Cardiac Electrophysiology Studies Research Articles

Wide QRS complex tachycardia with a 1:1 AV relationship

or the management of sudden-onset tachycardia. He had experienced 3 episodes of palpitation attacks, lasting for a couple of hours each, during the last 6 months. A regular, wide QRS complex tachycardia (WCT) at 150 beats/min with a prominent retrograde P wave on the surface electrocardiogram (ECG) was documented during the last attack, which was terminated by drip infusion of pilsicainide administered at another hospital. He did not experience loss of consciousness or dizziness during his palpitation attacks. The findings of other investigations, including physical examination, two-dimensional echocardiography, chest radiography, and laboratory tests, were unremarkable. Cardiac electrophysiological study (EPS) was performed after written informed consent was obtained. Venous access was performed via the right femoral and subclavian veins. Three 5-French quadripolar catheters were advanced to the right ventricular apex, right atrial appendage, and His-bundle region. A 5-French decapolar catheter was placed within the coronary sinus (CS), with a proximal electrode located at its ostium. During the EPS study, a WCT with a cycle length of 330 ms was induced by a ventricular extrastimulus. The morphology of the 12-lead ECG was consistent with that of the clinical tachycardia and showed the right bundlebranch block pattern and left axis deviation. Intracardiac ECG showed a 1:1 atrioventricular (A-V) relationship (Fig. 1). What is the cause of this tachycardia?

Correlation of cardiac magnetic resonance imaging and electrophysiology study findings among patients with frequent premature ventricular contractions

Summary Despite inclusion in the diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy, this study of 87 consecutive patients with isolated frequent LBBBmorphology PVCs and high PVC burden (mean 19%) demonstrated only a rare association with CMR diagnostic criteria for ARVC, no cases of ARVC diagnosis, no association of minor wall motion abnormalities (hypokinesis) with markers of ARVC, and no cardiac events in follow-up. Interestingly, however, RV dilation was very common and paralleled LV dilation. Background Frequent premature ventricular contractractions (PVCs) is typically a benign disorder, but has become a common indication for cardiac magnetic resonance imaging (CMR) due to inclusion in diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC). A recent study also suggested a worse prognosis in these patients associated with findings on CMR. The purpose of this study was to correlate CMR data with electrophysiology study (EP) findings and clinical outcomes in patients with frequent PVCs. Methods We studied 87 consecutive patients referred for catheter ablation of isolated frequent left bundle branch block morphology PVCs. The 2010 ARVC Task Force criteria were used to define major and minor criteria for ARVC. The CMR exam included steady-state free precession imaging for wall motion and volume/function quantification and black blood imaging for fatty infiltration. Major RV wall motion abnormalities (WMA) were defined by akinesis, dyskinesis, or dyssynchrony, while minor wall motion abnormalities were defined by hypokinesis. The EP study included program stimulation for inducibility of VT and either activation or pace mapping for determination of PVC origin. Results The mean PVC burden was 19 + 13%, and no patients had a history of syncope or family history of early sudden death. 15 patients met a minor (10) or major (5) Task Force criterion for ARVC by EKG. Major WMAs by CMR were present in 2 (2%) of patients, but only 1 of these had RV dilation and the PVCs in this case mapped to the left ventricle. No patients met full diagnostic criteria for ARVC. Hypokinetic segments were present in 7 patients, but did not correlate with EKG criteria for ARVC (p=0.41), NSVT on 24-hour EKG (p=0.51), RV dilation (p=0.43), RV fatty infiltration (p=1.0), inducibility of VT (p=1.0), or RV versus LV site of origin of the PVC (p=0.67). RV dilation was present in 74 (84%) patients, and correlated with LV dilation (R 2 =0.69, see Figure). RV dysfunction was present in 34 (39%). During a median follow-up of 16 (range, 3 - 71) months, no syncope, VT, heart failure, or sudden death was documented. Conclusions Despite frequent RV dilation that paralleled LV dilation, other CMR findings diagnostic of ARVC in patients with isolated LBBB-morphology PVCs are rare. Hypokinetic segments do not correlate with EKG criteria for

The cardiac electrophysiologic study

The cardiac electrophysiologic study

Experimental Mapping of the Canine KCNJ2 and KCNJ12 Gene Structures and Functional Analysis of the Canine KIR2.2 ion Channel

For many model organisms traditionally in use for cardiac electrophysiological studies, characterization of ion channel genes is lacking. We focused here on two genes encoding the inward rectifier current, KCNJ2 and KCNJ12, in the dog heart. A combination of RT-PCR, 5′-RACE, and 3′-RACE demonstrated the status of KCNJ2 as a two exon gene. The complete open reading frame (ORF) was located on the second exon. One transcription initiation site was mapped. Four differential transcription termination sites were found downstream of two consensus polyadenylation signals. The canine KCNJ12 gene was found to consist of three exons, with its ORF located on the third exon. One transcription initiation and one termination site were found. No alternative splicing was observed in right ventricle or brain cortex. The gene structure of canine KCNJ2 and KCNJ12 was conserved amongst other vertebrates, while current GenBank gene annotation was determined as incomplete. In silico translation of KCN12 revealed a non-conserved glycine rich stretch located near the carboxy-terminus of the KIR2.2 protein. However, no differences were observed when comparing dog with human KIR2.2 protein upon ectopic expression in COS-7 or HEK293 cells with respect to subcellular localization or electrophysiological properties.

Effect of informed consent format on patient anxiety, knowledge, and satisfaction

Multiple formats have been used to deliver information needed for informed consent before a medical procedure, but data comparing formats are conflicting. Sixty-three patients (45 men, age 61 ± 16 years) undergoing an initial diagnostic cardiac electrophysiology study were randomly assigned to 1 of 3 groups: oral, written, or video informed consent using a standardized text for all 3 formats. Anxiety levels were assessed with the Spielberger State-Trait Anxiety Inventory (STAI), and questionnaires were used to assess patient comprehension and satisfaction with the informed consent process. Physician time needed to obtain informed consent was also measured. The effect of informed consent format on anxiety state was evaluated by comparing STAI before and after consent. Multivariable analysis was performed to assess the effects of baseline characteristics on the state anxiety scores. For the oral, written, and video formats, the mean anxiety trait scores were 39 ± 9, 34 ± 8, and 31 ± 7, respectively (P = .005), and baseline anxiety state scores were 49 ± 12, 37 ± 12, and 36 ± 11, respectively (P = .0006). None of the formats had a significant effect on patient anxiety state after consent was obtained. After the procedure, anxiety state declined (P < .0001). There were no differences among the comprehension scores, and patient satisfaction was equivalent among formats. The oral format required the longest physician time (P = .06). For electrophysiologic testing, all 3 formats have similar effects on anxiety and produce equivalent patient comprehension. The oral format requires more physician time. Given the standardization achievable with a written or video format, physicians may consider these options to facilitate obtaining informed consent.

Skin injury following prolonged fluoroscopy: early and late appearances

In October 2005, a 45-year-old woman presented to our centre for evaluation of recurrence of palpitations following a cardiac electrophysiology study performed 7 weeks previously at another centre. The patient had a long history of a hypercoagulable disorder (anti-phospholipid syndrome). At age 40, she had suffered an extensive inferolateral wall myocardial infarction. Coronary angiography demonstrated an occluded large marginal branch of the circumflex artery. This was treated by balloon angioplasty and stent placement. Unfortunately, despite optimal medical therapy, the patient developed progressive left ventricular systolic dysfunction. Indeed, by 4 years after her myocardial infarction, her left ventricular ejection fraction had fallen to 25%. Given the considerable potential for the development of malignant ventricular cardiac dysrhythmias associated with such depressed cardiac function,1 she then underwent prophylactic placement of an implantable cardioverter-defibrillator (ICD) device. She also underwent repeat coronary angiography at this time. This showed continuing patency of the previously placed stent and no other significant stenosis. One year later, the patient experienced multiple ICD shocks. Analysis of the device revealed that the ICD discharges had been caused by episodes of supraventricular tachycardia that had been mistakenly interpreted by the device as episodes of ventricular tachycardia. To address the problem of these inappropriate ICD discharges, the patient underwent a cardiac …

Radiofrequency Catheter Ablation of Life-Threatening Ventricular Arrhythmias Caused by Left Ventricular Metastatic Infiltration

Metastases to the cardiac ventricles are rare and, unfortunately, often follow a rapidly fatal course.1,2 Occasionally, they cause symptomatic ventricular arrhythmias (VAs) for which limited therapeutic options exist, such as antiarrhythmic drugs, whereas the use of catheter ablation, to our knowledge, has never been reported to date. We present the case of a 27-year-old man with a metastatic tumor in the left ventricle and intractable malignant VAs. In February 2009, the patient had been diagnosed with a gluteal sarcoma and initially treated with combined chemotherapy (including anthracyclines) and radiation. Since December 2009, a mild reduction in left ventricular ejection fraction (45%) was detected, and since January 2010, frequent monomorphic premature ventricular contractions (PVCs) and nonsustained ventricular tachycardias (VTs) were documented. Treatment with amiodarone proved helpful, and no life-threatening VAs could be induced on standard electrophysiological study.3 Since April 2010, however, the patient suffered from multiple drug-refractory episodes of sustained VT and ventricular fibrillation, requiring several direct current shocks (Figure 1). His left ventricular ejection fraction had remained stable. Electrical storm resulted in immediate hemodynamic instability and dramatically affected his quality of life. The patient was referred to our institution, where multiple antiarrhythmic drug combinations were tested, both orally and intravenously, allowing a relative stabilization of cardiac rhythm. Cardiac MRI showed a T2-hyperintense, weakly gadolinium-enhanced area at the basis of the anterior papillary muscle, compatible with metastatic infiltration (Figure 2, online-only Data Supplement Movie 1). An oncology consultation hypothesized a life expectancy of <6 months. After about 2 weeks, the recurrence of multiple episodes of VT and ventricular fibrillation required intensive care treatment with deep sedation and assisted ventilation, but still VAs could not be controlled. Thus, a repeat electrophysiological evaluation and radiofrequency …

Ferrets ‐ a small animal alternative to dogs in cardiovascular pharmacology studies

Ferret cardiac ion channels are similar to those in human, dog and to those in species used for in vitro cardiac electrophysiology studies. The ferret heart is relatively large making it suitable for instrumentation while their overall small size (approximately 900g) allows for reduced compound use. The ferret can be a suitable alternative to the dog for early screening of compounds with potential cardiovascular effects. Recent technology improvements in small animal telemetry allow the acquisition of two pressure signals in a single animal. We implanted HD‐S21† pressure transmitters into ferrets and recorded arterial and left ventricular pressures and ECGs in response to milrinone.Dose responsive increases were observed in left ventricular function including indices of inotropy, lusitropy and heart rate. Systemic arterial blood pressure decreased at 3 and 10 mg/kg of milrinone. Milrinone Dose Systolic Pressure* (mmHg) LV Heart Rate* (beats/min) dP/dtmax * (mmHg/sec) dP/dtmin * (mmHg/sec) 1 mg/kg no change ↑ 51.7 ± 16.2 ↑ 6953 ± 1693 ↑ 1419 ± 987 3 mg/kg ↓ 23.6 ± 4.8 ↑ 92.0 ± 14.7 ↑ 8011 ± 1212 ↑ 1840 ± 563 10 mg/kg ↓ 26.1 ± 4.9 ↑ 114.2 ± 9.7 ↑ 8490 ± 661 ↑ 2006 ± 880 Change from vehicle‐treated group In summary, data with a high degree of fidelity and reproducibility can be obtained in a small animal species like the ferret. This species can be used as an alternative to the dog in cardiovascular pharmacology studies.

Severe muscle cramps after intravenous administration of amiodarone - a novel, potentially dose-dependent adverse effect

Amiodarone is a widely available anti-arrhythmic agent used to treat both ventricular and refractory supra-ventricular tachyarrhythmias. The most widely recognized adverse effects of amiodarone include those affecting the eyes, lungs, liver, heart, skin and thyroid. Amiodarone also causes a spectrum of neuromuscular adverse effects, but these usually develop after long-term administration. This report describes a case of acute onset severe muscle cramps in a young man, which developed after initiation of intravenous amiodarone therapy. A 32-year-old Caucasian man was admitted to the cardiac electrophysiology service for ongoing management of recurrent intra-atrial tachycardia. He had a history of congenital heart disease, and had several cardiac electrophysiology studies which showed re-entrant intra-atrial tachycardia, which had recurred in spite of treatment with various anti-arrhythmic agents, multiple electrical cardioversions, radiofrequency catheter ablation and a Cox maze IV procedure. His medication regimen included digoxin, sotalol, furosemide, lisinopril and coumadin. Laboratory tests on admission revealed normal serum electrolytes, hepatic and renal function, normal thyroid-stimulating hormone concentration and an international normalized ratio (INR) of 2.9. After being aggressively diuresed with intravenous furosemide, he received two 250 mg doses of intravenous amiodarone and was then started on a continuous infusion of 900 mg over the next 24 h. About 12 h after initiation of intravenous amiodarone, the patient started complaining of episodic, severe muscle cramps affecting his neck, back, thighs and calves. He described these episodes as involuntary, sustained, painful contractions of the muscles, about 6–8 episodes every hour, each lasting up to 2 min in duration, and not associated with tremors or paresthesiae. A detailed neurological examination revealed no cranial nerve deficits, no focal motor or sensory deficits, normal gait and co-ordination, symmetric deep tendon reflexes and no muscle fasciculations. The only relevant positive finding on physical examination was mild tenderness over the affected muscle groups in his calves. Repeat laboratory tests showed a normal serum chemistry profile (including ionized and total calcium, magnesium and phosphorus concentrations), normal serum creatinine and creatine phosphokinase (CK), normal free T4 concentrations and a normal urinalysis without myoglobinuria. No relevant drug–drug interactions were identified to explain his muscle cramps. He was started on low dose cyclobenzaprine (2.5 mg three times a day) with partial improvement in his symptoms, and amiodarone was continued orally at a dose of 400 mg three times a day. The following day, he underwent direct current cardioversion with 50 joules, and his cardiac rhythm converted to a normal sinus rhythm alternating with an atrial-paced rhythm. His muscle cramps continued unabated, and follow-up neurological examination and laboratory tests remained normal, except for mild elevation of total serum CK (348 units per litre). The oral maintenance dose of amiodarone was reduced to 200 mg once daily, and over the next 12 h or so, the patient's cramps completely resolved. A battery of screening tests for an inherited metabolic myopathy, including serum ketones, lactate, pyruvate, lactate dehydrogenase, uric acid, free and total serum carnitine concentrations, a quantitative serum acylcarnitine profile and serum free fatty acid profile, were within normal limits. Using the Naranjo probability scale for adverse drug effects [1], this case of acute onset severe muscle cramps scored 7 points. This score places this adverse event in the ‘probable’ category for causal association with amiodarone treatment. The patient was continued on the lower maintenance dose of oral amiodarone, and has not had recurrence of muscle cramps after 6 weeks' follow-up. This case has been reported to the United States Food and Drug Administration (FDA) through its Safety Information and Adverse Event Reporting (MedWatch) Program [2]. The prevalence of amiodarone-induced neurotoxicity ranges from 27.5% to 74% [3–5]. The most commonly reported neurologic adverse effects of amiodarone include tremors, ataxia and peripheral neuropathy, but cases of encephalopathy, parkinsonism, optic neuropathy and myopathy have also been reported. Most reports of amiodarone-induced neurotoxicity are in patients on long-term oral maintenance therapy. However, in the literature there are no reports of acute neurotoxicity or myopathy after the use of intravenous amiodarone. A recent consensus guideline recommends monitoring for neurologic adverse effects such as weakness, paresthesiae, tremors and gait abnormalities during follow-up of patients on long-term amiodarone therapy [6]. However, many widely used adverse event monitoring guidelines [7, 8] do not include specific recommendations for monitoring neurologic symptoms. Clinicians need to be cognizant of the known neurotoxic effects of amiodarone therapy. A baseline neurologic examination should be performed in all patients being started on amiodarone therapy, and published recommendations for pharmacovigilance of amiodarone induced adverse effects should include baseline assessment and monitoring for neurologic adverse effects. In conclusion, this is a case of acute, severe muscle cramps associated with the use of intravenous amiodarone in a young man with congenital heart disease, which resolved spontaneously after conversion to oral amiodarone and dose reduction.

Study of Parallel Algorithm Based on OpenMP in Myocardial Simulation

Computer simulation is an important method in the study of cardiac electrophysiology. However, complicated studies in tissues are difficult because of the long computation time. In order to speed up the simulation, in this paper a parallel algorithm based on OpenMP was studied on a multi-core computer. The Noble 91 mathematical model was used to develop a two-dimensional tissue. By initiating a reentrant wave, properties of the conventional sequential program, programs of the data parallelism and functional parallelism were analyzed and compared. The results showed that the execution time of the data parallelism was only about one-fourth of the sequential execution time and its efficiency was high, however, the execution time of the functional parallelism was approximately ten times of the sequential execution time and its efficiency became low. Therefore, the method of the data parallelism could significantly reduce the computation time and was suggested to be a good choice in the myocardial simulation.

Panoramic Imaging Reveals Mechanisms of Resistance to Ventricular Arrhythmias Under Blebbistatin as Compared to 2,3-Butanedione Monoxime (BDM)

Unlike other excitation-contraction uncouplers (such as BDM), blebbistatin does not have apparent side effects, and is increasingly used in cardiac electrophysiology studies using optical mapping. However, the effects of blebbistatin on restitution and ventricular arrhythmia remain unknown. Determining these effects is important for the use of blebbistatin and a better understanding of the mechanisms of arrhythmia. Monophasic action potentials at various cycle lengths were measured before and after the application of blebbistatin in Langendorff-perfused rabbit hearts (n=5). Optical mapping experiments were conducted in rabbit hearts (n=7) which were sequentially perfused with BDM and blebbistatin. Action potential duration (APD) restitution, conduction velocity (CV) restitution, and vulnerability to shock-induced arrhythmia were measured. Panoramic imaging system was used to optically record the action potentials and the reentry circuits from the entire ventricular epicardium. Application of blebbistatin did not change the APD restitution. In contrast, BDM significantly decreased the APD and flattened the APD restitution. BDM also significantly decreased the CV at both longitudinal and transverse directions, and thus decreased the wavelength (APD × CV). Vulnerability to shock-induced arrhythmia was much higher under BDM compared with that under blebbistatin (inducibility of sustained arrhythmia: 23/99 vs. 2/123). Stable reentry was responsible for the sustained arrhythmia under BDM, while wave breaks and wave extinctions were frequent and facilitated the self-termination of shock-induced arrhythmia under blebbistatin. In conclusion, blebbistatin has no significant effect on the APD restitution in the normal rabbit heart, and is associated with low sustainability of shock-induced arrhythmias. Low dynamic instability under BDM facilitates the maintenance of stable reentrant arrhythmia, while the combination of relatively high dynamic instability and long wave length under blebbistatin facilitates the self-termination of reentrant arrhythmia and thus explains the resistance to arrhythmia.

A Case of Manifest WPW Syndrome and Atrioventricular Reentrant Tachycardia Combined with Persistent Left Superior Vena Cava

A case of 41 years old female: She suffered from palpitation which onset and termination occurred suddenly. She was diagnosed as manifest WPW syndrome and admitted in May 2010 to perform a cardiac electrophysiological study and radiofrequency catheter ablation (RFCA). When we delivered the catheter to coronary sinus (CS), it was deviated largely out of the heart to the cranial direction. A persistent left superior vena cava (PLSVC) and dilated CS were confirmed by CS angiography. A narrow QRS tachycardia was induced by atrial pacing, and it was diagnosed as orthodromic atrioventricular reentrant tachycardia which conducts antegradely with normal conducting system and retrogradely with left posterolateral accessory pathway. Also, reverse common type atrial flutter was induced. RFCA was performed. We mapped mitral annulus retrogradely and successfully ablated the accessory pathway. We also made an electrical blockline at cavotricuspid isthmus and ended the session. She had no palpitation since then. Case reports of WPW syndrome combined with PLSVC are rare. The accessory pathway reported in our case was connected to ventricle and atrium in ordinary pattern, though there is a case report of accessory pathway connected with CS musculature. The relation between PLSVC and accessory pathway is unknown, though it may be possible because there is a report that the developmental timing of atrioventricular annulus and CS is same.

Effect of reperfusion time on inducible ventricular tachycardia early and spontaneous ventricular arrhythmias late after ST elevation myocardial infarction treated with primary percutaneous coronary intervention

Prompt thrombolytic reperfusion reduces postinfarct ventricular electrical instability after ST elevation myocardial infarction (STEMI). The purpose of this study was to examine the relationship between reperfusion time and inducible ventricular tachycardia (VT) early and spontaneous ventricular arrhythmias (VAs) late after primary percutaneous coronary intervention (PCI) for STEMI. Consecutive patients were recruited if they (1) had no prior coronary disease, (2) had been reperfused with primary PCI, (3) had postinfarct ejection fraction ≤40%, and (4) had undergone cardiac electrophysiologic study (n = 128). Three groups were compared according to reperfusion time: early (≤3 hours, n = 26), intermediate (>3-5 hours, n = 45), or delayed reperfusion (>5 hours, n = 57). Spontaneous VA was a composite endpoint of sudden death or defibrillator-treated VA. Mean ejection fraction (33% ± 5%, 31% ± 6%, and 31% ± 7%, P = .41) and peak creatinine kinase (P = .37) were similar between groups. VT was inducible in 11.5%, 17.8%, and 36.8% of patients in the early, intermediate, and delayed reperfusion groups, respectively (P = .003). At 2 years, the incidence of spontaneous VA was 0%, 8.9%, and 14% in the early, intermediate, and delayed reperfusion groups, respectively (P = .025). By multivariable analysis, delayed reperfusion conferred a sixfold increase in the odds of inducible VT (P = .01). Although inducible VT was the strongest predictor of spontaneous VA (hazard ratio 14.31, P = .001), delayed reperfusion conferred a threefold increase in risk when inducible VT was excluded from the multivariable model (P = .035). Reperfusion time is a critical determinant of postinfarct ventricular electrical instability early and late after STEMI treated with primary PCI.

Novel Chemical Suppressors of Long QT Syndrome Identified by an In Vivo Functional Screen

Genetic long QT (LQT) syndrome is a life-threatening disorder caused by mutations that result in prolongation of cardiac repolarization. Recent work has demonstrated that a zebrafish model of LQT syndrome faithfully recapitulates several features of human disease, including prolongation of ventricular action potential duration, spontaneous early afterdepolarizations, and 2:1 atrioventricular block in early stages of development. Because of their transparency, small size, and absorption of small molecules from their environment, zebrafish are amenable to high-throughput chemical screens. We describe a small-molecule screen using the zebrafish KCNH2 mutant breakdance to identify compounds that can rescue the LQT type 2 phenotype. Zebrafish breakdance embryos were exposed to test compounds at 48 hours of development and scored for rescue of 2:1 atrioventricular block at 72 hours in a 96-well format. Only compounds that suppressed the LQT phenotype in 3 of 3 fish were considered hits. Screen compounds were obtained from commercially available small-molecule libraries (Prestwick and Chembridge). Initial hits were confirmed with dose-response testing and time-course studies. Optical mapping with the voltage-sensitive dye di-4 ANEPPS was performed to measure compound effects on cardiac action potential durations. Screening of 1200 small molecules resulted in the identification of flurandrenolide and 2-methoxy-N-(4-methylphenyl) benzamide (2-MMB) as compounds that reproducibly suppressed the LQT phenotype. Optical mapping confirmed that treatment with each compound caused shortening of ventricular action potential durations. Structure activity studies and steroid receptor knockdown suggest that flurandrenolide functions via the glucocorticoid signaling pathway. Using a zebrafish model of LQT type 2 syndrome in a high-throughput chemical screen, we have identified 2 compounds, flurandrenolide and the novel compound 2-MMB, as small molecules that rescue the zebrafish LQT type 2 syndrome by shortening the ventricular action potential duration. We provide evidence that flurandrenolide functions via the glucocorticoid receptor-mediated pathway. These 2 molecules and future discoveries from this screen should yield novel tools for the study of cardiac electrophysiology and may lead to novel therapeutics for human LQT patients.

E0227 Intracoronary infusion of mesenchymal stem cells reduces proarrhythmogenic risks in swine with myocardial infarction

ObjectiveTo evaluate the risk of ventricular arrhythmias (VAs) after MSC transplantation in swine model with acute myocardial infarction.MethodsSwine models with myocardial infarction were created by intracoronary balloon occlusion and then...

Inappropriate shock delivery by implantable cardioverter defibrillator due to electrical leak from bathroom tap

There are some case reports of electromagnetic interference (EMI) mimicking cardiac arrhythmias and causing inappropriate implantable cardioverter defibrillator (ICD) shocks. EMI can arise from appliances, such as slot machines, electric razors, hand held radiofrequency remote controls or abdominal muscle stimulator units, but it can also arise from alternating current leak from, for example, a washing machine, swimming pool, etc. [1–8]. Such interference is recognized easily in the stored intracardiac electrograms of ICDs because of the typical pattern of electrical noise. Here, we report a case who experienced inappropriate ICD shock, resulting from the ICD sensing alternating current (AC) from an unexpected external source (a bathroom tap). The patient is a 77-year-old male with depressed left ventricular function, who suffered from recurrent symptomatic ventricular tachycardia (VT). Electrocardiography documented monomorphic VT and cardiac electrophysiological study revealed inducible sustained monomorphic VT. A single chamber ICD (Maximo VR 7232, Medtronic Inc., Minneapolis, MN, USA) was implanted. The ICD lead was a Sprint Quattro RV/SVC model 6944 (Medtronic Inc., Minneapolis, MN, USA) with true bipolar sensing. He had five episodes of VT terminated by antitachycardia pacing or low energy cardioversion in January 2009. After hospitalization and intravenous amiodarone therapy, he had no further recurrence of ventricular arrhythmias. He experienced an ICD shock in January 2010. Device interrogation revealed typical EMI consistent with 50-Hz alternating current on the ventricular channel. A 15-J shock was delivered. Sensitivity was programmed to 0.3 mV. Pacing lead impedance was 816 X and shocking lead impedance was 53 X. There was no evidence of ICD system malfunction. He was preparing to wash his hands in the bathroom and touched the tap with his wet left hand shortly before the inappropriate shock. He felt the shock and then remained asymptomatic. Review of the intracardiac EGM (Fig. 1) reveals the onset of high-frequency noise detected by the ICD as VF, superimposed on normal R-waves marching through the noise. The tap of the bathroom was inspected by a licensed electrician and a small amount of current leak was detected. The electrician found that the leak originated from inappropriately earthed bathroom socket which was attached to the water pipe for grounding. The socket was regrounded properly and the patient was advised again about electrical appliances. This case is a typical example of potential environmental hazards to patients who have ICDs, particularly when electrical appliances and instruments are not sufficiently earthed. When household appliances are earthed improperly, the potential for electrical leak is the result. Detailed advice on handling electrical appliances by ICD recipients is of utmost importance. In patients who experience ICD shocks because of electrical leak, the history and examination of stored intracardiac electrograms are typical. The high-frequency noise of the leak was easily detected by the ICD. Because household appliances are not earthed in some rural parts of Turkey, the potential for electrical leak is very high like our patient. The noise on the stored intracardiac electrogram is typical of this type of EMI. It is recommended that checking for electrical leaks and grounding should be A. Camsari (&) D. C. Yilmaz T. Ozcan Department of Cardiology, Mersin University Medical Faculty, Mersin, Turkey e-mail: ahmetcamsari@yahoo.com

Feasibility of high‐density electrophysiological study using multiple‐electrode array in isolated small animal atria

1. High-density cardiac electrophysiological study (EPS) of small animal atria has been limited to optical mapping techniques, which require complex and expensive equipment setup. We aim to evaluate the feasibility of carrying out EPS in isolated atrial tissues using a custom made high-density multiple-electrode array (MEA). 2. Isolated rat atrial preparations were studied. The MEA (4 × 5 mm) consisted of 90 silver chloride coated electrodes (0.1 mm diameter, 0.5 mm pitch) and was connected to a conventional EP system yielding 80 bipolar signals. Atrial tissues were placed over the MEA in a dish bubbled with 100% oxygen and superfused with modified HEPES solution at pH 7.35 and 37°C. Then, 1 mmol of 2,3-butanedione monoxime was added to suppress motion artifacts from muscle contractions. Custom plaque analysis software was used for offline conduction analysis. 3. Isolated atrial tissues showed good viability of > 30 min, allowing ample time for complete EPS. High quality electrograms with excellent signal to noise ratio were obtained. All electrophysiological parameters showed good reproducibility: effective refractory period, conduction velocity and heterogeneity index. Tachycardia was also inducible in these normal atria. 4. The present study shows the feasibility of performing high-density EPS of small isolated atrial tissues with a conventional electrode-based technique. The MEA system is compatible with standard electrophysiology recording systems and provides a novel, inexpensive option for detailed EPS in small animal models. In particular, it presents new research avenues to further explore the mechanisms of atrial arrhythmias in various transgenic and knockout rodent models.

Selection and collection of multi parameter physiological data for cardiac rhythm diagnostic algorithm development

Automated diagnostic algorithms are used in implantable cardioverter-defibrillators (ICD's) to detect abnormal heart rhythms. Algorithms misdiagnose and improved specificity is needed to prevent inappropriate therapy. Knowledge engineering (KE) and artificial intelligence (AI) could improve this. A pilot study of KE was performed with artificial neural network (ANN) as AI system. A case note review analysed arrhythmic events stored in patients ICD memory. 13.2% patients received inappropriate therapy. The best ICD algorithm had sensitivity 1.00, specificity 0.69 (p<0.001 different to gold standard). A subset of data was used to train and test an ANN. A feed-forward, back-propagation network with 7 inputs, a 4 node hidden layer and 1 output had sensitivity 1.00, specificity 0.71 (p<0.001). A prospective study was performed using KE to list arrhythmias, factors and indicators for which measurable parameters were evaluated and results reviewed by a domain expert. Waveforms from electrodes in the heart and thoracic bio-impedance; temperature and motion data were collected from 65 patients during cardiac electrophysiological studies. 5 incomplete datasets were due to technical failures. We concluded that KE successfully guided selection of parameters and ANN produced a usable system and that complex data collection carries greater risk of technical failure, leading to data loss.

Acute electrophysiologic consequences of pyridostigmine inhibition of cholinesterase in humans

The cardiovascular electrophysiologic basis for the action of pyridostigmine, an acetylcholinesterase inhibitor, has not been investigated. The objective of the present study was to determine the cardiac electrophysiologic effects of a single dose of pyridostigmine bromide in an open-label, quasi-experimental protocol. Fifteen patients who had been indicated for diagnostic cardiac electrophysiologic study underwent two studies just before and 90-120 min after the oral administration of pyridostigmine (45 mg). Pyridostigmine was well tolerated by all patients. Wenckebach nodal anterograde atrioventricular point and basic cycle were not altered by pyridostigmine. Sinus recovery time (ms) was shorter during a 500-ms cycle stimulation (pre: 326 +/- 45 vs post: 235 +/- 47; P = 0.003) but not during 400-ms (pre: 275 +/- 28 vs post: 248 +/- 32; P = 0.490) or 600-ms (pre: 252 +/- 42 vs post: 179 +/- 26; P = 0.080) cycle stimulation. Pyridostigmine increased the ventricular refractory period (ms) during the 400-ms cycle stimulation (pre: 238 +/- 7 vs post: 245 +/- 9; P = 0.028) but not during the 500-ms (pre: 248 +/- 7 vs post: 253 +/- 9; P = 0.150) or 600-ms (pre: 254 +/- 8 vs post: 259 +/- 8; P = 0.255) cycle stimulation. We conclude that pyridostigmine did not produce conduction disturbances and, indeed, increased the ventricular refractory period at higher heart rates. While the effect explains previous results showing the anti-arrhythmic action of pyridostigmine, the clinical impact on long-term outcomes requires further investigation.

Blebbistatin Effectively Uncouples the Excitation-Contraction Process in Zebrafish Embryonic Heart

Background/Aims: The zebrafish is an emerging model system for the study of cardiac electrophysiology and human arrhythmias. High resolution imaging techniques are powerful tools for the study of zebrafish cardiac electrophysiology, but these methods require the complete absence of cardiac contraction. Many pharmacological agents that uncouple cardiac contraction also markedly alter the cardiac action potential (AP). In this study, we compared the effects two uncoupling agents, 2,3-Butanedione monoxime (BDM) and blebbistatin, on contractility and AP parameters in embryonic zebrafish heart. Methods: Zebrafish hearts were explanted (48 hpf) and superfused with either BDM (15 mM) or blebbistatin (1, 5 or 10 µM), while recording atrial or ventricular APs with the disrupted patch technique. Calcium transients were recorded with a high-speed confocal scanning microscope in hearts loaded intracellularly with 10 µM fluo-4 and superfused with 10 µM blebbistatin. Results: Despite abolishing cardiac contractility, BDM altered ventricular AP morphology and inhibited spontaneous APs. In contrast, blebbistatin (10 µM) abolished contractility without significantly altering AP morphology or generation of spontaneous APs. Blebbistatin allowed for high fidelity measurements of atrial and ventricular calcium transients. Conclusion: Blebbistatin is a potent and effective excitation-contraction uncoupling agent in embryonic zebrafish heart.