Surface ECG and intracardiac spectral measures predict atrial fibrillation recurrence after catheter ablation.

INTRODUCTION: Outcome of patients undergoing catheter ablation of atrial fibrillation (AF) varies widely. We sought to investigate whether parameters derived from the spectral analysis of surface ECG and intracardiac AF electrograms can predict outcome in patients referred for pulmonary vein isolation (PVI). METHODS: We performed spectral analysis on the surface ECG and intracardiac electrograms from patients referred for AF ablation. After filtering and QRST subtraction, we measured the dominant frequency (DF), regularity index (RI) and the organizational index (OI) of fibrillatory electrograms and determined their value for predicting AF recurrence after ablation. A subjective, blinded prediction based on the surface ECG was also performed. RESULTS: We analyzed data from 153 PVI procedures in 140 patients (67.1% with persistent or longstanding AF). In a multivariable model, DF in the right atrium (RA) and distal coronary sinus (CSd)-to-RA DF gradient predicted AF recurrence (OR, 3.52, P = 0.023 and OR, 0.2, P = 0.034, respectively). DF in RA and CSd to RA DF gradient had a good predictive value for PVI outcome (area under the curve [AUC] of 0.73, P = 0.007 and 0.74, P = 0.007, respectively). These performed better than the subjective predictions of experienced electrophysiologists ( P = 0.2). CONCLUSIONS: Higher RA DF, lower CSd to RA DF gradient predicted recurrence after AF ablation. These spectral measures suggest a more remodeled atrial substrate and may provide simple tools for risk stratification or predict the need for additional substrate modification in patients referred for AF ablation.

Atrial fibrillation patients with isolated pulmonary veins: Is sinus rhythm achievable?

BACKGROUND: The cornerstone of atrial fibrillation (AF) ablation is isolation of the pulmonary veins (PVs). Patients with recurrent AF undergoing repeat ablation usually have PV reconnection (PVr). The ablation strategy and outcome of patients undergoing repeat ablation who have persistent isolation of all PVs (PVi) at the time of repeat ablation is unknown. METHODS AND RESULTS: We studied consecutive patients with recurrent AF undergoing repeat ablation and compared patients with PVi to those with PVr. One hundred fifty-two patients underwent repeat ablation, and of these, 25 patients (16.4%) had PVi. Patients with PVi underwent ablation targeting any isoproterenol induced AF triggers, atrial substrate, or inducible atrial tachycardias or flutters. Patients with PVi compared to PVr were more likely to have a history of persistent AF (64% vs. 26%; P < 0.0001), obesity (BMI 30.4 vs. 28.2; P = 0.05), and prior use of contact force sensing catheters (28% vs. 0.8%, P < 0.0001). After a mean follow-up of 19 ± 15 months, 56% of PVi patients remained in sinus rhythm compared to 76.3% of PVr patients (P = 0.036). In a multivariable model, PVi patients and those with cardiomyopathy had a higher risk of recurrent atrial tachyarrhythmias (HR = 3.6 95%, CI 1.6-8.3, P = 0.002 and HR = 6.2, 95% CI 2.3-16.3, P < 0.0001, respectively). CONCLUSION: In patients who have all PVs isolated at the time of the redo AF ablation, a strategy of targeting non-PV AF triggers and inducible flutters can still lead to AF freedom in more than half of patients. Patients with PVr, however, have a better long-term outcome.

Comparison of in vitro and vivo efficacy of caspofungin against Candida parapsilosis, C. orthopsilosis, C. metapsilosis and C. albicans.

Caspofungin activity was determined in vitro and in vivo against three Candida orthopsilosis, three C. metapsilosis, two C. parapsilosis sensu stricto and two C. albicans isolates. MIC values and killing activity were determined in RPMI-1640 plus 50 % human serum. Neutropenic (cyclophosphamide-treated) mice were infected intravenously. Five-day intraperitoneal treatment with caspofungin was started after 24 h postinfection. Kidney burden was analyzed using the Kruskal-Wallis test with Dunn's post-test. In killing studies, caspofungin was fungistatic and fungicidal against C. albicans at ≥0.25 and ≥2 µg/ml concentrations, respectively. Caspofungin was fungistatic at ≥8-16, ≥2-8 and at ≥2-8 µg/ml against C. parapsilosis, C. orthopsilosis and C. metapsilosis, respectively. In the murine model, C. albicans was inhibited by 1, 2 and 5 mg/kg of caspofungin (P < 0.001 compared to the controls). Against C. parapsilosis, only 5 mg/kg caspofungin was effective against both isolates (P < 0.05). Two and five mg/kg of caspofungin was effective against all C. orthopsilosis and C. metapsilosis isolates (P < 0.05 to <0.001). Serum-based killing tests proved to be useful in predicting in vivo efficacy of caspofungin against four Candida species. Caspofungin at clinically attainable concentrations proved to be effective against all four species.

Atrial Remodeling in Atrial Fibrillation. Comorbidities and Markers of Disease Progression Predict Catheter Ablation Outcome.

Atrial fibrillation is the most common supraventricular arrhythmia affecting an increasing proportion of the population in which mainstream therapy, i.e. catheter ablation, provides freedom from arrhythmia in only a limited number of patients. Understanding the mechanism is key in order to find more effective therapies and to improve patient selection. In this review, the structural and electrophysiological changes of the atrial musculature that constitute atrial remodeling in atrial fibrillaton and how risk factors and markers of disease progression can predict catheter ablation outcome will be discussed in detail.

Dyssynchrony and Fibrosis Persist After Resolution of Cardiomyopathy in a Swine Premature Ventricular Contraction Model.

OBJECTIVES: This study sought to prospectively study the development and then regression of premature ventricular contraction (PVC)-induced cardiomyopathy, with the hypothesis that structural left ventricular (LV) changes that are of potential clinical significance may endure beyond the period of exposure to PVCs. BACKGROUND: Recovery of LV function after eradication of PVCs in PVC-induced cardiomyopathy is incompletely defined. METHODS: Fifteen swine were exposed to: 1) 50% paced PVCs from the LV lateral epicardium for 12 weeks (LV PVC, n = 5); 2) no pacing for 12 weeks (Control, n = 5); or 3) 50% paced LV PVCs for 12 weeks followed by pacing cessation for 4 weeks (Recovery, n = 5). LV function was quantified biweekly in sinus rhythm with echocardiography. Dyssynchrony was measured from pressure-volume loops at baseline and terminal studies. LV fibrosis was quantified after sacrifice. RESULTS: LV ejection fraction during sinus rhythm fell between baseline and terminal studies in the LV PVC group (65.8 ± 3.0 to 39.3 ± 3.2; p < 0.05), whereas there was no significant change in the Control group (69.6 ± 3.0 to 72.2 ± 3.0; p = NS) or after Recovery (64.5 ± 3.4% to 61.4 ± 3.4%; p = NS) groups. There was a significant increase in LV dyssynchrony measured during sinus rhythm between baseline and terminal studies in the LV PVC group (4.0 ± 1.5% to 9.0 ± 1.5%; p < 0.05); there was a similar increase in dyssynchrony that persisted 4 weeks after PVC cessation in the Recovery group (4.4 ± 1.7% to 12.8 ± 1.7%; p < 0.05). After sacrifice, percent fibrosis was higher in the LV PVC group compared with Control (5.7 ± 0.3% vs. 3.0 ± 0.3%; p < 0.05) and remained elevated in Recovery (4.1 ± 0.3% vs. 3.0 ± 0.3%; p < 0.05) despite return to baseline LV ejection fraction. CONCLUSIONS: In a swine model of PVC-induced cardiomyopathy, cessation of PVCs for 4 weeks leads to normalization of LV systolic function but significant changes in myocardial fibrosis and LV dyssynchrony during sinus rhythm persist.

Safety and outcomes of catheter ablation for atrial fibrillation in adults with congenital heart disease: A multicenter registry study.

BACKGROUND: An increasing number of adults with congenital heart disease (CHD) are undergoing catheter ablation for atrial fibrillation (AF). Data on ablation strategy and outcomes in CHD are limited. Rhythm control is often believed to be of greater importance among patients with complex CHD. OBJECTIVE: The purpose of this study was to examine the safety and efficacy of AF ablation in adult patients with CHD. METHODS: A multicenter retrospective analysis was performed of CHD patients undergoing AF ablation. Clinical data were collected, including AF and CHD type, procedural data, and outcomes. Patients were divided into 3 groups (simple, moderate, and severe) based on CHD complexity, as defined by the 2014 PACES/HRS (Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society) consensus statement. One-year procedural success was defined as freedom from recurrent AF, off antiarrhythmic drugs (complete) or off/on previously failed antiarrhythmic drugs (partial). RESULTS: Overall, 84 CHD patients (mean age 51.5 ± 12.1 years; 65.5% male; 45.2% with paroxysmal AF) undergoing AF ablation (51 simple, 22 moderate, 11 severe complexity) were included. Pulmonary vein isolation was performed in 80 (95.2%), of whom 30 (35.7%) underwent pulmonary vein isolation alone. Overall, complete and complete/partial freedom was achieved at 1 year in 53.1% and 71.6%, respectively, with no significant differences between those with simple, moderate, or severe complexity. There were no major complications and 7 minor complications, and 2 patients died during follow-up. CONCLUSION: There are dramatic differences in the degree of CHD complexity among patients referred for AF ablation. When performed at experienced centers, AF ablation is safe and effective even among patients with the most complex forms of CHD.

Left Ventricular Dyssynchrony Predicts the Cardiomyopathy Associated With Premature Ventricular Contractions.

BACKGROUND: The pathophysiology of cardiomyopathy associated with premature ventricular contractions (PVCs) remains unclear. OBJECTIVES: This study prospectively explored cardiomyopathy development in a swine model of paced ectopic beats. METHODS: A total of 35 swine underwent pacemaker implantation. A group exposed to paced bigeminy from the right ventricular apex (RVA) for 14 weeks (RVA PVC) (n = 10) were compared with a group exposed to regular pacing from the RVA at 140 beats/min (RV-140) (n = 5) and a control group (n = 5). To test the role of ectopic beat dyssynchrony, further groups were exposed for 12 weeks to bigeminy from the right ventricular free wall (RVFW PVC) (n = 5), the left ventricular epicardium (LV Epi PVC) (n = 5) or the right atrium (premature atrial complex) (n = 5). RESULTS: After 14 weeks, the mean left ventricular ejection fraction (LVEF) was significantly lower in the RVA PVC group than in the RV-140 or control groups (p < 0.05). LVEF declined significantly in the LV Epi PVC (65.2 ± 2.4% to 39.7 ± 3.0%; p < 0.01) and RVFW PVC (66.1 ± 2.6% to 48.6 ± 2.7%; p < 0.01) groups, with final LVEF significantly lower and ventricular fibrosis significantly higher in the LV Epi PVC group compared with all others (p < 0.05). Protein levels of pRyR2, NCX-1, CaMKII-α, and PLN were up-regulated and levels of SERCA2a were down-regulated in the LV Epi PVC group compared with the control group (p < 0.05). Longer ectopic beat QRS duration and greater LV dyssynchrony were significantly associated with larger declines in LV systolic function. CONCLUSIONS: In a swine model of paced ectopic beats, PVC-induced cardiomyopathy is phenotypically distinct from a tachycardia-induced cardiomyopathy. Cardiomyopathy severity is strongly associated with severity of the hemodynamic derangement associated with the paced ectopic beats, particularly the extent of LV dyssynchrony.

Should the Aortic Root Be the Preferred Route for Ablation of Focal Atrial Tachycardia Around the AV Node?: Support From Intracardiac Echocardiography.

OBJECTIVES: The purpose of this study was to determine the optimal approach to focal atrial tachycardia originating from around the atrioventricular node. BACKGROUND: Focal atrial tachycardia (FAT) demonstrating earliest activation around the atrioventricular (AV) node during right atrial (RA) mapping has been eliminated by ablation at the RA para-Hisian region, from the left atrium (LA) or the noncoronary aortic cusp (NCC). However the optimal approach has not been determined. METHODS: We conducted a retrospective analysis of a consecutive series of 148 patients undergoing catheter ablation for FAT between 2006 and 2014 in our institution. RESULTS: Earliest activation was recorded in the peri-AV nodal region during RA mapping in 34 patients (23%). Of these, 7 patients (20.5%) had successful ablation at the RA septum, using either radiofrequency (n = 4) or cryoenergy (n = 3). Seven FATs (20.5%) were ablated from the LA at the region of the aortomitral continuity, and 20 patients (59%) had successful ablation in the NCC, including 1 patient with a recurrence after a temporarily successful cryoablation from the RA. The proportion of the 3 approaches in this series showed a significant temporal evolution and overall frequency favoring ablation in the NCC (p = 0.011 for time trend and 0.013 for actual vs. expected frequencies). Intracardiac echocardiography proved superior catheter stability with the NCC approach. There were 2 cases of atrioventricular block and 1 recurrence after RA ablation versus no complications or recurrent FAT with NCC and LA approaches. CONCLUSIONS: Most peri-AV nodal FATs can be safely and effectively ablated from the NCC. The strategy of preferential NCC approach avoids RA para-Hisian ablation with the accompanying risk of AV block.

Impaired adaptation to left atrial pressure increase in patients with atrial fibrillation.

BACKGROUND OR PURPOSE: Episodes of left atrial (LA) pressure increase predispose to atrial fibrillation (AF). The adaptation of LA mechanical function and electrophysiology to pressure elevation in healthy adults, and in patients with AF, is largely unknown. METHODS: Eleven patients with left-sided accessory pathway (controls) and 16 patients with paroxysmal AF undergoing catheter ablation were studied. LA pressure (LAP) was recorded through transseptal catheterization, while speckle tracking-derived peak LA longitudinal strain (PALS) was measured using transthoracic echocardiography. Stiffness index (SI) was calculated as mean LAP/PALS. Effective refractory period (ERP) of the LA was determined during simultaneous atrioventricular (AV) pacing and during atrial pacing. RESULTS: At baseline, AF patients had higher LA pressure (mean LAP 8.3 ± 4.7 vs. 5.1 ± 3.1 mmHg, p = 0.048), reduced LA mechanical function (PALS 15.1 ± 5.1 vs. 21.6 ± 6.2 %, p = 0.006, SI 0.69 ± 0.75 vs. 0.28 ± 0.22, p = 0.015), and longer LA ERP (242.3 ± 33.4 vs. 211.7 ± 15.6 ms, p = 0.017). Mean LAP was increased to the same extent by AV pacing in controls and AF patients (mean change 12.6 ± 7.4 vs. 12.6 ± 7.5 mmHg, p = 0.980). At the same time PALS decreased (from 15.1 ± 5.1 to 11.6 ± 3.3 %, p = 0.008), SI increased (from 0.69 ± 0.75 to 1.29 ± 1.17, p < 0.001) and ERP shortened (from 242.3 ± 33.4 to 215.9 ± 26.3 ms, p = 0.003) in AF patients, while they remained unchanged in controls. CONCLUSIONS: The stiffened LA in patients with AF responds to acute pressure elevation with an exaggerated increase in wall tension and decrease in ERP, which is not seen in the normal LA. This may underlie the propensity for AF during episodes of atrial stretch in these patients.

Effect of nikkomycin Z and 50% human serum on the killing activity of high-concentration caspofungin against Candida species using time-kill methodology.

Caspofungin and nikkomycin Z (NIK) efficacy alone and in combination were tested against seven Candida species showing or not showing paradoxical growth (PG) against caspofungin in time-kill test in RPMI-1640. Selected isolates against caspofungin and NIK were also tested in 50% serum. PG was always eliminated by NIK as well as by serum. In the serum, 1 and 16 µg/ml caspofungin yielded 0.14-4.0 and 0.34-4.0 log CFU decreases from the starting inocula for C. albicans, C. glabrata, C. tropicalis, and C. dubliniensis, respectively. CFU decrease (0.10-2.08 log) at 16 µg/ml, but not at lower caspofungin concentration was noted against C. parapsilosis, C. orthopsilosis, and C. metapsilosis. One C. parapsilosis isolate was not inhibited even by 16 µg/ml caspofungin. Caspofungin against C. albicans, C. glabrata, C. tropicalis, and C. dubliniensis maintained its activity in serum at even 1 µg/ml concentration. PG seems to an in vitro phenomenon, without clinical relevance.

Effect of 50% human serum on the killing activity of micafungin against eight Candida species using time-kill methodology.

Micafungin activity was determined against 24 wild-type clinical isolates and 5 American Type Culture Collection strains belonging to 8 Candida species in RPMI-1640 with and without 50% serum using broth microdilution and time-kill methodology. MIC values increased from 4- to 128-folds in 50% serum for all Candida species. Micafungin was not fungicidal against C. albicans, C. tropicalis, and against 2 of 3 C. metapsilosis at ≥0.25, 1, and 1 µg/mL, respectively, after 48 h with 50% serum, showing good fungistatic activity. Fungicidal activity at ≥2, 4, and 32 µg/mL was noticed against C. glabrata, C. inconspicua, and C. krusei isolates, respectively. Micafungin at 8-32 µg/mL showed fungistatic activity against C. parapsilosis and C. orthopsilosis. Serum decreased the in vitro activity of micafungin. With serum binding of echinocandins taken into account, safely fungistatic or fungicidal concentrations seem to require elevated doses against some Candida species, including C. parapsilosis, C. orthopsilosis, and C. krusei.

In vitro efficacy of 5 antifungal agents against Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis as determined by time-kill methodology.

Killing activity of amphotericin B, fluconazole, voriconazole, posaconazole, and 5-fluorocytosine was determined against 6 Candida parapsilosis, 3 Candida orthopsilosis, and 4 Candida metapsilosis clinical isolates. After 24 h, 1 of 6 C. parapsilosis, 1 of 3 C. orthopsilosis, and 3 of 4 C. metapsilosis isolates were killed at 1 to 4 microg/mL (1-8x MIC) amphotericin B. The remaining isolates were killed by 2 to 4 microg/mL amphotericin B after 48 h. Fluconazole was fungistatic at > or =1x MIC (0.5-2 microg/mL) against C. parapsilosis and at > or =2x MIC (4-8 microg/mL) against C. orthopsilosis and C. metapsilosis isolates. Voriconazole inhibited C. parapsilosis at > or =1x MIC (0.015-0.12 microg/mL), but the other 2 species were inhibited only at 4 to 8x MIC (0.25-0.5 microg/mL). Against C. orthopsilosis and C. metapsilosis, posaconazole was fungistatic close to the MIC (0.03-0.06 and 0.015-0.03 microg/mL, respectively). Against C. orthopsilosis and C. metapsilosis, fluconazole and voriconazole, but not posaconazole, seem to be less active in vitro than against C. parapsilosis.