Spatiotemporal electrophysiological changes in a murine ablation model.

AIMS: High recurrence rates after complex radiofrequency ablation procedures, such as for atrial fibrillation, remain a major clinical problem. Local electrophysiological changes that occur following cardiac ablation therapy are incompletely described in the literature. The purpose of this study was to determine whether alterations in conduction velocity, action potential duration (APD), and effective refractory period resolve dynamically following cardiac ablation. METHODS AND RESULTS: Lesions were delivered to the right ventricle of mice using a subxiphoid approach. The sham-operated control group (SHAM) received the same procedure without energy delivery. Hearts were isolated at 0, 1, 7, 30, and 60 days following the procedure and electrophysiological parameters were obtained using high-resolution optical mapping with a voltage-sensitive dye. Conduction velocity was significantly decreased at the lesion border in the 0, 7, and 30 day groups compared to SHAM. APD(70) at the lesion border was significantly increased at all time points compared to SHAM. Effective refractory period was significantly increased at the lesion border at 0, 1, 7, and 30 days but not at 60 days post-ablation. This study demonstrated that post-ablation electrophysiological changes take place immediately following energy delivery and resolve within 60 days. CONCLUSIONS: Cardiac ablation causes significant electrophysiological changes both within the lesion and beyond the border zone. Late recovery of electrical conduction in individual lesions is consistent with clinical data demonstrating that arrhythmia recurrence is associated with failure to maintain bi-directional conduction block.

Feasibility of Rapid Linear-Endocardial and Epicardial Ventricular Ablation Using an Irrigated Multipolar Radiofrequency Ablation Catheter.

BACKGROUND: A common strategy for ablation of scar-based ventricular tachycardia is delivering multiple lesions in a linear pattern. METHODS AND RESULTS: We tested the efficacy of a novel linear irrigated multipolar ablation catheter capable of creating linear lesions with a single application. Healthy swine underwent endocardial and epicardial linear ablation using a novel linear irrigated ablation catheter; control animals underwent focal lesions in a linear pattern over 3.5 cm with an irrigated radiofrequency catheter. The linear catheter contained 7 irrigated electrodes spaced over 3.5 cm and could deliver ≤25 W to each electrode. Linear ablation required significantly less radiofrequency time than focal ablation (56±11 versus 497±110 seconds; P<0.0001). At gross pathology, linear (n=18) epicardial lines were longer than focal (n=8) epicardial lines (3.3±0.7 versus 2.1±0.9 cm; P<0.0005), with greater volume (3.8±2.9 versus 1.5±1.6 cm3; P=0.002). There was no difference between linear (n=22) and focal (n=7) endocardial line length or volume. Gaps (length 2.8±0.9 mm) were present in 53% of focal lines and 0% of linear ablation lines. No perforations, steam pops, or thrombus were noted. CONCLUSIONS: Compared with sequential focal radiofrequency ablation in a linear pattern, an irrigated multipolar linear ablation catheter safely delivers contiguous endocardial or epicardial lesions without gaps in a single ablation. This catheter shows promise for decreasing ventricular tachycardia ablation procedure time and improving outcome.

Diffuse fibrosis leads to a decrease in unipolar voltage: Validation in a swine model of premature ventricular contraction-induced cardiomyopathy.

BACKGROUND: Frequent premature ventricular contractions (PVCs) may lead to dilated cardiomyopathy. A leftward shift in the unipolar voltage distribution in patients with cardiomyopathy has also been described and attributed to increased fibrosis. OBJECTIVES: We established a swine model of PVC-induced cardiomyopathy and assessed (1) whether an increase in left ventricular fibrosis occurs and (2) whether increased fibrosis leads to a leftward shift in the unipolar voltage distribution. METHODS: Ten swine underwent implantation of ventricular pacemakers; 6 programmed to deliver a 50% PVC burden and 4 controls without pacing. Voltage maps were acquired at baseline and after 14 weeks of ventricular bigeminy. RESULTS: In the PVC group, left ventricular ejection fraction decreased from 67% ± 7% to 44% ± 15% (P < .05) with no change in controls (71% ± 6% to 73% ± 4%; P = .56). The fifth percentile of the bipolar and unipolar voltage distribution at baseline was 1.63 and 5.36 mV, respectively. In the control group, after 14 weeks of pacing there was no significant change in % bipolar voltage <1.5 mV (pre 1.2% vs post 2.2%; P = .34) or % unipolar voltage <5.5 mV (pre 4.0% vs post 3.5%; P = .20). In the PVC group, there was a significant increase in % unipolar voltage <5.5 mV (5.4% vs 12.6%; P < .01), with a leftward shift in the unipolar voltage distribution. Histologically, % fibrosis was increased in the PVC group (control 1.8% ± 1.3% vs PVC 3.4% ± 2.6%; P < .01). CONCLUSION: PVC-induced cardiomyopathy in swine leads to an increase in interstitial fibrosis and a leftward shift in the unipolar voltage distribution. These findings are consistent with findings in humans with PVC-induced cardiomyopathy.

Atrial fibrillation ablation: indications, emerging techniques, and follow-up.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and its prevalence is expected to increase as our population ages. The medical management of AF has yielded only modest success, and over the past 15years, catheter ablation (CA) has become a mainstay in the treatment for AF. Advancements in the tools used for CA have improved outcomes in patients with both paroxysmal and persistent forms of AF. Additionally, the use of various post-procedure ECG monitoring devices is important for guiding the long-term management of patients with AF. However, long-term AF control in these patients also requires management of other medical comorbidities and risk factors associated with AF.

Epicardial Catheter Ablation Using High-Intensity Ultrasound: Validation in a Swine Model.

BACKGROUND: Epicardial radiofrequency catheter ablation of ventricular tachycardia remains challenging because of the presence of deep myocardial scar and adjacent cardiac structures, such as the coronary arteries, phrenic nerve, and epicardial fat that limit delivery of radiofrequency energy. High-intensity ultrasound (HIU) is an acoustic energy source able to deliver deep lesions through fat, while sparing superficial structures. We developed and tested an epicardial HIU ablation catheter in a closed chest, in vivo swine model. METHODS AND RESULTS: The HIU catheter is an internally cooled, 14-French, side-facing catheter, integrated with A-mode ultrasound guidance. Swine underwent percutaneous subxyphoid epicardial access and ablation with HIU (n=10 swine) at 15, 20, and 30 W. Compared with irrigated radiofrequency lesions in control swine (n = 5), HIU demonstrated increased lesion depth (HIU 11.6±3.2 mm versus radiofrequency 4.7±1.6 mm; mean±SD) and epicardial sparing (HIU 2.9±2.1 mm versus radiofrequency 0.1±0.2 mm) at all HIU powers, and increased lesion volume at HIU 20 and 30 W (P<0.0001 for all comparisons). HIU ablation over coronary arteries and surrounding epicardial fat resulted in deep lesions with normal angiographic flow. Histological disruption of coronary adventitia, but not media or intima, was noted in 44% of lesions. CONCLUSIONS: Compared with radiofrequency, HIU ablation in vivo demonstrates significantly deeper and larger lesions with greater epicardial sparing in a dose-dependent manner. Further development of this catheter may lead to a promising alternative to epicardial radiofrequency ablation.

Natriuretic peptide gene expression after beta-adrenergic stimulation in adult mouse cardiac myocytes.

The role of A- and B-type natriuretic peptides (ANP and BNP) in cardiac pathophysiology are of increasing interest. Isolated neonatal mouse cardiac myocytes express increased levels of ANP mRNA in the absence of growth factors in culture. Expression of ANP and BNP mRNA has not been studied in isolated adult mouse cardiac myocytes (AMCM). We examined expression of ANP and BNP mRNA in isolated AMCM with and without stimulation with beta-adrenergic receptor agonists and antagonists. AMCM were isolated and maintained in culture for 24-48 h with and without stimulation with the beta-adrenergic receptor agonist isoproterenol (Iso), the beta1-antagonist CGP20712A (CGP), or the beta2-antagonist ICI-118,551 (ICI). Northern blot analysis was performed using probes for mouse ANP and BNP mRNA. TUNEL assay was performed after beta-adrenergic receptor stimulation of AMCM. BNP mRNA expression was increased fivefold (P < 0.001) after 48 h in culture without adrenergic stimulation. BNP mRNA expression was reduced (P < 0.0001) after stimulation with Iso while ANP expression remained similar to unstimulated cells. CGP prevented the Iso reduction in BNP mRNA. Iso stimulation at doses that reduced BNP mRNA expression increased TUNEL positive nuclei, an effect blocked by the beta1-antagonist CGP. In conclusion, we have demonstrated differential gene expression of ANP and BNP in AMCM in culture. Expression of BNP mRNA increases in AMCM in culture and beta1-adrenergic receptor stimulation attenuates increased BNP gene expression and results in apoptosis.

Optimizing cardiac resynchronization therapy for congestive heart failure.

In patients with advanced systolic heart failure and mechanical dyssynchrony, cardiac resynchronization therapy (CRT) is an effective means of improving symptoms and reducing mortality. There are now several recognized approaches to optimize CRT. Imaging modalities can assist with identifying the myocardium with the latest mechanical activation for targeted left ventricular lead implantation. Device programming can be tailored to maximize biventricular pacing, and thereby is its benefit. Cardiac imaging has shown that atrioventricular and interventricular intervals can be adjusted to further reduce dyssynchrony. We review these various approaches that maximize the benefit derived from CRT.