Search

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 multi-variable 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.

Background Atrial refractoriness may be an important determinant of atrial fibrillation (AF) risk, but its measurement is not clinically accessible. Because the QT interval predicts incident AF and the atrium and ventricle share repolarizing ion currents, we investigated the association between an individual's QT interval and atrial effective refractory period (AERP). Methods In paroxysmal AF patients presenting for catheter ablation, the QT interval was measured from the surface 12-lead electrocardiogram. The AERP was defined as the longest S1–S2 coupling interval without atrial capture using a 600-ms drive cycle length. Results In 28 patients, there was a positive correlation between QTc and mean AERP. After multivariate adjustment, a 1-ms increase in QTc predicted a 0.70-ms increase in AERP. Conclusions The QTc interval reflects the AERP, suggesting that the QTc interval may be used as a marker of atrial refractoriness relevant to assessing AF risk and mechanism-specific therapeutic strategies.

Introduction : Genome wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with atrial fibrillation (AF), but the mechanisms underlying these relationships have not yet been elucidated. Inflammation and fibrosis have been posited as important mechanisms responsible for AF. We sought to investigate the impact of SNP carrier status on inflammation and fibrosis in left atrial appendage tissue. Methods and Results : Carrier status of 10 AF-associated SNPs was evaluated on DNA extracted from left atrial appendage tissue in 176 individuals (120 with AF). The presence of inflammation was evaluated through visual quantification of leukocyte infiltration following hematoxylin and eosin staining, while fibrosis was quantified using picrosirius red with fast green staining. Unadjusted and adjusted linear and logistic regression models were utilized to evaluate for an association between SNP carrier status and inflammation and fibrosis. On adjusted logistic regression analysis, the rs7164883 SNP (intronic within HCN4) was associated with a reduced odds of inflammation (odds ratio: 0.42; 95% CI: 0.22-0.81, p = 0.01), and was not associated with fibrosis on adjusted linear regression analysis (β-coefficient: -0.31; 95% CI: -1.03-0.40, p = 0.40). None of the remaining SNPs exhibited significant associations with left atrial inflammation or fibrosis. Conclusions : Among 10 AF-associated SNPs, a single genetic variant was associated with reduced left atrial inflammation, while no histologic differences were observed in the remaining 9. The known AF-associated SNPs do not appear to predispose to the development of pro-inflammatory or pro-fibrotic AF sub-phenotypes. This article is protected by copyright. All rights reserved

Despite the controversy in mechanism, rodent and clinical studies have demonstrated beneficial effects of stem/progenitor cell therapy after myocardial infarction (MI). In a rat ischaemic reperfusion MI model, we investigated the effects of immunomodification of CD 34(+) cells on heart function and myocardial conduction. Bispecific antibody (BiAb), consisting of an anti-myosin light chain antibody and anti-CD45 antibody, injected intravenously was used to direct human CD34(+) cells to injured myocardium. Results were compared to echocardiography guided intramyocardial (IM) injection of CD34(+) cells and PBS injected intravenously. Treatment was administered 2 days post MI. Echocardiography was performed at 5 weeks and 3 months which demonstrated LV dilatation prevention and fractional shortening improvement in both the BiAb and IM injection approaches, with BiAb achieving better results. Histological analyses demonstrated a decrease in infarct size and increase in arteriogenesis in both BiAb and IM injection. Electrophysiological properties were studied 5 weeks after treatments by optical mapping. Conduction velocity (CV), action potential duration (APD) and rise time were significantly altered in the MI area. The BiAb treated group demonstrated a more normalized activation pattern of conduction and normalization of CV at shorter pacing cycle lengths. The ventricular tachycardia inducibility was lowest in the BiAb treatment group. Intravenous administration of BiAb offers an effective means of stem cell delivery for myocardial repair post-acute MI. Such non-invasive approach was shown to offer a distinct advantage to more invasive direct IM delivery.

Predictors of LV Dysfunction with Idiopathic PVC Introduction Patients with frequent premature ventricular complexes (PVCs) might be at risk for the developing or exacerbation of left ventricular (LV) dysfunction. However, some patients with a high-PVC burden do not develop cardiomyopathy, while other patients with low-PVC burden can develop cardiomyopathy. The purpose of this study was to evaluate the positive predictors of idiopathic PVCs-induced cardiomyopathy. Methods and Results We investigated 214 patients undergoing successful ablation of PVCs who had no other causes of cardiomyopathy. We divided the study cohort into 2 groups: ejection fraction (EF) ≥ 50% (normal LV) and EF 30 kg/m2; 37% vs. 13%; P = 0.001). Logistic regression analysis showed that CI-dispersion, PVC burden, and BMI (>30 kg/m2) are independent predictors of PVC-induced cardiomyopathy. Conclusions In addition to the PVC burden, the CI-dispersion and BMI are associated with PVC-induced cardiomyopathy.

Role of a 4q25 Genetic Variant in Atrial Flutter Background The prediction of atrial fibrillation (AF) following catheter ablation of atrial flutter (Afl) would be helpful to facilitate targeted arrhythmia monitoring and anti-coagulation strategies. A single nucleotide polymorphism, rs2200733, is strongly associated with AF. We sought to characterize the association between rs2200733 and prevalent Afl and to determine if the variant could predict AF after cavotricuspid isthmus ablation. Methods and Results We performed a genetic association study of 295 patients with Afl and/or AF and 469 controls using multivariable logistic regression. The variant was then assessed as a predictor of incident AF after cavotricuspid isthmus ablation in 87 consecutive typical Afl patients with Cox proportional hazards models. The rs2200733 rare allele was associated with an adjusted 2.06-fold increased odds of isolated Afl (95% CI: 1.13–3.76, P = 0.019) and an adjusted 2.79-fold increased odds of a combined phenotype of AF and Afl (95% CI: 1.81–4.28, P

Background: The axillary vein is a commonly used extrathoracic access site for cardiac rhythm device lead implantation. We sought to describe variation in axillary vein location and identify predictors of a more cranial or caudal radiographic location to facilitate blind venous cannulation. Methods: This was a single-center, retrospective study of patients undergoing lead implantation between 2006 and 2010. The cranial-caudal location of the axillary vein lateral and medial to the rib cage border was determined by reviewing peripheral contrast venograms. Multivariate linear regression was performed. Results: Of 155 patients, the majority were men (62%) and White (53%). The most frequent position of the lateral and medial axillary vein was over the third rib (40%) and top of the third rib (15%), respectively. In multivariate analysis, whites had a more caudal location of both the lateral (0.56 rib spaces lower, 95% confidence interval [CI] 0.22–0.91, P = 0.002) and medial axillary vein (0.50 rib spaces lower, 95% CI 0.85–0.91, P = 0.019). Other independent predictors included an approximate 3–4% higher rib space location for every digit increase in body mass index (BMI) (P = 0.049 for the lateral location and P = 0.016 for the medial location) and an approximate half rib space higher location for males (P = 0.015 for the lateral location and P = 0.013 for the medial location). Conclusions: The most common radiographic position of the axillary vein was over the third rib. Whites have a more caudal axillary vein location while men and patients with higher BMI have a more cranial position of the axillary vein. (PACE 2011; 34:1585–1592)

Background: An unusual 12-lead electrocardiographic pattern may be present in patients with cavotricuspid isthmus (CTI)-dependent flutter. Objective: Using baseline patient characteristics and echocardiography, we sought to study predictors of unusual electrocardiogram (ECG) characteristics in patients with CTI-dependent atrial flutter. Methods: This was a dual-center, retrospective cohort study of 147 patients undergoing electrophysiology study and ablation for CTI-dependent atrial flutter. Results: Among this cohort, 23 patients (16%) had unusual 12-lead ECG characteristics. Using multivariatelogisticregression,wefoundtwoclinicalpredictorsforhavinganunusualECGpattern.Aclockwise (CW) pattern at time of electrophysiology study was the strongest predictor of an unusual ECG pattern (odds ratio 15.3, 95% confidence interval [CI] 4.0‐59.4, P < 0.005). In addition, patients with decreased systolic function had a 3.5 greater odds (95% CI 1.1‐11.5, P = 0.037) of having an unusual ECG pattern. Conclusions: Our data demonstrate that among patients suffering from CTI-dependent atrial flutter who are referred for ablation, 16% will have unusual ECG patterns. Patients with CW atrial activation and left ventricle dysfunction have greater odds of manifesting unusual patterns by surface electrocardiogram. (PACE 2011; 34:1251‐1257)

ECG and EGM of IIR. Introduction: Intra-isthmus reentry (IIR) is a circuit within the cavotricuspid isthmus (CTI). The purpose of this study is to prospectively define the electrogram and surface ECG characteristics of IIR, and its clinical implications. Methods and Results: Fourteen patients underwent electrophysiological studies and were found to have IIR. Detailed electrogram mapping of the CTI was available in all, electroanatomic mapping (EAM) in 8 of 14 (57%) patients. In all, entrainment mapping during tachycardia proved reentry, and showed that the anteroinferior CTI was out of the circuit and the septal CTI was in the circuit in 12 of 14 patients, whereas in 2, the circuit was confined within the mid and/or anteroinferior CTI. Fractionated potentials (FPs) spanning 34–71% of the tachycardia cycle length were recorded within the CTI in all, and double potentials were inscribed in 10 of 14 (71%). Analysis of the tricuspid annulus electrograms showed spontaneous shifts from a counterclockwise (CCW) to clockwise or fusion patterns. Surface ECGs showed either typical CCW pattern (12 patients) or atypical patterns (3 patients). The EAMs showed a focal pattern in 3, a CCW pattern in 5. The successful ablation site always occurred at the area with maximal FP duration. Over the same period, 33 of 384 (9%) patients who underwent ablation for CTI-dependent flutter had prior successful CTI ablation, 7 of 33 (21%) were found to have IIR during the redo procedure. Conclusions: (1) Electrogram and ECG patterns of IIR frequently show atypical flutter. (2) IIR was successfully ablated in an area of the CTI associated with maximal duration of FPs. (3) IIR is a significant cause of “recurrent flutter” in patients with prior CTI ablation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1099-1106)

Safety Versus Lesion Size of Ablation Catheters. Introduction: Different technologies have been developed for radiofrequency ablation (RFA), which include increasing electrode (tip) size and cooling the tip through irrigation either internally (closed-loop) with D5W or externally (open-loop) with saline. Although these catheters are widely used clinically, the propensity for adverse events and the lesion profiles of each of these catheter technologies have not been directly compared under a wide range of controlled conditions. Methods and Results: Freshly excised canine thigh muscle was placed in a chamber filled with circulating, heparinized blood heated to 37°C. Five different catheters were tested: 4 mm tip, 10 mm tip single thermistor, 10 mm tip multitemperature sensor, 4 mm closed-loop irrigated cooled-tip, and 4 mm open-loop irrigated cooled tip at several different contact and power settings. The catheter and tissue interface was continuously monitored with intracardiac echocardiography (echo) (Acuson). During the RFA, any bubbling generated from the tip and/or popping seen on echo was noted, and after each RFA, the catheter and lesion were examined for the presence of thrombus. For all of the catheters, complications correlated to the electrode tip temperature and power setting. All of the catheters experienced complications at any lesion size except for the open-irrigated catheter, which only had complications at the largest lesions. Overall, the cooled tip catheters experienced an at least sixfold greater odds of popping, bubbling, and impedance rises than the 4 mm, but the majority occurred at power levels greater than 20 W. The open-irrigated catheters created eccentric lesions that extended away from the tissue-catheter interface, in the direction of blood flow. In addition, it produced saline filled blisters at the lesion site in 16.7% of the burns. The 10 mm catheter had an at least twofold greater odds of thrombus, charring, and bubbling, but larger lesions than the 10 mm multitemperature sensor catheter. Conclusions: Catheter type, contact conditions, and power settings all play a role in lesion size and in the frequency of complications that occur during an RFA. Cooling the electrode tip, either internally or externally, does not prevent complications from occurring, especially at the higher power control settings. Adding more temperature sensors to the 10 mm seems to reduce the amount of complications that can occur. (J Cardiovasc Electrophysiol, Vol. 20, pp. 325-335, March 2009)

Background: Atrial fibrillation (AF) has been linked to an inflammatory process detected through various biomarkers, including C-Reactive Protein (CRP). Early recurrence of AF within the first 3 months after curative AF ablation is not felt to reflect success or failure of the procedure. We hypothesized that this early recurrence is due to an inflammatory response to the ablation itself. We therefore sought to evaluate levels of CRP after AF ablation. Methods: We prospectively enrolled subjects undergoing AF ablation. A control group of patients undergoing ablation for supraventricular tachycardia (SVT) was also enrolled. Each patient had CRP drawn on the day of the procedure (prior to ablation) and during their first follow-up (median 49 days, interquartile range [IQR] 37–93) and second follow-up (median 147 days, IQR 141–257) clinic visits. Patient interviews were performed and medical histories reviewed for evidence of recurrent AF prior to the first follow-up. Results: CRP levels significantly increased from baseline to first follow-up in the AF ablation group (P = 0.0017). CRP did not significantly change after SVT ablation (P = 0.92). Seventeen (45%) of the AF subjects exhibited recurrence of AF prior to first follow-up. After adjusting for multiple potential confounders, AF ablation patients with recurrent AF prior to their first follow-up had a statistically significant greater odds of having an increase in CRP (OR 21, 95% CI 1.1–417, P = 0.045). Conclusions: AF ablation generates an inflammatory response that persists for several weeks. This inflammation may explain early recurrence of AF after curative ablation.

Introduction: A substantial number of patients require a second left atrial procedure after ablation for atrial fibrillation (AF), either for left atrial flutter or recurrent AF. The success and complication rates of repeat transseptal catheterization in these patients are unknown. The aim of this study was to determine the difficulty and/or success rates of repeat transseptal catheterization after left atrial ablation for AF. Methods and Results: Consecutive patients undergoing repeat left atrial procedures after ablation for AF over a 1-year period were enrolled. Difficulties with, success rates, and complications of the first and second transseptal catheterizations were recorded. Sixteen patients underwent a repeat transseptal catheterization. Of the 4 in whom the first procedure was performed with an ablation catheter across a patent foramen ovale (PFO), 3 required a transseptal puncture for their repeat procedure. The remaining 12 underwent transseptal puncture without difficulty for their first procedure, and, despite the same operators for each patient, the repeat transseptal was noted to be difficult in 5. Of those 5, the transseptal puncture was unsuccessful due to increased interatrial septal thickness in 2 patients. One repeat transseptal attempt was aborted after posterior right atrial puncture with the transseptal needle occurred, attributed to distorted interatrial septal anatomy not observed prior to the first case. Conclusions: Compared with the first procedure, repeat transseptal catheterization after ablation for AF, whether initially performed across a PFO or via a transseptal puncture, is more difficult, less often successful, and potentially associated with more complications.

Thoracic Cord Stimulation and Cardiac Autonomics.Introduction: Thoracic spinal cord stimulation (SCS) has been used to treat angina pectoris and to produce cardiac autonomic control. We studied the effect of thoracic SCS on sinus node and AV nodal function to test the hypothesis that SCS modulated autonomic regulation of the electrophysiology of these structures. Methods and Results: The effects of thoracic SCS on sinus cycle length and AH interval were studied in 47 dogs in five experimental groups: group 1: intact autonomic nerves; group 2: bilateral ansae subclaviae transection and efferent stellate stimulation; group 3: ansae transection, bilateral vagi transection, and efferent stellate stimulation; group 4: bilateral vagi transection and efferent vagal stimulation; and group 5: bilateral vagal stimulation and bilateral ansae subclaviae transection. Under fluoroscopic guidance, the spinal stimulator electrode was advanced to the T1-T2 position and threshold determined by adjusting the output to produce muscle contraction. Parameters were measured at baseline prior to SCS and during SCS, at 90% threshold. Ansae subclaviae and vagi nerves were isolated using standard approaches. Stellate and vagal stimulation were each performed using a constant current stimulator and at three different frequencies. Sinus cycle length and AH intervals (the latter at constant right atrial pacing of 400 msec) were measured with and without SCS at baseline and at each level of nerve stimulation. Nitric oxide was measured using the coronary sinus overflow method, from a luminal balloon catheter placed deep in the coronary sinus. SCS resulted in an increase in sinus cycle length from 507 ± 23 msec to 544 ± 22 msec (P = 0.02) and AH interval from 71 ± 4 msec to 74 ± 4 msec (P = 0.03). Ansae subclaviae transection had no effect on this increase, while vagal transection eliminated the increase in sinus cycle length and AH with SCS. The increase in these parameters with SCS was maintained during both stellate stimulation (group 2) and vagal stimulation (group 5) across all three levels of neural stimulation. Conclusion: SCS appears to enhance parasympathetic activity, mediated via the vagus. This may have implications for use of thoracic SCS to treat chronic angina and perhaps prevent sudden cardiac death.

Atrial flutter involving either clockwise or counterclockwise rotation around the tricuspid annulus utilizing the subeustachian isthmus has been well described. However, macroreentrant atrial circuits in atypical atrial flutter in patients who have not undergone previous surgery or without atrial disease are not well defined. We describe a patient without structural heart disease who presented with an atrial macroreentrant rhythm. Entrainment mapping demonstrated a critical isthmus within the coronary sinus. Activation mapping demonstrated double potential throughout the length of the coronary sinus with disparate activation sequences. A circuit involving the myocardium of the coronary sinus, exiting in the lateral left atrium, down the interatrial septum, and reentering into the coronary sinus was identified. Successful ablation of the rhythm was accomplished by a circumferential radiofrequency application within the coronary sinus.

Animal models of atrial flutter and early mapping studies of human atrial flutter have suggested the importance of barriers in this reentrant arrhythmia. The consistency of rate and morphology of typical atrial flutter suggest a common anatomic substrate for this arrhythmia. The unique endocardial architecture of the right atrium provides anatomic barriers around which reentry occurs. In typical human atrial flutter, the crista terminalis, eustachian ridge, and tricuspid annulus have been identified as barriers to conduction. The importance of conduction barriers, methodology for defining barriers, the anatomic substrate for these barriers, and the role of these barriers in other atrial arrhythmias are discussed.

Pathology of Slow Pathway Ablation. Introduction: AV nodal reentrant tachycardia is routinely cured using radiofrequency catheter ablation techniques. However, there remains controversy as to whether the reentrant circuit for this tachycardia exists solely in the AV node or whether perinodal atrial tissues are vital to the circuit. In addition, the effects of radiofrequency ablation of the slow pathway of AV nodal reentrant tachycardia on the AV node are not known. We examined an autopsy specimen to determine the anatomical location and extent of AV nodal damage of radiofrequency slow pathway ablation for cure of AV nodal reentrant tachycardia. Methods and Results: A 64-year-old woman with confirmed AV nodal reentrant tachycardia underwent a successful “slow pathway” AV modification with a single radiofrequency application. Five months after the procedure, the patient died from a spontaneous intracranial hemorrhage. Postmortem gross pathological examination of the heart was performed. The heart was then sectioned and stained for histologic examination. On gross examination, a pale lesion 0.5 cm in diameter was seen on the endocardial surface adjacent to the tricuspid annulus. approximately 0.85 cm anterior to the coronary sinus os and 1.15 cm from the apex of the triangle of Koch where the AV node resides. Histologic examination revealed a right atrial lesion composed of connective tissue and fat. The compact AV node and surrounding transitional cells were unaffected histologically, with normal atrial cells lying between the AV node and the lesion. Conclusion: Ablation of the slow pathway to cure AV nodal reentrant tachycardia does not produce any gross or histologic damage to the AV node, suggesting that the AV nodal reentrant circuit does not exist in its entirety in the AV node.