Newer generation cryoballoon vs. contact force-sensing radiofrequency ablation catheter in the ablation of paroxysmal atrial fibrillation.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) has become an effective treatment to control symptoms. The second generation cryoballoon (CB) was designed for more efficient and homogenous freeze. Radiofrequency (RF) ablation catheters using three-dimensional electroanatomical mapping with the use of contact-force radiofrequency (CF RF) technology has achieved good results in several studies. OBJECTIVES: To compare the efficacy and safety of second-generation CB ablation in contrast to CF RF ablation in the ablation of paroxysmal AF. METHODS: A total of 81 consecutive patients suffering from paroxysmal AF underwent pulmonary vein isolation (PVI) either by the second generation cryoballoon (n = 44) or a contact force-sensing RF catheter (n = 37). The study was conducted at Ain Shams University Hospitals and Royal Brompton & Harefield NHS trust. Baseline data, procedural data and patient follow up-at 3, 6 and 12 months-were collected and analysed. RESULTS: The mean age was 53.8 ± 15 years in the CB group and 62.4 ± 12 years in the RF group, females representing 40.9% and 48.6% respectively. The baseline characteristics were comparable, but the CB group had less left atrial diameter and more left ventricular ejection fraction. The CB procedure was shorter (94.4 ± 39.3 vs. 140.8 ± 44.3 min, p < 0.0001), with longer fluoroscopy time (30 vs. 15.1 min, p = 0.047). Procedural complications were comparable between the two groups (CB 4.6%, CF RF 2.7%, p = 0.411). After 1 year, the recurrence rate in the CB group was similar to RF (27.3% vs. 27% respectively, p = 0.980). CONCLUSION: Second-generation CB ablation of paroxysmal AF has similar efficacy and safety to contact force-sensing RF catheters, with shorter procedure times and more fluoroscopy.

Characterization of the Mechanism and Substrate of Atrial Tachycardia Using Ultra-High-Density Mapping in Adults With Congenital Heart Disease: Impact on Clinical Outcomes.

Background Atrial tachycardia ( AT ) is common in patients with adult congenital heart disease and is challenging to map and ablate. We used ultra-high-density mapping to characterize the AT mechanism and investigate whether substrate characteristics are related to ablation outcomes. Methods and Results A total of 50 AT s were mapped with ultra-high-density mapping in 23 procedures. Patients were followed up for up to 12 months. Procedures were classified to group A if there was 1 single AT induced (n=12) and group B if there were ≥2 AT s induced (n=11 procedures). AT mechanism per procedure was macro re-entry (n=10) and localized re-entry (n=2) in group A and multiple focal (n=6) or multiple macro re-entry (n=5) in group B. Procedure duration, low voltage area (0.05-0.5 mV), and low voltage area indexed for volume were higher in group B (159 [147-180] versus 412 [352-420] minutes, P<0.001, 22.6 [12.2-29.8] versus 54.2 [51.1-61.6] cm2, P=0.014 and 0.17 [0.12-0.21] versus 0.26 [0.23-0.27] cm2/mL, P=0.024 accordingly). Dense scar (<0.05 mV) and atrial volume were similar between groups. Acute success and freedom from arrhythmia recurrence were worse in group B (100% versus 77% P=0.009 and 11.3, CI 9.8-12.7 versus 4.9, CI 2.2-7.6 months, log rank P=0.004). Indexed low voltage area ≥0.24 cm2/mL could predict recurrence with 100% sensitivity and 77% specificity (area under the curve 0.923, P=0.007). Conclusions Larger low voltage area but not dense scar is associated with the induction of multiple focal or re-entry AT s, which are subsequently associated with longer procedure duration and worse acute and midterm clinical outcomes.

Comparison of a high throughput day case atrial fibrillation ablation service in a local hospital with standard regional tertiary cardiac centre care.

AIMS: We investigated safety and efficacy of a high throughput atrial fibrillation (AF) ablation service within a local non-cardiac centre compared with matched patients at the regional tertiary cardiac centre. METHODS AND RESULTS: Patients were consented in clinic and pre-assessed by clerical staff. Locally, other than physicians, staff had no experience of ablation and were trained with simulations. Pulmonary vein isolation (PVI) was performed with conscious sedation, on uninterrupted anticoagulation for at least 4 weeks. No transoesophageal echocardiogram (TOE) was performed. A 28 mm Arctic Front Advance Cryoballoon was used. A 20 mm Achieve wire demonstrated PVI on a portable laptop-based EP recording system. Phrenic nerve function was monitored during right PVI. Finally, a transthoracic echocardiogram excluded a pericardial effusion. A Femostop was applied. Two hundred and seventy-six patients were matched. Average age was 61 ± 0.7 years, 39% female. CHA2DS2 VASc score varied from 0 to 7. Procedure time was significantly shorter at the local hospital (63.5 ± 1.1 vs. 101.7 ± 2.9 min, P < 0.0001). Fluoroscopy time (5.5 ± 0.2 vs. 12.6 ± 0.6 min, P < 0.0001) and fluoroscopy dose were lower (17.2 ± 2.1 vs. 97.6 ± 14.6 mGy, P < 0.0001). Successful PVI was achieved in all. The complication rate was low (5.4% vs. 6.3%, P = not significant). Four (1.4%) patients were not day case discharges. At 3 month follow-up, 54.3% had complete resolution, and 26.1% had improvement of symptoms. A total of 16.6% patients requested repeat procedures for ongoing symptoms. CONCLUSION: In experienced hands, cryoballoon for paroxysmal AF is delivered safely and effectively in a local centre. Outcomes remain excellent. These short, day case procedures allow utilization of non-cardiac centres. The service provides a model to meet increasing demands.

The contribution of pathways initiated via the Gq\11 G-protein family to atrial fibrillation.

Atrial fibrillation is the commonest cardiac arrhythmia and leads to significant clinical morbidity and mortality. It has a complex pathophysiology but is often initiated by atrial ectopic beats and because of atrial remodelling once it occurs it can become established. Thus therapeutic interventions designed to prevent the initial occurrence of the arrhythmia are particularly needed. At the cellular level, these ectopic beats arise because of abnormal calcium release events from the sarcoplasmic reticulum leading to an inward current mediated by the sodium-calcium exchanger. There has been considerable interest in this over the last few years largely focused on the ryanodine receptor and related signalling pathways. However, atrial myocytes also possess a well-developed inositol trisphosphate (IP3) dependent calcium release system and this has been less studied. In this review we focus on pathways and molecules that couple via the Gq\11 family of G-proteins including regulators of G-protein signalling that may influence IP3 mediated calcium release and atrial fibrillation.

Absence of the Regulator of G-protein Signaling, RGS4, Predisposes to Atrial Fibrillation and Is Associated with Abnormal Calcium Handling.

The description of potential molecular substrates for predisposition to atrial fibrillation (AF) is incomplete, and it is unknown what role regulators of G-protein signaling might play. We address whether the attenuation of RGS4 function may promote AF and the mechanism through which this occurs. For this purpose, we studied a mouse with global genetic deletion of RGS4 (RGS4(-/-)) and the normal littermate controls (RGS4(+/+)). In vivo electrophysiology using atrial burst pacing revealed that mice with global RGS4 deletion developed AF more frequently than control littermates. Isolated atrial cells from RGS4(-/-) mice show an increase in Ca(2+) spark frequency under basal conditions and after the addition of endothelin-1 and abnormal spontaneous Ca(2+) release events after field stimulation. Isolated left atria studied on a multielectrode array revealed modest changes in path length for re-entry but abnormal electrical events after a pacing train in RGS4(-/-) mice. RGS4 deletion results in a predisposition to atrial fibrillation from enhanced activity in the Gαq/11-IP3 pathway, resulting in abnormal Ca(2+) release and corresponding electrical events.

iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death.

Desmosomes are anchoring junctions that exist in cells that endure physical stress such as cardiac myocytes. The importance of desmosomes in maintaining the homeostasis of the myocardium is underscored by frequent mutations of desmosome components found in human patients and animal models. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a phenotype caused by mutations in desmosomal components in ∼ 50% of patients, however, the causes in the remaining 50% of patients still remain unknown. A deficiency of inhibitor of apoptosis-stimulating protein of p53 (iASPP), an evolutionarily conserved inhibitor of p53, caused by spontaneous mutation recently has been associated with a lethal autosomal recessive cardiomyopathy in Poll Hereford calves and Wa3 mice. However, the molecular mechanisms that mediate this putative function of iASPP are completely unknown. Here, we show that iASPP is expressed at intercalated discs in human and mouse postmitotic cardiomyocytes. iASPP interacts with desmoplakin and desmin in cardiomyocytes to maintain the integrity of desmosomes and intermediate filament networks in vitro and in vivo. iASPP deficiency specifically induces right ventricular dilatation in mouse embryos at embryonic day 16.5. iASPP-deficient mice with exon 8 deletion (Ppp1r13l(Δ8/Δ8)) die of sudden cardiac death, displaying features of ARVC. Intercalated discs in cardiomyocytes from four of six human ARVC cases show reduced or loss of iASPP. ARVC-derived desmoplakin mutants DSP-1-V30M and DSP-1-S299R exhibit weaker binding to iASPP. These data demonstrate that by interacting with desmoplakin and desmin, iASPP is an important regulator of desmosomal function both in vitro and in vivo. This newly identified property of iASPP may provide new molecular insight into the pathogenesis of ARVC.

Essential role of the m2R-RGS6-IKACh pathway in controlling intrinsic heart rate variability.

Normal heart function requires generation of a regular rhythm by sinoatrial pacemaker cells and the alteration of this spontaneous heart rate by the autonomic input to match physiological demand. However, the molecular mechanisms that ensure consistent periodicity of cardiac contractions and fine tuning of this process by autonomic system are not completely understood. Here we examined the contribution of the m2R-I(KACh) intracellular signaling pathway, which mediates the negative chronotropic effect of parasympathetic stimulation, to the regulation of the cardiac pacemaking rhythm. Using isolated heart preparations and single-cell recordings we show that the m2R-I(KACh) signaling pathway controls the excitability and firing pattern of the sinoatrial cardiomyocytes and determines variability of cardiac rhythm in a manner independent from the autonomic input. Ablation of the major regulator of this pathway, Rgs6, in mice results in irregular cardiac rhythmicity and increases susceptibility to atrial fibrillation. We further identify several human subjects with variants in the RGS6 gene and show that the loss of function in RGS6 correlates with increased heart rate variability. These findings identify the essential role of the m2R-I(KACh) signaling pathway in the regulation of cardiac sinus rhythm and implicate RGS6 in arrhythmia pathogenesis.

The Role of Inhibitory G Proteins and Regulators of G Protein Signaling in the in vivo Control of Heart Rate and Predisposition to Cardiac Arrhythmias.

Inhibitory heterotrimeric G proteins and the control of heart rate. The activation of cell signaling pathways involving inhibitory heterotrimeric G proteins acts to slow the heart rate via modulation of ion channels. A large number of Regulators of G protein signalings (RGSs) can act as GTPase accelerating proteins to inhibitory G proteins and thus it is important to understand the network of RGS\G-protein interaction. We will review our recent findings on in vivo heart rate control in mice with global genetic deletion of various inhibitory G protein alpha subunits. We will discuss potential central and peripheral contributions to the phenotype and the controversies in the literature.

Cryoablation versus radiofrequency ablation for treatment of atrioventricular nodal reentrant tachycardia: cryoablation with 6-mm-tip catheters is still less effective than radiofrequency ablation.

BACKGROUND: The treatment of choice for atrioventricular nodal reentrant tachycardia (AVNRT) is catheter ablation of the atrioventricular nodal slow pathway. OBJECTIVE: The purpose of this study was to ascertain whether cryoablation (Cryo) with 6-mm-tip catheters is as effective as radiofrequency ablation (RF). METHODS: Patients who had catheter ablation for AVNRT between 2005 and 2008 were identified. The main outcome measure was overall success without the use of an alternative energy source and no recurrence. RESULTS: Two hundred eighty-eight procedures in 272 patients were identified; 184 were female (68%), and the mean age was 53 +/- 14 (17-88) years. There were 123 Cryo and 149 RF procedures. Cryo had a lower overall success rate (83% vs. 93%; P = .02). Mean procedure times were similar in both groups (90 minutes; P = .5). Fluoroscopy time was longer with Cryo: 16 (7-48) versus 14 (5-50) minutes (P = .04). Only one case of atrioventricular block was observed in the RF group (0.7%). Cryo was more expensive than RF ( pounds sterling 3141 vs. pounds sterling 2153). CONCLUSION: Even when delivering multiple lesions with 6-mm-tip catheters, Cryo is less effective than RF. RF is recommended as a first-line treatment, although the only major complication occurred in the RF group.