Inducible Sustained Monomorphic Ventricular Tachycardia Research Articles

MSA-VT Score for Assessment of Long-Term Prognosis after Electrical Storm Ablation.

Prognosis after electrical storm (ES) ablation remains severe, especially in patients with recurrent sustained monomorphic ventricular tachycardia (SMVT) or progressive heart failure (HF). However, single-factor-based prediction is suboptimal and may be refined by more complex algorithms. We sought to evaluate if a novel score MSA-VT (M = moderate/severe mitral regurgitation, S = severe HF at admission, A = atrial fibrillation at admission, VT = inducible SMVT after ablation) may improve prediction of death and recurrences compared to single factors and previous scores (PAINESD, RIVA and I-VT). A total of 101 consecutive ES ablation patients were retrospectively analyzed over a 32.8-month (IQR 10-68) interval. The MSA-VT score was calculated as the sum of the previously mentioned factors' coefficients based on hazard ratio values in Cox regression analysis. The AUC for death prediction by MSA-VT was 0.84 (p < 0.001), superior to PAINESD (AUC 0.63, p = 0.03), RIVA (AUC 0.69, p = 0.02) and I-VT (0.56, p = 0.3). MSA-VT ≥ 3 was associated with significantly higher mortality during follow-up (52.7%, p < 0.001). Prediction by single factors and previously published scores after ES ablation may be improved by the novel MSA-VT score; however, this requires further external validation in larger samples.

Programmed ventricular stimulation for predicting arrhythmic events in patients with myocardial infarction: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular ejection fraction (LVEF) is at present the main parameter used to guide the implantation of cardioverter-defibrillators (ICD) in patients with ischaemic cardiomyopathy. However, LVEF alone is a poor predictor of ventricular arrhythmias (VA) and sudden cardiac death (SCD). The majority of ICDs implanted for the primary prevention of SCD never deliver appropriate therapies, while being an expensive therapy and being potentially iatrogenic. Therefore, insertion of ICDs based solely on LVEF is not efficient and calls for an improvement in the risk-stratification of post-myocardial infarction patients. Inducibility of ventricular arrhythmias with programmed ventricular stimulation (PVS) has been used in the past to assess the risk of malignant arrhythmias. However, its current role in clinical practice is unknown. Purpose The aim of this meta-analysis was to study the role of PVS to predict future arrhythmic events in patients with previous myocardial infarction. Methods We performed a systematic review and a random-effect meta-analysis of studies reporting VAs –defined as SCD, sudden cardiac arrest, sustained monomorphic ventricular tachycardia (SMVT) or appropriate ICD therapies– after PVS in patients with ischaemic heart disease. Whenever possible, we used inducibility of SMVT as the positive response to PVS. Otherwise, we used the definition pre-specified in the corresponding study. The primary outcome was to estimate the positive and negative predictive value (PPV and NPV, respectively) of PVS. Subgroup analyses were performed according to the PVS timing (&amp;lt;1 or ≥1 month after infarction), definition of a positive PVS, use of ICD, or study era (before or after 2000). We searched in MEDLINE, EMBASE and Cochrane Library electronic databases up to November 2021. Results Thirty studies were included with a total of 8253 patients (mean age 58.5 years, mean LVEF 38.8%). A total of 909 arrhythmic events occurred after a mean follow-up of 24.5 months. Overall, 23% (95% confidence interval [CI] 18-29%) of subjects had inducible arrhythmias with PVS. Inducibility was associated with a higher risk of subsequent VAs (odds ratio 6.26, 95% CI 3.97-9.89, p&amp;lt;0.001). The pooled NPV was 95%, (95% CI 93-96%, p&amp;lt;0.001) and the PPV was 25% (95% CI 20-31%, p&amp;lt;0.001). There was significant heterogeneity between studies (I2 78% for the odds ratio, 96% for the NPV and 68% for the PPV). There were no statistically significant differences in any of the values according to the pre-specified subgroups. Meta-regression showed a reduction of the NPV with longer follow-up (B coefficient –0.033; p=0.012). Conclusion PVS has a high NPV (95%) and could be useful to rule out subjects at low risk of arrhythmic events. However, it decreases with longer follow-ups and, thus, the arrhythmic risk may need to be reassessed.

Catheter ablation of polymorphic ventricular tachycardia/fibrillation in patients with and without structural heart disease

Catheter ablation for polymorphic ventricular tachycardia and ventricular fibrillation (PMVT/VF) may target triggering premature ventricular contractions (PVCs). Targeting ventricular scar has also been suggested, but data are limited. The purpose of this study was to characterize the electrophysiological findings and ablation outcomes for patients with PMVT/VF and structural heart disease (SHD) compared to those with idiopathic VF. Data from 32 consecutive patients (13 idiopathic VF, 19 SHD) with recurrent PMVT/VF who underwent catheter ablation were reviewed. A low-voltage area of myocardial scar was present in 15 of 19 patients with SHD. Sustained monomorphic ventricular tachycardia (SMVT) associated with scar was inducible and targeted in 8, 3 of whom had previous SMVT episodes separate from PMVT/VF episodes and 5 had no history of SMVT. Triggering PVCs were identified in 11 patients and arose from an area of endocardial scar in 6. Only scar ablation was performed in 8 patients who did not have triggering PVCs. All idiopathic VF patients underwent PVC ablation only. During a median of 540 days, 74% of SHD patients and 77% of idiopathic VF patients were free of recurrence, including 75% of those with only PVC ablation, 86% of those with scar plus PVC ablation, and 63% of those with only scar ablation. Patients with recurrent PMVT/VF and SHD often have a low-voltage scar associated with PVCs or inducible SMVT, which may also be the substrate for PMVT/VF. When present, substrate ablation targeting scar is a reasonable option for treatment of PMVT/VF even if PVCs are absent.

Significance of Inducible Nonsustained Ventricular Tachycardias After Catheter Ablation for Ventricular Tachycardia in Ischemic Cardiomyopathy.

Noninducibility of sustained monomorphic ventricular tachycardia (SMVT) postablation does not insure absence of later recurrence in patients with ischemic cardiomyopathy. This study aims to determine the relation between inducible nonsustained VT postablation and VT recurrences. One hundred sixty-five consecutive patients (156 male; age 68±9 years) underwent ablation for SMVT because of ischemic cardiomyopathy; 44 patients who did not have induction testing or in whom only ventricular fibrillation was induced after ablation were excluded. In 38 patients (23%), SMVT was inducible (group C). Of the 83 patients without inducible SMVT after ablation, nonsustained VT defined as ≥5 beats lasting for <30 s, was induced in 34 patients (group B, 21%), whereas the remaining 49 patients had no VT induced by the induction test (group A, 30%). Over a median follow-up of 18.7 months, freedom from recurrent VT at 24 months was 60% in group A, 45% in group B (P=0.017 versus group A), and 38% in group C (P=0.005 versus group A). In patients without inducible SMVT, inducible nonsustained VT and left ventricular ejection fraction was independently associated with VT recurrence (hazard ratio, 3.66 and 1.07; 95% CI, 1.3-11.1 and 1.01-1.14). Inducible nonsustained VT postablation suggests the continued presence of functional arrhythmia substrate. Further trials are needed to assess whether additional ablation would improve outcome in this group.

Scar characteristics for prediction of ventricular arrhythmia in ischemic cardiomyopathy.

Better risk-stratification tools are needed to identify the best candidates for implantable cardioverter defibrillator implantation. Infarct characterization by cardiac magnetic resonance (CMR) has become an evolving potential tool for risk stratification. We assessed the ability of scar characteristics by CMR in patients with postinfarction left ventricular (LV) dysfunction to predict sustained monomorphic ventricular tachycardia (SMVT). Forty-eight patients with postinfarction LV dysfunction underwent CMR study. Twenty-four patients had history of SMVT and the other 24 were control group and underwent electrophysiological study to assess SMVT inducibilty. Various scar characteristics were assessed in the spontaneous SMVT group and were compared with the inducible and noninducible SMVT groups. Only six patients in the control group had inducible SMVT. In univariable analysis, total scar (absolute and as percent of LV), scar core (absolute and as percent of LV), peri-infarct zone (absolute and as percent of LV), mean infarct transmurality, and number of segments with late gadolinium enhancement (LGE) were statistically significant predictors of spontaneous SMVT experience and SMVT inducibility. In multivariable analysis, total infarct as percent of LV mass was the only significant independent predictor of spontaneous SMVT experience (odds ratio [OR] 1.33 per% change, 95% confidence interval [CI] 1.12-1.6, P = 0.001) and SMVT inducibility (OR 1.3 per% change, 95% CI 1.1-1.6, P = 0.004). Characterization of myocardial infarct by LGE-CMR, specifically total infarct size, is better predictor of spontaneous SMVT experience and SMVT inducibility than LV ejection fraction.

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.

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.

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

The effect of configuration parameters of time-frequency maps in the detection of intra-QRS electrical transients of the signal-averaged electrocardiogram: Impact in clinical diagnostic performance

Time-frequency maps of signal-averaged electrocardiogram based on a short time Fourier transform (STFT) technique analysis was employed to assess the presence of high frequency electrical transients (turbulence) and arrhythmia risk assessment. The optimal configuration set of STFT variables aiming at risk stratification for sustained monomorphic ventricular tachycardia (SMVT) is still undetermined. Different configuration variables, including analyzing time-window widths, starting positions, relative displacements, and zero-padding for STFT time-frequency maps constructions were combined on each analyzing averaged signal from 18 healthy controls and 18 subjects presenting inducible SMVT. Spectral turbulence analysis (STA) was, thus, carried out according to conventional procedures. The optimal configuration set of variables for STA was obtained by assessing the total diagnostic accuracy of all combinations of parameters. The optimal diagnostic performance was found at 86% total diagnostic accuracy as compared to 56% using previous defined normality thresholds (p=0.01). Present configuration set of variables is distinctive from previously defined set of variables and improves risk stratification.

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.

Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction

AimsTo determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF ≤ 0.40).Methods and resultsA total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 ± 11 years) with a mean LVEF of 31 ± 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component (<5.7 ln ms2) adjusted for clinical variables was 7.0 (95% CI: 2.4–20.3, P < 0.001). Induction of sustained monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7–13.4, P = 0.003) also predicted the primary endpoint.ConclusionFatal or near-fatal arrhythmias can be predicted by many risk stratification methods, especially by heart rate variability, in patients with reduced LVEF after AMI.

Post-Infarction Ventricular Tachycardia With a QRS Complex Narrower Than 140 ms: Characterization and Catheter Ablation

Typically, sustained monomorphic ventricular tachycardia (SMVT) in patients with a previous myocardial infarction (MI) is characterized by a wide QRS complex. However, occasionally patients present with SMVT and a narrow QRS complex (N-SMVT). We studied retrospectively the incidence of N-SMVT (i.e., QRS interval <140 ms) in patients with a previous MI and inducible SMVT who underwent electrophysiological evaluation. Of the 135 consecutive patients with inducible SMVT, 8 (5.9%) presented with inducible N-SMVT. The mean QRS complex duration in patients with N-SMVT was 126 (8) ms. Radiofrequency ablation was successful in 5 out of 6 patients (83%). One of the remaining two received an implantable defibrillator, while the other was given amiodarone. Findings during radiofrequency ablation showed that the reentry circuit was located in the left septum in 4 out of the 5 patients (80%). N-SMVT is relatively uncommon, but the success rate of radiofrequency ablation is high. The reentry circuit is most often located in the septum.

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.

Characterization and incidence of inducible monomorphic ventricular tachycardia in a postinfarction rabbit model

Objective Ventricular tachycardia (VT), occurring late after myocardial infarction, is an important cause of sudden death. Animal models are useful for the investigation of this arrhythmia. The aim of this study is to develop and characterize a model of late postinfarction monomorphic VT in the rabbit. Methods and Results Myocardial infarction was created by ligation of the left circumflex artery. Cardiac electrophysiologic studies were performed 10 to 17 days postinfarction in 39 rabbits, in 10 sham-operated rabbits, and 6 control rabbits. Ventricular tachycardia was defined as a broad-complex tachycardia with a cycle length of more than 100 milliseconds, a duration of more than 10 seconds, and monomorphic QRS complexes. Using programmed stimulation, we induced VT in 9 rabbits (23%) in the infarct group but in none of the sham or control animals. The mean infarct size was 23% ± 9% (mean ± SD) of the left ventricle. Conclusion Coronary ligation in the rabbit creates a substrate, which allows the induction of sustained monomorphic VT with programmed stimulation. Monomorphic VT is not inducible in rabbits without myocardial infarction. This model might allow the testing of interventions that reduce the incidence of VT late after myocardial infarction.

Programmed ventricular stimulation in patients with idiopathic dilated cardiomyopathy and syncope receiving implantable cardioverter-defibrillators: a case series and a systematic review of the literature

Background: The role of programmed ventricular stimulation (PVS) in patients with idiopathic dilated cardiomyopathy (DCM) and syncope receiving implantable cardioverter-defibrillators (ICD) remains controversial. Methods and results: Between 1994 and July 2002, 20 patients with DCM and syncope underwent PVS and ICD implantation at the Onassis Cardiac Surgery Center or the Alexandra General Hospital. At PVS 10 patients had inducible sustained monomorphic ventricular tachycardia (SMVT), 3 patients had inducible sustained polymorphic ventricular tachycardia or ventricular fibrillation, and 7 patients had no inducible arrhythmia. The latter 7 patients received an ICD because of clinical occurrence of ventricular tachycardia ( n=5) or fibrillation ( n=2). Mean age was 55±14 years; 80% were men. During a mean follow-up of 2.8±2.3 years, 12 of the 20 patients received an appropriate shock. The incidence of appropriate shocks at 1 and 3 years was 69% and 84% in the inducible SMVT group, and 56% and 67% in the group without inducible SMVT ( p=0.93, log rank test). Overall survival was similar in both groups ( p=0.53). In a systematic review of the published literature 18 of 75 (24%) patients with DCM, syncope and a negative PVS had an appropriate ICD shock after a mean follow-up of 27 months. Conclusion: PVS has a limited role in risk stratification of patients with DCM and syncope.

Long-term prognosis of inducible ventricular flutter: not an innocent finding

Background The prognostic significance of ventricular flutter (VFL) induced during programmed electrical stimulation (PES) is currently unknown. Methods This study examined patients who had PES-induced VFL and assessed their long-term prognosis compared with patients who had inducible sustained monomorphic ventricular tachycardia (SMVT). Results Of 3414 patients undergoing PES, 74 (2%) had sustained VFL. They were compared with a group of 71 patients undergoing PES in the same time frame who had inducible SMVT. Patients with inducible VFL had a higher ejection fraction than patients with SMVT (0.39 vs 0.33; P = .05). More aggressive pacing was required for arrhythmia induction in patients with VFL, with more stimuli (2.7 ± 0.5 vs 2.2 ± 0.6; P <.01) and tighter S 2, S 3, and S 4 intervals. After a mean follow-up of 30 ± 31 months, the mortality rate was 34% in patients with VFL and 30% in patients with SMVT ( P = .41). No difference in the 2 groups in overall survival or a combined end point of sudden death or appropriate implantable cardioverter defibrillator shock was revealed with Kaplan-Meier analysis. Conclusion The long-term prognosis of patients with inducible VFL is similar to that of patients with inducible SMVT, even when VFL is induced with a relatively aggressive protocol.

Utility of stress myocardial perfusion imaging performed before electrophysiologic testing

Background Patients considered for electrophysiologic study (EPS) are often first referred for stress myocardial perfusion scintigraphy (MPS) to assess for inducible ischemia before testing. The purpose of this investigation was to determine the utility of this approach by examining the relationship between MPS and any interim cardiac catheterization and revascularization, as well as the results and safety of EPS. Methods and results All patients undergoing EPS within 30 days after MPS at our institution between January 1997 and June 2000 were studied. Two hundred fifty-one patients met the inclusion criteria. The incidence of inducible sustained monomorphic ventricular tachycardia at EPS (IND) was 16%. One hundred twenty-nine patients had MPS ischemia (83 with high-risk features), but only twelve patients in all underwent revascularization between MPS and EPS. There were no ischemic complications during EPS. The presence of isolated ischemia on MPS was associated with a low rate of IND, not different from normal MPS findings (2%-3%). The combination of infarct and ischemia on MPS was associated with a high rate of IND that was similar to infarct alone (34% and 50%, respectively; P = .28). Conclusions Patients with high-risk MPS results are more likely to undergo revascularization before EPS than patients with low-risk or normal MPS results. However, most patients with high-risk MPS results undergo EPS without interim revascularization, and no patient had an ischemia-related complication at EPS. Larger studies will be required to confirm this observation. MPS infarct, not ischemia, is associated with IND at EPS.

Usefulness of QRS prolongation in predicting risk of inducible monomorphic ventricular tachycardiain patients referred forelectrophysiologic studies

QRS prolongation on surface electrocardiography has been identified as a marker for increased cardiac mortality. A potential mechanism for increased mortality is ventricular tachycardia (VT). This study aimed to evaluate the relation between bundle branch block and sustained monomorphic VT inducibility in patients referred for electrophysiologic studies. We analyzed a cohort of 777 patients (age 63 ± 18 years, 67% men, left ventricular [LV] ejection fraction [EF] 45% ± 16, prior myocardial infarction 41%) referred for electrophysiologic studies between 1994 and 2001 who underwent programmed stimulation for VT. Forty-five percent of patients were referred for syncope or a history of VT and/or ventricular fibrillation. Thirty-one percent of patients had prolonged QRS duration (≥120 ms). Patients with prolonged QRS duration were older, had lower LVEFs, and were more likely to have a history of myocardial infarction. Prolonged QRS was a significant predictor of sustained monomorphic VT inducibility (p <0.0001). On multivariate analysis correcting for age, sex, LVEF, history of myocardial infarction, medications, and QRS conduction delay proved to be independently associated with sustained monomorphic VT inducibility (relative risk 3.290, 95% confidence interval 2.185 to 4.953 for prolonged vs normal QRS duration). Thus, a prolonged QRS duration on surface electrocardiography is a strong, independent predictor of inducible sustained monomorphic VT. Conduction delay may be an important risk factor, providing a substrate for the development of reentrant monomorphic VT, and furthermore suggests a potential mechanism for the increased mortality observed in patients with prolonged QRS.