Duration of Inducible Ventricular Tachycardia Early After ST-Segment-Elevation Myocardial Infarction and Its Impact on Mortality and Ventricular Tachycardia Recurrence.

Background The clinical significance of the duration of inducible ventricular tachycardia (VT) at electrophysiology study (EPS) in patients soon after ST-segment-elevation myocardial infarction and its predictive utility for VT recurrence are not known. Methods and Results Consecutive ST-segment-elevation myocardial infarction patients with day 3 to 5 left ventricular ejection fraction ≤40% underwent EPS. A positive EPS was defined as sustained monomorphic VT with cycle length ≥200 ms. The induced VT was terminated by overdrive pacing or direct current shock at 30 s or earlier if hemodynamic decompensation occurred. Patients with inducible VT duration 2 to 10 s were compared with patients with inducible VT >10 s. The primary end point was survival free of VT or cardiac mortality. From 384 consecutive ST-segment-elevation myocardial infarction patients who underwent EPS, 29% had inducible VT (n=112, 87% men). After mean follow-up of 5.9±3.9 years, primary end point occurred in 35% of patients with induced VT 2 to 10 s duration (n=68) and in 22% of patients with induced VT >10 s (n=41) (P=0.61). This was significantly different from the noninducible VT group, in which primary end point occurred in 3% of patients (n=272) (P=0.001). Conclusions This study is the first to show that in patients who undergo EPS early after myocardial infarction, inducible VT of short duration (2-10 s) has similar predictive utility for ventricular tachyarrhythmia as longer duration (>10 s) inducible VT, which was significantly different to those without inducible VT. It is possible that immediate cardioversion of rapid VT might have contributed to some of the short durations of inducible VT.

Sex Differences in Electrophysiology, Ventricular Tachyarrhythmia, Cardiac Arrest and Sudden Cardiac Death Following Acute Myocardial Infarction.

BACKGROUND: Women experience less appropriate implantable cardioverter-defibrillator (ICD) interventions and are underrepresented in randomised ICD trials. Sex-differences in inducible and spontaneous ventricular tachycardia/fibrillation (VT/VF), cardiac arrest and sudden cardiac death (SCD) early post-myocardial infarction (MI) require further study. METHODS: Consecutive ST-elevation MI patients with left ventricular ejection fraction (LVEF)≤40% underwent electrophysiology study (EPS) to target early prevention of SCD. An ICD was implanted for a positive (inducible monomorphic VT) but not a negative (no arrhythmia or inducible VF) EPS. The combined primary endpoint of VT/VF (spontaneous or ICD-treated), cardiac arrest or SCD was assessed using competing risk survival analysis in women versus men with adjustment for confounders. Logistic regression was used to determine independent predictors of inducible VT at EPS. RESULTS: A total of 403 patients (16.9% female) underwent EPS. Women were significantly older than men but with similar LVEF (31.5 ± 6.3 versus 31.6 ± 6.4%, p = 0.91). Electrophysiology study was positive for inducible VT in 22.1% and 33.4% (p = 0.066) and an ICD implanted in 25.0% and 33.4% (p = 0.356) of women versus men. Appropriate ICD activations (VT/VF) occurred in 5.9% of women and 36.6% of men (p = 0.012). The adjusted cumulative primary endpoint incidence was significantly lower in women than men (1.6% versus 26.5%, p = 0.03). Female sex was not an independent predictor of inducible VT at EPS (HR 0.63, 95% CI 0.33-1.23, p = 0.178). CONCLUSIONS: Women with early post-MI cardiomyopathy had lower VT/VF, cardiac arrest and SCD, compared to men. In ICD recipients the rate of appropriate activations was six-fold less in women compared to men.

Early and long-term outcomes after manual and remote magnetic navigation-guided catheter ablation for ventricular tachycardia.

Aims: Remote magnetic navigation (RMN) is a safe and effective means of performing ventricular tachycardia (VT) ablation. It may have advantages over manual catheter ablation due to ease of manoeuvrability and catheter stability. We sought to compare the safety and efficacy of RMN vs. manual VT ablation. Methods and results: Retrospective study of procedural outcomes of 139 consecutive VT ablation procedures (69 RMN, 70 manual ablation) in 113 patients between 2009 and 2015 was performed. Remote magnetic navigation was associated with overall higher acute procedural success (80% vs. 60%, P = 0.01), with a trend to fewer major complications (3% vs. 9% P = 0.09). Seventy-nine patients were followed up for a median of 17.0 [interquartile range (IQR) 3.0-41.0] months for the RMN group and 15.5 (IQR 6.5-30.0) months for manual ablation group. In the ischaemic cardiomyopathy subgroup, RMN was associated with longer survival from the composite endpoint of VT recurrence leading to defibrillator shock, re-hospitalization or repeat catheter ablation and all-cause mortality; single-procedure adjusted hazard ratio (HR) 0.240 (95% CI 0.070-0.821) P = 0.023, multi-procedure HR 0.170 (95% CI 0.046-0.632) P = 0.002. In patients with implanted defibrillators, multi-procedure VT-free survival was superior with RMN, HR 0.199 (95% CI 0.060-0.657) P = 0.003. Conclusion: Remote magnetic navigation may improve clinical outcomes after catheter ablation of VT in patients with ischaemic cardiomyopathy. Further prospective clinical studies are required to confirm these findings.

Influence of Intramyocardial Adipose Tissue on the Accuracy of Endocardial Contact Mapping of the Chronic Myocardial Infarction Substrate.

BACKGROUND: Recent studies have demonstrated that intramyocardial adipose tissue (IMAT) may contribute to ventricular electrophysiological remodeling in patients with chronic myocardial infarction. Using an ovine model of myocardial infarction, we aimed to determine the influence of IMAT on scar tissue identification during endocardial contact mapping and optimal voltage-based mapping criteria for defining IMAT dense regions. METHOD AND RESULTS: In 7 sheep, left ventricular endocardial and transmural mapping was performed 84 weeks (15-111 weeks) post-myocardial infarction. Spearman rank correlation coefficient was used to assess the relationship between endocardial contact electrogram amplitude and histological composition of myocardium. Receiver operator characteristic curves were used to derive optimal electrogram thresholds for IMAT delineation during endocardial mapping and to describe the use of endocardial mapping for delineation of IMAT dense regions within scar. Endocardial electrogram amplitude correlated significantly with IMAT (unipolar r=-0.48±0.12, P<0.001; bipolar r=-0.45±0.22, P=0.04) but not collagen (unipolar r=-0.36±0.24, P=0.13; bipolar r=-0.43±0.31, P=0.16). IMAT dense regions of myocardium reliably identified using endocardial mapping with thresholds of <3.7 and <0.6 mV, respectively, for unipolar, bipolar, and combined modalities (single modality area under the curve=0.80, P<0.001; combined modality area under the curve=0.84, P<0.001). Unipolar mapping using optimal thresholding remained significantly reliable (area under the curve=0.76, P<0.001) during mapping of IMAT, confined to putative scar border zones (bipolar amplitude, 0.5-1.5 mV). CONCLUSIONS: These novel findings enhance our understanding of the confounding influence of IMAT on endocardial scar mapping. Combined bipolar and unipolar voltage mapping using optimal thresholds may be useful for delineating IMAT dense regions of myocardium, in postinfarct cardiomyopathy.

Spatial characterization of electrogram morphology from transmural recordings in the intact normal heart.

PURPOSE: Unipolar (UE) and bipolar electrograms (BE) are utilized to identify arrhythmogenic substrate. We quantified the effect of increasing distance from the source of propagation on local electrogram amplitude; and determined if transmural electrophysiological gradients exist with respect to propagation and stimulation depth. METHODS: Mapping was performed on 5 sheep. Deployment of >50 quadripolar transmural needles in the LV were located in Cartesian space using Ensite. Contact electrograms from all needles were recorded during multisite bipolar pacing from epicardial then endocardial electrodes. Analysis was performed to determine stimulus distance to local activation time, peak negative amplitude (V-P), and peak-peak amplitude (VP-P) for (1) unfiltered UE, and (2) unfiltered and 30 Hz high-pass filtered BEs. Each sheep was analysed using repeated ANOVA. RESULTS: Increasing distance from the pacing sites led to significant (p<0.01) attenuation of UEs (V-P = 7.0±0.5%; VP-P = 5.4±0.3% per cm). Attenuation of BE with distance was insignificant (Vp-p unfiltered = 2.2±0.5%; filtered = 1.7±1.4% per cm). Independent of pacing depth, significant (p<0.01) transmural electrophysiological gradients were observed, with highest amplitude occurring at epicardial layers for UE and endocardial layers for BE. Furthermore, during pacing, propagation was earlier at the epicardium than endocardial layer by 1.6±2.0 ms (UE) and 1.4±2.8 ms (BE) (all p>0.01) during endocardial stimulation, and 2.3±2.4 ms (UE) and 1.8±3.7 ms (BE) during epicardal stimulation (all p<0.01). CONCLUSIONS: Electrogram amplitude is inversely proportional to propagation distance for unipolar modalities only, which affected V-P>VP-P. Conduction propagates preferentially via the epicardium during stimulation and is believed to contribute to a transmural amplitude gradient.

Ventricular tachyarrhythmia recurrence in primary versus secondary implantable cardioverter-defibrillator patients and role of electrophysiology study.

PURPOSE: In recent years, there has been a shift away from performing electrophysiologic study (EPS) to guide implantable cardioverter-defibrillator (ICD) implantation with a reliance on left ventricular ejection fraction (LVEF) alone. METHODS: ICD patients were prospectively recruited from the multicentre COMFORT (Concept of Optimal Management of ventricular Fibrillation Or Very fast ventricular Tachycardia) trial. Primary prevention ICD patients (n = 260, groups 1 and 2) were compared to secondary prevention ICD patients (n = 210, group 3). Primary prevention ICDs were implanted in patients with ischemic cardiomyopathy based on LVEF ≤ 40 % and inducible ventricular tachycardia (VT) at EPS (n = 123, group 1) or impaired LVEF alone (LVEF ≤ 30 % or LVEF ≤ 35 % with NYHA class II or III; n = 137, group 2). EPS was performed in 61 % of secondary prevention ICD patients (n = 129). Patients were followed up for >12 months with a primary endpoint of spontaneous VT/ventricular fibrillation (VF). RESULTS: A significantly higher rate of spontaneous VT/VF occurred in secondary versus primary prevention ICD patients (P < 0.001) and in EPS-guided versus LVEF-guided primary prevention ICD patients (P = 0.029). At 2 years, the proportion of patients with ≥1 VT/VF episode was 24.6 ± 4.2 %, 19.9 ± 4.6 % and 37.1 ± 3.9 % for groups 1, 2 and 3, respectively. In the secondary prevention, patients who underwent EPS, VT/VF occurred in 44.4 ± 5.9 % and 14.1 ± 6.6 % with a positive versus negative result, respectively (P = 0.02). CONCLUSIONS: Secondary prevention ICD patients have more spontaneous VT/VF than primary prevention ICD patients. Secondary and primary prevention ICD patients with inducible VT at EPS have more VT/VF than patients without inducible VT or impaired LVEF alone.

Right ventricular dysfunction predisposes to inducible ventricular tachycardia at electrophysiology studies in patients with acute ST-segment-elevation myocardial infarction and reduced left ventricular ejection fraction.

BACKGROUND: Inducible ventricular tachycardia (VT) is a strong predictor of spontaneous ventricular tachyarrhythmia following ST-segment-elevation myocardial infarction. Reduced left ventricular ejection fraction (EF) predisposes patients to inducible VT after ST-segment-elevation myocardial infarction. However, the role of right ventricular (RV) dysfunction in predisposing to inducible VT has not been described previously. METHODS AND RESULTS: Consecutive patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention underwent predischarge radionuclide gated heart pool scan to assess ventricular EF. The study cohort included patients with reduced left ventricular EF (left ventricular EF ≤40%) who underwent electrophysiology study (n=220) in an attempt to induce VT. We defined RV dysfunction as RVEF ≤35%. The end point was sustained monomorphic VT (cycle length ≥200 ms). This was considered a positive study. No inducible arrhythmia, ventricular fibrillation, or flutter (cycle length <200 ms) was considered a negative study. Infarct region, infarct-related artery, male sex, and RVEF ≤35% were univariable predictors of positive test. After multivariable analysis, RVEF ≤35% had the strongest association as an independent predictor of inducible VT at electrophysiology study (P<0.001; odds ratio, 5.8; 95% confidence interval, 3.005-11.262). CONCLUSIONS: RV dysfunction (RVEF ≤35%) predisposed to inducible VT at electrophysiology study in patients with impaired left ventricular EF (≤40%) after acute ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention.

Atrial tachycardias utilizing the Ligament of Marshall region following single ring pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Organized atrial tachycardias (OATs) after pulmonary vein isolation (PVI) procedure are common. Arrhythmia mechanisms include mitral annular, ring gap, or roof-dependent gap-related flutters. In this series, we describe a mechanism of arrhythmia utilizing the ridge between left pulmonary vein (PV) and left atrial appendage (LAA) in the Ligament of Marshall (LOM) region. METHODS AND RESULTS: Five tachycardias involving the LOM region were identified from a group of 240 patients who underwent a single ring PVI procedure for symptomatic atrial fibrillation. The common characteristics of these tachycardias were the endocardial breakout over a broad area adjacent to the LOM region, presence of presystolic or mid-diastolic potentials, and abolition by ablation of the presystolic or mid-diastolic potentials remote from the endocardial breakout site. In all five cases, tachycardias were present after isolation of the veins and posterior left atria. All demonstrated characteristic areas of very slow conduction in the LOM region highlighted by presence of either low voltage, long duration fractionated potentials, or mid-diastolic potentials with a fixed temporal relationship to the subsequent endocardial activation. The pattern of activation and termination of tachycardia during ablation was consistent with an arrhythmia utilizing an electrically insulated tract within LOM and the PV-LAA ridge region. CONCLUSIONS: We identified a pattern of arrhythmias involving a concealed presystolic component and a broad endocardial breakout site related to the LOM region. Successful ablation site involved careful identification of small diastolic potentials in the LAA/ridge region or adjacent to the coronary sinus.

Sedation for electrophysiological procedures.

Administration of intravenous sedation (IVS) has become an integral component of procedural cardiac electrophysiology. IVS is employed in diagnostic and ablation procedures for transcutaneous treatment of cardiac arrhythmias, electrical cardioversion of arrhythmias, and the insertion of implantable electronic devices including pacemakers, defibrillators, and loop recorders. Sedation is frequently performed by nursing staff under the supervision of the proceduralist and in the absence of specialist anesthesiologists. The sedation requirements vary depending on the nature of the procedure. A wide range of sedation techniques have been reported with sedation from the near fully conscious to levels approaching that of general anesthesia. This review examines the methods employed and outcomes associated with reported sedation techniques. There is a large experience with the combination of benzodiazepines and narcotics. These drugs have a broad therapeutic range and the advantage of readily available reversal agents. More recently, the use of propofol without serious adverse events has been reported. The results provide a guide regarding the expected outcomes of these approaches. The complication rate and need for emergency assistance is low in reported series where sedation is administered by nonspecialist anesthesiology staff.

Significance of repeat programmed ventricular stimulation at electrophysiology study for arrhythmia prediction after acute myocardial infarction.

BACKGROUND: The prognostic significance of a second programmed ventricular stimulation (PVS) at electrophysiology study (EPS), when the first PVS is negative for inducible ventricular tachycardia (VT), in patients following myocardial infarction (MI) is unknown. METHODS: Consecutive ST-elevation MI patients with left ventricular ejection fraction ≤ 40% following revascularization underwent early EPS. An implantable cardioverter defibrillator (ICD) was implanted for a positive (inducible monomorphic VT) but not a negative (no arrhythmia or inducible ventricular fibrillation [VF]/flutter) EPS. The combined primary end point of death or arrhythmia (sudden death, resuscitated cardiac arrest, and spontaneous VT/VF) was assessed in EPS-positive patients grouped according to if VT was induced on the first PVS application, or the second PVS application, when the first was negative. RESULTS: EPS performed a median 8 days post-MI in 290 patients was negative in 70% (n = 203) and positive in 30% (n = 87). In patients with a positive EPS, VT was induced on the first PVS in 67% (n = 58) and the second PVS, after the first was negative, in 33% (n = 29). Predischarge ICD was implanted in 79 of 87 patients with a positive EPS. Three-year primary end point occurred in 20.9 ± 5.6% and 38.3 ± 9.7% of patients with VT induced by the first and second PVS, respectively (P = 0.042) and in 6.3 ± 1.9% of electrophysiology-negative patients (P < 0.001). CONCLUSIONS: In patients with post-MI left ventricular dysfunction, VT can be induced in a significant proportion with a second PVS when negative on the first. These patients have a similar higher risk of death or arrhythmia compared to patients with VT induced on the first PVS.

Coronary artery reperfusion for ST elevation myocardial infarction is associated with shorter cycle length ventricular tachycardia and fewer spontaneous arrhythmias.

AIMS: Ventricular tachycardia (VT) induction at electrophysiological (EP) study early after ST elevation myocardial infarction (STEMI) has been a predictor of spontaneous ventricular arrhythmia. Reperfusion therapy for STEMI may have resulted in altered VT character. We attempted to determine differences in VT cycle length (CL) and VT recurrence rates, in patients who received early and late reperfusion treatment for STEMI. METHODS AND RESULTS: Of 180 consecutive patients with left ventricular ejection fraction < 40%, 77 patients had positive EP studies. Forty-nine patients receiving early reperfusion treatment (group 1, n = 49) were compared with 28 patients who received late reperfusion (group 2; n = 28). Seventy-five patients had defibrillators implanted for primary prevention of sudden death. Patients were followed for up to 6 years to assess long-term rates of spontaneous ventricular tachyarrhythmia. Patients who received early reperfusion demonstrated shorter CL inducible VT (231 ± 43 ms vs. 252 ± 56 ms; P = 0.016). They also had fewer spontaneous arrhythmias (adjusted hazard ratio of 2.94, 95% confidence interval: 1.07-8.13; P = 0.03) with shorter CL spontaneous VT (266 ± 54 ms vs. 320 ± 80 ms; P = 0.02) at 53 ± 33 months. Ventricular tachycardia CL was the only independent predictor of spontaneous arrhythmia or sudden cardiac death (1.22, 1.07-1.47; P = 0.016). CONCLUSIONS: Patients receiving early reperfusion for STEMI had faster inducible and spontaneous VT and fewer spontaneous recurrences. This may be due to changes in the myocardial substrate as a result of early coronary artery reperfusion.

Primary radiofrequency ablation of ventricular tachycardia early after myocardial infarction: evaluation in an ovine model.

BACKGROUND: Ventricular tachycardia (VT) is a significant complication of myocardial infarction. Radiofrequency ablation for postinfarct VT is reserved for drug refractory VT or VT storms. Our hypothesis is that radiofrequency ablation in the early postinfarct period could abolish or diminish late recurrences of VT. METHODS AND RESULTS: Myocardial infarct was induced by balloon occlusion of the left anterior descending artery in 35 sheep. The 25 survivors underwent programmed ventricular stimulation and electroanatomical mapping 8 days postinfarct. Animals with inducible VT (12 out of 25 animals) underwent immediate radiofrequency ablation. Further VT inductions were performed 100 and 200 days postinfarct. At day 8, 3.0±0.9 VT morphologies per animal were inducible. All were successfully ablated with 24±6 applications of radiofrequency energy. All had ablations on the left ventricular endocardium, and 67% had ablations on the right ventricular aspect of the interventricular septum. All targeted arrhythmias were successfully ablated acutely. One animal was euthanized because of hypotension from a serious pericardial effusion. The other 11 survived and remained arrhythmia free on subsequent inductions on the 100th and 200th days (P<0.001). The 13 animals without inducible VT remained noninducible at the subsequent studies. A historical control arm of 9 animals with inducible VT at day 8 remained inducible at day 100. CONCLUSIONS: Radiofrequency ablation on the eighth day after infarction abolished inducibility of VT at late induction studies ≤200 days in an ovine model. Early identification and ablation of VT after infarction may prevent or reduce late ventricular arrhythmias but needs to be validated in clinical studies.

Significance of inducible very fast ventricular tachycardia (cycle length 200-230 ms) after early reperfusion for ST-segment-elevation myocardial infarction.

BACKGROUND: Electrophysiological study (EPS) after myocardial infarction may have a role in identifying patients at risk of sudden cardiac death. It has been shown previously that inducible very fast ventricular tachycardia (VT; cycle length [CL], 200-230 ms) is predictive of arrhythmia recurrence; however, its significance early after reperfusion in ST-segment-elevation myocardial infarction is unknown. METHODS AND RESULTS: Consecutive patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention with a left ventricular ejection fraction ≤40% underwent early EPS with an implantable-cardioverter defibrillator implanted for inducible VT, but not for a negative EPS. The end point was the cumulative incidence of death or first arrhythmic event (defined as resuscitated cardiac arrest or spontaneous ventricular tachyarrhythmia). A total of 1721 patients with ST-segment-elevation myocardial infarction underwent early left ventricular ejection fraction assessment (median, 4 days after myocardial infarction) with a left ventricular ejection fraction≤40% in 24%. EPS was performed in 290 eligible patients with no arrhythmia or ventricular fibrillation/flutter (CL<200 ms) induced in 203 patients (EPS negative, group 1), monomorphic VT induced in 87 patients, consisting of very fast VT in 67% (group 2; n=58), and standard VT (CL>230 ms) in 33% (group 3; n=29). Kaplan-Meier 4-year cumulative incidence of death or arrhythmia was 8.2±2.3%, 33.1±7.1%, and 37.0±10.2% in groups 1, 2, and 3, respectively (P<0.001). CONCLUSIONS: The majority of inducible VT in patients who have been reperfused early after ST-segment-elevation myocardial infarction is very fast VT (CL, 200-230 ms). This very fast VT incurs at least a similar risk of arrhythmia or death as inducible standard VT (CL>230 ms) and a significantly higher risk than patients with a negative EPS.

Evolution of ventricular tachycardia and its electrophysiological substrate early after myocardial infarction: an ovine model.

BACKGROUND: Sudden arrhythmic death after myocardial infarction (MI) is most frequent in the first month. Early programmed ventricular stimulation (within 1 week) post-MI has been able to identify long-term ventricular tachycardia (VT) occurrence. We aimed to determine the timing of development and stabilization of VT circuits after MI and how the evolution of the underlying substrate differs with VT inducibility. METHODS AND RESULTS: MIs were induced in 36 sheep. The 21 survivors underwent serial electroanatomic mapping and programmed ventricular stimulation. Animals were classified as VTpos (inducible VT) or VTneg (noninducible VT) at day 8. Forty-three percent of MI survivors were VTpos on day 8 (9/21), and all remained inducible on day 100 with 1.5 (1.0-2.0) and 1.0 (1.0-2.0) morphologies per animal on days 8 and 100, respectively. Twelve-lead electrocardiogram matched in 15 of 19 VTs between days 8 and 100. The earliest presystolic ventricular activations during VT circuits were in similar locations at the 2 time points. The 12 VTneg animals remained noninducible on day 100. There was no difference in voltage or velocity substrate with time or inducibility. The area with fractionated signals increased with time and VT inducibility. VTpos animals had more linear regions of slowed conduction forming conducting channels. CONCLUSIONS: The inducibility and earliest presystolic endocardial activation sites of VT as well as voltage and velocity substrate on day 8 predicted those on day 100 postinfarct, indicating early formation and stabilization of the arrhythmogenic substrate. VT inducibility was influenced by the distribution of conducting channels and increased complex fractionated signals.

Intramyocardial adiposity after myocardial infarction: new implications of a substrate for ventricular tachycardia.

BACKGROUND: Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. METHODS AND RESULTS: Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI-; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT-; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass-independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation (r) with conduction velocity (r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (P>0.29). However, the MI+VT+ group demonstrated a significant (all P≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT- group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength (P<0.001). CONCLUSIONS: Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.

Induction of ventricular tachycardia with the fourth extrastimulus and its relationship to risk of arrhythmic events in patients with post-myocardial infarct left ventricular dysfunction.

AIMS: The prognostic significance of ventricular tachycardia (VT) induced by three extrastimuli (ES) is similar to that of VT induced by one or two ES in patients with coronary disease and abnormal left ventricular (LV) function. The significance of VT inducible with four ES is unclear. To examine the prognostic significance of VT inducible with the fourth ES in patients with post-myocardial infarct (MI) LV dysfunction. METHODS AND RESULTS: Consecutive patients (n= 432) with post-MI LV ejection fraction ≤40% underwent electrophysiological (EP) studies for risk stratification. Inducible VT ≥ 200 ms cycle length (CL) with one to four ES was considered inducible. The primary endpoint of arrhythmia (sudden death or spontaneous VT/ventricular fibrillation) was compared among patients with VT inducible with less than or equal to two, three, and four ES. The incidence of inducible VT was 37.9% (n= 164). In patients with inducible VT, inducibility was with less than or equal to two, three, and four ES in 24% (n= 39), 46% (n= 75), and 30% (n= 50). Compared to VT induced with less than or equal to three ES, VT induced with the fourth ES was of shorter CL (218 vs. 256 ms, P = 0.01) and more likely to be haemodynamically unstable requiring cardioversion (77 vs. 55%, P = 0.05). After 3 years the primary endpoint occurred in 28 ± 8, 28 ± 6, and 18 ± 6% in patients with VT induced with less than or equal to two, three, and four ES, respectively (P= 0.31) and in 5 ± 2% of EP-negative patients (P< 0.01). CONCLUSION: In patients with post-MI LV dysfunction, VT can be induced in a significant proportion of patients with the fourth ES. These patients are at comparable risk of arrhythmia to patients with inducible VT with less than or equal to three ES.

In vivo evaluation of virtual electrode mapping and ablation utilizing a direct endocardial visualization ablation catheter.

BACKGROUND: Radiofrequency (RF) ablation utilizing direct endocardial visualization (DEV) requires a "virtual electrode" to deliver RF energy while preserving visualization. This study aimed to: (1) examine the virtual electrode RF ablation efficacy; (2) determine the optimal power and duration settings; and (3) evaluate the utility of virtual electrode unipolar electrograms. METHODS AND RESULTS: The DEV catheter lesions were compared to lesions formed using a 3.5 mm open irrigated tip catheter within the right atria of 12 sheep. Generator power settings for DEV were titrated from 12W, 14W and 16W for 20, 30 and 40 seconds duration with 25 mL/min saline irrigation. Standard irrigated tip catheter settings of 30W, 50°C for 30 seconds and 30 mL/min were used. The DEV lesions were significantly greater in surface area and both major and minor axes compared to irrigated tip lesions (surface area 19.43 ± 9.09 vs 10.88 ± 4.72 mm, P<0.01) with no difference in transmurality (93/94 vs 46/47) or depth (1.86 ± 0.75 vs 1.85 ± 0.57 mm). Absolute electrogram amplitude reduction was greater for DEV lesions (1.89 ± 1.31 vs 1.49 ± 0.78 mV, P = 0.04), but no difference in percentage reduction. Pre-ablation pacing thresholds were not different between DEV (0.79 ± 0.36 mA) and irrigated tip (0.73 ± 0.25 mA) lesions. There were no complications noted during ablation with either catheter. CONCLUSIONS: Virtual electrode ablation consistently created wider lesions at lower power compared to irrigated tip ablation. Virtual electrode electrograms showed a comparable pacing and sensing efficacy in detecting local myocardial electrophysiological changes.

Revised non-contact mapping of ventricular scar in a post-infarct ovine model with validation using contact mapping and histology.

AIMS: Identification of arrhythmogenic scar using non-contact (NC) sinus rhythm (SR) mapping is limited. Dynamic substrate mapping (DSM) overcomes these limitations but is less accurate than plunge needle electrode mapping. We developed a revised method for calculating DSM which was validated using detailed histological analysis and compared with conventional mapping modalities. METHODS AND RESULTS: Mapping was performed in eight sheep, >9 weeks post-myocardial infarction. Twenty multielectrode needles were deployed at thoracotomy in the left ventricle within and surrounding scar, and located using Ensite. Simultaneous catheter, needle, and NC electrograms were recorded during SR and multisite pacing. Dynamic substrate mapping maps were calculated as the maximum local peak negative voltage (PNV). Absolute mean DSM (AMDSM) maps, based on peak-peak voltage (P-PV), were calculated to minimize local pacing effects and take into account anisotropic influence. Dynamic substrate mapping and AMDSM maps were normalized based on global maximum voltages attained. Histologically quantified scar and mapping criteria were compared using Spearman's correlation and receiver operator curves (area under the curve, AUC) using 50% scar cut-off. For unipolar mapping, needles had greatest sensitivity at identifying scar which was better for P-PV (AUC; needle = 0.90, catheter = 0.70, NC = 0.66) than for PNV (AUC; needle = 0.79, NC = 0.38). AMDSM (AUC = 0.75) had superior scar discrimination than either catheter (AUC; unipolar = 0.70, bipolar = 0.71) or DSM (AUC = 0.67). Absolute mean DSM accuracy was improved when valvular geometries were excluded (AUC = 0.77). CONCLUSION: Absolute mean DSM was comparably accurate in identifying scarred myocardium as PNV needle mapping but was superior to conventional catheter and NC mapping.

Simultaneous biventricular noncontact mapping and ablation of septal ventricular tachycardia in a chronic ovine infarct model.

BACKGROUND: We assessed a novel simultaneous biventricular mapping and ablation approach for septal ventricular tachycardia (VT) in a chronic ovine infarct model. METHODS AND RESULTS: In 8 sheep with inducible VT, mapping and ablation were performed 9+/-3 months after percutaneously induced myocardial infarction, with left ventricular ejection fraction 23+/-8%. Scar was identified by EnSite Dynamic Substrate Mapping plus CARTO voltage mapping. Thirty VT episodes (cycle length, 235+/-42 ms) were mapped with simultaneous analyses using EnSite arrays deployed in both the left ventricle and the right ventricle. Short ablation lines were created perpendicular to the breakout pathway along the scar border in the ventricle with earliest activity. If septal VT was still inducible, this line was extended before ablation in the second chamber. The end point of noninducibility of VT was achieved in all animals. The mean difference in delay in noncontact breakout timing between the ventricles was shorter for VT with (n=18) than without (n=12) septal breakout (32+/-7.8 ms, P<0.001). In 5 of 6 animals, after ablation in one ventricle, septal VT was still inducible with a common breakout site in the second ventricle. After septal ablation in the second ventricle, VT was no longer inducible. In the 6 animals in which septal VT had been ablated, transmural septal ablation was identified at the scar border, with overlapping left ventricular and right ventricular ablation lesions present in 5 of 6 (septal thickness 8 to 17 mm) and left ventricular endocardial ablation being transmural in 1 of 6 (6 mm). CONCLUSIONS: Biventricular scar and VT activation mapping correctly localizes septal VT pathways, directing ablation from one or both septal endocardial aspects. Creation of a transmural septal lesion at the scar border interrupting VT exit points is highly effective at ablating septal VT.

Comparison of electroanatomic contact and noncontact mapping of ventricular scar in a postinfarct ovine model with intramural needle electrode recording and histological validation.

BACKGROUND: Substrate-based ablation is useful for nonhemodynamically tolerated postinfarct ventricular tachycardia. We assessed the accuracy of the CARTO contact and EnSite noncontact systems at identifying scar in a chronic ovine model with intramural plunge needle electrode recording and histological validation. METHODS AND RESULTS: Scar mapping was performed on 8 male sheep with previous percutaneous-induced myocardial infarction. Up to 20 plunge needles were inserted into the left ventricle of each animal in areas of dense scar, scar border, and normal myocardium. A simultaneous CARTO map and EnSite geometry were acquired using a single catheter, and needle electrode locations were registered. A dynamic substrate map was constructed using ratiometric 50% peak negative voltage. The scar percentage around each needle location was quantified histologically. Analysis was performed on 152 plunge needles and corresponding histological blocks. Spearman correlation with histology was 0.690 (P<0.001) for needle electrode peak-to-peak voltage (PPV), 0.362 (P<0.001) and 0.492 (P<0.001) for CARTO bipolar and unipolar PPV, and 0.381 (P<0.001) for EnSite dynamic substrate map (< or =40 mm from array). The area under the receiver operator characteristics curve (<50% and > or =50% scar) was 0.896 for needle electrode PPV, 0.726 and 0.697 for CARTO bipolar and unipolar PPV, and 0.703 for EnSite dynamic substrate map (< or=40 mm from array). CONCLUSIONS: Both the CARTO contact and EnSite noncontact systems were moderately accurate in identifying postinfarct scar when compared with intramural electrodes and confirmed with histology. The EnSite dynamic substrate map was comparable to the CARTO contact bipolar PPV when points >40 mm from the array were excluded.