David S. Frankel

FREEDOM FROM RECURRENT VENTRICULAR TACHYCARDIA AFTER CATHETER ABLATION IS ASSOCIATED WITH IMPROVED SURVIVAL IN PATIENTS WITH STRUCTURAL HEART DISEASE: AN INTERNATIONAL VT ABLATION CENTER COLLABORATIVE GROUP STUDY

BACKGROUND The impact of catheter ablation of ventricular tachycardia (VT) on all-cause mortality remains unknown. OBJECTIVE The purpose of this study was to examine the association between VT recurrence after ablation and survival in patients with scar-related VT. METHODS Analysis of 2061 patients with structural heart disease referred for catheter ablation of scar-related VT from 12 international centers was performed. Data on clinical and procedural variables, VT recurrence, and mortality were analyzed. Kaplan-Meier analysis was used to estimate freedom from recurrent VT, transplant, and death. Cox proportional hazards frailty models were used to analyze the effect of risk factors on VT recurrence and mortality. RESULTS One-year freedom from VT recurrence was 70% (72% in ischemic and 68% in nonischemic cardiomyopathy). Fifty-seven patients (3%) underwent cardiac transplantation, and 216 (10%) died during follow-up. At 1 year, the estimated rate of transplant and/or mortality was 15% (same for ischemic and nonischemic cardiomyopathy). Transplant-free survival was significantly higher in patients without VT recurrence than in those with recurrence (90% vs 71%, P<.001). In multivariable analysis, recurrence of VT after ablation showed the highest risk for transplant and/or mortality [hazard ratio 6.9 (95% CI 5.3-9.0), P<.001]. In patients with ejection fraction <30% and across all New York Heart Association functional classes, improved transplant-free survival was seen in those without VT recurrence. CONCLUSION Catheter ablation of VT in patients with structural heart disease results in 70% freedom from VT recurrence, with an overall transplant and/or mortality rate of 15% at 1 year. Freedom from VT recurrence is associated with improved transplant-free survival, independent of heart failure severity.

Reversal of outflow tract ventricular premature depolarization–induced cardiomyopathy with ablation: Effect of residual arrhythmia burden and preexisting cardiomyopathy on outcome

BACKGROUND Outflow tract ventricular premature depolarizations (VPDs) can be associated with reversible left ventricular cardiomyopathy (LVCM). Limited data exist regarding the outcome after ablation of outflow tract VPDs from the LV and the impact of residual VPDs or preexisting LVCM prior to the diagnosis of VPDs on recovery of LV function. OBJECTIVE To examine the safety, efficacy, and long-term effect of radiofrequency ablation on LV function in patients with LVCM and frequent outflow tract VPDs and examine the effect of ablation in patients with LVCM known to precede the onset of VPDs and the impact of residual VPD frequency on recovery of LV function. METHODS Sixty-nine patients (43 men; age 51 ± 16 years) with nonischemic LVCM (left ventricular ejection fraction [LVEF] 35% ± 9%, left ventricular diastolic diameter [LVDD] 5.8 ± 0.7 cm) were referred for ablation of frequent outflow tract VPDs (29% ± 13%). RESULTS VPDs originated in the right ventricular outflow tract in 27 (39%) patients and the left ventricular outflow tract in 42 (61%) patients. After follow-up of 11 ± 6 months, 44 (66%) patients had rare (<2%) VPDs, 15 (22%) had decreased VPD burden (>80% reduction and always <5000 VPDs), and 8 (12%) had no clinical improvement with persistent (5 patients) or recurrent (3 patients) VPDs. Only patients with either rare or decreased VPD burden had a significant improvement in LVEF (ΔLVEF 14% ± 9% vs 13% ± 7% vs -3% ± 6%, respectively, P <.001) and LVDD (ΔLVDD -4 ± 5 vs -2 ± 4 vs 0 ± 4, respectively, P = .038), regardless of chamber of origin. The magnitude of LVEF improvement correlated with the decline in residual VPD burden (r = 0.475, P = .007). Patients with preexisting LVCM had a more modest but still significant improvement in LV function compared to patients without preexisting LVCM (ΔLVEF 8% vs 13%, P = .046). Multivariate analysis revealed ablation outcome, higher LVEF, and absence of preexisting LVCM were independently associated with LVEF improvement. CONCLUSION Frequent outflow tract VPDs are associated with LVCM regardless of ventricle of origin. Significant (>80%) reduction in VPD burden has comparable improvement in LV function to complete VPD elimination. Successful VPD ablation may be beneficial even in patients with preexisting LVCM.

Von Willebrand Factor, Type 2 Diabetes Mellitus, and Risk of Cardiovascular Disease The Framingham Offspring Study

Background— Von Willebrand factor (vWF) is inconsistently associated with cardiovascular disease (CVD). This might be explained by associations of vWF with type 2 diabetes mellitus and insulin resistance. Methods and Results— We tested whether vWF predicted incident CVD in 3799 Framingham Offspring Study participants, and in particular, among those with type 2 diabetes mellitus or insulin resistance. During 11 years of follow-up, 351 participants developed CVD. In proportional hazards models (with adjustment for age, sex, blood pressure, smoking, body mass index, total and high-density lipoprotein cholesterol, and treatment with aspirin, insulin, antihypertensives, and lipid-lowering medications) with the lowest quartile of the vWF distribution as the referent, the hazard ratio (HR) for CVD was 0.94 in the second quartile, 0.98 in the third, and 1.32 in the highest (P=0.04 for trend). Additional adjustment for type 2 diabetes mellitus or insulin resistance (homeostasis model) partially attenuated the association (multivariable HRs for top quartile 1.28 and 1.21, respectively). We then stratified the models by diabetes status or the homeostasis model of insulin resistance distribution (top quartile versus lower 3 quartiles). vWF was associated with CVD among participants with diabetes mellitus (HR for top quartile relative to bottom 1.47, P=0.04 for trend) but not among nondiabetic participants (HR 1.15, P=0.5) and similarly among insulin-resistant (HR 1.50, P=0.01) but not insulin-sensitive (HR 1.02, P=0.9) participants. Conclusions— Higher levels of vWF were associated with risk of CVD in people with type 2 diabetes mellitus or insulin resistance, which suggests that vWF may be a risk factor unique to these populations.

Ablation of ventricular arrhythmias arising near the anterior epicardial veins from the left sinus of Valsalva region: ECG features, anatomic distance, and outcome.

BACKGROUND Left ventricular outflow tract tachycardia/premature depolarizations (VT/VPDs) arising near the anterior epicardial veins may be difficult to eliminate through the coronary venous system. OBJECTIVE To describe the characteristics of an alternative successful ablation strategy targeting the left sinus of Valsalva (LSV) and/or the adjacent left ventricular (LV) endocardium. METHODS Of 276 patients undergoing mapping/ablation for outflow tract VT/VPDs, 16 consecutive patients (8 men; mean age 52 ± 17 years) had an ablation attempt from the LSV and/or the adjacent LV endocardium for VT/VPDs mapped marginally closer to the distal great cardiac vein (GCV) or anterior interventricular vein (AIV). RESULTS Successful ablation was achieved in 9 of the 16 patients (56%) targeting the LSV (5 patients), adjacent LV endocardium (2 patients), or both (2 patients). The R-wave amplitude ratio in lead III/II and the Q-wave amplitude ratio in aVL/aVR were smaller in the successful group (1.05 ± 0.13 vs 1.34 ± 0.37 and 1.24 ± 0.42 vs 2.15 ± 1.05, respectively; P = .043 for both). The anatomical distance from the earliest GCV/AIV site to the closest point in the LSV region was shorter for the successful group (11.0 ± 6.5 mm vs 20.4 ± 12.1 mm; P = .048). A Q-wave ratio of <1.45 in aVL/aVR and an anatomical distance of <13.5 mm had sensitivity and specificity of 89%, 75% and 78%, 64%, respectively, for the identification of successful ablation. CONCLUSIONS VT/VPDs originating near the GCV/AIV can be ablated from the LSV/adjacent LV endocardium. A Q-wave ratio of <1.45 in aVL/aVR and a close anatomical distance of <13.5 mm help identify appropriate candidates.

Predictors of recovery of left ventricular dysfunction after ablation of frequent ventricular premature depolarizations.

BACKGROUND Frequent ventricular premature depolarizations (VPDs) can cause reversible left ventricular (LV) dysfunction. However, not all patients normalize their LV function after VPD elimination. OBJECTIVE To evaluate predictors of recovery of LV function following the elimination of frequent VPDs. METHODS We identified patients with ≥10% VPDs/24 h and an LV ejection fraction of <50% who underwent successful ablation between 2007 and 2011. Subjects were classified as having reversible (≥10% increase to a final LV ejection fraction of ≥50%) or irreversible (≤10% increase or final LV ejection fraction <50%) LV dysfunction on the basis of echocardiographic follow-up. A reference group with ≥10% VPDs but normal LV function was identified. RESULTS One hundred fourteen patients with ≥10% VPDs were identified; 66 had preserved and 48 had impaired LV function. Over a median follow-up of 10.6 months, 24 of 48 were classified as reversible and 13 of 48 as irreversible and 11 of 44 were excluded. There was a gradient of VPD QRS duration between the control, reversible, and irreversible groups (mean VPD QRS 135, 158, and 173 ms, respectively; P < .001). This gradient persisted even for the same site of origin. In multivariate analysis, the only independent predictor of irreversible LV function was VPD QRS duration (odds ratio 5.07 [95% confidence interval 1.22-21.01] per 10-ms increase). CONCLUSION In patients with LV dysfunction and frequent VPDs, we identified VPD QRS duration as the only independent predictor for the recovery of LV function after ablation. This suggests that VPD QRS duration may be a marker for the severity of underlying substrate abnormality.

Incidence and predictors of right ventricular pacing-induced cardiomyopathy

BACKGROUND Frequent right ventricular (RV) pacing can lead to a decline in left ventricular ejection fraction (LVEF). OBJECTIVE This study aimed to identify incidence and predictors of RV pacing-induced cardiomyopathy (PICM). METHODS We retrospectively studied 1750 consecutive patients undergoing pacemaker implantation between 2003 and 2012. Patients were included if baseline LVEF was normal, single-chamber ventricular or dual-chamber pacemaker (but not implantable cardioverter-defibrillator or biventricular pacemaker) was implanted, frequent (≥20%) RV pacing was present, and repeat echocardiogram was available ≥1 year after implantation. PICM was defined as ≥10% decrease in LVEF, resulting in LVEF <50%. Patients with alternative causes of cardiomyopathy were excluded. Predictors of the development of PICM were identified using multivariate Cox proportional hazards modeling. RESULTS Of 257 patients meeting study criteria, 50 (19.5%) developed PICM, with a decrease in mean LVEF from 62.1% to 36.2% over a mean follow-up period of 3.3 years. Those who developed PICM were more likely to be men, with lower baseline LVEF and wider native QRS duration (bundle branch blocks excluded; P = .005, P = .03, and P = .001, respectively). In multivariate analysis, male gender (hazard ratio 2.15; 95% confidence interval 1.17-3.94; P = .01) and wider native QRS duration (hazard ratio 1.03 per 1 ms increase; 95% confidence interval 1.01-1.05; P < .001) were independently associated with the development of PICM. Native QRS duration >115 ms was 90% specific for the development of PICM. CONCLUSION PICM may be more common than previously reported, and risk for its occurrence begins below the commonly accepted threshold of 40% pacing burden. Men with wider native QRS duration (particularly >115 ms) are at increased risk. These patients warrant closer follow-up with a lower threshold for biventricular pacing.

Noninvasive Programmed Ventricular Stimulation Early After Ventricular Tachycardia Ablation to Predict Risk of Late Recurrence

OBJECTIVES The goal of this study was to evaluate the ability of noninvasive programmed stimulation (NIPS) after ventricular tachycardia (VT) ablation to identify patients at high risk of recurrence. BACKGROUND Optimal endpoints for VT ablation are not well defined. METHODS Of 200 consecutive patients with VT and structural heart disease undergoing ablation, 11 had clinical VT inducible at the end of ablation and 11 recurred spontaneously. Of the remaining 178 patients, 132 underwent NIPS through their implantable cardioverter-defibrillator 3.1 ± 2.1 days after ablation. At 2 drive cycle lengths, single, double, and triple right ventricular extrastimuli were delivered to refractoriness. Clinical VT was defined by comparison with 12-lead electrocardiograms and stored implantable cardioverter-defibrillator electrograms from spontaneous VT episodes. Patients were followed for 1 year. RESULTS Fifty-nine patients (44.7%) had no VT inducible at NIPS; 49 (37.1%) had inducible nonclinical VT only; and 24 (18.2%) had inducible clinical VT. Patients with inducible clinical VT at NIPS had markedly decreased 1-year VT-free survival compared to those in whom no VT was inducible (<30% vs. >80%; p = 0.001), including 33% recurring with VT storm. Patients with inducible nonclinical VT only, had intermediate 1-year VT-free survival (65%). CONCLUSIONS When patients with VT and structural heart disease have no VT or nonclinical VT only inducible at the end of ablation or their condition is too unstable to undergo final programmed stimulation, NIPS should be considered in the following days to further define risk of recurrence. If clinical VT is inducible at NIPS, repeat ablation may be considered because recurrence over the following year is high.

Pulmonary Vein Antral Isolation and Nonpulmonary Vein Trigger Ablation without Additional Substrate Modification for Treating Longstanding Persistent Atrial Fibrillation

PV Ablation for Persistent Atrial Fibrillation. Introduction: Effectiveness of antral pulmonary vein isolation (PVAI) and ablation of non‐PV triggers (non‐PVTA) in controlling longstanding persistent atrial fibrillation (AF) has not been reported. We sought to describe clinical outcomes with this ablation strategy in patients (pts) followed for at least 1 year.

Efforts to enhance catheter stability improve atrial fibrillation ablation outcome

BACKGROUND Contemporary techniques to enhance anatomical detail and catheter contact during atrial fibrillation (AF) ablation include (1) the integration of preacquired tomographic reconstructions with electroanatomical mapping (3-dimensional image integration [I-EAM]), (2) the use of steerable introducers (SIs), and (3) high-frequency jet ventilation (HFJV). OBJECTIVE To prove that using these stabilizing techniques during AF ablation improves 1-year procedural outcome. METHODS We studied 300 patients undergoing AF ablation at our institution. Patients were divided into 3 equal treatment groups (100 patients each) on the basis of the tools utilized: (1) group 1: AF ablation performed without I-EAM, SI, or HFJV; (2) group 2: AF ablation performed using I-EAM and SI, but without HFJV; and (3) group 3: AF ablation performed with I-EAM, SI, and HFJV. The primary outcome was freedom from AF 1 year after a single ablation procedure. The burden of both acute and chronic pulmonary vein reconnection was also assessed. RESULTS Patients from groups 2 and 3 had significantly more nonparoxysmal AF (17% vs 30% vs 39%; P = .002), larger left atria (4.2 ± 0.8 cm vs 4.4 ± 0.7 cm vs 4.5 ± 0.8 cm; P<.001), and higher body mass index (BMI; 28.5 ± 5.8 kg/m² vs 29.1 ± 4.8 kg/m² vs 31.2 ± 5.4 kg/m²; P<.001). Despite these differences, with adoption of I-EAM, SI, and HFJV we noted a significant improvement in 1-year freedom from AF (52% vs 66% vs 74%; P = .006) as well as fewer acute (1.1 ± 1.2 vs 0.9 ± 1.1 vs 0.6 ± 0.9; P = .03) and chronic (3.5 ± 0.9 vs 3.2 ± 0.9 vs 2.4 ± 1.0; P = .02) pulmonary vein reconnections. CONCLUSIONS The incorporation of contemporary tools to enhance anatomical detail and ablation catheter stability significantly improved 1-year freedom from AF after ablation.

Catheter ablation of ventricular fibrillation: Importance of left ventricular outflow tract and papillary muscle triggers

BACKGROUND Monomorphic ventricular premature depolarizations (VPDs) have been found to initiate ventricular fibrillation (VF) or polymorphic ventricular tachycardia (PMVT) in patients with and without structural heart disease. OBJECTIVE The purpose of this study was to describe and characterize sites of origin of VPDs triggering VF and PMVT. METHODS The distribution of mapping-confirmed VPDs, electrophysiology laboratory findings, and results of radiofrequency catheter ablation were analyzed. RESULTS Among 1132 consecutive patients who underwent ablation for ventricular arrhythmias, 30 patients (2.7%) with documented VF/PMVT initiation were identified. In 21 patients, VF/PMVT occurred in the setting of cardiomyopathy; in 9 patients, VF/PMVT was idiopathic. The origin of VPD trigger was from the Purkinje network in 9, papillary muscles in 8, left ventricular outflow tract in 9, and other low-voltage areas unrelated to Purkinje activity in 4. Each distinct anatomic area of origin was associated with VF/PMVT triggers in patients with and without heart disease. Acute VPD elimination was achieved in 26 patients (87%), with a decrease in VPDs in another 3 patients (97%). During median follow-up of 418 days (interquartile range [IQR] 144-866), 5 patients developed a VF/PMVT recurrence after a median of 34 days (IQR 1-259). Rare recurrence was noted in patients with and without structural disease and from each distinct anatomic origin. The total burden of VF/PMVT episodes/shocks was reduced from a median of 9 (IQR 2.5-22.5) in the 3 months before ablation to 0 (IQR 0-0, total range 0-2) during follow-up (P <.0001). CONCLUSION Catheter ablation of VPD-triggered VF/PMVT is highly successful. Left ventricular outflow tract and papillary muscles are common and are previously unrecognized sites of origin of these triggers in patients with and without structural heart disease.