Library

Notes: Monophasic Action Potential Recording in Brugada Syndrome. A 48-year-old patient with recurrent episodes of palpitations and syncope presented with transient ST segment elevation in the right precordial ECG leads. Structural heart disease was excluded. No arrhythmias were inducible by programmed ventricular stimulation. Parallel to ST elevation after intravenous ajmaline, a gradual and reversible delay in the upstroke of right ventricular (RV) monophasic action potentials (MAPs) occurred that was most marked in the RV outflow tract and nearly absent at right free-wall recordings. Ajmaline led to a cycle length-dependent increase in RV dispersion of repolarization. Thus, right endocardial MAPs may demonstrate regionally different action potential changes that may contribute to the ECG changes in Brugada syndrome.

Notes: Arrhythmias in Heart Failure. About one half of deaths in patients with heart failure are sudden, mostly due to ventricular tachycardia (VT) degenerating to ventricular fibrillation or immediate ventricular fibrillation. In severe heart failure, sudden cardiac death also may occur due to bradyarrhythmias. Other dysrhythmias complicating heart failure include atrial and ventricular extrasystoles, atrial fibrillation (AF), and sustained and nonsustained ventricular tachyarrhythmias. The exact mechanism of the increased vulnerability to arrhythmias is not known. Depending on the etiology of heart failure, different preconditions, including ischemia or structural alterations such as fibrosis or myocardial scarring, may he prominent. Reentrant mechanisms around scar tissue, afterdepolarizations, and triggered activity due to changes in calcium metabolism significantly contribute to arrhythmogenesis. Furthermore, alterations in potassium currents leading to action potential prolongation and an increase in dispersion of repolarization play a significant role. Treatment of arrhythmias is necessary either because patients are symptomatic or to reduce the risk for sudden cardiac death. The individual history, left ventricular function, electrophysiologic testing, and the signal-averaged ECG give useful information for identifying patients at risk for sudden cardiac death. The implantable cardioverter defibrillator (ICD) has evolved as a promising therapy for life-threatening arrhythmias. A potential role may exist for antiarrhythmic drugs, mainly amiodarone. There is growing evidence that patients with sustained VT or a history of resuscitation have the best outcome with ICD therapy regardless of the degree of heart failure. Many of these patients require additional antiarrhythmic therapy because of AF or nonsustained VTs that may activate the device. Catheter ablation or map-guided endocardial resection are additional options in selected patients but seldom represent the only therapeutic strategy.

Notes: Evidence suggests that infarct related artery (IRA) patency may improve survival after acute myocardial infarction, which is thought to be partially due to a lower incidence of malignant ventricular tachyarrhythmias. However, little is known about the effect of IRA patency on antiarrhythmic drug response and long-term outcome in patients with previous infarction who already experienced sustained ventricular tachyarrhythmias. A total of 152 patients with remote myocardial infarction and documented ventricular tachycardia (VT) or ventricular fibrillation (VF) underwent coronary angiography and programmed ventricular stimulation before and after oral administration of d,l-sotalol (240–640 mg/day). D.l-sotalol suppressed inducibility of VT/VF in 37 (25.2%) patients. The IRA was patent in 38.1% of all patients. There was no significant difference in the frequency of drug response between patients with patent or occluded IRAs (26.8% vs 24.2%, P = 0.87). In patients with a patent IRA, d.l-sotalol tended to be more effective in the absence of a left ventricular aneurysm. although this difference did not reach statistical significance (P = 0.38). Ejection fraction and collateral blood flow had no effect on drug response in the presence or absence of IRA patency. During follow-up (13.0 ± 19.9 months) of 29 patients discharged on oral d,1-so-talol, 3 patients experienced symptomatic VT and 4 sudden death. Arrhythmia recurrence and death of all cause (n = 6) and cardiac death (n = 4) were independent of IRA patency status. IRA patency had no effect on short-term drug response to d,1-sotalol in patients with remote myocardial infarction and documented VT/VF. Long-term outcome of patients with sustained ventricular tachyarrhythmias is independent of IRA patency status. In contrast to a previous report, outcome of electropharmacological testing was not predicted by the patency of the IRA.

Notes: Introduction: Prolongation of the QT interval and torsades de pointes tachycardias due to altered expression or function of repolarizing ion channels are the hallmark of congenital long QT syndrome (LQTS). The same ion channels also contribute to atrial repolarization, and familial atrial fibrillation may be associated with a mutated KVLQT1 gene. We therefore assessed atrial action potential characteristics and atrial arrhythmias in LQTS patients. Methods and Results: Monophasic action potentials (MAPs) were simultaneously recorded from the right atrial appendage and the inferolateral right atrium in 10 patients with LQTS (8 with identifiable genotype) and compared to 7 control patients. Atrial arrhythmias also were compared to MAPs recorded in patients with persistent (n = 10) and induced (n = 4) atrial fibrillation. Atrial action potential durations (APD) and effective refractory periods (ERP) were prolonged in LQTS patients at cycle lengths of 300 to 500 msec (APD prolongation 30–41 msec; ERP prolongation 26–52 msec; all P 〈 0.05). Short episodes of polymorphic atrial tachyarrhythmias (polyAT, duration 4–175 sec) occurred spontaneously or during pauses after pacing in 5 of 10 LQTS patients, but not in controls (P 〈 0.05). P waves showed undulating axis during polyAT. Cycle lengths of polyAT were longer than during persistent and induced atrial fibrillation. Afterdepolarizations preceded polyAT in 2 patients. The electrical restitution curve was shifted to longer APD in LQTS patients and to even longer APD in LQTS patients with polyAT. Conclusion: This group of LQTS patients has altered atrial electrophysiology: action potentials are prolonged, and polyAT occurs. PolyAT appears to be a specific arrhythmia of LQTS reminiscent of an atrial form of “torsades de pointes.”(J Cardiovasc Electrophysiol, Vol. 14, pp ***-***, October 2003)

Notes: 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. Methods and Results: A 120-channel body surface potential map was recorded at rest and after administration of a Class I agent (ajmaline, 1 mg/kg) to measure the body surface area of ST elevation (≥0.2 mV) in 23 individuals (16 patients had been resuscitated from near sudden cardiac death or had suffered syncope) with an ECG compatible with the diagnosis of Brugada syndrome as well as in 15 healthy controls and in 15 patients with arrhythmogenic right ventricular cardiomyopathy. Late potentials were assessed in 20 of the Brugada patients using signal-averaged ECG. Programmed ventricular stimulation was performed at two ventricular sites with up to three extrastimuli. Mean body surface area of ST elevation (≥0.2 mV) of all Brugada syndrome patients was 154 ± 139 cm2 (control 9 ± 9 cm2; P 〈 0.001). In the group of patients with arrhythmogenic right ventricular cardiomyopathy, only one patient was found to have an area of ST elevation (165 cm2). In the presence of ajmaline, area size increased to 330 ± 223 cm2 in Brugada syndrome patients (P 〈 0.05). In patients with inducible sustained (n = 15) and nonsustained VT (n = 3), a mean area of 183 ± 139 cm2 was found, whereas the area was only 52 ± 58 cm2 in those with no VT induction (P 〈 0.05). For an area ≥ 50 cm2, there were positive and negative predictive values of 92% and 60%, respectively. Positive late potentials were found in 60% of patients and correlated to the inducibility during programmed ventricular stimulation (positive predictive value 100%, negative predictive value 75%; P 〈 0.001). Conclusion: In patients with Brugada syndrome, the body surface area of ST elevation and the presence of late potentials correlate to the inducibility of VT during programmed ventricular stimulation and may be of value as a new noninvasive marker for risk stratification in these patients.

Notes: A patient with a family history of sudden cardiac death and a structurally normal heart presented with a resting ECG intermittently displaying a saddle-type Brugada-ECG, which could be reproducibly converted to a coved-type ECG pattern suggestive of Brugada syndrome. However, no ST-segment changes occurred in the presence of a true right bundle branch block (RBBB) in the same patient. In consideration of the inalienable diagnostic criterion of dynamic ECG abnormalities in the right precordial leads in Brugada syndrome, setting the diagnosis in patients with true RBBB may be unattainable.

Notes: Ventricular Dilatation and d,l-Sotalol/Flecainide in Isolated Rabbit Heart. Introduction: The interaction between acute ventricular dilatation (AVD) as one aspect of ventricular dysfunction and Class I and III antiarrhythmic drugs is uncertain. We therefore investigated the effects of AVD on the electrophysiologic properties of d,l-sotalol and flecainide. Methods and Results: The isolated rabbit heart was used as a model of AVD. The ventricular size and, therefore, the diastolic pressure were modified by sudden volume changes of a fluid-filled balloon placed in the left ventricle. Pacing was performed alternately using epi- and endocardial monophasic action potential (MAP)-pacing catheters at cycle lengths from 1,000 to 300 msec. d,l-Sotalol (10 μM) resulted in a significant (P 〈 0.05) lengthening of refractoriness (+13.5%± 3.1%), MAP duration (+14.9%± 3.2%), and QT interval (+15.5%± 4.1%) (mean ± SEM at 1,000 msec). These effects had a reverse rate-dependence. AVD to a diastolic pressure of 30 mmHg reduced refractoriness and left ventricular MAP duration. In comparison with the control group with the same extent of WD, d,l-sotalol still led to a significant prolongation of repolarization for all cycle lengths except 300 msec, so that its effects were not absolutely but relatively preserved. In contrast, flecainide (2μM) had no significant effects on refractoriness or MAP duration. It led to a significant, rate-dependent increase of pacing thresholds (+47.6%± 8.2%), prolongation of QRS (+48.8%± 5.6%), and conduction time (+78.6%± 8.6%) (mean ± SEM at 300 msec). In the flecainide group, AVD significantly increased the normal rate-dependent prolongation of QRS (+16.7%± 5.5%) and conduction time (+17.1%± 4.3%). Conclusion: Our data demonstrate that, during AVD, the Class III effect of d,l-sotalol is preserved, whereas flecainide's effect of slowing conduction is exaggerated. This may contribute to flecainide-related proarrhythmia in certain clinical situations.

Notes: 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). Methods and Results: In 210 surface and 305 telemetric ECGs recorded in wild-type (C57BL/6; wt; n = 40) and SCP2 null mice (n = 40), no difference was observed at baseline. However, on diet, cycle lengths were prolonged in SCP2 null mice (262.9 ± 190 vs 146.3 ± 43 msec), AV conduction was prolonged (58.3 ± 17 vs 42.6 ± 4 ms), and QRS complexes were wider (19.1 ± 5 vs 14.0 ± 4 ms). In 11 gene-targeted Langendorff-perfused hearts isolated from SCP2 null mice after dietary challenge, complete AV blocks (n = 5/11) or impaired AV conduction (Wenckebach point 132 ± 27 vs 92 ± 10 msec; P 〈 0.05) could be confirmed. Monophasic action potentials were not different between the two genotypes. Left ventricular function studied by echocardiography was similar in both strains. Phytanic acid but not pristanic acid accumulated in the phospholipid fraction of myocardial membranes isolated from SCP2 null mice. Conclusion: Accumulation of phytanic acid in myocardial phospholipid membranes is associated with bradycardia and impaired AV nodal and intraventricular impulse conduction, which could provide an explanation for sudden cardiac death in this model.