Inducible Sustained Ventricular Tachycardia Research Articles

Sustained Ventricular Tachycardia in a Patient with Tetralogy of Fallot—with a “Twist”

KEY POINTS There are common and uncommon associated conditions that may accompany patients with tetralogy of Fallot (TOF). These associated conditions may significantly complicate surgical or percutaneous treatment of patients with TOF. Arrhythmias are often the result of hemodynamic compromise in TOF. Most commonly this is due to progressive right ventricular dilatation secondary to chronic pulmonary valve regurgitation. Evaluation of arrhythmias should always be preceded by an evaluation of the patient’s surgical repair (valves, conduits, ventricular septal defect) and hemodynamics. Surgical pulmonary valve replacement has been demonstrated to reduce the risk of ventricular tachycardia in patients with severe pulmonary regurgitation and RV enlargement. Among patients who present with ventricular tachycardia in the absence of a correctable lesion or hemodynamic compromise, an electrophysiologic study and radiofrequency ablation may be an effective option for the treatment of ventricular tachycardia. Although clinical risk factors associated with ventricular arrhythmias and sudden death have been identified, appropriate selection of patients who would benefit from an implantable cardioverterdefibrillator (ICD) for primary or even secondary prevention of sudden death remains a clinical challenge. Preliminary data have demonstrated that appropriate ICD shocks occur frequently among patients who have an ICD implanted, but inappropriate shocks and immediate and long-term complications are frequent in the population, and should be weighed carefully when considering ICD implantation. Current guidelines for ICD implantation endorse implantation of an ICD for secondary prevention, or among patients who experience syncope that is concerning for cardiac arrhythmia and inducible sustained monomorphic ventricular tachycardia at electrophysiologic study.

Abstract 18950: Invasive Electrophysiology Study has Higher Sensitivity and Specificity for Sudden Cardiac Death in Patients with Congenital Heart Disease than those with Structurally Normal Hearts

Introduction: The use of electrophysiology study (EPS) in pediatric and congenital heart disease (CHD) patients to identify at risk subjects for sudden cardiac death (SCD) and implantable cardiac defibrillator (ICD) is often debated. Objectives: We assessed the hypothesis that EPS was more predictive for SCD or appropriate ICD discharge in patients with CHD compared to those with structurally normal hearts. Methods: A 15 year retrospective database review was performed for subjects undergoing EPS risk stratification for SCD. Positive EPS was defined as inducible sustained ventricular tachycardia or fibrillation by programmed stimulation. Data included demographics, EPS indications, outcome of EPS, ICD complications, and follow up SCD or ICD discharge. The primary endpoint was SCD or appropriate ICD discharge. Results: The study included169 subjects with mean age of 19.1 ± 7.8 years, mean follow up after EPS of 5.8 ± 4.3 years. Of these, 50 subjects (30%) had positive EPS, with ICDs subsequently placed in 28 (56%). There were 119 subjects (70%) with negative EPS, and ICDs were placed in 9 (7%). There were 85 subjects (50%) with CHD. There were no SCDs in either group. During follow-up, 10 of 37 subjects (24%) with ICDs had appropriate discharges (6 with CHD and 4 without CHD). Device related complications including recalls were seen in 21 of 37 patients (57%). The ICD shock rate, sensitivity and specificity of EPS are shown in the Table. Sub group analysis of right heart obstruction CHD lesions (n=44) showed similar results between these patients and all CHD patients (Table). Conclusions: The use of diagnostic EPS has a higher sensitivity and specificity for appropriate ICD discharge in pediatric patients with CHD compared to those with structurally normal hearts.

Usefulness of Inducible Ventricular Tachycardia to Predict Long-Term Adverse Outcomes in Arrhythmogenic Right Ventricular Cardiomyopathy

The role of the electrophysiologic (EP) study for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy is controversial. We investigated the role of inducible sustained monomorphic ventricular tachycardia (SMVT) for the prediction of an adverse outcome (AO), defined as the occurrence of cardiac death, heart transplantation, sudden cardiac death, ventricular fibrillation, ventricular tachycardia with hemodynamic compromise or syncope. Of 62 patients who fulfilled the 2010 Arrhythmogenic Right Ventricular Cardiomyopathy Task Force criteria and underwent an EP study, 30 (48%) experienced an adverse outcome during a median follow-up of 9.8 years. SMVT was inducible in 34 patients (55%), 22 (65%) of whom had an adverse outcome. In contrast, in 28 patients without inducible SMVT, 8 (29%) had an adverse outcome. Kaplan-Meier analysis showed an event-free survival benefit for patients without inducible SMVT (log-rank p= 0.008) with a cumulative survival free of an adverse outcome of 72% (95% confidence interval [CI] 56% to 92%) in the group without inducible SMVT compared to 26% (95% CI 14% to 50%) in the other group after 10 years. The inducibility of SMVT during the EP study (hazard ratio [HR] 2.99, 95% CI 1.23 to 7.27), nonadherence (HR 2.74, 95% CI 1.3 to 5.77), and heart failure New York Heart Association functional class II and III (HR 2.25, 95% CI 1.04 to 4.87) were associated with an adverse outcome on univariate Cox regression analysis. The inducibility of SMVT (HR 2.52, 95% CI 1.03 to 6.16, p= 0.043) and nonadherence (HR 2.34, 95% CI 1.1 to 4.99, p= 0.028) remained as significant predictors on multivariate analysis. This long-term observational data suggest that SMVT inducibility during EP study might predict an adverse outcome in patients with arrhythmogenic right ventricular cardiomyopathy, advocating a role for EP study in risk stratification.

Connexin43 Gene Transfer Reduces Ventricular Tachycardia Susceptibility After Myocardial Infarction

The aim of this study was to evaluate the links between connexin43 (Cx43) expression, myocardial conduction velocity, and ventricular tachycardia in a model of healed myocardial infarction. Post-infarction ventricular arrhythmias frequently cause sudden death. Impaired myocardial conduction has previously been linked to ventricular arrhythmias. Altered connexin expression is a potential source of conduction slowing identified in healed scar border tissues. The functional effect of increasing border-zone Cx43 has not been previously evaluated. Twenty-five Yorkshire pigs underwent anterior infarction by transient left anterior descending coronary artery occlusion, followed by weekly testing for arrhythmia inducibility. Twenty animals with reproducibly inducible sustained monomorphic ventricular tachycardia were randomized 2:1:1 to receive AdCx43, Adβgal, or no gene transfer. One week later, animals underwent follow-up electrophysiologic study and tissue assessment for several functional and molecular measures. Animals receiving AdCx43 had less electrogram fractionation and faster conduction velocity in the anterior-septal border zone. Only 40% of AdCx43 animals remained inducible for ventricular tachycardia, while 100% of controls were inducible after gene transfer. AdCx43 animals had 2-fold higher Cx43 protein levels in the anterior-septal infarct border, with similar percents of phosphorylated and intercalated disk-localized Cx43 compared with controls. These data mechanistically link Cx43 expression to slow conduction and arrhythmia susceptibility in the healed scar border zone. Targeted manipulation of Cx43 levels improved conduction velocity and reduced ventricular tachycardia susceptibility. Cx43 gene transfer represents a novel treatment strategy for post-infarction arrhythmias.

Symptomatic but not asymptomatic non-sustained ventricular tachycardia is associated with appropriate implantable cardioverter therapy in tetralogy of Fallot

BackgroundA recently developed risk score model aims to predict appropriate implantable cardioverter defibrillator (ICD) therapy for primary prevention of sudden cardiac death in tetralogy of Fallot (TOF). We assessed the validity of the proposed risk score model. MethodsPatients included in a retrospective international cohort were stratified according to the risk score system. Risk factors were prior shunt, inducible sustained ventricular tachycardia, QRS≥180ms, ventriculotomy incision, nonsustained ventricular tachycardia (NSVT) and left ventricular end-diastolic pressure≥12mmHg (LVEDP). Left ventricular ejection fraction ≤35% measured by means of echocardiography was used because LVEDP values were incomplete in our cohort. ResultsThirty-six adults had TOF and ICD for primary prevention (72% male, mean age 37±12). Seven patients (19%) received appropriate shocks during a median follow-up of 5.5years. Of the proposed risk factors only NSVT was associated with appropriate shocks (HR 2.6, CI 1.1–6.0, P=0.02). Patients with asymptomatic NSVT did not receive any appropriate shocks. The 8-year Kaplan–Meier estimate from the first appropriate shock was 86%, 78% and 75% for low, intermediate and high risk patients, respectively. In this study, the annual rate of appropriate shocks was 4.1% in the high risk group which was considerably lower than that reported by Khairy and colleagues (17.5%). ConclusionsThe risk score model of Khairy and colleagues was capable of identifying low versus intermediate/high risk patients. However, event rates of lethal arrhythmias were lower in our cohort than previously reported. Symptomatic but not asymptomatic NSVT was the sole clinical variable associated with appropriate ICD therapy in TOF.

Characterization of Gap Junction Remodeling in Epicardial Border Zone of Healing Canine Infarcts and Electrophysiological Effects of Partial Reversal by Rotigaptide

The border zone of healing myocardial infarcts is an arrhythmogenic substrate, partly the result of structural and functional remodeling of the ventricular gap junction protein, Connexin43 (Cx43). Cx43 in arrhythmogenic substrates is a potential target for antiarrhythmic therapy. We characterized Cx43 remodeling in the epicardial border zone (EBZ) of healing canine infarcts 5 days after coronary occlusion and examined whether the gap junction-specific agent rotigaptide could reverse it. Cx43 remodeling in the EBZ was characterized by a decrease in Cx43 protein, lateralization, and increased Cx43 phosphorylation at serine (S) 368. Rotigaptide partially reversed the loss of Cx43 but did not affect the increase in S368 phosphorylation, nor did it reverse Cx43 lateralization. Rotigaptide did not prevent conduction slowing in the EBZ, nor did it decrease the induction of sustained ventricular tachycardia by programmed stimulation, although it did decrease the EBZ effective refractory period. We conclude that partial reversal of Cx43 remodeling in healing infarct border zone may not be sufficient to restore normal conduction or prevent arrhythmias.

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

CAN SLEEP-DISORDERED BREATHING BE AN INDEPENDENT PREDICTOR OF MALIGNANT VENTRICULAR ARRHYTHMIAS IN PATIENTS WITH HEART FAILURE?

Background: Sleep-disordered breathing (SDB) is common and increases mortality rate independently in patients with heart failure (HF). Furthermore, current research suggests that SDB might be an independent predictor of life-threatening ventricular arrhythmias. However, it is still unknown whether SDB have a role to play in electrophysiological background in patient with HF. We assessed the hypothesis that SDB plays an important role in electrophysiological background and contributes to the risk of life-threatening ventricular arrhythmia in patients with HF. Methods: We performed both sleep study and electrophysiologic study in consecutive 33 HF patients and analyzed the relationship between SDB and electrophysiologic data such as AV conduction, ventricular effective refractory period and the inducibility of sustained ventricular tachycardia or fibrillation. All patients had an ejection fraction 10 events/hour on the sleep study. Results: SDB was diagnosed in 22 of 33 patients (67%). There were no statistical differences between patients with and without SDB in baseline characteristics with respect to age, male gender, NYHA class, left ventricular ejection fraction, underlying cardiac disease and medications. AV nodal conduction and ventricular effective refractory period were not significantly differences among two groups. However, the induciblity of ventricular tachyarrhythmia was significantly higher in patients with SDB than those without SDB (73%vs.27%, p=0.013). Conclusions: The present study suggests that SDB can be a risk factor of malignant ventricular arrhythmias without affecting ventricular refractory period in patients with HF.

Effect of biventricular pacing on ventricular repolarization and functional indices in patients with heart failure: lack of association with arrhythmic events

We prospectively assessed the effects of biventricular (BiV) pacing on electrocardiographic (ECG) and vectorcardiographic (VCG) descriptors of ventricular depolarization and repolarization and their association with appropriate implantable cardioverter defibrillator (ICD) activation. We studied 70 consecutive heart failure (HF) (37 ischaemic) patients (64 males, age 66.3 years) with a history of syncope or sustained ventricular tachycardia (VT) who underwent implantation of a BiV-ICD. An invasive electrophysiological study (EPS) was performed before the implantation and 12-lead digital ECGs before and 30 days after implantation. Serial echocardiographic studies were performed. Follow-up duration was 1 year. Maximum (P < 0.001) and minimum (P = 0.004) QT intervals were significantly decreased, whereas QT dispersion was not altered (P = 0.086). QRS duration was shortened (P < 0.001), whereas QRS dispersion was significantly decreased (P = 0.034). Spatial T and QRS vector amplitudes decreased (P < 0.001, for both), whereas the spatial QRS-T angle was not affected (P = 0.671). Twenty-seven (38.6%) patients, experienced appropriate ICD therapies during follow-up. None of the ECG or VCG parameters (pre- or post-implant) were able to identify patients with appropriate ICD therapies during follow-up. Only the presence of a previous episode of sustained VT (spontaneous or inducible on EPS) was strongly associated with appropriate ICD therapies (multivariate P = 0.00 014; odds ratio 24.5). Improvement or no alteration of ECG and VCG descriptors of ventricular depolarization and repolarization was demonstrated after implantation of a BiV-ICD in HF patients. None of these parameters were associated with appropriate ICD therapies, whereas a previous episode of VT or induction of sustained VT on EPS predicted appropriate ICD treatments.

Malignant Ventricular Arrhythmia in a Case of Adult Onset of Spinal Muscular Atrophy (Kugelberg–Welander Disease)

We present a case of a 43-year-old male patient with adult onset of spinal muscular atrophy (SMA). The patient first came to our attention with atrioventricular (AV) block. A dual-chamber pacemaker (DDD-PM) was implanted. Four years later, the PM data log showed occurrence of frequent episodes of nonsustained ventricular tachycardia (NSVT). The episodes progressed in duration and frequency. An electrophysiological study revealed prolonged His-ventricular (HV) interval duration and induction of sustained ventricular tachycardia. The patient was successfully upgraded to a prophylactic dual-chamber cardioverter defibrillator. Our case is the first description of a patient with adult-onset SMA (Kugelberg-Welander disease [KWD]) and malignant ventricular arrhythmias.

Compliance to MADIT and MUSTT criteria for implantable cardioverter defibrillator therapy in the pre-SCD-Heft and MADIT II era. Data from a multicenter Italian study

The follow-up of 1440 consecutive post-MI patients (68.9 ± 10.9 years) with an LVEF ≤ 40% was analyzed in 19 Italian hospitals to evaluate how many patients with clinical nonsustained VT and inducible sustained VT or VF underwent post-discharge risk assessment (RA). During 38 (range, 4-76) months follow-up, 611 patients (42.4%) qualified for and 294 (20.4%) effectively underwent RA combining LVEF assessment and Holter monitoring, 29 (2.0%) subsequently underwent programmed electrical stimulation and 19 (1.3%) received an ICD.

ECG Quantification of Myocardial Scar in Cardiomyopathy Patients With or Without Conduction Defects

Background— Myocardial scarring from infarction or nonischemic fibrosis forms an arrhythmogenic substrate. The Selvester QRS score has been extensively validated for estimating myocardial infarction scar size in the absence of ECG confounders, but has not been tested to quantify scar in patients with hypertrophy, bundle branch/fascicular blocks, or nonischemic cardiomyopathy. We assessed the hypotheses that (1) QRS scores (modified for each ECG confounder) correctly identify and quantify scar in ischemic and nonischemic patients when compared with the reference standard of cardiac magnetic resonance using late-gadolinium enhancement, and (2) QRS-estimated scar size predicts inducible sustained monomorphic ventricular tachycardia during electrophysiological testing. Methods and Results— One hundred sixty-two patients with left ventricular ejection fraction ≤35% (95 ischemic, 67 nonischemic) received 12-lead ECG and cardiac magnetic resonance using late-gadolinium enhancement before implantable cardioverter defibrillator placement for primary prevention of sudden cardiac death. QRS scores correctly diagnosed cardiovascular magnetic resonance scar presence with receiver operating characteristics area under the curve of 0.91 and correlation for scar quantification of r =0.74 ( P &lt;0.0001) for all patients. Performance within hypertrophy, conduction defect, and nonischemic subgroups ranged from area under the curve of 0.81 to 0.94 and r =0.60 to 0.80 ( P &lt;0.001 for all). Among the 137 patients undergoing electrophysiological or device testing, each 3-point QRS-score increase (9% left ventricular scarring) was associated with an odds ratio for inducing monomorphic ventricular tachycardia of 2.2 (95% CI, 1.5 to 3.2; P &lt;0.001) for all patients, 1.7 (1.0 to 2.7, P =0.04) for ischemics, and 2.2 (1.0 to 5.0, P =0.05) for nonischemics. Conclusions— QRS scores identify and quantify scar in ischemic and nonischemic cardiomyopathy patients despite ECG confounders. Higher QRS-estimated scar size is associated with increased arrhythmogenesis and warrants further study as a risk-stratifying tool.

Abstract 2122: ECG Quantification of Myocardial Scar in Cardiomyopathy Patients with or without Conduction Defects: Correlation with Cardiac Magnetic Resonance and Arrhythmogenesis

Background : Myocardial scarring from infarction (MI) or nonischemic fibrosis forms an arrhythmogenic substrate. The Selvester QRS-score estimates MI size by quantifying changes in Q-, R- and S-wave durations, amplitudes and morphologies from the 12-lead electrocardiogram (ECG). It provides 32 possible points with each point reflecting scarring of 3% of the left ventricle (LV). Although QRS scoring has been extensively validated for estimating MI scar size in the absence of ECG confounders, it has not been validated in patients with left ventricular hypertrophy (LVH), fascicular/bundle branch blocks or nonischemic scar. We assessed the hypotheses that QRS-scores (modified for each conduction type) correctly identify and quantify both ischemic and nonischemic scar as compared to the reference standard of Cardiac Magnetic Resonance - Late Gadolinium Enhancement (CMR-LGE) and QRS-estimated scar size is associated with inducible sustained monomorphic ventricular tachycardia (MVT) during electrophysiologic (EP) testing. Methods and Results: A prospective 162 patient cohort with LV dysfunction (95 ischemic, 67 nonischemic) received 12-lead ECG and CMR-LGE before defibrillator (ICD) implantation for primary prevention of sudden cardiac death. QRS-scores correctly diagnosed CMR-scar presence with receiver operating characteristics (ROC) area under the curve (AUC)=0.91 and correlation for scar quantification of r=0.74, p&lt;0.0001, for all patients. Performance within the LVH, bundle branch/fascicular block and nonischemic subgroups ranged from AUC 0.81– 0.94, r=0.60 – 0.80, p&lt;0.001 for all. Of the 137 patients undergoing EP or device testing, 37/82 (45%) of ischemic and 7/55 (13%) of nonischemic patients had inducible MVT. For each 3 QRS point increase (9% LV scarring), the odds ratio for inducing MVT was 2.2 [95% CI: 1.5–3.2, p&lt;0.001] for all patients; 1.7 [1.0 –2.7, p=0.04)] for ischemics; and 2.2 [1.0 –5.0, p=0.05] for nonischemics. Conclusions : Compared to CMR, QRS-scores identify and quantify MI and nonischemic scar despite ECG confounders. Higher QRS-estimated scar size is associated with increased arrhythmogenic potential and warrants further study as a risk-stratifying tool for patients with left ventricular dysfunction.

Usefulness of Nonlinear Analysis of ECG Signals for Prediction of Inducibility of Sustained Ventricular Tachycardia by Programmed Ventricular Stimulation in Patients with Complex Spontaneous Ventricular Arrhythmias

The aim of our study was to assess the effectiveness of the nonlinear analysis (NLA) of ECG in predicting the results of invasive electrophysiologic study (EPS) in patients with ventricular arrhythmias. We evaluated 25 patients with history of cardiac arrest, syncope, sustained, or nonsustained ventricular tachycardia (VT). All patients underwent electrophysiologic study (EPS) and nonlinear analysis (NLA) of ECG. The study group was compared with a control group of 25 healthy subjects, in order to define the normal range of NLA. ECG was processed in order to obtain numerical values, which were analyzed by nonlinear mathematical functions. Patients were classified through the application of a clustering procedure to the whole set of functions, and the correlation between the results of nonlinear analysis of ECG and EPS was tested. NLA assigned all patients with negative EPS to the same class of healthy subjects, whereas the patients in whom VT was inducible had been correctly and clearly isolated into a separate cluster. In our study, the result of NLA with application of the clustering technique was significantly correlated to that of EPS (P < 0.001), and was able to predict the result of EPS, with a negative predictive value of 100% and a positive predictive value of 100%. NLA can predict the results of EPS with good negative and positive predictive value. However, further studies are needed in order to verify the usefulness of this noninvasive tool for sudden death risk stratification in patients with ventricular arrhythmias.

ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities

ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities

Limitations of Ejection Fraction for Prediction of Sudden Death Risk in Patients With Coronary Artery Disease: Lessons From the MUSTT Study

We determined the contribution of multiple variables to predict arrhythmic death and total mortality risk in patients with coronary disease and left ventricular dysfunction. We then constructed an algorithm to predict risk of mortality and sudden death. Many factors in addition to ejection fraction (EF) influence the prognosis of patients with coronary disease. However, there are few tools to use this information to guide clinical decisions. We evaluated the relationship between 25 variables and total mortality and arrhythmic death in 674 patients enrolled in the MUSTT (Multicenter Unsustained Tachycardia Trial) study that did not receive antiarrhythmic therapy. We then constructed risk-stratification algorithms to weight the prognostic impact of each variable on arrhythmic death and total mortality risk. The variables having the greatest prognostic impact in multivariable analysis were functional class, history of heart failure, nonsustained ventricular tachycardia not related to bypass surgery, EF, age, left ventricular conduction abnormalities, inducible sustained ventricular tachycardia, enrollment as an inpatient, and atrial fibrillation. The model demonstrates that patients whose only risk factor is EF < or =30% have a predicted 2-year arrhythmic death risk <5%. Multiple variables influence arrhythmic death and total mortality risk. Patients with EF < or =30% but no other risk factor have low predicted mortality risk. Patients with EF >30% and other risk factors may have higher mortality and a higher risk of sudden death than some patients with EF < or =30%. Thus, risk of sudden death in patients with coronary disease depends on multiple variables in addition to EF.

Sustained Polymorphic Arrhythmias Induced by Programmed Ventricular Stimulation have Prognostic Value in Patients Receiving Defibrillators

Patients with ischemic cardiomyopathy (ICM) who have monomorphic ventricular tachycardia (VT) induced by programmed ventricular stimulation (PVS) are at increased risk of sudden cardiac death (SCD). Among a primary prevention population, the prognostic significance of induced polymorphic ventricular arrhythmias is unknown. A total of 105 consecutive patients who received an implantable cardioverter-defibrillator (ICD) for primary prevention of SCD in the setting of ICM and non-sustained VT were retrospectively evaluated. Seventy-five patients (group I) had induction of monomorphic VT and 30 patients (group II) had a sustained ventricular arrhythmia other than monomorphic VT (ventricular flutter, ventricular fibrillation, and polymorphic VT) induced during PVS. Baseline characteristics were similar between group I and group II except for ejection fraction (25% vs. 31%, P = 0.0001) and QRS duration (123 milliseconds vs. 109 milliseconds, P = 0.04). Sixteen of 75 (21.3%) patients in group I and 6 of 30 (20%) patients in group II received appropriate ICD therapy (P = 0.88). Survival free from ICD therapy was similar between groups (P = 0.54). There was a trend toward increased all-cause mortality among patients in group I by Kaplan-Meier analysis (P = 0.08). However, when adjusted for age, EF, and QRS duration mortality was similar (P = 0.45). There is no difference in rates of appropriate ICD discharge or mortality between patients dichotomized by type of rhythm induced during PVS. These results suggest that patients in this population who have inducible VF or sustained polymorphic VT have similar rates of subsequent clinical ventricular tachyarrhythmias as those with inducible monomorphic VT.

Clinical and Electrophysiological Spectrum of Idiopathic Ventricular Outflow Tract Arrhythmias

This study sought to compare and contrast the clinical and electrophysiological characteristics of outflow tract arrhythmias. Idiopathic ventricular outflow tract arrhythmias manifest clinically in 3 forms: 1) paroxysmal sustained monomorphic ventricular tachycardia (SMVT), 2) repetitive nonsustained ventricular tachycardia (NSVT), or 3) premature ventricular contractions (PVCs). Although these arrhythmias have a similar site of origin, it is unknown whether they share a common mechanism or similar clinical features. A total of 127 patients (63 female [50%], mean age 51 +/- 15 years) were evaluated for outflow tract arrhythmias. A total of 36 (28%) presented with the index clinical arrhythmia of SMVT, 46 (36%) with NSVT, and 45 (35%) with PVCs. The sites of origin of the arrhythmias were similar among the 3 groups, occurring in the right ventricular outflow tract in 82%. Sustained ventricular tachycardia was more likely to be induced during exercise in the SMVT (10 of 15 patients [67%]) than NSVT or PVCs groups (p < 0.01). Sustained outflow tract ventricular tachycardia was induced at electrophysiology study in 78% of SMVT patients, 48% of NSVT patients, and 4% of PVCs patients. Adenosine was similarly effective in all 3 groups (p = NS). Patients with outflow tract arrhythmias can be differentiated based on the subtype of arrhythmia. However, the observation that approximately 50% of patients with NSVT and approximately 5% of patients with PVCs have inducible sustained ventricular tachycardia that behaves in an identically unique manner to those who present with sustained ventricular tachycardia (e.g., adenosine-sensitive) suggests that rather than representing distinct entities, outflow arrhythmias may be considered a continuum of a single mechanism.

Unusual Presentation of Cardiac Sarcoidosis

A 46-year-old white woman presented to the emergency department with hemodynamically stable sustained ventricular tachycardia (VT). She was chemically cardioverted with lidocaine. Her electrocardiogram, showing sinus rhythm, was unremarkable, and serial cardiac enzyme tests excluded myocardial infarction. A signal-averaged electrocardiogram was abnormal, with a filtered QRS duration of 187 milliseconds. Echocardiography showed normal left and right ventricular systolic function but revealed diastolic dysfunction of the left ventricle. Electrophysiologic testing revealed easily inducible sustained VT of 4 distinct morphologies. A diagnosis of possible arrhythmogenic right ventricular dysplasia was made based on the signal-averaged electrocardiographic and electrophysiologic findings. Cardiac magnetic resonance imaging showed no evidence of arrhythmogenic right ventricular dysplasia, however. An endomyocardial biopsy revealed noncaseating granulomas consistent with sarcoidosis. This case illustrates the importance of complete testing, including invasive studies such as endomyocardial biopsy, in patients presenting with life-threatening ventricular arrhythmias to establish a correct diagnosis.

Abstract 573: Abnormal Impulse Propagation and Susceptibility to Ventricular Tachycardia in a Murine Model of Oculodentodigital Dysplasia

Mutations in the gene encoding connexin43 (Cx43), have been identified in families with oculodentodigital dysplasia (ODDD), a dominantly inherited disorder with pleiotropic phenotypic manifestations. In one family with ODDD due to an isoleucine to threonine missense mutation at residue 130 (I130T), several individuals developed cardiac rhythm disturbances including ventricular tachycardia and sudden cardiac death. To explore the molecular pathology linking Cx43 mutations with arrhythmic behavior, we established a murine model of ODDD by introducing the disease causing I130T mutation into the Cx43 gene through homologous recombination. Approximately 20% of heterozygous Cx43-I130T mutant mice died in the immediate perinatal period, whereas the other 80% have survived for at least 5 months. Heterozygous mutant mice develop hindlimb syndactyly - a common phenotypic characteristic of humans with ODDD. The hearts of mutant mice did not display gross anatomical abnormalities and evaluation of left ventricular chamber size, wall thickness and contractile performance as assessed by echocardiography was not significantly different than wildtype littermates. Western blot analysis of heterozygous I130T mice demonstrated substantially less than 50% of wildtype levels of Cx43, whereas Cx43 transcript levels were normal, suggesting a dominant-negative effect of the mutation on Cx43 protein stability. Immunohistochemical stainining demonstrated less efficient trafficking of Cx43 to the intercaled disk in mutant hearts. Optical mapping studies of impulse propagation in Langendorff-perfused hearts demonstrated significant slowing (p&lt;0.05) of conduction velocity in both the longitudinal (.61 ± .03 m/s vs .74 ± .04 m/s) and transverse (.30 ± .02 m/s vs .43 ± .02) directions in mutant hearts compared to wildtype littermates. Moreover 7/7 mutant hearts developed spontaneous and inducible sustained monomorphic ventricular tachycardia where 0/7 wildtype littermates developed sustained arrhythmias. In summary, Cx43-I130T mutant mice display phenotypic features of human ODDD including syndactyly and rhythm disturbances. Additional study of this novel mouse model will provide insights into aberrant function of Cx43 and pro-arrhythmic behavior.