Age and Gender Difference in ST Height at Rest and after Double Autonomic Blockade in Normal Adults

Background: ST elevation is commonly seen in young, healthy men. The exact mechanisms that cause ST height to be greater in young men are not yet completely understood. The purpose of the present study was to determine whether autonomic tone is responsible for age and gender differences in ST height. Methods: Gender and age differences in ST height were studied at rest and after double autonomic blockade (DAB) with atropine and propranolol. Fifty healthy men and women were included (16 men, 14 women, age 23–32 years; 9 men, 11 women, age 65–79 years). Twelve‐lead ECGs were registered at rest and after DAB. Leads II and V₁–V₄ were chosen for analysis. ST height (in mm) was measured manually at the J‐point, and 40 ms and 80 ms after the J‐point. Values were corrected for QRS amplitude. Results : Gender and age differences in ST height were seen in both rest and DAB data. Men had greater ST height compared to women at J‐point, 40 and 80 ms after the J‐point (P ≤ 0.0001), and younger subjects had greater ST height than older subjects at J‐point (P = 0.0140), 40 and 80 ms after the J‐point (P ≤ 0.0001). DAB did not change ST height at J‐point or at 40 ms, but increased ST height at 80 ms. Women had less of an increase in ST height following DAB than men did. Conclusions: ST elevation in the absence of structural or electrical heart disease is mainly seen in young men. Age and gender difference persist after DAB and thus are not due to differences in autonomic tone.     

Impact of Pharmacological Autonomic Blockade on Complex Fractionated Atrial Electrograms

Autonomic Blockade During Atrial Fibrillation . Introduction: The influence of the autonomic nervous system on the pathogenesis of complex fractionated atrial electrograms (CFAE) during atrial fibrillation (AF) is incompletely understood. This study evaluated the impact of pharmacological autonomic blockade on CFAE characteristics. Methods and Results: Autonomic blockade was achieved with propanolol and atropine in 29 patients during AF. Three‐dimensional maps of the fractionation degree were made before and after autonomic blockade using the Ensite Navx^® system. In 2 patients, AF terminated following autonomic blockade. In the remaining 27 patients, 20,113 electrogram samples of 5 seconds duration were collected randomly throughout the left atrium (10,054 at baseline and 10,059 after autonomic blockade). The impact of autonomic blockade on fractionation was assessed by blinded investigators and related to the type of AF and AF cycle length. Globally, CFAE as a proportion of all atrial electrogram samples were reduced after autonomic blockade: 61.6 ± 20.3% versus 57.9 ± 23.7%, P = 0.027. This was true/significant for paroxysmal AF (47 ± 23% vs 40 ± 22%, P = 0.003), but not for persistent AF (65 ± 22% vs 62 ± 25%, respectively, P = 0.166). Left atrial AF cycle length prolonged with autonomic blockade from 170 ± 33 ms to 180 ± 40 ms (P = 0.001). Fractionation decreases only in the 14 of 27 patients with a significant (>6 ms) prolongation of the AF cycle length (64 ± 20% vs 59 ± 24%, P = 0.027), whereas fractionation did not reduce when autonomic blockade did not affect the AF cycle length (58 ± 21% vs 56 ± 25%, P = 0.419). Conclusions: Pharmacological autonomic blockade reduces CFAE in paroxysmal AF, but not persistent AF. This effect appears to be mediated by prolongation of the AF cycle length. (J Cardiovasc Electrophysiol, Vol. pp. 766‐772, July 2010)     

Effects of Menstrual Cycle on Cardiac Autonomic Innervation As Assessed By Heart Rate Variability

Objective: The aim of the study was to investigate the effects of menstrual cycle on cardiac autonomic function parameters in young healthy women by means of heart rate variability (HRV). Methods: Forty‐three nonobese regularly cycling women (age 29 ± 6, range 20–38) were enrolled. Recordings for HRV analysis were obtained during the two phases of the menstrual cycle when the estrogen and progesterone levels peaked (follicular phase 11 ± 1 days and luteal phase 21 ± 1 days from the start of bleeding). Power spectral analysis of HRV was performed to calculate the low frequency peak (LF, 0.04–0.15 Hz), high frequency peak (HF, 0.15–0.40 Hz), LF in normalized unit (LF nU), HF in normalized unit (HF nU), and LF/HF ratio during the two phases of menstrual cycle. Results: The heart rates, LF and HF, were similar in both phases (P > 0.05). A significant increase was noted in the LF NU in the luteal phase compared to follicular phase of the menstrual cycle (P = 0.014), whereas a tendency for increased HF NU was observed in the follicular phase (P = 0.053). Furthermore, LF/HF ratio was significantly higher in the luteal phase compared to follicular phase (2.1 ± 1.5 vs 1.6 ± 0.9, P = 0.002), suggesting increased sympathetic activity in the luteal phase. Conclusion: We concluded that regulation of autonomic tone is modified during menstrual cycle. The alteration in the balance of ovarian hormones might be responsible for these changes in the cardiac autonomic innervation. A.N.E. 2002;7(1):60–63     

Safety and Efficacy of Flecainide in Subjects with Long QT‐3 Syndrome (ΔKPQ Mutation): A Randomized,Double‐Blind,Placebo‐Controlled Clinical Trial

Background : We conducted a study of chronic therapy with flecainide versus placebo in a small group of LQT‐3 patients with the ΔKPQ deletion to evaluate the safety and efficacy of flecainide in this genetic disorder. In vitro studies have shown that flecainide provides correction of the impaired inactivation associated with the ΔKPQ deletion. Methods: A randomized, double‐blind, placebo‐controlled clinical trial was conducted with flecainide and placebo in six male LQT‐3 subjects with the ΔKPQ deletion. Results: The lowest possible dose of flecainide associated with at least a 40 ms reduction in the QTc interval was determined in an initial open‐label, dose‐ranging investigation using one‐fourth or half of the recommended maximal antiarrhythmic flecainide dose. QTc reduction was achieved with a flecainide dose of 1.5 mg/kg per day in 4 subjects and with 3.0 mg/kg per day in 2 subjects. Subjects were randomized to four 6‐month alternating periods of flecainide and placebo therapy based on the open‐label dose findings. Average QTc values during placebo and flecainide therapies were 534 ms and 503 ms, respectively, with an adjusted reduction in QTc of ?27.1 ms (95% confidence interval: ?36.8 ms to ?17.4 ms; P < 0.001) at a mean flecainide blood level of 0.11 ±0.05 μg/ml. Minimal prolongation in QRS occurred (mean: +2.5 ms), and there were no major adverse cardiac effects. Conclusions: Chronic low‐dose flecainide significantly shortens the QTc interval in LQT‐3 subjects with the ΔKPQ mutation. No major adverse drug effects were observed with flecainide during this trial, but the sample size is not large enough to evaluate the safety of flecainide therapy in patients with this mutation.     

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)     

Magnetocardiographic Assessment of Healed Myocardial Infarction

Background: We evaluated the capability of multichannel magnetocardiography (MCG) to detect healed myocardial infarction (MI). Methods: Multichannel MCG over frontal chest was recorded at rest in 21 patients with healed MI, detected by cine‐ and contrast‐enhanced magnetic resonance imaging, and in 26 healthy controls. Of the 21 MI patients, 11 had non‐Q wave and 10 Q wave MIs. QRS, ST‐segment, T wave and ST‐T wave integrals, ST‐segment and T wave amplitudes, and QRS and ST‐T wave magnetic field map orientations were measured. Results: The MCG repolarization indexes, such as ST segment and ST‐T wave integrals, separated the MI group from the controls (ST‐T wave integral ?1.4 ± 5.3 vs 1.5 ± 4.7 pTs , P = 0.034 ). The abnormalities were more distinct in the Q wave‐MI than in the non‐Q wave MI subgroup. In the latter, however, a trend similar to the Q wave MI group was found. The relation of QRS area to ST segment and T wave integral improved the detection of healed MIs compared to the ST‐T wave indexes alone (QRS‐ST‐T discordance 14 ± 10 vs 5.0 ± 7.1 pTs, P = 0.003 ). When comparing the MI group to the controls, the orientation of the magnetic field maps differed in the ST‐T wave maps (163 ± 119° vs 58 ± 17°, P < 0.001) but not in the QRS maps (111 ± 95° vs 106 ±93°, P = 0.646) . Conclusions: The MCG repolarization variables can detect healed MI. These ST‐T wave abnormalities are more pronounced in patients with Q wave MI than in patients with non‐Q wave MIs. Relating the signals of depolarization and repolarization phases improves the detection of healed MI. Repolarization abnormalities are common in healed MI and thus should not always be interpreted as present ongoing ischemia.     

Influence of menstrual cycle on p wave dispersion

Female gender is an independent risk factor for some types of arrhythmias. We sought to determine whether the menstrual cycle affects P wave dispersion, which is a predictor of atrial fibrillation. The study population consisted of 59 women in follicular phase (mean age, 29.3 ± 7.7 years) (group F) and 53 women in luteal phase (mean age, 28.1 ± 6.8 years) (group L). The ECGs of 35 patients (mean age, 26.4 ± 4.5) were obtained in both follicular and luteal phase. Both groups underwent a standard 12-lead surface electrocardiogram recorded at 50 mm/s. Maximal (Pmax) and minimal P wave durations (Pmin) were measured. P wave dispersion (PD) was defined as the difference between Pmax and Pmin. PD was significantly higher in group L than group F (46.6 ± 18.5 versus 40.1 ± 12.7; P < 0.05). Pmin was significantly lower in group L than group F (51.6 ± 12.1 versus 59.1 ± 12.1; P = 0.002). When we compared ECGs in different phases of the 35 patients, PD was significantly higher in luteal phase than follicular phase (53.2 ± 12.3 versus 42.8 ± 10.2; P < 0.05). Pmin was significantly lower in luteal phase than follicular phase (47.6 ± 6.6 versus 56 ± 10.1; P = 0.05). We detected a significant correlation between the day of the menses and PD (r = 0.27; P < 0.05). PD was increased in luteal phase compared to follicular phase, and this difference was more prominent as the days of the cycle progressed.     

Detection of Multivessel Disease Post Myocardial Infarction Using an Exercise‐Induced QRS Score

Objective: The aim of this study was to investigate the ability of Athens QRS score values to detect stenoses in other coronary arteries than the obstructed ones (which caused the myocardial infarction [MI]) in patients with a history of MI. Methods: We studied 125 patients (93 males and 32 females, mean age 54 ± 7 years [range 45–68 years]) with a history of MI (46 patients with anterior MI, 54 patients with inferior MI, 25 patients with lateral MI). All patients underwent treadmill exercise testing and coronary arteriography. Results: Athens QRS score values were inversely related to the extent of CAD: ?0.5 ± 0.3 mm for patients with 1‐VD (obstructed vessel), ?3.4 ± 2.2 mm for patients with 2‐VD (obstructed vessel and stenosis in another vessel), and ?5 ± 1.8 mm for patients with 3‐VD (obstructed vessel and stenoses in two more vessels). The ROC curves for the detection of multivessel disease showed that the area under the curve for QRS score values < ?3 mm is significantly higher than the curve for ST‐segment depression ≥1 mm (0.948 vs 0.792, P < 0.001). Conclusions: Values of the Athens QRS score less than ?3 may distinguish single‐ from multivessel coronary artery disease in patients with a history of MI.     

QRS characteristics fail to reliably identify ventricular tachycardias that require epicardial ablation in ischemic heart disease

Criteria for Epicardial Origin in Ischemic VT. Objectives: We tested proposed algorithms for idiopathic and nonischemic tachycardias for their ability to identify epicardial LV‐VT origins. Backgroud: Several ECG features have been reported to identify epicardial origins for left ventricular tachycardias (LV‐VTs) in the absence of myocardial infarction. Only limited data exist in postinfarction patients. Methods: The QRS features of 24 VTs that were ablated from the epicardium and 39 left ventricular VTs ablated from the endocardium were retrospectively analyzed for various 12‐lead ECG features previously reported. Results: No ECG feature consistently predicted an epicardial LV‐VT origin in infarct‐related tachycardias, with epicardial VTs showing slightly longer QRS durations (189 ± 32 ms in epicardial vs 179 ± 37 ms in endocardial, P = 0.28). Pseudo‐delta duration was 38 ± 27 versus 47 ± 27 ms (P = 0.2), intrinsicoid deflection time 93 ± 35 versus 86 ± 32 ms (P = 0.4), shortest RS 97 ± 38 versus 99 ± 32 ms (P = 0.77), and median deflection index 0.82 ± 0.25 versus 0.87 ± 0.22 (P = 0.43). The finding of a Q wave in lead I and the absence of a Q wave in the inferior leads failed to predict an epicardial origin in superior LV‐VT sites. Q waves in any inferior lead and aVR/aVL‐ratio<1 were not specific for an epicardial origin in inferior sites (all P = ns). Furthermore, all inferior LV‐VTs showed a Q wave in the inferior leads which correlated with pre‐existing Q‐waves in sinus rhythm (P = 0.045). Conclusion : Proposed 12‐lead ECG features for differentiation of epicardial versus endocardial sites for nonischemic LV‐VTs do not reliably identify VTs that require ablation from the epicardium. Endocardial mapping should be the first approach to catheter ablation for VTs in patients with ischemic heart disease. (J Cardiovasc Electrophysiol, Vol. 23, pp. 188‐193, February 2012)     

The Predictive Value of Exercise QRS Duration Changes for Post‐PTCA Coronary Events

Background: The sensitivity and predictive values of exercise ECG testing using ST‐T criteria after percutaneous transluminal coronary angioplasty (PTCA) are low, precluding its routine use for screening for restenosis. The predictive value of QRS duration criteria during exercise testing (ET) ECG after PTCA for future coronary events has not been reported. The aim of the study was to compare QRS duration changes with ST‐T criteria during ET, as a predictor of coronary events after PTCA. Methods: A prospective study of 206 consecutive patients who underwent ET at a mean of 34 ± 14 days after their first PTCA, and were the followed for a mean of 23 ± 9 months. Patients were divided by QRS duration into two groups—Q1: ischemic response (QRS duration prolongation of more than 3 ms relative to the resting duration), and Q2: normal response (QRS duration shortening or without change from resting duration). Patients were also divided by their ST‐T response, S1: ischemic response, and S2: normal response. Results: During follow‐up 52 patients (58%) experienced restenosis or MI, or underwent CABG—Q1: 44 (85%), Q2: 8(15%) (P < 0.0002), S1: 8 (15%), S2: 44 (85%), (P < 0.641) , two patients died—Q1: 1 (1%) and Q2: 1 (1%). For QRS and ST‐T, the relative risk of having at least one of the coronary events was 4.02 (CI 2.1–9.9) versus 1.13 (CI 0.8–2.9), respectively. The sensitivity for future coronary events was 85% and 52% and the specificity was 48% and 98% for the QRS and ST‐T criteria, respectively. Conclusion: QRS prolongation during peak ET ECG after PTCA is a more sensitive marker than ST‐T criteria for detection of patients at risk for later coronary events.     

Spontaneous pulmonary vein firing in man: relationship to tachycardia-pause early afterdepolarizations and triggered arrhythmia in canine pulmonary veins in vitro

Introduction: Rapid firing originating within pulmonary veins (PVs) initiates atrial fibrillation (AF). The following studies were performed to evaluate spontaneous PV firing in patients with AF to distinguish focal versus reentrant mechanisms. Methods: Intracardiac recordings were obtained in 18 patients demonstrating paroxysmal AF. Microelectrode (ME) recordings were obtained from superfused canine PV sleeves (N = 48). Results: Spontaneous PV firing (566 ± 16 bpm; 127 ± 6 ms cycle length) giving rise to AF (52 episodes) was observed. Tachycardia‐pause initiation was present in 132 of 200 episodes of rapid PV firing and 34 of 52 AF episodes. The pause cycle length preceding PV firing was 1,039 ± 86 ms following tachycardia (420 ± 40 ms cycle length). The remaining episodes were initiated following a 702 ± 32 ms pause during sinus rhythm (588 ± 63 ms). Spontaneous firing recorded with a multipolar mapping catheter did not detect electrical activity bridging the diastolic interval between the initial ectopic and preceding post‐pause sinus beat. Tachycardia‐pause initiated PV firing (138 ± 7 ms coupling interval) in patients correlated with tachycardia‐pause enhanced isometric force, early afterdepolarization (EAD) amplitude, and triggered firing within canine PVs. Rapid firing (1,172 ± 134 bpm; 51 ± 8 ms cycle length) following an abbreviated coupling interval (69 ± 12 ms) was initiated in 13 of 18 canine PVs following tachycardia‐pause pacing during norepinephrine + acetylcholine superfusion. Stimulation selectively activating local autonomic nerve terminals facilitated tachycardia‐pause triggered firing in canine PVs (5 of 15 vs 0 of 15; P < 0.05). Conclusions: The studies demonstrate (1) tachycardia‐pause initiation of rapid, short‐coupled PV firing in AF patients and (2) tachycardia‐pause facilitation of isometric force, EAD formation, and autonomic‐dependent triggered firing within canine PVs, suggestive of a common arrhythmia mechanism.     

心肌梗死急性期QRS波增宽预测远期心脏性猝死发生的价值

目的探讨急性心肌梗死后早期无创性指标左心室射血分数(LVEF)、QRS波时限和QTc间期预测远期心脏性猝死(SCD)发生的价值。方法采集289例急性心肌梗死后存活患者在急性期(<30 d)超声测定LVEF、体表心电图测定QRS波时限和QTc间期的数据,临床随访观察远期(>1年)发生的SCD事件。LVEF降低的界值为35%,QRS波增宽的界值为110 ms,QTc间期延长的界值为450 ms(男)/460 ms(女)。根据随访结果将患者分为SCD组和幸存组。结果在心肌梗死后平均(15±3)个月内,15例(5.2%)患者发生SCD。与幸存组患者相比,SCD组患者的LVEF明显降低[35%(28%～52%)比50%(33%～60%),P<0.0001],QRS波时限明显延长[115(88～152)ms比105(91～126)ms,P=0.0222],而两组患者QTc间期差异无统计学意义[458(416～513)ms比450(394～493)ms,P=0.1836]。SCD组患者中LVEF降低、QRS波增宽和QTc间期延长的比率依次为40%、67%和60%。生存分析提示,LVEF降低(26.1%比3.4%,P<0.0001)和QRS波增宽(9.7%比2.7%,P=0.0098)患者远期SCD发生率增加。多元Logistic回归分析显示,LVEF降低[RR:6.0(2.0～17.8),P=0.0011]和QRS波增宽[RR:3.1(1.0～9.0),P=0.0345]均为SCD发生的独立危险因素。结论急性心肌梗死后早期QRS波增宽能独立预测远期SCD的发生。     

End-recovery QTc: a useful metric for assessing genetic variants of unknown significance in long-QT syndrome

QTc for Assessing Significance of LQT Variants. Introduction: Genetic variants represent benign single‐nucleotide polymorphisms, disease causing mutations or variants of unknown significance (VUS). Resting, exercise, and recovery QTc intervals have been utilized to detect long‐QT syndrome (LQTS) mutations. We sought to provide clinical data that may assist in classifying the presented VUS as disease causing/benign and to determine whether resting and/or end‐recovery QT parameters can evaluate the significance of VUS. Methods and Results: Twenty‐six patients with a VUS in genes associated with LQTS (15 females, age 38 ± 16 years) and 26 age and gender matched controls (age 37 ± 20 years) were included. There were 10 VUS (5 KCNQ1, 4 KCNH2, 1 KCNE1) in 12 families. All but 1 VUS was associated with sudden cardiac death (SCD), aborted SCD or Torsade de pointes. A Schwartz score of ≥3.5 was observed in at least 1 family member with each VUS. Resting QTc was marginally longer in VUS patients compared with controls (458 ± 48 vs 437 ± 25, P = 0.052). A prolonged resting QTc (>470 ms males, >480 ms females) identified 6 VUS carriers and 1 control. VUS carriers had a substantially longer end‐recovery QTc (502 ± 68 vs 427 ± 17, P < 0.01) with an end‐recovery QTc > 445 ms in 20/26 VUS patients compared to 2/26 controls (P < 0.01). The area under the receiver operating characteristic curve for resting QTc was 0.68 (95% CI, 0.53–0.83, P = 0.03) compared to the end‐recovery QTc of 0.88 (95% CI, 0.76–0.99, P < 0.0001). Conclusion: Variants in the current study appear to be disease causing. The end‐recovery QTc is a useful metric when interpreting LQT VUS. (J Cardiovasc Electrophysiol, Vol. 23, pp. 637–642, June 2012)     

QT Interval Length and Diabetic Autonomic Neuropathy

QT interval length was measured in ECG recordings from three groups of age-matched male subjects: 36 normal subjects, 41 diabetic patients without (DAN-ve), and 34 with (DAN+ve) autonomic neuropathy. ECG samples were selected from previously recorded 24-h ECGs on the basis of a clearly defined T wave and a steady RR interval over 2 min of around 750 ms (80 beats min^?1). There were no significant differences in RR interval between the groups. The two diabetic groups had slightly longer QT measurements (normal 365 ± 14 (±SD) ms, DAN-ve 373 ± 18 ms, DAN+ve 375 ± 23 ms, p = 0.05), and corrected QT (QTc) values (normal 423 ± 15 ms, DAN-ve 430 ± 20 ms, DAN+ve 435 ± 24 ms, p = 0.05). Ten diabetic patients fell above our defined upper limit of normal for QTc (>mean + 2SD). There was a significant correlation in the DAN-ve group between the QT indices and 24-h RR counts (QT r = ?0.38, p < 0.01; QTc r = ?0.40, p < 0.01). We conclude that there are some small alterations in QT interval length in the steady state in diabetic autonomic neuropathy. The changes appear to be due to autonomic impairment, rather than diabetes per se.     

Reduced delayed rectifier K+ current, altered electrophysiology, and increased ventricular vulnerability in MLP-deficient mice

BackgroundMice with a knockout (KO) of muscle LIM protein (MLP) exhibit many morphologic and clinical features of human cardiomyopathy. In humans, MLP-expression is downregulated both in ischemic and dilative cardiomyopathy. In this study, we investigated the effects of MLP on the electrophysiologic phenotype in vivo and on outward potassium currents.Methods and ResultsMLP-deficient (MLPKO) and wild-type (MLPWT) mice were subjected to long-term electrocardiogram (ECG) recording and in vivo electrophysiologic study. The whole-cell, patch-clamp technique was applied to measure voltage dependent outward K⁺ currents in isolated cardiomyocytes. Long-term ECG revealed a significant prolongation of RR mean (108 ± 9 versus 99 ± 5 ms), P (16 ± 3 versus 14 ± 1 ms), QRS (17 ± 3 versus 13 ± 1 ms), QT (68 ± 8 versus 46 ± 7 ms), QTc (66 ± 6 versus 46 ± 7 ms), JT (51 ± 7 versus 34 ± 7 ms), and JTc (49 ± 5 versus 33 ± 7 ms) in MLPKO versus MLPWT mice (P < .05). During EP study, QT (80 ± 8 versus 58 ± 7 ms), QTc (61 ± 6 versus 45 ± 5 ms), JT (62 ± 9 versus 43 ± 6 ms), and JTc (47 ± 5 versus 34 ± 5 ms) were also significantly prolonged in MLPKO mice (P < .05). Nonsustained VT was inducible in 9/16 MLPKO versus 2/15 MLPWT mice (P < .05). Analysis of outward K⁺ currents in revealed a significantly reduced density of the slowly inactivating outward K⁺ current IK, slow in MLPKO mice (11 ± 5pA/pF versus 18 ± 7pA/pF; P < .05).ConclusionMice with KO of MLP exhibit significant prolongation of atrial and ventricular conduction and an increased ventricular vulnerability. A reduction in repolarizing outward K⁺ currents may be responsible for these alterations.     

Age,Gender, and Autonomic Tone Effects on Surface Electrocardiographic Indices of Ventricular Repolarization

Background: Prolonged QT offset dispersion (QToD), an index of heterogeneity of ventricular repolarization, is thought to be an independent predictor of all‐cause and cardiovascular mortality. However the influence of gender and autonomic tone in healthy adults on age‐related changes in measures of ventricular repolarization are not well characterized. Methods: QToD and T wave complexity were measured in 56 healthy subjects with no detectable heart disease (by echo and stress test)—38 young subjects with a mean age of 28 ± 4 years and 18 old subjects with a mean age of 71 ± 7 years. QToD and T wave complexity were computed from 12‐lead ECGs using the GE Marquette QT Guard automated analysis program with manual over‐reading at rest (baseline), following exercise, and double autonomic blockade with atropine and propranolol. Data was analyzed using factorial ANOVA. Results: Young males had a significantly greater QToD than young and old females at baseline (28 ± 5 ms, 23 ± 5 ms, and 22 ± 5 ms, respectively, P < 0.01), an intrinsic effect independent of changes in autonomic tone. In contrast, females had significantly greater T wave complexity than males following exercise and double autonomic blockade with a definite trend at baseline. There was no correlation between T wave complexity and QToD. Conclusions: Age and gender demonstrate a complex interaction on indices of myocardial repolarization with different measures behaving differently. These findings have implications for better understanding age and gender effects on myocardial electrophysiology. A.N.E. 2001;6(4):290–297     

Immediate and short term effects of percutaneous atrial septal defect device closure on cardiac electrical remodeling in children

Background

The beneficial effects of atrial septal defect (ASD) device closure on electrical cardiac remodeling are well established. The timing at which these effects starts to take place has yet to be determined.

An Evaluation of the Impact of Gender and Age on QT Dispersion in Healthy Subjects

Objectives: To determine if gender, age, and gender per age category, have an impact on QT and QTc dispersion in healthy volunteers. Methods: This study was undertaken in 150 patients (50 per age group, 75 males, 75 females). The age groups included young (20–40 years), middle‐aged (41–69 years) and elderly (> 70 years) subjects. The QT intervals on a 12 lead ECG were determined and Bazett's formula was used to derive the QTc intervals. The QT and QTc dispersion were determined by subtracting the shortest QTc interval from the longest on each 12‐lead recording. Results: Males had higher QT dispersion than females (50 ± 22 vs 42 ± 18 ms, P = 0.017) but QTc dispersion was not significantly changed. No significant differences were seen among the different age categories for QT or QTc dispersion. In elderly subjects, males had higher QT and QTc dispersion than females (54 ± 23 vs 42 ±15 ms, P = 0.039 and 63 ± 23.7 vs 48 ± 21 ms, P = 0.032, respectively). Conclusions: When evaluating the effect of gender in different age categories, elderly males have significantly greater QT and QTc dispersion than elderly female subjects. No other gender differences were noted for QT or QTc dispersion in the other two age categories. When evaluating a population of healthy volunteers, regardless of age, gender has an impact on QT dispersion but no significant interaction with QTc dispersion. Evaluating age without dividing the data by gender yields no significant differences in QT or QTc dispersion. A.N.E. 2001;6(2):129–133     

Effects of digitalis on the human sick sinus node after pharmacologic autonomic blockade

To study the effects of digitalis on the sinus node and the mechanisms involved, 16 patients with the sick sinus syndrome had electrophysiologic assessment of sinus nodal function during (1) control study, (2) after pharmacologic autonomic blockade with propranolol (0.2 mg/kg body weight and atropine sulfate 0.04 mg/kg intravenously), and (3) 10 minutes after 0.01 mg/kg of intravenous ouabain. The study was completed within 30 minutes of pharmacologic autonomic blockade. During the control study 50 percent of patients had an abnormal corrected sinus nodal recovery time or abnormal sinoatrial conduction time, or both. The effects of ouabain on sinus nodal function were compared with those after pharmacologic autonomic blockade. Ouabain significantly increased both intrinsic sinus cycle length (ouabain 975 ± 194 ms [mean ± standard deviation]; autonomic blockade 1,025 ± 218 ms, probability [p] < 0.001) and corrected sinus nodal recovery time (ouabain 615 ± 503 ms; autonomic blockade 575 ± 536 ms, p < 0.05). In contrast there was no significant change in sinoatrial conduction time after ouabain (ouabain 141 ± 56 ms; autonomic blockade 132 ± 45 ms; difference not significant). The effects of ouabain were similar in patients with both normal and abnormal sinus nodal function.These findings suggest that (1) digitalis in therapeutic doses has a depressant effect on intrinsic sinus nodal automaticity in patients with normal as well as abnormal sinus nodal function; (2) digitalis has no significant effects on sinoatrial conduction; and (3) the effects of digitalis on sinus nodal automaticity are primary and independent of its vagal and antiadrenergic effects.     

Serum 13–14-diOH-15-keto-Prostaglandin F2alpha and Airway Response to Meclofenamate and Metaproterenol in Relation to the Menstrual Cycle

In order to evaluate whether adverse reactions to a nonsteroidal antiinflammatory agent (NSAIA) were related to variations in prostaglandin levels during the menstrual cycle, we measured 13–14-diOH-15-keto-prostaglandin F2alpha in serum and the effect on airways of a single dose of 100 mg oral meclofenamate and 1.5 mg inhaled metaproterenol during the early (follicular phase) and late (luteal phase) menstrual cycle. Among 24 women with premenstrual asthma (PMA), four women with regular asthma (REA), and four healthy women, the 13–14-diOH-15-keto-PGF2alpha averaged 140.9 ± 68.4 pg/0.1 ml during the follicular phase but only 14.4 ± 2.2 pg/0.1 ml during the luteal phase (p < 0.0001). Acute asthma reactions to the meclofenamate occurred during the follicular phase in six women with PMA but were never observed during the luteal phase (p = 0.016). These reactions occurred preferentially in patients on corticosteroids (p = 0.004). Conversely, one patient with PMA had 18% improvement in FEV₁ with meclofenamate during the luteal phase. A placebo-controlled, double-blind evaluation of the healthy women and the women with REA revealed a trend toward improvement in FEV₁ during the luteal phase (0.15 < p < 0.10) but no change during the follicular phase. The effect of metaproterenol did not vary with the menstrual cycle, and there was no interaction between the effects of meclofenamate and those of metaproterenol. It appears that meclofenamate causes adverse effects on pulmonary function in asthmatic women primarily during the follicular phase of the menstrual cycle. This effect is associated with corticosteroid treatment and may be related to monthly variation in serum 13–14-diOH-15-keto-PGF2alpha.