Congenital long QT syndrome presenting with a history of epilepsy: misdiagnosis or relationship between channelopathies of the heart and brain?

A 60-year-old man with a long history of epilepsy was referred for cardiologic evaluation. An earlier diagnosis of epilepsy was made on the basis of his clinical manifestation of tonic-clonic seizure. Electroencephalography (EEG) demonstrated paroxysmal slow waves in response to intermittent photic stimulation. However, electrocardiography (ECG) revealed bradycardia (heart rate, 48 bpm) and marked QT prolongation (QTc 477 ms). ECG monitoring confirmed remarkable QT prolongation; ventricular ectopy triggering torsades de pointes was recorded during seizure. The patient underwent temporary antitachycardia pacing, and an implantable cardioverter defibrillator (ICD) was finally implanted. Long QT syndrome (LQTS) genetic testing was conducted and a diagnosis of LQT2 was confirmed by the identification of mutation in KCNH2 (HERG). LQTS is associated with abnormal channel function due to mutations in ion channel genes. Epilepsy, a disorder of neural function, is also associated with abnormal channel function. The possibility that some channelopathies can manifest as both LQTS and epilepsy is discussed.

Ischemia-induced Brugada-type ST-segment alternans and Brugada syndrome.

UNLABELLED: The mechanisms of Brugada-type electrocardiographic (ECG) pattern remain unclear. METHODS: The ST-segment was evaluated during coronary intervention of proximal right coronary artery (RCA). We measured ST-segment elevation with a drug challenge test with a sodium channel blocker. The ST-segment changes were compared with those in true Brugada syndrome. RESULTS: Brugada-type ECG was observed in 6 patients but not in 9 patients during coronary intervention. Five patients demonstrated Brugada-type ST elevation and alternans from coved type to saddleback type during coronary intervention. The patients with ST alternans demonstrated the conus branch occlusion or RV branch occlusion. A drug challenge test developed a significant ST-segment elevation neither in patients with Brugada-type ECG nor in patients without Brugada-type ECG. (0.69±0.48 mv vs. 0.48±0.31 mv, p=NS) There was a significant difference in the ST-segment elevation between patients with Brugada-type ECG during the coronary intervention and patients with true Brugada syndrome (n=5). (0.69±0.48 mv vs. 2.86±0.61 mv, p<0.05). CONCLUSIONS: Ischemia of proximal RCA can masquerade as the Brugada syndrome, ST-segment elevation and alternans. Ischemia of proximal RCA could be one of the different entities showing Brugada-type ECG from true Brugada syndrome.

Synergistic effects of cardiac resynchronization therapy and Bachmann's bundle pacing on heart failure with atrial tachyarrhythmias.

Cardiac resynchronization therapy (CRT) is electrical resynchronization of the ventricles. Bachmann's bundle (BB) pacing is considered to be electrical resynchronization of the atria. Atrial fibrillation (AF) and congestive heart failure (HF) often coexist in the same patient. A 69 year-old man who underwent CRT combined with BB pacing for HF and atrial tachycardias or atrial fibrillation (AF) improved HF symptoms. The combined therapy reduced the number of admissions and occurrence of atrial tachyarrhythmias. It is possible that CRT combined with BB pacing could provide synergistic, beneficial effects on symptoms in patients with HF and AF and hence break a vicious circle.

Improvement of cardiac function and neurological remodeling in a patient with tachycardia-induced cardiomyopathy after catheter ablation.

Incessant ventricular tachycardia and long-standing ectopic beats lead to tachycardia-induced cardiomyopathy. Catheter ablation eliminates ventricular tachycardia and reverses left ventricular (LV) dysfunction. 201-Thallium ((201)Tl) scintigraphy demonstrates perfusion defects with ischemic cardiomyopathy. Reversible perfusion defects are observed even in non-ischemic cardiomyopathy, related to regional flow or metabolism derangements. 123-I-metaiodobezylguanidine ((123)I-MIBG) scintigraphy delineates regional cardiac sympathetic denervation and heterogeneity. We demonstrated the progression of tachycardia-induced cardiomyopathy in a patient with idiopathic LV outflow tract tachycardia using (201)Tl and (123)I-MIBG scintigraphic findings. Regional defects were reversed predominantly in the basal interventricular septal wall in (201)Tl scintigraphy and (123)I-MIBG scintigraphic findings. This report suggests that incessant ventricular tachycardia or long-standing ventricular ectopic beats may develop adverse myocardial remodeling and sympathetic neurological remodeling. Treatment with catheter ablation for tachycardia-induced cardiomyopathy can reverse sympathetic neurological remodeling as well as myocardial structural remodeling.

Changes in autonomic nervous activity after catheter ablation of atrial tachycardia arising from the atrioventricular annulus.

Radiofrequency (RF) catheter ablation of supraventricular tachycardias causes local parasympathetic denervation. This study used heart rate variability (HRV) to evaluate the effects of ablation of atrial tachycardia (AT) arising from the atrioventricular annulus (AVAT) on autonomic function. Ten patients with AVAT were referred for ablation (group AT) and compared with 8 patients with paroxysmal atrial fibrillation who underwent PV isolation (group Paf), and 13 patients with idiopathic ventricular tachycardia successfully treated by ablation (group VT). Time and frequency domain analysis of HRV on 24-hour ambulatory ECG recordings was performed before and after ablation. Root mean square of differences of consecutive N-N intervals (rMSSD), percentage of difference between consecutive N-N intervals >50 ms (pNN50), and high frequency (HF) component were measured to examine the effects on parasympathetic nerve activity. In group AT, rMSSD, pNN50, and HF decreased significantly after ablation, while they remained unchanged in group Paf and group VT. These observations suggest that parasympathetic denervation after ablation was limited to group AT, and depended on the site of energy delivery along the tricuspid or mitral valve as opposed to atrial or ventricular muscle.

Two cases of giant aneurysm in coronary-pulmonary artery fistula associated with atherosclerotic change.

Giant sacclar aneurysm in a coronary-pulmonary artery fistula is extremely rare. In this article, we presented two cases of giant aneurysms in coronary-pulmonary artery fistula with atherosclerosis.

Effect of left atrial-coronary sinus musculature connections on the coronary sinus activation pattern via retrograde conduction in patients with WPW syndrome.

BACKGROUND: Double potential (DP) activation patterns observed in coronary sinus (CS) electrograms recorded during left lateral atrial pacing, were explained by an initial low-frequency left atrial (LA) activation potential and secondary high-frequency CS musculature activation potential in canine hearts. Moreover, the connections between the LA and CS musculature vary greatly in size and location in the human heart. The purpose of this study was to investigate the relationship between the CS activation pattern during retrograde conduction via an accessory pathway (AP) and the location of left-sided APs. METHODS AND RESULTS: Fifty-one patients (31 males, mean age 48.6 years) who underwent radiofrequency catheter ablation of left-sided APs were divided into two groups according to the successful ablation site. The CS electrograms during retrograde AP conduction were classified into 3 types; single, fractionated, and DP activation patterns. A DP pattern was identified in 10 of 12 patients (83.3%) with posteroseptal to posterolateral APs, and in particular, 9 had a divergent sequence. Twenty-six of 39 patients (66.7%) with lateral to anterolateral APs, demonstrated a single pattern. The number of radiofrequency applications was significantly higher in patients with a DP pattern than in those with a single pattern (3.4 +/- 3.3 vs. 7.8 +/- 6.8, p < 0.01). CONCLUSION: Misleading information obtained when mapping for optimal ablation sites might result from DP patterns with a divergent sequence produced by discrete muscular connections between the LA and CS musculature. Ablation around left posterior APs may require meticulous observation of the CS activation patterns.

Intracellular Ca dynamics in ventricular fibrillation.

In the heart, membrane voltage (Vm) and intracellular Ca (Cai) are bidirectionally coupled, so that ionic membrane currents regulate Cai cycling and Cai affects ionic currents regulating action potential duration (APD). Although Cai reliably and consistently tracks Vm at normal heart rates, it is possible that at very rapid rates, sarcoplasmic reticulum Cai cycling may exhibit intrinsic dynamics. Non-voltage-gated Cai release might cause local alternations in APD and refractoriness that influence wavebreak during ventricular fibrillation (VF). In this study, we tested this hypothesis by examining the extent to which Cai is associated with Vm during VF. Cai transients were mapped optically in isolated arterially perfused swine right ventricles using the fluorescent dye rhod 2 AM while intracellular membrane potential was simultaneously recorded either locally with a microelectrode (5 preparations) or globally with the voltage-sensitive dye RH-237 (5 preparations). Mutual information (MI) is a quantitative statistical measure of the extent to which knowledge of one variable (Vm) predicts the value of a second variable (Cai). MI was high during pacing and ventricular tachycardia (VT; 1.13 +/- 0.21 and 1.69 +/- 0.18, respectively) but fell dramatically during VF (0.28 +/- 0.06, P < 0.001). Cai at sites 4-6 mm apart also showed decreased MI during VF (0.63 +/- 0.13) compared with pacing (1.59 +/- 0.34, P < 0.001) or VT (2.05 +/- 0.67, P < 0.001). Spatially, Cai waves usually bore no relationship to membrane depolarization waves during nonreentrant fractionated waves typical of VF, whereas they tracked each other closely during pacing and VT. The dominant frequencies of Vm and Cai signals analyzed by fast Fourier transform were similar during VT but differed significantly during VF. Cai is closely associated with Vm closely during pacing and VT but not during VF. These findings suggest that during VF, non-voltage-gated Cai release events occur and may influence wavebreak by altering Vm and APD locally.

Age-related sensitivity to nicotine for inducible atrial tachycardia and atrial fibrillation.

The influence of nicotine in modulating vulnerability to atrial tachycardia and fibrillation (AT/AF) remains ill defined. The isolated hearts of six young (2-3 mo) and six old (22-24 mo) male Fischer 344 rats were Langendorff perfused at 5 ml/min with oxygenated Tyrode solution at 37 degrees C, and the whole heart was also super-fused with warmed oxygenated Tyrode solution at 15 ml/min. Nicotine prolonged the interatrial conduction time and effective refractory period that were significantly (P < 0.05) higher in the old than in the young rats in a concentration-dependent manner. Nicotine had a biphasic effect on burst atrial pacing-induced AT in both groups, increasing it at 10-30 ng/ml while decreasing it at 50-100 ng/ml (P < 0.01). Nicotine at 10-100 ng/ml increased burst atrial pacing-induced AF in the young rats but suppressed it in the old rats (P < 0.01). Optical mapping showed the presence of multiple independent wavefronts during AF and a single periodic large wavefront during AT in both groups. Nicotine, at concentrations found in the blood of smokers (30-85 ng/ml), exerts biphasic effects on inducible AT/AF in young rats and suppresses it in the old rats by causing high degrees of interatrial conduction block.

High resolution mapping of the pulmonary vein and the vein of Marshall during induced atrial fibrillation and atrial tachycardia in a canine model of pacing-induced congestive heart failure.

OBJECTIVES: The study examined the activations in the pulmonary veins (PVs) and the vein of Marshall (VOM) during atrial fibrillation (AF) in dogs with congestive heart failure (CHF). BACKGROUND: The patterns of activation within the PVs and the VOM during AF in CHF are unclear. METHODS: We induced CHF in nine dogs by rapid ventricular pacing. The patterns of activation during induced AF were studied one week after ceasing ventricular pacing. RESULTS: The duration of induced AF averaged 80.7 +/- 177.3 s. The termination of low-amplitude fractionated activity in the PVs preceded the termination of AF in 25 of 29 episodes. High-density mapping (1-mm resolution) showed that the PV was activated by a focal wave front independent of left atrial (LA) activation in 22 AF episodes. Frequent intra-PV conduction blocks and multiple wave fronts in the PVs were recorded during 10 AF episodes. Focal activations were observed within the VOM in 4 of 12 episodes of AF. Three atrial tachycardia (AT) episodes originated from a focus within a PV. Histological studies showed extensive fibrosis in the PVs and in the atria. The PVs in five normal dogs did not have focal or fractionated activity during induced AF. CONCLUSIONS: Atrial fibrillation in canine CHF is associated with independent focal activations in the PVs and the VOM, and with complex wave fronts within the PVs. The PVs may also serve as the origin of AT. These findings suggest that electrical and anatomical remodeling of the PVs and the VOM are important in the maintenance of AF and AT in dogs with CHF.

Aging-related increase to inducible atrial fibrillation in the rat model.

INTRODUCTION: Aging is associated with atrial interstitial fibrosis and increased incidence of atrial fibrillation (AF). We hypothesized that aged rats are suitable for study of aging-related AF and that partial atrial cellular uncoupling induced with heptanol in young rats mimics aging-related AF. METHODS AND RESULTS: Interatrial conduction time and atrial response to burst atrial pacing were evaluated in 11 young (2-3 months) and 12 old (22-24 months) male rats (Fisher 344) in the Langendorff-perfused setting. At baseline, sustained (>30 sec) atrial tachycardia (AT) and AF were induced in 10 of 12 and in 7 of 12 old rats, respectively. No such arrhythmias could be induced in the young rats. Old rats had significantly (P < 0.01) longer interatrial conduction time and P wave durations than the young rats. Burst pacing failed to induce AT and AF in all 11 young rats studied. The effects of heptanol 2 to 10 microM were studied in both groups. Heptanol 2 to 5 microM promoted inducible AT in all 5 young rats studied; however, when its concentration was raised to 10 microM, AT could no longer be induced in any of the 5 young rats. No AF could be induced in any of the 5 young rats at heptanol concentrations of 2 to 10 microM. In the old rats, AF could still be induced during perfusion of 2 microM heptanol. However, when its concentration was raised to 5 and 10 microM, AF could not be induced in any of the 6 old rats studied. Optical mapping using a potentiometric dye showed a periodic single wavefront of activation during AT in both groups and 2 to 4 independent wavefronts propagating in different directions during AF in the old rats. Histology revealed a significant increase in interstitial atrial fibrosis (P < 0.01), atrial cell size (P < 0.05), and heart weight in old versus young rats. Fibrosis in the old rats was highly heterogeneous. CONCLUSION: The rat model is suitable for study of aging-related AF. Uniform partial atrial cellular uncoupling with heptanol perfusion in the young rats, although promoting inducible AT, does not mimic aging-related AF. The results suggest that heterogeneous atrial interstitial fibrosis and atrial cell hypertrophy might contribute to the aging-related increase in atrial conduction slowing, conduction block, and inducible AF in the old rat model.

Increased vulnerability to inducible atrial fibrillation caused by partial cellular uncoupling with heptanol.

We hypothesized that partial cellular uncoupling produced by low concentrations of heptanol increases the vulnerability to inducible atrial fibrillation (AF). The epicardial surface of 12 isolated-perfused canine left atria was optically mapped before and after 1-50 microM heptanol infusion. At baseline, no sustained (>30 s) AF could be induced in any of the 12 tissues. However, after 2 microM heptanol infusion, sustained AF was induced in 9 of 12 tissues (P < 0.001). Heptanol >5 microM caused loss of 1:1 capture during rapid pacing, causing no AF to be induced. AF was initiated by conduction block across the fiber leading to reentry, which broke up after one to two rotations into two to four independent wavelets that sustained the AF. Heptanol at 2 microM had no effect on the cellular action potential duration restitution or on the maximal velocity rate over time of the upstroke. The effects of heptanol were reversible. We conclude that partial cellular uncoupling by heptanol without changing atrial active membrane properties promotes wavebreak, reentry, and AF during rapid pacing.

Nonreentrant focal activations in pulmonary veins in canine model of sustained atrial fibrillation.

Repetitive rapid activities are present in the pulmonary veins (PVs) in dogs with pacing-induced sustained atrial fibrillation (AF). The mechanisms are unclear. We induced sustained (>48 h) AF by rapidly pacing the left atrium (LA) in six dogs. High-density computerized mapping was done in the PVs and atria. Results show repetitive focal activations in all dogs and in 12 of 18 mapped PVs. Activation originated from the middle of the PV and then propagated to the LA and distal PV with conduction blocks. The right atrium (RA) was usually activated by a single large wavefront. Mean AF cycle length in the PVs (left superior, 82 +/- 6 ms; left inferior, 83 +/- 6 ms; right inferior, 83 +/- 4 ms) and LA posterior wall (87 +/- 5 ms) were significantly (P < 0.05) shorter than those in the LA anterior wall (92 +/- 4 ms) and RA (107 +/- 5 ms). PVs in normal dogs did not have focal activations during induced AF. No reentrant wavefronts were demonstrated in the PVs. We conclude that nonreentrant focal activations are present in the PVs in a canine model of pacing-induced sustained AF.

Electrophysiological features of atrial tachycardia arising from the atrioventricular annulus.

Atrial tachycardia (AT) arises from various sites in the atrium and the mechanisms are nonuniform. McGuire et al. reported that the cells around the atrioventricular annuli resembled nodal cells in their cellular electrophysiology. The purpose of this study was to delineate the electrophysiological features of AT arising from the atrioventricular (AV) annulus (AVAT). The study included five patients with six AVATs that were abolished by the radiofrequency energy delivery. The location of the AV annuli was defined by using the AV ratio of the local electrograms and the amplitude of the ventricular electrograms, in addition to the anatomic findings under fluoroscopic guidance. The tachycardia cycle lengths were 403 +/- 117 ms. An AV ratio of the electrograms at the successful ablation sites was 0.4 +/- 0.4 at the tricuspid annulus and 1.5 +/- 0.3 at the mitral annulus. Small doses (mean 3.2 +/- 1.8 mg) of adenosine triphosphate could terminate all the tachycardia episodes for five of the ATs without the development of AV nodal conduction block. The successful ablation sites were located at the right mid-septum in 1 AT, right posteroseptum in 2 ATs, right posterolateral region in 1 AT, and left anteroseptum in 2 ATs. These findings suggest that the cells with nodal-type action potentials around both annuli might play an important role in the genesis of AVAT.

Frequency analysis of ventricular fibrillation in Swine ventricles.

It has been suggested from frequency analysis that cardiac fibrillation is driven by stable intramural reentry, with wavebreak occurring due to failure of 1:1 propagation. We tested this hypothesis with a combined experimental and theoretical approach. Optical mapping was performed on epicardial, endocardial, and transmural cut surfaces of fibrillating swine ventricles. Wavelets were characterized, the frequency content of optical signals analyzed, and space-time plots (STPs) constructed to detect Wenckebach-like conduction. The findings were compared with simulations in 2D and 3D cardiac tissue using the Luo-Rudy action potential model. The incidence of reentry in the cut transmural surface (11.8% in right ventricle, 14.3% in left ventricle) was similar to that on the endocardial surface (13.1%, P=NS) but greater than on the epicardial surface (7.7%, P<0.01). Frequency spectra of optically recorded membrane voltage were organized into spatial domains with the same dominant frequency, but these domains were nonstationary. In STPs, pseudo-2:1 conduction block was caused by double potentials arising when reentry occurred on the recording site rather than true Wenckebach conduction. The latter was observed in 11 of 166 STPs but did not occur at borders of high-to-low frequency domains. In simulations, similar findings were obtained when action potential duration (APD) restitution slope was steep. Stationary dominant frequency domains with Wenckebach conduction patterns were observed only in the presence of shallow APD restitution slope and marked nonuniform tissue heterogeneity. In conclusion, stable intramural reentry as the engine of fibrillation was not observed. Our findings support the idea that dynamic wavebreak plays a fundamental role in the generation and maintenance of ventricular fibrillation.

Effects of amiodarone on wave front dynamics during ventricular fibrillation in isolated swine right ventricle.

The effects of acute amiodarone infusion on dynamics of ventricular fibrillation (VF) are unclear. Six isolated swine right ventricles (RVs) were studied in vitro. Activation patterns during VF were mapped optically, whereas action potentials were recorded with a glass microelectrode. At baseline, VF was associated with frequent spontaneous wave breaks. Amiodarone (2.5 microg/ml) reduced spontaneous wave breaks and increased the cycle length (CL) of VF from 83.3 +/- 17.8 ms at baseline to 118.4 +/- 25.8 ms during infusion (P < 0.05). Amiodarone increased the reentrant wave front CL (114.4 +/- 15.5 vs. 78.2 +/- 19.0 ms, P < 0.05) and central core area (4.1 +/- 3.8 vs. 0.9 +/- 0.3 mm2, P < 0.05). Within 30 min of infusion, VF terminated (n = 1), converted to ventricular tachycardia (VT) (n = 1) or continued at a slower rate (n = 4). Amiodarone flattened the APD restitution curves. We conclude that amiodarone reduced spontaneous wave breaks. It might terminate VF or convert VF to VT. These effects were associated with the flattening of APD restitution slope and increased core size of reentrant wave fronts.

Idiopathic left ventricular aneurysm associated with pleomorphic ventricular tachycardia: a case report.

A 39-year-old Japanese woman presented with an idiopathic left ventricular aneurysm manifesting as recurrent episodes of palpitation. She was referred to our hospital for evaluation of sustained ventricular tachycardia. Echocardiography disclosed a dyskinetic well-defined wall bulge during both systole and diastole at the basal region of the interventricular septum, and reduced left ventricular wall thickness and severe hypokinesis at the anterolateral to posterolateral region. These appearances were confirmed by the angiographic findings. The sustained ventricular tachycardia was reproducibly induced by a single extrastimulus from the right ventricular apex. Subsequently, 4-type ventricular tachycardias were induced during the electrophysiological study and the mechanism of these ventricular tachycardias was considered reentry. Radiofrequency catheter ablation failed due to the changing QRS morphologies during the entrainment study. The patient was treated with cibenzoline 300 mg a day, and there has been no recurrence of tachycardia during the 18-month follow-up period.

Demonstration of electrical and anatomic connections between Marshall bundles and left atrium in dogs: implications on the generation of P waves on surface electrocardiogram.

INTRODUCTION: The muscle bundles within the ligament of Marshall (LOM) are electrically active. The importance of these muscle bundles (Marshall bundle [MB]) to atrial activation and the generation of the ECG P wave is unclear. METHODS AND RESULTS: We used optical mapping techniques to study epicardial activation patterns in isolated perfused left atrium in four dogs. In another seven dogs, P waves were studied before and after in vivo radiofrequency (RF) ablation of the connection between coronary sinus (CS) and the LOM. Computerized mapping was performed before and after RF ablation. Optical mapping studies showed that CS pacing resulted in broad wavefronts propagating from the middle and distal LOM directly to the adjacent left atrium (LA). Serial sections showed direct connection between MB and LA near the orifice of the left superior pulmonary vein in two dogs. In vivo studies showed that MB potentials were recorded in three dogs. After ablation, the duration of P waves remained unchanged. In the other four dogs, MB potentials were not recorded. Computerized mapping showed that LA wavefronts propagated to the MB region via LA-MB connection and then excited the CS. After ablation, the activation of CS muscle sleeves is delayed, and P wave duration increased from 65.3 +/- 14.9 msec to 70.5 +/- 17.2 msec (P = 0.025). CONCLUSION: In about half of the normal dogs, MB provides an electrical conduit between LA free wall and CS. Severing MB alters the atrial activation and lengthens the P wave. MB contributes to generation of the P wave on surface ECG.