Hans-Jürgen Bruns

The ajmaline challenge in Brugada syndrome: Diagnostic impact, safety, and recommended protocol

AIMS The diagnostic ECG pattern in Brugada syndrome (BS) can transiently normalize and may be unmasked by sodium channel blockers such as ajmaline. Proarrhythmic effects of the drug have been well documented in the literature. A detailed protocol for the ajmaline challenge in Brugada syndrome has not yet been described. Therefore, we prospectively studied the risks of a standardized ajmaline test. METHODS AND RESULTS During a period of 60 months, 158 patients underwent the ajmaline test in our institution. Ajmaline was given intravenously in fractions (10mg every two minutes) up to a target dose of 1mg/kg. In 37 patients (23%) the typical coved-type ECG pattern of BS was unmasked. During the test, symptomatic VT appeared in 2 patients (1.3%). In all other patients, the drug challenge did not induce VT if the target dose, QRS prolongation >30%, presence/appearance of the typical ECG, or the occurrence of premature ventricular ectopy were considered as end points of the test. A positive response to ajmaline was induced in 2 of 94 patients (2%) with a normal baseline ECG, who underwent evaluation solely for syncope of unknown origin. CONCLUSION The ajmaline challenge using a protocol with fractionated drug administration is a safe method to diagnose BS. Because of the potential induction of VT, it should be performed under continuous medical surveillance with advanced life-support facilities. Due to the prognostic importance all patients with aborted sudden death or unexplained syncope without demonstrable structural heart disease and family members of affected individuals should presently undergo drug testing for unmasking BS.

Body surface area of ST elevation and the presence of late potentials correlate to the inducibility of ventricular tachyarrhythmias in Brugada syndrome.

BSPM and Late Potentials in Brugada Syndrome. Introduction: The value of noninvasive markers reflecting repolarization and/or conduction abnormalities in identifying patients with abnormal ECG showing a pattern of atypical right bundle branch block and ST elevation syndrome (Brugada syndrome) at risk for life‐threatening arrhythmias is controversial. Because right precordial ST elevation reflects inhomogeneous repolarization, we hypothesized that a correlation between the area of ST elevation, that is, the area of inhomogeneous repolarization, and the inducibility of ventricular tachyarrhythmias (VT) exists. Therefore, the body surface area of ST elevation and the presence of late potentials were compared to the inducibility of VT in patients with the characteristic ECG of Brugada syndrome.

Atrial fibrillation burden during the post-implant period after crt using device-based diagnostics.

Aims: Cardiac resynchronization therapy (CRT) is increasingly used in congestive heart failure (CHF) patients (with cardiac dyssynchrony). In addition to delivering therapy, CRT devices offer a variety of diagnostic tools for continuous long‐term monitoring of clinically relevant information (i.e., occurrence and duration of arrhythmia episodes).

Body surface potential mapping in patients with Brugada syndrome: right precordial ST segment variations and reverse changes in left precordial leads

OBJECTIVE The aim of this study was to perform quantitative signal analysis of high-resolution body surface potential mapping (BSPM) recordings to assess its usefulness for the electrocardiographic characterization of patients with Brugada syndrome. The diagnostic value of the QRS integral and of the gradient of the ST segment have not been elucidated in Brugada syndrome. METHODS In 27 subjects (16 with Brugada syndrome and 11 healthy subjects), 120-lead BSPMs were recorded at baseline and after pharmacological provocation with intravenous administration of ajmaline (1 mg/kg). The recordings were analyzed for two regions outside the positions of the standard ECG leads: the right precordial leads (RPL) on the second and third intercostal space (high RPL) and the left precordial leads (LPL) between the fifth and seventh intercostal space (low LPL). RESULTS At baseline, in high RPL regions, patients with Brugada syndrome showed more positive QRS integrals (-5+/-8 vs. -16+/-8 mV ms) and a steeper negative ST segment gradient (-0.62+/-0.41 vs. -0.29+/-0.40 mV/s) compared to healthy subjects, P<0.001. In contrast, in low LPL regions, reduced QRS integrals and positive ST segment gradients were observed. These ECG signs were even more pronounced after intravenous ajmaline and showed a better discrimination for patients with Brugada syndrome than differences in RPL or LPL during baseline, respectively. CONCLUSIONS In the left precordial leads, patients with Brugada syndrome showed ECG changes which were reversed in relation to the ECG changes observed in right precordial leads. BSPM measurement is a useful tool to improve the understanding of the electrocardiographic changes in the Brugada syndrome.

Phytanic Acid Accumulation Is Associated with Conduction Delay and Sudden Cardiac Death in Sterol Carrier Protein-2/Sterol Carrier Protein-x Deficient Mice

Introduction: The sterol carrier protein‐2 gene encodes two functionally distinct proteins: sterol carrier protein‐2 (SCP2, a peroxisomal lipid carrier) and sterol carrier protein‐x (SCPx, a peroxisomal thiolase known as peroxisomal thiolase‐2), which is involved in peroxisomal metabolism of bile acids and branched‐chain fatty acids. We show in this study that mice deficient in SCP2 and SCPx (SCP2null) develop a cardiac phenotype leading to a high sudden cardiac death rate if mice are maintained on diets enriched for phytol (a metabolic precursor of branched‐chain fatty acids).

Direct epicardial mapping predicts the recovery of left ventricular dysfunction in chronic ischaemic myocardium

AIMS This study investigated the hypothesis that direct epicardial bipolar mapping is able to predict the recovery of left ventricular (LV) dysfunction in ischaemic myocardium. METHODS AND RESULTS In 34 patients with CAD, a maximum of 102 bipolar epicardial electrograms per patient (n=3468 electrograms) were simultaneously recorded with a ventricular jacket array intraoperatively immediately prior to revascularization. Only LV electrograms with good myocardial contact (n=1813, 52+/-14 per patient, mean+/-SD) were analyzed. In accordance to the position of each electrode, segmental myocardial function was assessed by transthoracic echocardiography before and 7+/-2 months (mean+/-SD; range 3-10 months) after CABG using a wall motion score. Preoperatively dysfunctional segments (n=700) were classified as viable (improvement in wall motion score of at least 20% following CABG, n=424) or non-viable (no improvement, n=276). Bipolar voltage was significantly lower in non-viable when compared to viable myocardium (P<0.001, ANOVA) At a cut-off value of 5.9mV, ROC-curve analysis for bipolar voltage (to discriminate between viable and non-viable myocardium) revealed a sensitivity of 83% at a specificity of 83% (area under the ROC-curve of 0.92+/-0.01, mean+/-SE). CONCLUSIONS Direct epicardial mapping is able to predict the recovery of chronically ischaemic dysfunctional myocardium and thereby proves the presence of myocardial viability.

T-wave integral: an electrocardiographic marker discriminating patients with arrhythmogenic right ventricular cardiomyopathy from patients with right ventricular outflow tract tachycardia

AIMS Clinical and electrocardiographic (ECG) presentation of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow-tract tachycardia (RVOT) may be similar. The aim of the study was to assess the validity and utility of T-wave integral measurement as an ECG discriminator of patients with ARVC and RVOT using a body surface mapping (BSM). METHODS AND RESULTS A 120-channel BSM with quantitative signal analysis of the T-wave integral was performed in 10 patients with ARVC. Results were compared with those obtained from 13 patients with RVOT and a control group of 12 healthy subjects (controls). Age, body mass index, and QRS-axis on surface ECG were not significantly different between the groups. Arrhythmogenic right ventricular cardiomyopathy patients showed a significantly negative T-wave integral in the right lower anterior region of the torso when compared with RVOT (P < 0.001). There was no statistically significant difference between RVOT patients and controls. At a cut-off level of -0.3 mV ms, sensitivity and specificity were 83% [area under curve (AUC) 0.85 ± 0.04 for the comparison of ARVC and RVOT]. These differences were pronounced in ARVC patients with a plakophlin-2 mutation (P < 0.001). CONCLUSION Quantitative analysis of the BSM T-wave integral in distinct anatomical regions discriminates ARVC patients from RVOT patients and controls and may serve as an additional diagnostic tool.

QRS integral: an electrocardiographic indicator of mechanical interventricular asynchrony

AIM The aim of this study was to investigate whether interventricular asynchrony (IVA) can be measured by electrocardiography. METHODS Sixty-two patients (New York Heart Association heart failure functional class III: age, mean +/- SD: 64 +/- 9 years; ejection fraction, mean +/- SD: 24% +/- 8%; dilative cardiomyopathy/ischemic cardiomyopathy, n = 39/23) with left bundle branch block (QRS duration, mean +/- SD: 165 +/- 21 milliseconds) underwent a 120-channel body surface mapping. QRS integral was analyzed and compared with IVA (echo). RESULTS Interventricular asynchrony was associated with significantly decreased QRS integrals 15 cm cranial and 6 cm lateral from V1 in patients with normal axis (n = 36): At a cutoff value of -26 milliseconds mV, receiver operating characteristic analysis to predict IVA revealed a sensitivity of 89% and a specificity of 83% (area under curve, mean +/- SEM: 0.9 +/- 0.07; P < .001). In patients with left axis deviation (n = 26), IVA showed significantly decreased QRS integrals 10 cm caudal from V1: at a cutoff value of -89 milliseconds mV, receiver operating characteristic analysis to predict IVA revealed a sensitivity of 83% and a specificity of 100% (area under curve, mean +/- SEM: 0.9 +/- 0.07; P < .002). CONCLUSIONS Interventricular asynchrony strongly correlates with QRS integral. Key lead positions, however, are axis dependent and outside standard leads.

Signal characteristics of multichannel epicardial electrograms in chronic ischaemic and scarred myocardium: electromechanical mismatch indicates viability in regions of myocardial dysfunction.

Background To predict the outcome after myocardial revascularisation, a clear separation between hibernation and/or repetitive stunning on the one hand and myocardial scarring on the other hand is of importance. Methods and results A total of 44 patients was included in this study. In 35 patients with chronic myocardial ischaemia and an indication for coronary bypass-surgery, epicardial mapping of local activation was performed. Nine patients with LV aneurysm and an indication for antitachycardia surgery were also included. For simultaneous recording of the local electrograms during sinus rhytm, a sock electrode with 102 bipolar leads was used. The regional myocardial contraction pattern was assessed from preoperative angiograms and regional myocardial metabolism (viability) from 18F-FDG PET, respectively. The results were projected on the grid of the intraoperative position of the sock electrode. This enabled regional comparison of electrogram characteristics to local contraction patterns and viability.For the characterisation of local electrograms, peak-to-peak amplitude and duration of activation were calculated using custom-made automated computer-algorithms. Dysfunctional but viable areas showed normal or almost normal electrographic signal characteristics. In contrast, dysfunctional and non-viable myocardium showed a distinct reduction of local amplitudes and prolongation of signal duration. These changes were even more intense in areas of LV aneurysms. Conclusions In patients with chronic ischaemic myocardium, a mismatch between mechanical function and local electrogram characteristics was observed in areas with preserved metabolism. Thus, normal epicardial electrograms in regions of myocardial dysfunction may be an indicator for myocardial viability.

Improved Clinical Risk Stratification in Patients with Long QT Syndrome? Novel Insights from Multi-Channel ECGs

Background We investigated whether multichannel ECG-recordings are useful to risk-stratify patients with congenital long-QT syndrome (LQTS) for risk of sudden cardiac death under optimized medical treatment. Methods In 34 LQTS-patients (11 male; age 31±13 years, QTc 478±51ms; LQT1 n = 8, LQT2 n = 15) we performed a standard 12-channel ECG and a 120-channel body surface potential mapping. The occurrence of clinical events (CE; syncope, torsade de pointes (TdP), sudden cardiac arrest (SCA)) was documented and correlated with different ECG-parameters in all lead positions. Results Seven patients developed TdP, four survived SCA and 12 experienced syncope. 12/34 had at least one CE. CE was associated with a longer QTc-interval (519±43ms vs. 458±42ms; p = 0.001), a lower T-wave integral (TWI) on the left upper chest (-1.2±74.4mV*ms vs. 63.0±29.7mV*ms; p = 0.001), a lower range of T-wave amplitude (TWA) in the region of chest lead V8 (0.10±0.08mV vs. 0.18±0.07mV; p = 0.008) and a longer T-peak-T-end time (TpTe) in lead V1 (98±23ms vs. 78±26ms; p = 0.04). Receiver-operating-characteristic (ROC) analyses revealed a sensitivity of 96% and a specificity of 75% (area under curve (AUC) 0.89±0.06, p = 0.001) at a cut-off value of 26.8mV*ms for prediction of CE by TWI, a sensitivity of 86% and a specificity of 83% at a cut-off value of 0.11mV (AUC 0.83±0.09, p = 0.002) for prediction of CE by TWA and a sensitivity of 83% and a specificity of 73% at a cut-off value of 87ms (AUC 0.80±0.07, p = 0.005) for prediction of CE by TpTe. Conclusions Occurrence of CE in LQTS-patients seems to be associated with a prolonged, low-amplitude T-wave.