Impact of Substrate-Based Ablation of Ventricular Tachycardia on Cardiac Mortality in Patients With Implantable Cardioverter-Defibrillators.

INTRODUCTION: This study sought to determine if the acute procedural outcome of ventricular tachycardia (VT) substrate ablation is associated with a mortality benefit in patients with implantable cardioverter-defibrillators (ICD). METHODS AND RESULTS: A total of 195 ICD recipients (65 ± 11years) with ischemic or nonischemic dilated cardiomyopathy underwent substrate-based ablation targeting elimination of local abnormal ventricular activities (LAVA). Acute procedural success, which was defined as elimination of all identified LAVA in addition to the lack of VT inducibility, was achieved in 95 (49%) patients. During a median follow-up of 23 months, patients with acute procedure success had a significantly lower incidence of ICD shocks compared to those with ablation failure (8% vs. 30%, P < 0.001). In multivariate analysis, acute procedural success was associated with a lower risk of VT recurrence (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.18-0.49, P < 0.001) and all-cause mortality (HR 0.32, 95% CI 0.17-0.60, P < 0.001). While the impact of ablation success on mortality was not statistically significant in patients with LVEF > 35% (HR 0.45, 95% CI 0.15-1.34, P = 0.15) and those with NYHA class I/II (HR 0.63, 95% CI 0.29-1.40, P = 0.26), it was marked in patients with LVEF ≤ 35% (HR 0.30, 95% CI 0.14-0.62, P = 0.001) and NYHA class III/IV (HR 0.17, 95% CI 0.05-0.57, P = 0.004). CONCLUSIONS: LAVA elimination in addition to VT noninducibility as a procedural outcome for substrate-based ablation is associated with reduced mortality and better VT-free survival during follow-up. This prognostic benefit may be most pronounced in patients with severe heart failure as indicated by severely depressed LV function and NYHA class III/IV symptoms.

Five-year outcome of catheter ablation of persistent atrial fibrillation using termination of atrial fibrillation as a procedural endpoint.

BACKGROUND: This study aimed to determine 5-year efficacy of catheter ablation for persistent atrial fibrillation (AF) using AF termination as a procedural end point. METHODS AND RESULTS: One hundred fifty patients (57±10 years) underwent persistent AF ablation using a stepwise ablation approach (pulmonary vein isolation, electrogram-guided, and linear ablation) with the desired procedural end point being AF termination. Repeat ablation was performed for recurrent AF or atrial tachycardia. AF was terminated by ablation in 120 patients (80%). Arrhythmia-free survival rates after a single procedure were 35.3%±3.9%, 28.0%±3.7%, and 16.8%±3.2% at 1, 2, and 5 years, respectively. Arrhythmia-free survival rates after the last procedure (mean 2.1±1.0 procedures) were 89.7%±2.5%, 79.8%±3.4%, and 62.9%±4.5%, at 1, 2, and 5 years, respectively. During a median follow-up of 58 (interquartile range, 43-73) months after the last ablation procedure, 97 of 150 (64.7%) patients remained in sinus rhythm without antiarrhythmic drugs. Another 14 (9.3%) patients maintained sinus rhythm after reinitiation of antiarrhythmic drugs, and an additional 15 (10.0%) patients regressed to paroxysmal recurrences only. Failure to terminate AF during the index procedure (hazard ratio 3.831; 95% confidence interval, 2.070-7.143; P<0.001), left atrial diameter≥50 mm (hazard ratio 2.083; 95% confidence interval, 1.078-4.016; P=0.03), continuous AF duration≥18 months (hazard ratio 1.984; 95% confidence interval, 1.024-3.846; P<0.04), and structural heart disease (hazard ratio 1.874; 95% confidence interval, 1.037-3.388; P=0.04) predicted arrhythmia recurrence. CONCLUSIONS: In patients with persistent AF, an ablation strategy aiming at AF termination is associated with freedom from arrhythmia recurrence in the majority of patients over a 5-year follow-up period. Procedural AF nontermination and specific baseline factors predict long-term outcome after ablation.

Endocardial ablation to eliminate epicardial arrhythmia substrate in scar-related ventricular tachycardia.

OBJECTIVES: We evaluated the feasibility and safety of epicardial substrate elimination with endocardial radiofrequency (RF) delivery in patients with scar-related ventricular tachycardia (VT). BACKGROUND: Epicardial RF delivery is limited by fat or associated with bleeding, extra-cardiac damages, coronary vessels and phrenic nerve injury. Alternative ablation approaches might be desirable. METHODS: Forty-six patients (18 ischemic cardiomyopathy [ICM], 13 nonischemic dilated cardiomyopathy [NICM], 15 arrhythmogenic right ventricular cardiomyopathy [ARVC]) with sustained VT underwent combined endo- and epicardial mapping. All patients received endocardial ablation targeting local abnormal ventricular activities in the endocardium (Endo-LAVA) and epicardium (Epi-LAVA), followed by epicardial ablation if needed. RESULTS: From a total of 173 endocardial ablations targeting Epi-LAVA at the facing site, 48 (28%) applications (ICM: 20 of 71 [28%], NICM: 3 of 39 [8%], ARVC: 25 of 63 [40%]) successfully eliminated the Epi-LAVA. Presence of Endo-LAVA, the most delayed and low bipolar amplitude of Epi-LAVA, low unipolar amplitude in the facing endocardium, and Epi-LAVA within a wall thinning area at computed tomography scan were associated with successful ablation. Endocardial ablation could abolish all Epi-LAVA in 4 ICM and 2 ARVC patients, whereas all patients with NICM required epicardial ablation. Endocardial ablation was able to eliminate Epi-LAVA at least partially in 15 (83%) ICM, 2 (13%) NICM, and 11 (73%) ARVC patients, contributing to a potential reduction in epicardial RF applications. Pericardial bleeding occurred in 4 patients with epicardial ablation. CONCLUSIONS: Elimination of Epi-LAVA with endocardial RF delivery is feasible and might be used first to reduce the risk of epicardial ablation.

Primary resistance to enfuvirtide (T20) in recently HIV-1 infected, antiretroviral-naive patients from the ANRS Aquitaine Cohort.

BACKGROUND: Transmission of HIV-1 variants with resistance to reverse transcriptase (RT) and protease inhibitors has been widely characterized in developed countries. However, no clear evidence of primary resistance to HIV-1 fusion inhibitors has been shown so far. We wished to investigate the possibility of genotypic resistance to enfuvirtide (T20) in a cohort of antiretroviral-naive, recently infected patients. METHODS: We included patients from the Aquitaine Cohort with an estimated date of seroconversion in 2004 and 2005, a plasma sample obtained less than 18 months after seroconversion and no prior history of antiretroviral therapy. RT, protease and gp41 sequences were determined by direct population sequencing from plasma samples and drug resistance mutations were reported. RESULTS: A total of 55 patients were included in the study. The overall prevalence of transmitted HIV-1 resistance was 20%. Two patients had viruses with resistance mutations to T20. The first case had an N42D mutation in the HR1 region of the gp41, along with transmitted resistance mutations in the protease (D30N, M361, N88D) and in the RT (M41L, L210W, T215D). The second case had a G36D HR1 mutation, with no evidence of other drug resistance mutations. CONCLUSION: We have shown the first cases of primary resistance to T20 in recently infected patients in southwestern France. Epidemiological surveillance of the transmission of drug-resistant HIV-1 should include the resistance to T20.

Pravastatin in HIV-infected patients treated with protease inhibitors: a placebo-controlled randomized study.

PURPOSE: The objectives of the study were to assess the effects of pravastatin on plasma HIV RNA, lipid parameters, and protease inhibitor (PI) concentrations in patients treated with PI-containing regimens and with total cholesterol (TC) > or = 5.5 mmol/L. METHOD: A clinical trial including patients randomized to receive pravastatin or matching placebo for 12 weeks was implemented. RESULTS: Twelve patients were included in the pravastatin group and 9 in the placebo group. At week 12 (W12), no patient had experienced virological failure. Between week 0 (W0) and W12, the median differences for TC were -1.4 mmol/L in the pravastatin group and +0.2 mmol/L in the placebo group (p = .005); for LDL, they were -1.0 mmol/L and +0.3 (p = .007), respectively. A significant decrease of the PI concentration (12 hours after administration) ratio W12 - W0/W0 was noticed in the pravastatin group (-0.2 [interquartile range, -0.3 to -0.1] as compared with the placebo group (0.1 [IQR, 0.0 to 0.3]) (p = .03). When the study was restricted to patients treated with lopinavir/ritonavir, a decrease from 3.8 microg/mL at baseline to 2.9 mug/mL at W12 was noticed in the pravastatin arm (p = .04) but not in the control arm (p = 1.00). No clinical adverse event reached a severity of grade 3. CONCLUSION: We observed in this study that the use of pravastatin in PI-treated patients was not associated with major change in the plasma HIV RNA on 12 weeks of follow-up. However, we found a trend of decrease of the trough PI concentration at W12, suggesting a possible drug-drug interaction of pravastatin on PI metabolism.

Resistance mutations in subtype C HIV type 1 isolates from Indian patients of Mumbai receiving NRTIs plus NNRTIs and experiencing a treatment failure: resistance to AR.

We present here the first data available on resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in India. In these subtype C isolates, we have observed most of the mutations noted in reverse transcriptase (RT) for subtype B with some additional substitutions (at positions 98, 203, 208, and 221) that will warrant attention in the algorithms used.

An additive/subtractive genotypic score as a determinant of the virological response to didanosine in HIV-1 infected patients.

OBJECTIVE: To assess the genotypic determinants of the virological response (VR) to didanosine (ddI) in nucleoside reverse transcriptase inhibitors (NRTI)-experienced patients. METHODS: Human immunodeficiency virus type 1 (HIV-1) genotype was determined at baseline in 74 ddI-naive-patients with baseline viral load >500 copies/ml and receiving ddI as part of a new regimen. VR was defined as a plasma HIV-1 RNA <50 copies/ml after three months on ddI. NRTI resistance mutations associated with higher or lower frequencies of VR with a p-value<0.25 were retained in different sets of mutations, where the mutations associated with a worse VR were added, whereas the mutations associated with a better VR were subtracted. The most significant mutation scores were then studied in a multivariate analysis. RESULTS: Changes at three codons (M41L, L210W, T215Y/F/D/C/E) were associated with a worse VR and three mutations (K70R, M184V, K219Q) with a better VR. The strongest association with the VR was obtained with the score M41L+L210W+T215Y/F/D/C/E-K70R-K219Q. The score was independently associated with the VR in the multivariate analysis. CONCLUSION: Taking into account the mutations associated with a better VR may improve genotypic resistance algorithms. Our results are of interest for the management of antiretroviral therapy in NRTI-experienced patients.

Change in atherosclerosis progression in HIV-infected patients: ANRS Aquitaine Cohort, 1999-2004.

This study reported the changes in carotid intima-media thickness (IMT) during a 36-month period in 233 HIV-infected patients. Median IMT increased in the first 12 months and then decreased by month 36. The prevalence of treatment with lipid-lowering agents and protease inhibitor-free highly active antiretroviral therapy regimens increased, whereas smoking prevalence decreased. The progression of atherosclerosis in HIV-infected patients can be controlled. The impact of individual measures to reduce the cardiovascular risk should be evaluated further.