and LQT2 compared to C. Baseline QTd and Tp‐e were greater in LQT2 than either LQT1 or C: QTd = 79 ± 29 ms (LQT2), 53 ± 26 (LQT1) , and 45 ± 15 (C) and Tp‐e = 120 ± 30 ms (LQT2), 99 ± 20 (LQT1) , and 90 ± 11 (C) . Overall, phenylephrine exerted no significant effect on either QTd or Tp‐e except with subgroup analysis of symptomatic LQTS where LQT1 and LQT2 patients had a divergent response with TDR. Conclusions: Phenylephrine‐induced bradycardia decreased TDR in symptomatic LQT1 but increased TDR in symptomatic LQT2. The observed effects of phenylephrine are consistent with the protective effect of beta‐blocker in LQT1 and the increased arrhythmogenicity noted during nonexertional states in LQT2.     

Optimal QT/JT Interval Assessment in Patients with Complete Bundle Branch Block

Background: Prolonged ventricular repolarization duration confers increased risk for malignant ventricular arrhythmias. We sought to clarify the optimal method of QT/JT interval assessment in patients with complete bundle branch block (BBB). Methods: Study patients (n = 71) were dual‐chamber device recipients with baseline left or right BBB who preserved intrinsic ventricular activation during incremental atrial pacing. Patients were classified according to the presence or not of structural heart disease. The former group received chronic amiodarone therapy. QT and JT intervals were recorded at baseline heart rate of 51 ± 4 beats/min and during atrial pacing at 60, 80, and 100 beats/min. We used linear mixed‐effects models to assess the effect of heart rate on the derived QTc and JTc values with the use of six different heart rate correction formulae. Results: Heart rate had a significant effect on the QTc and the JTc intervals regardless of the correction formula used (P < 0.001 for all formulae). The formula of Hodges demonstrated the least variability in QTc and JTc measurements across the different heart rates in both patients groups without (F = 15.05 and F = 13.53, respectively) and with structural heart disease (F = 5.71 and F = 7.69, respectively), followed by the Nomogram and Framingham methods, whereas the uncorrected QT and JT intervals showed comparable heart rate–dependency. The application of Bazett's JTc and QTc led to the most pronounced interval variations in any case with BBB. Conclusions: The Hodges, Nomogram and Framingham correction methods provide best assessment of QT/JT intervals in BBB, whereas Bazett's formula exaggerates heart rate–dependency of ventricular repolarization intervals.     

Repolarization Dynamics During Exercise Discriminate Between LQT1 and LQT2 Genotypes

Genotype and Exercise in LQTS . Background: Repolarization dynamics during exercise in patients with long‐QT Syndrome (LQTS) may be influenced by various factors such as a patient's genotype. We sought to systematically characterize the repolarization dynamics during exercise in patients with LQTS with a particular focus on the influence of genotype. Methods: Three groups of patients were studied on the basis of clinical status and genotype: LQT1, LQT2, and normal controls. Twenty‐five age‐ and gender‐matched patients were selected for each group. The QTc was measured during bicycle exercise testing and its dynamics were compared between the 3 groups. Results: The degree of QTc prolongation during exercise was greater in LQTS patients (LQT1 80 ± 47 ms, LQT2 64 ± 41 ms, Control 46 ± 20 ms, P = 0.02), with significant differences between LQT1 and LQT2 patients observed at heart rates ≥60% of the predicted maximum (P < 0.05). LQT1 patients demonstrated progressive or persistent QTc prolongation at higher heart rates, whereas LQT2 patients demonstrated maximum QTc prolongation at submaximal heart rates (～50% of the predicted maximum) with subsequent QTc correction toward baseline values at higher heart rates. Importantly, these observations were consistent regardless of age, gender, or exercise type in subgroup analyses. Conclusions: Reduced repolarization reserve in LQTS is genotype and heart rate specific. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1242‐1246, November 2010)     

Correction for Heart Rate Is Not Necessary for QT Dispersion in Individuals without Structural Heart Disease and Patients with Ventricular Tachycardia

Background: It remains controversial whether QT dispersion should be corrected for heart rate, especially when the limitations of rate correction formulae are considered. We investigated whether incremental atrial pacing affects QT dispersion and the rate‐corrected values according to Bazett's formula in individuals without structural heart disease and in patients with history of sustained ventricular tachycardia. Methods: We studied 32 individuals without structural heart disease (group A), and 16 patients with a history of sustained ventricular tachycardia (group B). QT dispersion and corrected for heart rate QT dispersion using Bazett's formula (QTc dispersion) were calculated in sinus rhythm, and during continuous right atrial pacing for one minute at 100 and 120 beats/min. Results: Interobserver variability was not significant (P ≧ 0.10). QT dispersion did not differ at rest between groups A and B and did not change significantly from baseline at any heart rate in both groups. However, QTc dispersion increased significantly with atrial pacing in a similar manner in group A and group B (42 ± 19 ms at rest vs 53 ± 23 ms at 120 beats/min, P < 0.001 for group A, 39 ± 16 ms at rest vs 60 ± 19 ms at 120 beats/min, P < 0.001 for group B). Conclusions: We conclude that QT dispersion remains unchanged during atrial pacing at heart rates up to 120 beats/min in both individuals without structural heart disease and in patients with a history of sustained ventricular tachycardia. Correction by Bazett's formula results in prolongation of QTc dispersion, yielding values which may be misleading. A.N.E. 2002;7(1):47–52     

Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT responses in patients with long QT syndrome: a bedside test for diagnosing long QT syndrome.

AIMS: As arrhythmias in the long QT syndrome (LQTS) are triggered by heart rate deceleration or acceleration, we speculated that the sudden bradycardia and subsequent tachycardia that follow adenosine injection would unravel QT changes of diagnostic value in patients with LQTS. METHODS AND RESULTS: Patients (18 LQTS and 20 controls) received intravenous adenosine during sinus rhythm. Adenosine was injected at incremental doses until atrioventricular block or sinus pauses lasting 3 s occurred. The QT duration and morphology were studied at baseline and at the time of maximal bradycardia and subsequent tachycardia. Despite similar degree of adenosine-induced bradycardia (longest R-R 1.7+/-0.7 vs. 2.2+/-1.3 s for LQTS and controls, P=NS), the QT interval of LQT patients increased by 15.8+/-13.1%, whereas the QT of controls increased by only 1.5+/-6.7% (P<0.001). Similarly, despite similar reflex tachycardia (shortest R-R 0.58+/-0.07 vs. 0.55+/-0.07 s for LQT patients and controls, P=NS), LQTS patients developed greater QT prolongation (QTc=569+/-53 vs. 458+/-58 ms for LQT patients and controls, P<0.001). The best discriminator was the QTc during maximal bradycardia. Notched T-waves were observed in 72% of LQT patients but in only 5% of controls during adenosine-induced bradycardia (P<0.001). CONCLUSION: By provoking transient bradycardia followed by sinus tachycardia, this adenosine challenge test triggers QT changes that appear to be useful in distinguishing patients with LQTS from healthy controls.     

Inaccurate electrocardiographic interpretation of long QT: The majority of physicians cannot recognize a long QT when they see one

BACKGROUND: Physicians in all fields of medicine may encounter patients with long QT syndrome (LQTS). It is important to define the percentage of physicians capable of distinguishing QT intervals that are long from those that are normal because LQTS can be lethal when left untreated. OBJECTIVES: The purpose of this study was to define the percentage of physicians in the different disciplines of medicine who can recognize a long QT when they see one. METHODS: We presented the ECGs of two patients with LQTS and two healthy females to 902 physicians (25 world-renowned QT experts, 106 arrhythmia specialists, 329 cardiologists, and 442 noncardiologists) from 12 countries. They were asked to measure the QT, calculate the QTc (the QT interval corrected for the heart rate), and determine whether the QT is normal or prolonged. RESULTS: For patients with LQTS, >80% of arrhythmia experts but <50% of cardiologists and <40% of noncardiologists calculated the QTc correctly. Underestimation of the QTc of patients with LQTS and overestimation of the QTc of healthy patients were common. Interobserver agreement was excellent among QT experts, moderate among arrhythmia experts, and low among cardiologists and noncardiologists (kappa coefficient = 0.82, 0.44, and < 0.3, respectively). Correct classification of all QT intervals as either "long" or "normal" was achieved by 96% of QT experts and 62% of arrhythmia experts, but by only <25% of cardiologists and noncardiologists. CONCLUSIONS: Most physicians, including many cardiologists, cannot accurately calculate a QTc and cannot correctly identify a long QT.     

76个长QT综合征先证者临床特征和治疗情况研究

为研究我国长QT综合征 (LQTS)患者的整体发病和治疗情况 ,选择按照 1993年Schwartz等提出的LQTS诊断标准确诊为本病的家系 76个。对先证者及其家族成员进行 6或 12导联ECG同步记录 ,对先证者的临床情况进行综合分析。结果 :先症者发病年龄 17.2± 14 .8岁 ,在 2 0岁以前发病的占 5 9.2 % ;以女性居多 ;发病症状有晕厥、黑、心悸、胸闷及其它如抽搐、胸背痛、头晕等 ;诱发因素有情绪紧张或激动、劳累、运动或体力劳动等 ;患者的QTc值为 0 .5 6± 0 .0 9s。LQTS患者的ECG上T波多变 ,QT间期可出现暂时正常化。在 76个LQTS先证者中 ,同时伴聋哑 1例 ,预激综合征 1例 ,心肌炎 2例 ,束支阻滞 2例 ,一过性房室阻滞 1例 ,高血压病 2例。根据ECG特点预测LQTS患者的基因型 :LQT1占 (31.6 % ) ,LQT2占 (5 3.9% ) ,LQT3占 (3.9% ) ,其余 (10 .5 % )心电图特征不明显 ,无法预测。多数患者服用 β 阻断剂类药物有效 ;在药物效果不好的患者中 ,有 4例安装起搏器 ,1例应用埋藏式心脏复律除颤器 (ICD) ,15例进行左心交感神经切除术 (LCSD) ,其中多数继续服用 β 阻断剂。结论 :我国的LQTS发病情况和临床表现与国外报道基本一致 ;根据ECG特点对LQTS患者进行的基因分型预测结果显示 ,我国的LQTS患者可能以LQT2为主。β 阻     

QTc interval on 24‐hour holter monitor: To trust or not to trust?

IntroductionQT interval represents the ventricular depolarization and repolarization. Its accurate measurement is critical since prolonged QT can lead to sudden cardiac death. QT is affected by heart rate and is corrected to QTc via several formulae. QTc is commonly calculated on the ECG and not the 24‐h Holter.Methods100 patients presenting to our institution were evaluated by an ECG followed by a 24‐h Holter. QTc measurement on both platforms using Bazett and Fridericia formulae was recorded and compared.ResultsMean age was 14.09 years, with the majority being males. Mean heart rate was 125.87. In the ECG, the mean QTc interval via the Bazett formula was 0.40 s compared with 0.38 s using the Fridericia formula. The mean corrected QT via the Bazett formula was 0.45, 0.39, and 0.42 s for the shortest RR, the longest RR, and the average RR, respectively. In contrast to the Fridericia formula, the corrected QT interval was 0.40, 0.39, and 0.40 s for the shortest RR, the longest RR, and the average RR, respectively. Using the Bazett formula, the highest specificity was reached during the longest RR interval (92.2%), while the highest sensitivity was recorded during the shortest RR interval (40%). As for the Fridericiaformula, sensitivity always reached 0%, while the highest specificity was reached during the average RR interval.ConclusionQTc measured during Holter ECG reached a high specificity regardless of RR interval using the Fridericia and during the longest and the average RR interval for the Bazett formula. The consistently low sensitivity reveals that Holter ECG should not be used to rule out prolonged QT.     

Response of the QT interval to mental and physical stress in types LQT1 and LQT2 of the long QT syndrome

OBJECTIVE—To study and compare the effects of mental and physical stress on long QT syndrome (LQTS) patients.
DESIGN—Case-control study.
MAIN OUTCOME MEASURES—QT intervals were measured from lead V3. Serum potassium and plasma catecholamine concentrations were also monitored.
PATIENTS—16 patients with type 1 LQTS (LQT1), 14 with type 2 LQTS (LQT2), both groups asymptomatic, and 14 healthy control subjects.
INTERVENTIONS—Three types of mental stress tests and a submaximal exercise stress test.
RESULTS—Heart rate responses to mental stress and exercise were similar in all groups. During mental stress, the mean QT interval shortened to a similar extent in controls (-29 ms), LQT1 patients (-34 ms), and LQT2 patients (-30 ms). During exercise, the corresponding QT adaptation to exercise stress was more pronounced (p < 0.01) in healthy controls (-47 ms) than in LQT1 (-38 ms) or LQT2 patients (-38 ms). During exercise changes in serum potassium concentrations were correlated to changes in QT intervals in controls, but not in LQTS patients. LQT1 and LQT2 patients did not differ in serum potassium, catecholamine or heart rate responses to mental or physical stress.
CONCLUSIONS—QT adaptation to mental and exercise stress in healthy people and in patients with LQTS is different. In healthy people QT adaptation is more sensitive to physical than to mental stress while no such diverging pattern was seen in asymptomatic LQTS patients.


Keywords: exercise; long QT syndrome; mental stress; potassium channel     

Two automatic QT algorithms compared with manual measurement in identification of long QT syndrome

Background

Long QT syndrome (LQTS) is an inherited disorder that increases the risk of syncope and malignant ventricular arrhythmias, which may result in sudden death.

Methods

We compared manual measurement by 4 observers (QT_manual) and 3 computerized measurements for QT interval accuracy in the diagnosis of LQTS:

1.

QT measured from the vector magnitude calculated from the 3 averaged orthogonal leads X, Y, and Z (QT_VCG) and classified using the same predefined QTc cut-points for classification of QT prolongation as in manual measurements;

2.

QT measured by a 12-lead electrocardiogram (ECG) program (QT_ECG) and subsequently classified using the same cut-points as in (1) above;

3.

The same QT value as in (2) above, automatically classified by a 12-lead ECG program with thresholds for QT prolongation adjusted for age and sex (QT_interpret).

The population consisted of 94 genetically confirmed carriers of KCNQ1 (LQT1) and KCNH2 (LQT2) mutations and a combined control group of 28 genetically confirmed noncarriers and 66 unrelated healthy volunteers.

Results

QT_VCG provided the best combination of sensitivity (89%) and specificity (90%) in diagnosing LQTS, with 0.948 as the area under the receiver operating characteristic curve. The evaluation of QT measurement by the 4 observers revealed a high interreader variability, and only 1 of 4 observers showed acceptable level of agreement in LQTS mutation carrier identification (κ coefficient >0.75).

Conclusion

Automatic QT measurement by the Mida1000/CoroNet system (Ortivus AB, Danderyd, Sweden) is an accurate, efficient, and easily applied method for initial screening for LQTS.     

Epinephrine Bolus Test in Detecting Long QT Syndrome Mutation Carriers with Indeterminable Electrocardiographic Phenotype

Background: In long QT syndrome (LQTS), prolonged and heterogeneous ventricular repolarization predisposes to serious arrhythmias. We examined how QT intervals are modified by epinephrine bolus in mutation carriers of three major LQTS subtypes with indefinite QT interval. Methods: Genotyped, asymptomatic subjects with LQTS type 1 (LQT1; n = 10; four different KCNQ1 mutations), type 2 (LQT2; n = 10; three different HERG mutations), and type 3 (LQT3; n = 10; four different SCN5A mutations), and healthy volunteers (n = 15) were examined. Electrocardiogram was recorded with body surface potential mapping system. After an epinephrine 0.04 μg/kg bolus QT end, QT apex, and T‐wave peak‐to‐end (Tpe) intervals were determined automatically as average of 12 precordial leads. Standard deviation (SD) of the 12 channels was calculated. Results: Heart rate increased 26 ± 10 bpm with epinephrine bolus, and similarly in all groups. QT end interval lengthened, and QT apex interval shortened in LQTS and normals, leading to lengthening of Tpe interval. However, the lengthening in Tpe was larger in LQTS than in normals (mean 32 vs 18 ms; P < 0.05) and SD of QT apex increased more in LQTS than in normals (mean 23 vs 7 ms; P < 0.01). The increase in Tpe was most pronounced in LQT2, and in SD of QT apex in LQT1 and LQT2. Conclusions: Abrupt adrenergic stimulation with a moderate dose of exogenous epinephrine affects ventricular repolarization in genotype‐specific fashion facilitating distinction from normals. This delicate modification may help in diagnosing electrocardiographically silent mutation carriers when screening LQTS family members. Ann Noninvasive Electrocardiol 2011;16(2):172–179     

Comparison of formulae for heart rate correction of QT interval in exercise ECGs from healthy children

OBJECTIVE—To investigate the differences in four formulae for heart rate correction of the QT interval in serial ECG recordings in healthy children undergoing a graded exercise test.
SUBJECTS—54 healthy children, median age 9.9 years (range 5.05-14.9 years), subjected to graded physical exercise (on a bicycle ergometer or treadmill) until heart rate reached > 85% of expected maximum for age.
DESIGN—ECG was recorded at baseline, at maximum exercise, and at one, two, four, and six minutes after exercise. For each stage, a 12 lead digital ECG was obtained and printed. In each ECG, QT and RR interval were measured (lead II), heart rate was calculated, and QTc values were obtained using the Bazett, Hodges, Fridericia, and Framingham formulae. A paired t test was used for comparison of QTc, QT, and RR interval at rest and peak exercise, and analysis of variance for all parameters for different stages for each formula.
RESULTS—From peak exercise to two minutes recovery there was a delay in QT lengthening compared with RR lengthening, accounting for differences observed with the formulae after peak exercise. At peak exercise, the Bazett and Hodges formulae led to prolongation of QTc intervals (p < 0.001), while the Fridericia and Framingham formulae led to shortening of QTc intervals (p < 0.001) until four minutes of recovery. The Bazett QTc shortened significantly at one minute after peak exercise.
CONCLUSIONS—The practical meaning of QT interval measurements depends on the correction formula used. In studies investigating repolarisation changes (for example, in the long QT syndromes, congenital heart defects, or in the evaluation of new drugs), the use of an ad hoc selected heart rate correction formula may bias the results in either direction. The Fridericia and Framingham QTc values at one minute recovery from exercise may be useful in the assessment of long QT syndromes.


Keywords: paediatric exercise testing; QT interval; QTc formulae     

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)     

Repolarization morphology in adult LQT2 carriers with borderline prolonged QTc interval

BACKGROUND: At least 50% of LQT2 carriers have borderline QTc (0.42-0.47 s), and they present a diagnostic difficulty to clinicians evaluating patients suspected of having long QT syndrome (LQTS). OBJECTIVES: Because QTc in this borderline range is nondiagnostic, the purpose of this study was to investigate whether analysis of phenotypic features of T-wave morphology could help identify LQT2 carriers with normal or near-normal QTc-interval duration. METHODS: Standard 12-lead ECGs recorded without beta-blockers from LQT2 carriers (n = 90, 33 +/- 14 years, 61% female) and noncarriers (n = 69, 38 +/- 17 years, 58% female) were digitized. The following parameters were automatically measured: RR interval, QT/QTc, QT apex, T-wave amplitude, ascending (alpha(L)) and descending slopes (alpha(R)) of the T wave, and T-wave symmetry. We used a linear logistic regression model to identify the most relevant parameters for separating LQT2 carriers from noncarriers, within the overall population and among patients without overt QTc prolongation (390 470).     

Utility of a Simplified Lidocaine and Potassium Infusion in Diagnosing Long QT Syndrome among Patients with Borderline QTc Interval Prolongation

Background: Congenital long QT syndrome (LQTS) is caused by mutations in the cardiac Na⁺ or K⁺ channels that result in a prolonged QTc interval and increased QT dispersion. Na⁺ channel blockers and K⁺ can reverse the repolarization abnormalities in the Na⁺ channel variant (LQT3) and K⁺ channel variant (LQT1, LQT2), respectively. The phenotype of LQTS can be difficult to recognize, especially when the QTc interval is mildly prolonged. Additional noninvasive testing methods are needed to enhance the diagnosis of LQTS. This study compared the response of the QTc interval and QT dispersion to a sequential lidocaine/K⁺ infusion in LQTS patients with borderline QTc interval prolongation and control patients as a means of diagnosing LQTS. Methods: In this study, eight LQTS patients with borderline QTc, defined as QTc < 470 ms, and 10 healthy controls received sequential lidocaine/K⁺ infusion. Results: At baseline, LQTS patients had a longer QTc (446 ± 29 vs 416 ± 28 ms, P < 0.05) but similar QT dispersion (43 ± 14 vs 29 ± 10 ms) compared to controls. After lidocaine administration, baseline QTc and QT dispersion did not change in either LQTS or controls. One LQTS patient had a 54 ms (12%) reduction in his QTc but no change in QT dispersion. Following K⁺ infusion, baseline QTc and QT dispersion decreased by 9% (P < 0.005) and 45% (P < 0.005), respectively in LQTS. No effect was seen in control patients, where QTc and QT dispersion shortened by 1% (5 ± 14 ms) and 20% (6 ± 7 ms), respectively, compared to baseline. The combined lidocaine/K⁺ infusion had a sensitivity, specificity, and accuracy of 88%, 100%, and 94%, respectively, in diagnosing LQTS. Conclusions: A simplified sequential lidocaine/K⁺ challenge is accurate in diagnosing LQTS among patients with borderline QTc prolongation.     

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.     

Surgical left cardiac sympathetic denervation for long QT syndrome: effects on QT interval and heart rate

The primary aim of the present study was to investigate the short-term effects of surgical left cardiac sympathetic denervation (LCSD) on the QT interval and heart rate in patients with congenital long QT syndrome (LQTS). Left cardiac sympathetic denervation was performed in five LQTS patients who had a history of syncope. The patients’ 12-lead and 24-h Holter monitoring ECG was recorded 24 h before and 24 h after LCSD. Treadmill exercise tests were also performed before and 6 days after surgery to assess changes in heart rate and the QT interval after surgery. Left cardiac sympathetic denervation was successful in all patients. The mean value of the corrected QT interval (QTc) in the five patients decreased from 0.59 ± 0.05 to 0.48 ± 0.04 s (P = 0.006) immediately after the procedure and remained short (0.47 ± 0.04, P < 0.05) after a 21-month follow-up. The mean value of QTc on the 24-h Holter monitoring ECG also decreased in all patients (0.67 ± 0.07 vs 0.60 ± 0.05 s, P < 0.01). The mean, maximum, and minimum heart rate on the 24-h ECG remained unchanged (P > 0.05). The maximum heart rate during the exercise tests decreased from 162 ± 4 beats/min before surgery to 129 ± 10 beats/min (P < 0.01). The exercise-induced increase in QTc remained unchanged after the surgery (P > 0.05). Although four of the five patients were syncope-free until 21 months postoperatively, the remaining patient had a recurrence of syncope, requiring an increased dose of β blocker. These findings indicate that LCSD shortens QTc and diminishes the exercise-induced increase in heart rate whereas the resting heart rate and exercise-induced increase in QTc remain unchanged. These results may have implications for the effectiveness and limitations of LCSD.     

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.     

改良的QT间期校正方法临床意义评价

为了评价改良的校正ＱＴ间期（ＱＴＬＣ）方法的准确性和临床实用价值，选取７２例健康成人，采用踏车运动试验逐步提高心率（ＨＲ），于ＨＲ每增加１０ｂｐｍ描记一次监测导联心电图，测定ＲＲ及ＱＴ间期，计算ＱＴｃ、ＱＴＬＣ［ＱＴＬＣ＝ＱＴ＋０．１５４（１－ＲＲ）］。发现当ＨＲ＜１２０ｂｐｍ时ＱＴｃ与ＨＲ呈显著正相关（ｒ＝０．８５，Ｐ＜０．００２）；ＨＲ＞１２０ｂｐｍ时ＱＴｃ与ＨＲ呈显著负相关（ｒ＝－０．８７，Ｐ＜０．００５）。ＨＲ在６０～１００ｂｐｍ之间时ＱＴＬＣ基本恒定，与ＨＲ无相关关系（ｒ＝－０．１９，Ｐ＞０．０５）；ＨＲ＞１００ｂｐｍ时，ＱＴＬＣ与ＨＲ呈显著负相关（ｒ＝－０．９１，Ｐ＜０．００１）。结果提示：在ＨＲ正常的前提下，ＱＴＬＣ基本不受ＨＲ影响，因而ＱＴＬＣ用于监测抗心律失常药物对心室肌电活动的影响、预测ＱＴ间期延长所致恶性心律失常及猝死等心脏事件，其准确性及临床实用价值似应优于ＱＴｃ。