Novel electrocardiographic criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

AIMS: In order to improve the electrocardiographic (ECG) diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC), we evaluated novel quantitative parameters of the QRS complex and the value of bipolar chest leads (CF leads) computed from the standard 12 leads. METHODS AND RESULTS: We analysed digital 12-lead ECGs in 44 patients with ARVC, 276 healthy subjects including 44 age and sex-matched with the patients and 36 genotyped members of ARVC families. The length and area of the terminal S wave in V1 to V3 were measured automatically using a common for all 12 leads QRS end. T wave negativity was assessed in V1 to V6 and in the bipolar CF leads computed from the standard 12 leads. The length and area of the terminal S wave were significantly shorter, whereas the S wave duration was significantly longer in ARVC patients compared with matched controls. Among members of ARVC families, those with mutations (n = 15) had shorter QRS length in V2 and V3 and smaller QRS area in lead V2 compared with those without mutations (n = 20). In ARVC patients, the CF leads were diagnostically superior to the standard unipolar precordial leads. Terminal S wave duration in V1 >48 ms or major T wave negativity in CF leads separated ARVC patients from matched controls with 90% sensitivity and 86% specificity. CONCLUSION: The terminal S wave length and area in the right precordial leads are diagnostically useful and suitable for automatic analysis in ARVC. The CF leads are diagnostically superior to the unipolar precordial leads.

Computed bipolar precordial leads for improved P wave detection.

We present an excerpt from a 24-hour 12-lead Holter recording acquired in an 85-year-old man investigated for the Brugada syndrome. The rhythm cannot be determined because no P waves can be discerned due to the high level of noise and to merging of the T and P waves. The P waves, however, are clearly visible and the noise is considerably reduced in bipolar precordial leads computed from the standard unipolar precordial leads. The case demonstrates the potential usefulness of various computed leads for rhythm analysis by detecting P waves that are not visible in the standard leads.

Thorough QT study of the effect of oral moxifloxacin on QTc interval in the fed and fasted state in healthy Japanese and Caucasian subjects.

AIMS: The aims of this study were three-fold and were to (i) investigate the effect of food (fasted and fed state) on the degree of QT prolongation caused by moxifloxacin under the rigorous conditions of a TQT study, (ii) differentiate the effects on QTc that arise from changes in PK from those arising as a result of electrophysiological changes attributable to raised levels of C-peptide [11] offsetting in part the IKr blocking properties of moxifloxacin and (iii) characterize the QTc F profile of oral moxifloxacin (400 mg) in healthy Japanese volunteers compared with Caucasian subjects. METHODS: The study population consisted of 32 healthy non-smoking, Caucasian (n = 13) and Japanese (n = 19), male and female subjects, aged between 20-45 years with a body mass index of between 18 to 25 kg m(-2). Female volunteers were required to use an effective contraceptive method or be abstinent. Subjects with ECGs which were deemed unsuitable for evaluation in a TQT study were excluded. ECGs were recorded in triplicate with subsequent blinded manual adjudication of the automated interval measurements. Electrocardiograms in the placebo arm were recorded twice in fasted and fed condition. RESULTS: The results demonstrated a substantial change in the typical moxifloxacin effect on the ECG. The effect on ΔΔQTc in the fed state led to a significant delay and a modest reduction compared with the fasted state correcting both conditions with the corresponding placebo data. The largest QTc F change from baseline in the fed state was observed at 4 h with a peak value of 11.6 ms (two-sided 90% CI 9.1, 14.1). In comparison, the largest QTc F change observed in the fasted state was 14.4 ms (90% CI 11.9, 16.8) and occurred at 2.5 h post-dose. The PK of moxifloxacin were altered by food and this change was consistent with the observed QTc F change. In the fed state plasma concentrations of moxifloxacin were considerably and consistently lower in comparison with the fasted state, and this applied to both ethnicities. The concentration-effect analysis revealed that there was no change in slope and confirmed that the difference in this analysis was caused by a change in the PK profile of moxifloxacin. Comparisons of the moxifloxacin effect in the fed state compared with fasted placebo also revealed a pharmacodynamic effect whereby a meal appears to antagonize the effects of moxifloxacin on the lengths of the QTc interval. CONCLUSIONS: Our findings demonstrate that the food effect by itself leads to a shortening of the QTc interval offsetting in part the effects of a 400 mg single dose of oral moxifloxacin. The typical moxifloxacin PK profile is also altered by food prior to dosing reducing the Cmax and delays the peak effects on QTc up to several hours thereby reducing the overall magnitude of the effect and delaying the peak QTc prolongation. The contribution of the two effects was clearly discernible. Given that moxifloxacin is sometimes given with food in TQT studies, consideration should be given to adequate baseline corrections and appropriate sampling time points. In this study the PK-PD relationship was similar for Japanese and Caucasian subjects in the fed and fasted conditions, thereby providing further evidence that the sensitivity to the QTc prolonging effects of fluoroquinolones was likely to be independent of ethnicity. The small differences observed between the two subpopulations were not statistically significant. However, future studies should give consideration to formal ethnic comparisons as a secondary outcome parameter as very little is known about the relationship between ethnicity and drug effects on cardiac repolarization.

Clinical utility of computed electrocardiographic leads.

The standard 12-lead electrocardiogram (ECG) is only one of the possible ways to present the voltage differences between the nine recording electrodes. Other "non-conventional" leads may be constructed by physically connecting two or more electrodes in a different manner or by computation from the digital 12-lead ECG. Examples include bipolar or multipolar precordial leads and bipolar chest leads (between one precordial and one limb electrode). Such leads can remove or decrease noise originating from a limb cable/electrode that is present in the unipolar precordial leads. They can be diagnostically useful in Brugada syndrome and can display QRS fractionation that is not visible in the respective unipolar precordial or limb leads. Multipolar precordial leads sometimes display potentially useful information that is not visible in the respective unipolar leads and in bipolar leads computed from them. In conclusion, these computed ECG leads represent a potentially useful supplement to the conventional 12-lead ECG.

Insulin at normal physiological levels does not prolong QT(c) interval in thorough QT studies performed in healthy volunteers.

AIMS: Food is known to shorten the QT(c) (QT(c)I and QT(c)F) interval and has been proposed as a non-pharmacological method of confirming assay sensitivity in thorough QT (TQT) studies and early phase studies in medicines research. Intake of food leads to a rise in insulin levels together with the release of C-peptide in equimolar amounts. However, it has been reported that euglycaemic hyperinsulinemia can prolong the QT(c) interval, whilst C-peptide has been reported to shorten the QT(c) interval. Currently there is limited information on the effects of insulin and C-peptide on the electrocardiogram (ECG). This study was performed to assess the effect of insulin, glucose and C-peptide on the QT(c) interval under the rigorous conditions of a TQT study. METHODS: Thirty-two healthy male and female, Caucasian and Japanese subjects were randomized to receive six treatments: (1) placebo, (2) insulin euglycaemic clamp, (3) carbohydrate rich 'continental' breakfast, (4) calorie reduced 'American' FDA breakfast, (5) moxifloxacin without food, and (6) moxifloxacin with food. Measurements of ECG intervals were performed automatically with subsequent adjudication in accordance with the ICH E14 guideline and relevant amendments. RESULTS: No effect was observed on QT(c)F during the insulin euglycaemic clamp period (maximal shortening of QT(c) F by 2.6 ms, not significant). Following ingestion of a carbohydrate rich 'continental' breakfast or a calorie reduced 'American' FDA standard breakfast, a rapid increase in insulin and C-peptide concentrations were observed. Insulin concentrations showed a peak response after the 'continental' breakfast observed at the first measurement time point (0.25 h) followed by a rapid decline. Insulin concentrations observed with the 'American' breakfast were approximately half of those seen with the 'continental' breakfast and showed a similar pattern. C-peptide concentrations showed a peak response at the first measurement time point (0.25 h) with a steady return to baseline at the 6 h time point. The response to the 'continental' breakfast was approximately double that of the 'American' FDA breakfast. A rapid onset of the effect on QT(c) F was observed with the 'continental' breakfast with shortening by >5 ms in the time interval from 1 to 4 h. After the 'American' FDA breakfast, a similar but smaller effect was seen. CONCLUSIONS: The findings of this study demonstrate that there was no change in QT(c) during the euglycaemic clamp. Given that insulin was raised to physiological concentrations comparable with those seen after a meal, whilst the release of C-peptide was suppressed, insulin appears to have no effect on the QT(c) interval in either direction. The results suggest a relationship exists between the shortening of QT(c) and C-peptide concentrations and indicate that glucose may have a QT(c) prolonging effect, which will require further research.

Ventricular automaticity as a predictor of sudden death in ischaemic heart disease.

Opinion has oscillated in the cardiology community regarding the significance of ventricular premature beats and non-sustained ventricular tachycardia as predictors of sudden cardiac death. Automaticity can be a marker of underlying structural heart disease. It is unclear whether the apparent association with sudden death is simply a reflection of this fact. Older data are unreliable as the populations studied probably had a high prevalence of unrecognized structural heart disease. Current risk stratification is imperfect. The balance of evidence suggests that automaticity does predict risk and it may have a role in risk-assessment algorithms, but at present the dataset is insufficient.

Dialysis-dependent changes in ventricular repolarization.

BACKGROUND: Epidemiological data suggest increased risk of sudden death during and immediately after hemodialysis. Microvolt T-wave alternans (mTWA) is an electrocardiogram (ECG) measure of abnormal ventricular repolarization, which can be used in sudden death risk stratification. The aim of this study was to determine whether mTWA measurements during dialysis indicate abnormal repolarization as a potential trigger to dialysis associated arrhythmias. METHODS: Forty-eight-hour, 12-lead Holter ECG recordings were taken on a cohort of maintenance hemodialysis patients. Modified moving average mTWA was examined for 48 hours from the start of dialysis. Predialysis biochemistry was taken and echocardiography was performed on a nondialysis day. RESULTS: Nineteen patients were analyzed (age 61 ± 14 years, time on dialysis 2.7 ± 2 years). mTWA increased during dialysis (P < 0.01) but returned to baseline 2 hours postdialysis (first hour mTWA = 10.1 ± 4.5µV, final hour mTWA = 12.2 ± 3.7µV, postdialysis mTWA = 10.3 ± 2.7µV, P = 0.015). The change in mTWA did not correlate with serum biochemistry or echocardiographic measurements of left ventricular mass and function. Peak mTWA and frequency of spikes in mTWA ≥ 65µV were not more common during dialysis compared to other times. Patients who showed greater frequency of spikes ≥65µV or increase in hourly mean mTWA during dialysis did not have a worse cardiovascular outcome over a mean follow-up of 2.6 years. CONCLUSIONS: Though there were subtle changes in mTWA during dialysis, there was no association with mTWA abnormalities previously shown to be associated with worse outcome. The presence of abnormal mTWA did not correlate with outcome.

Specificity of elevated intercostal space ECG recording for the type 1 Brugada ECG pattern.

BACKGROUND: Right precordial (V1-3) elevated electrode placement ECG (EEP-ECG) is often used in the diagnosis of Brugada syndrome (BrS). However, the specificity of this has only been studied in smaller studies in Asian populations. We aimed to study this in a larger European population. METHODS: Two different populations consisting of healthy subjects were used. A total of 340 subjects were included, 80% were men, the median age was 43 year (interquartile range: 31-51) and all were of European ethnicity. RESULTS: No type 1 ECG patterns were identified but 16 (4.7%) subjects with a type 2 ECG and 32 (9.4%) subjects with a type 3 ECG were identified in any lead placement. In total 43 (13%) subjects had any BrS ECG pattern in any lead placement. The specificity was 100% (one-sided 97.5% CI: 99%) for the use of EEP-ECG to uncover type 1 pattern. For type 2 pattern the specificity was 95% (95% CI: 92-97%) and for type 3 pattern 91% (95% CI: 88-94%). CONCLUSIONS: Elevated electrode placement ECG in the diagnosis of BrS seems to have a very high specificity with regards to the finding of a type 1 ECG pattern in a European population; conversely a finding of a type 2 or 3 pattern is of a significantly lower specificity and should perhaps be disregarded.

Prevalence of the type 1 Brugada electrocardiogram in Caucasian patients with suspected coronary spasm.

AIMS: Sporadic cases have reported the coexistence of coronary spasm and Brugada syndrome. However, the prevalence of the Brugada phenotype in coronary spasm is unknown, particularly in non-Japanese populations. In this study, we sought to examine the prevalence of the type 1 Brugada electrocardiogram (ECG) in a large European patient population undergoing intracoronary provocation testing for suspected coronary spasm. METHODS AND RESULTS: We retrospectively evaluated ECG data for the presence of type 1, 2, and 3 Brugada ECGs from 955 consecutive German patients without obstructive coronary artery disease undergoing intracoronary acetylcholine (ACH) provocation (ACH-test). Eight hundred and twenty-seven patients (age 63 ± 12 years; 42% male) with complete ECG data were eligible for further analysis. The ACH-test revealed coronary spasm in 325 patients (39.3%). A Brugada ECG of any type was found in six patients (0.7%) at baseline and eight patients (0.9%) at any time. There was no difference in the prevalence of coronary spasm in patients with (37.5%) and without (39.3%) Brugada-type ECGs. The type 1 Brugada ECG was not seen at baseline, but two type 1 Brugada ECGs were observed during ACH-administration into the right coronary artery (RCA; 0.2%), one with simultaneous RCA spasm and one without. Ajmaline provocation testing reproduced the type-1 Brugada ECG in the patient without coronary spasm but she had no other features of the Brugada syndrome. CONCLUSIONS: This study reports a low prevalence of the type 1 Brugada ECG in the largest known European collection of intracoronary ACH provocation. In these patients, we found no evidence for the coexistence of Brugada syndrome and coronary spasm. This is in contrast to available Japanese data.

Heart rate turbulence for prediction of heart transplantation and mortality in chronic heart failure.

BACKGROUND: Previous studies have shown conflicting results about the value of heart rate turbulence (HRT) for risk stratification of patients (pts) with chronic heart failure (CHF). We prospectively evaluated the relation between HRT and progression toward end-stage heart failure or all-cause mortality in patients with CHF. METHODS: HRT was assessed from 24-hour Holter recordings in 110 pts with CHF (54 in NYHA class II, 56 in class III-IV; left ventricular ejection fraction (LVEF) 30%+/- 10%) on optimal pharmacotherapy and quantified as turbulence onset (TO,%), turbulence slope (TS, ms/RR interval), and turbulence timing (beginning of RR sequence for calculation of TS, TT). TO > or = 0%, TS < or = 2.5 ms/RR, and TT >10 were considered abnormal. End point was development of end-stage CHF requiring heart transplantation (OHT) or all-cause mortality. RESULTS: During a follow-up of 5.8 +/- 1.3 years, 24 pts died and 10 required OHT. TO, TS, TT, and both (TO and TS) were abnormal in 35%, 50%, 30%, and 25% of all patients, respectively. Patients with at least one relatively preserved HRT parameter (TO, TS, or TT) (n = 98) had 5-year event-free rate of 83% compared to 33% of those in whom all three parameters were abnormal (n = 12). In multivariate Cox regression analysis, the most powerful predictor of end point events was heart rate variability (SDNN < 70 ms, hazard ratio (HR) 9.41, P < 0.001), followed by LVEF < or = 35% (HR 6.23), TT > or = 10 (HR 3.14), and TO > or = 0 (HR 2.54, P < 0.05). CONCLUSION: In patients with CHF on optimal pharmacotherapy, HRT can help to predict those at risk for progression toward OHT or death of all causes.

SCN5A Mutation Type and a Genetic Risk Score Associate Variably With Brugada Syndrome Phenotype in SCN5A Families.

BACKGROUND: Brugada syndrome (BrS) is characterized by the type 1 Brugada ECG pattern. Pathogenic rare variants in SCN5A (mutations) are identified in 20% of BrS families in whom incomplete penetrance and genotype-negative phenotype-positive individuals are observed. E1784K-SCN5A is the most common SCN5A mutation identified. We determined the association of a BrS genetic risk score (BrS-GRS) and SCN5A mutation type on BrS phenotype in BrS families with SCN5A mutations. METHODS: Subjects with a spontaneous type 1 pattern or positive/negative drug challenge from cohorts harboring SCN5A mutations were recruited from 16 centers (n=312). Single nucleotide polymorphisms previously associated with BrS at genome-wide significance were studied in both cohorts: rs11708996, rs10428132, and rs9388451. An additive linear genetic model for the BrS-GRS was assumed (6 single nucleotide polymorphism risk alleles). RESULTS: In the total population (n=312), BrS-GRS ≥4 risk alleles yielded an odds ratio of 4.15 for BrS phenotype ([95% CI, 1.45-11.85]; P=0.0078). Among SCN5A-positive individuals (n=258), BrS-GRS ≥4 risk alleles yielded an odds ratio of 2.35 ([95% CI, 0.89-6.22]; P=0.0846). In SCN5A-negative relatives (n=54), BrS-GRS ≥4 alleles yielded an odds ratio of 22.29 ([95% CI, 1.84-269.30]; P=0.0146). Among E1784K-SCN5A positive family members (n=79), hosting ≥4 risk alleles gave an odds ratio=5.12 ([95% CI, 1.93-13.62]; P=0.0011). CONCLUSIONS: Common genetic variation is associated with variable expressivity of BrS phenotype in SCN5A families, explaining in part incomplete penetrance and genotype-negative phenotype-positive individuals. SCN5A mutation genotype and a BrS-GRS associate with BrS phenotype, but the strength of association varies according to presence of a SCN5A mutation and severity of loss of function.

Repolarization changes induced by mental stress in normal subjects and patients with coronary artery disease: effect of nitroglycerine.

OBJECTIVES: Mental stress can significantly affect ventricular repolarization, which could potentially trigger arrhythmias. We compared the effect of mental stress on repolarization indexed by the amplitude and area of the T wave in patients with coronary artery disease (CAD) and healthy subjects. METHODS: Fourteen healthy controls (11 M, mean age 42 years) and 14 patients with stable CAD (12 M, mean age 64) underwent a mental stress protocol consisting of mental arithmetic followed by a speech (5 minutes each), which was performed on two occasions following either nitroglycerine (NTG) or placebo. Multiple 12-lead electrocardiograms were acquired and repolarization was analyzed using automatically measured T wave amplitude (T(amp)) and area (T(area)). RESULTS: When preceded by placebo the overall effect of mental stress, whether induced by arithmetic or speech, was significantly different in CAD patients compared with controls, with a decrease in T(amp) and T(area) in controls and an increase in patients; e.g., change in T(amp) during arithmetic -20 +/- 3 microV in controls versus 4 +/- 2 microV in patients, p < .001, and during speech -9 +/- 3 microV in controls versus 7 +/- 1 microV in patients, p < .001. Following NTG, the effect of stress on repolarization was similar in the 2 groups, with a reversed effect, i.e., decrease instead of increase in T(amp) and T(area) in CAD patients. CONCLUSIONS: The effect of mental stress on ventricular repolarization is significantly different in CAD patients compared with healthy controls. These differences are considerably reduced by NTG.

Brugada-like changes in the peripheral leads during diagnostic ajmaline test in patients with suspected Brugada syndrome.

BACKGROUND: Although cases of Brugada-type electrocardiographic (ECG) pattern in peripheral (limb) leads have been reported ("atypical" Brugada syndrome [BS]), their incidence in patients investigated for BS is unknown. METHODS: We retrospectively analyzed an ECG database collected during ajmaline test in 143 patients (89 men) with suspected BS. In 42 patients, 12-lead ECGs were recorded, whereas in 101 patients, leads V1-V3 from the third intercostal space were also recorded. The presence of types 1, 2, and 3 Brugada pattern in each limb and precordial lead was noted and the PR, QRS, and QTc intervals were calculated. RESULTS: There were 114 (79.7%) negative and 29 (20.3%) positive tests. Type 1 pattern developed in >or=1 limb lead in six patients (4.2%) (3/29 with positive tests, 10.3%); all of them were male, symptomatic, and/or with family history of BS or sudden cardiac death. Their pre- and posttest QRS were significantly longer compared with the rest with positive (n = 26) or negative (n = 111) test (pretest: 129 +/- 31 ms vs 101 +/- 11 ms and 97 +/- 12 ms, P < 0.001; posttest: 175 +/- 44 ms vs 134 +/- 14 ms and 131 +/- 19 ms, P < 0.001). The posttest QTc was longer in patients with peripheral changes compared with the rest (507 +/- 47 ms vs 453 +/- 22 ms and 447 +/- 24 ms, P < 0.001). The pretest QTc and pre- and posttest heart rate and PR intervals were not significantly different between the three groups. CONCLUSIONS: Type 1 Brugada pattern in the peripheral leads was observed in 4.2% of patients during ajmaline test (10.3% of positive tests) and was associated with longer QRS and greater QTc prolongation compared with the rest of the patients.

Technical mistakes during the acquisition of the electrocardiogram.

In addition to knowledge of normal and pathological patterns, the correct interpretation of electrocardiographic (ECG) recordings requires the use of acquisition procedures according to approved standards. Most manuals on standard electrocardiography devote little attention to inadequate ECG recordings. In this article, we present the most frequent ECG patterns resulting from errors in limb and precordial lead placement, artifacts in 12-lead ECG as well as inadequate filter application; we also review alternative systems to the standard ECG, which may help minimize errors.

Prognostic significance of inverse spatial QRS-T angle circadian pattern in myocardial infarction survivors.

BACKGROUND: We investigated the predictive value of the spatial QRS-T angle (QRSTA) circadian variation in myocardial infarction (MI) patients. METHODS: Analyzing 24-hour recordings (SEER MC, GE Marquette) from 151 MI patients (age 63 +/- 12.7), the QRSTA was computed in derived XYZ leads. QRS-T angle values were compared between daytime and night time. The end point was cardiac death or life-threatening ventricular arrhythmia in 1 year. RESULTS: Overall, QRSTA was slightly higher during the day vs. the night (91 degrees vs. 87 degrees, P = .005). However, 33.8% of the patients showed an inverse diurnal QRSTA variation (higher values at night), which was correlated to the outcome (P = .001, odds ratio 6.7). In multivariate analysis, after entering all factors exhibiting univariate trend towards significance, inverse QRSTA circadian pattern remained significant (P = .036). CONCLUSION: Inverse QRSTA circadian pattern was found to be associated with adverse outcome (22.4%) in MI patients, whereas a normal pattern was associated (96%) with a favorable outcome.

Comparison of Ajmaline and Procainamide Provocation Tests in the Diagnosis of Brugada Syndrome.

OBJECTIVES: The authors studied the response rates and relative sensitivity of the most common agents used in the sodium-channel blocker (SCB) challenge. BACKGROUND: A type 1 Brugada electrocardiographic pattern precipitated by an SCB challenge confers a diagnosis of Brugada syndrome. METHODS: Patients undergoing an SCB challenge were prospectively enrolled across Canada and the United Kingdom. Patients with no prior cardiac arrest and family histories of sudden cardiac death or Brugada syndrome were included. RESULTS: Four hundred twenty-five subjects underwent SCB challenge (ajmaline, n = 331 [78%]; procainamide, n = 94 [22%]), with a mean age of 39 ± 15 years (54% men). Baseline non-type 1 Brugada ST-segment elevation was present in 10%. A total of 154 patients (36%) underwent signal-averaged electrocardiography, with 41% having late potentials. Positive results were seen more often with ajmaline than procainamide infusion (26% vs. 4%, p < 0.001). On multivariate analysis, baseline non-type 1 Brugada ST-segment elevation (odds ratio [OR]: 6.92; 95% confidence interval [CI]: 3.15 to 15.2; p < 0.001) and ajmaline use (OR: 8.76; 95% CI: 2.62 to 29.2; p < 0.001) were independent predictors of positive results to SCB challenge. In the subgroup undergoing signal-averaged electrocardiography, non-type 1 Brugada ST-segment elevation (OR: 9.28; 95% CI: 2.22 to 38.8; p = 0.002), late potentials on signal-averaged electrocardiography (OR: 4.32; 95% CI: 1.50 to 12.5; p = 0.007), and ajmaline use (OR: 12.0; 95% CI: 2.45 to 59.1; p = 0.002) were strong predictors of SCB outcome. CONCLUSIONS: The outcome of SCB challenge was significantly affected by the drug used, with ajmaline more likely to provoke a type 1 Brugada electrocardiographic pattern compared with procainamide. Patients undergoing SCB challenge may have contrasting results depending on the drug used, with potential clinical, psychosocial, and socioeconomic implications.

Postextrasystolic changes in the complexity of the QRS complex and T wave.

We tested the hypothesis that ventricular repolarization of the first sinus beat following a ventricular premature beat (VPB) can be modulated in the absence of clearly discernible T-wave changes. We applied principal component analysis (PCA) to assess QRS and T-wave complexity of sinus beats preceding and following VPBs in multiple 10-second resting 12-lead electrocardiograms of two subjects with frequent VPBs and no apparent heart disease. In both subjects, T-wave complexity of the first post-VPB beat was significantly increased compared to the beats preceding the VPB.

Prolongation of the QT interval and post-extrasystolic augmentation of the TU-wave during emotional stress.

We present a case of a 25-year-old woman with multiple blackouts and no structural heart disease, with abnormal T-U waves and borderline QT interval on her resting electrocardiogram. During emotional stress she developed frequent monomorphic ventricular premature beats, with characteristic changes of the sinus complexes immediately following the premature beats, namely augmentation and greater degree of merging of the T and U waves and QTc interval prolongation. The changes alert about the possibility of congenital long QT syndrome, specifically genotype 2 or 1.

The Diagnostic Yield of Brugada Syndrome After Sudden Death With Normal Autopsy.

BACKGROUND: Familial evaluation after a sudden death with negative autopsy (sudden arrhythmic death syndrome; SADS) may identify relatives at risk of fatal arrhythmias. OBJECTIVES: This study aimed to assess the impact of systematic ajmaline provocation testing using high right precordial leads (RPLs) on the diagnostic yield of Brugada syndrome (BrS) in a large cohort of SADS families. METHODS: Three hundred three SADS families (911 relatives) underwent evaluation with resting electrocardiogram using conventional and high RPLs, echocardiography, exercise, and 24-h electrocardiogram monitor. An ajmaline test with conventional and high RPLs was undertaken in 670 (74%) relatives without a familial diagnosis after initial evaluation. Further investigations were guided by clinical suspicion. RESULTS: An inherited cardiac disease was diagnosed in 128 (42%) families and 201 (22%) relatives. BrS was the most prevalent diagnosis (n = 85, 28% of families; n = 140, 15% of relatives). Ajmaline testing was required to unmask the BrS in 97% of diagnosed individuals. The use of high RPLs showed a 16% incremental diagnostic yield of ajmaline testing by diagnosing BrS in an additional 49 families. There were no differences of the characteristics between individuals and families with a diagnostic pattern in the conventional and the high RPLs. On follow-up, a spontaneous type 1 Brugada pattern and/or clinically significant arrhythmic events developed in 17% (n = 25) of the concealed BrS cohort. CONCLUSIONS: Systematic use of ajmaline testing with high RPLs increases substantially the yield of BrS in SADS families. Assessment should be performed in expert centers where patients are counseled appropriately for the potential implications of provocation testing.

Incorrect electrode cable connection during electrocardiographic recording.

Incorrect electrode cable connections during electrocardiographic (ECG) recording can simulate rhythm or conduction disturbance, myocardial ischaemia and infarction, as well as other clinically important abnormalities. When only precordial or only limb cables, excluding the neutral cable, have been interchanged the waveforms in the different leads are re-arranged, inverted, or unchanged, whereas the duration of intervals is not changed. The mistake can be recognized by the presence of unusual P-QRS patterns (e.g. negative P-QRS in lead I or II, positive in lead AVR, P-QRS complexes of opposite direction in leads I and V6, etc.), change in the P-QRS axis, or abnormal precordial QRS-T wave progression. Interchange of limb cables with the neutral cable distorts Wilson's terminal and the morphology of all precordial and unipolar limb leads. The telltale sign of the mistake is the presence of (almost) a flat line in lead I, II or III. Interchange of even one of the limb cables, except for the neutral cable, with a precordial cable distorts the morphology of most leads and leaves not more than one lead (I, II, or III) unchanged. Computerized algorithms for detection of lead misplacement, such as those based on artificial neural networks, or on correlation between original and reconstructed leads, have been developed.