Better outcome of ablation for sustained outflow-tract ventricular tachycardia when tachycardia is inducible.

AIMS: In patients presenting with spontaneous sustained ventricular tachycardia (VT) from the outflow-tract region without overt structural heart disease ablation may target premature ventricular contractions (PVCs) when VT is not inducible. We aimed to determine whether inducibility of VT affects ablation outcome. METHODS AND RESULTS: Data from 54 patients (31 men; age, 52 ± 13 years) without overt structural heart disease who underwent catheter ablation for symptomatic sustained VT originating from the right- or left-ventricular outflow region, including the great vessels. A single morphology of sustained VT was inducible in 18 (33%, SM group) patients, and 11 (20%) had multiple VT morphologies (MM group). VT was not inducible in 25 (46%) patients (VTni group). After ablation, VT was inducible in none of the SM group and in two (17%) patients in the MM group. In the VTni group, ablation targeted PVCs and 12 (48%) patients had some remaining PVCs after ablation. During follow-up (21 ± 19 months), VT recurred in 46% of VTni group, 40% of MM inducible group, and 6% of the SM inducible group (P = 0.004). Analysis of PVC morphology in the VTi group further supported the limitations of targeting PVCs in this population. CONCLUSION: Absence of inducible VT and multiple VT morphologies are not uncommon in patients with documented sustained outflow-tract VT without overt structural heart disease. Inducible VT is associated with better outcomes, suggesting that attempts to induce VT to guide ablation are important in this population.

Surgical cryoablation for ventricular tachyarrhythmia arising from the left ventricular outflow tract region.

BACKGROUND: Ventricular arrhythmias (VAs) from the left ventricular outflow tract (LVOT) region can be inaccessible for ablation because of epicardial fat or overlying coronary arteries. OBJECTIVE: We describe surgical cryoablation of this type of VA. METHODS: From March 2009 to 2014, 190 consecutive patients with VAs originating from the LVOT underwent ablation at our institution. Four patients (2%) underwent surgical cryoablation for highly symptomatic VAs after failing catheter ablation. RESULTS: In all patients, endocardial or percutaneous epicardial mapping was consistent with origin in the LVOT. In 2 patients, the points of earliest activation during VAs were marked with a bipolar pacing lead in the overlying cardiac vein for guidance during surgery. Surgical cryoablation was successful in 3 of the 4 patients. The fourth patient subsequently had successful endocardial catheter ablation. During a mean follow-up of 22 ± 16 months (range 4-42 months), all patients showed abolition of or marked reduction in symptomatic VA. However, 1 patient subsequently required percutaneous intervention to the left anterior descending coronary artery; another developed progressive left ventricular systolic dysfunction caused by nonischemic cardiomyopathy; and a third patient underwent permanent pacemaker implantation because of complete atrioventricular block after concomitant aortic valve replacement. CONCLUSION: Surgical cryoablation is an option for highly symptomatic drug-resistant VAs emanating from the LVOT region. Despite extensive preoperative mapping, the procedure is not effective for all patients, and coronary injury is a risk.

Correlates and prognosis of early recurrence after catheter ablation for ventricular tachycardia due to structural heart disease.

BACKGROUND: Catheter ablation for ventricular tachycardia (VT) from structural heart disease has a significant risk of recurrence, but the optimal duration for in-hospital monitoring is not defined. This study assesses the timing, correlates, and prognostic significance of early VT recurrence after ablation. METHODS AND RESULTS: Of 370 patients (313 men; aged 63.0±13.2 years) who underwent a first radiofrequency ablation for sustained monomorphic VT associated with structural heart disease from 2008 to 2012, sustained VT recurred in 81 patients (22%) within 7 days. In multivariable analysis, early recurrence was associated with New York Heart Association classification ≥III (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.03-3.48; P=0.04), dilated cardiomyopathy (OR 1.93, 95% CI 1.03-3.57; P=0.04), prevalence of VT storm before the procedure (OR 2.62, 95% CI 1.48-4.65; P=0.001), a greater number of induced VTs (OR 1.24, 95% CI 1.07-1.45; P=0.006), and acute failure or no final induction test (OR 1.88, 95% CI 1.03-3.40; P=0.04). During a median of 2.5 (1.2, 4.0) years of follow-up, early VT recurrence was an independent correlates of mortality (hazard ratio 2.59, 95% CI 1.52-4.34; P=0.0005). CONCLUSIONS: Patients who have early recurrences of VT after ablation are a high risk group who may be identifiable from their clinical profile. Further study is warranted to define the optimal treatment strategies for this patient group.

Ventricular arrhythmias near the distal great cardiac vein: challenging arrhythmia for ablation.

BACKGROUND: Catheter ablation for ventricular arrhythmia (VA) near the distal great cardiac vein (GCV) is often challenging, and data are limited. METHODS AND RESULTS: Analysis was performed in 30 patients (19 men; age, 52.8±15.5 years) who underwent catheter ablation for focal VA (11 ventricular tachycardia and 19 premature contractions) with early activation in the GCV (36.7±8.0 ms pre-QRS). Angiography in 27 patients showed earliest GCV site within 5 mm of a coronary artery in 20 (74%). Ablation was performed in the GCV in 15 patients and abolished VA in 8. Ablation was attempted at adjacent non-GCV sites in 19 patients and abolished VA in 5 patients (4 from the left ventricular endocardium and 1 from the left coronary cusp); all success had VA with an initial r wave in lead I and activation ≤7 ms after the GCV (GCV-non-GCV interval). In 13 patients, percutaneous epicardial mapping was performed, but because of adjacent coronaries only 2 received radiofrequency application with VA elimination in 1. Surgical cryoablation was performed in 3 patients and abolished VA in 2. Overall acute success was achieved in 16 (53%) patients. After a median of 2.8 months, 13 patients remained free of VA. Major complications occurred in 4 patients, including coronary injury requiring stenting. CONCLUSIONS: Ablation for this arrhythmia is challenging and often limited by the adjacent coronary vessels. Success of anatomically guided endocardial ablation may be identified by a short GCV-non-GCV interval and r wave in lead I.

Priming characteristics of peptide mimotopes of carbohydrate antigens.

Immunization with peptide mimetics of carbohydrate antigens can induce functional carbohydrate-reactive antibodies. Here, we examine the immune characteristics of alternative approaches in prime and boost strategies using glycosylated HIV-1 envelope protein and model tumor associated carbohydrate antigens. Our results indicate that peptide mimotopes either in a DNA or carrier-conjugated format can induce comparable levels of IgM and IgG. Carbohydrate boosting of peptide-primed animals does not affect end-point titer, however, boosting mediates a stable long lasting carbohydrate reactive IgM response, not achievable by carbohydrate immunization alone. Boosting with carbohydrate in animals primed with DNA- or peptide-conjugate, facilitates the induction of detectable IgG with a dominant IgG2a isotype. Immunization with HIV-1 envelope glycoprotein of peptide-primed animals induces different IgG isotype profiles with a dominant IgG1 antibody. We observed that HIV-1 envelope glycoprotein immunization of peptide primed mice induces a cross-reactive cellular response, as detected by cytokine secretion, which lends to IFN-gamma production upon splenocyte stimulation and CTL activity against recombinant vaccinia virus infected cells after in vitro stimulation. DNA immunization with mimotope, inclusion of a T-cell epitope from the HIV-1 envelope protein in the expression cassette and co-administration with IL-12 or GM-CSF encoding plasmids activate a cellular response to the HIV-1 envelope protein.