Takehito Tokuyama

Left atrial thickness under the catheter ablation lines in patients with paroxysmal atrial fibrillation: insights from 64-slice multidetector computed tomography

A detailed understanding of the left atrial (LA) anatomy in patients with atrial fibrillation (AF) would improve the safety and efficacy of the radiofrequency catheter ablation. The objective of this study was to examine the myocardial thickness under the lines of the circumferential pulmonary vein isolation (CPVI) using 64-slice multidetector computed tomography (MDCT). Fifty-four consecutive symptomatic drug-refractory paroxysmal AF patients (45 men, age 61 ± 12 years) who underwent a primary CPVI guided by a three-dimensional electroanatomic mapping system (Carto XP; Biosense-Webster, Diamond Bar, CA, USA) with CT integration (Cartomerge; Biosense-Webster) were enrolled. Using MDCT, we examined the myocardial thickness of the LA and pulmonary vein (PV) regions in all patients. An analysis of the measurements by the MDCT revealed that the LA wall was thickest in the left lateral ridge (LLR; 4.42 ± 1.28 mm) and thinnest in the left inferior pulmonary vein wall (1.68 ± 0.27 mm). On the other hand, the thickness of the posterior wall in the cases with contact between the esophagus and left PV antrum was 1.79 ± 0.22 mm (n = 30). After the primary CPVI, the freedom from AF without any drugs during a 1-year follow-up period was 78 % (n = 42). According to the multivariate analysis, the thickness of the LLR was an independent positive predictor of an AF recurrence (P = 0.041). The structure of the left atrium and PVs exhibited a variety of myocardial thicknesses in the different regions. Of those, only the measurement of the LLR thickness was associated with an AF recurrence.

A Nonsynonymous Polymorphism in Semaphorin 3A as a Risk Factor for Human Unexplained Cardiac Arrest with Documented Ventricular Fibrillation

Unexplained cardiac arrest (UCA) with documented ventricular fibrillation (VF) is a major cause of sudden cardiac death. Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation. Further, adequate expression of SEMA3A was reported to be critical for normal patterning of cardiac sympathetic innervation. We investigated the relevance of the semaphorin 3A (SEMA3A) gene located at chromosome 5 in the etiology of UCA. Eighty-three Japanese patients diagnosed with UCA and 2,958 healthy controls from two different geographic regions in Japan were enrolled. A nonsynonymous polymorphism (I334V, rs138694505A>G) in exon 10 of the SEMA3A gene identified through resequencing was significantly associated with UCA (combined P = 0.0004, OR 3.08, 95%CI 1.67–5.7). Overall, 15.7% of UCA patients carried the risk genotype G, whereas only 5.6% did in controls. In patients with SEMA3A I334V, VF predominantly occurred at rest during the night. They showed sinus bradycardia, and their RR intervals on the 12-lead electrocardiography tended to be longer than those in patients without SEMA3A I334V (1031±111 ms versus 932±182 ms, P = 0.039). Immunofluorescence staining of cardiac biopsy specimens revealed that sympathetic nerves, which are absent in the subendocardial layer in normal hearts, extended to the subendocardial layer only in patients with SEMA3A I334V. Functional analyses revealed that the axon-repelling and axon-collapsing activities of mutant SEMA3A I334V genes were significantly weaker than those of wild-type SEMA3A genes. A high incidence of SEMA3A I334V in UCA patients and inappropriate innervation patterning in their hearts implicate involvement of the SEMA3A gene in the pathogenesis of UCA.

Learning curve for ablation of atrial fibrillation in medium-volume centers

PURPOSE We evaluated whether time-dependent procedural improvement was independently associated with reduction in atrial fibrillation (AF) recurrences or periprocedural complications in patients who underwent catheter ablation for AF at a single medium-volume center. METHODS A total of 208 consecutive patients who underwent AF ablation from June 2006 to June 2009 were enrolled. All procedures were performed by an experienced operator, and the ablation protocol, devices, and equipment remained unchanged throughout the study period. The study period was divided into quarters (1-4 Q) to include the same number of patients within each quarter. The incidence of AF recurrences or periprocedural complications requiring a prolonged hospital stay or surgical intervention was retrospectively compared across the quarters. RESULTS During follow-up (15 ± 3 months), we observed 26 (13%) AF recurrences (27% in 1Q, 15% in 2Q, 6% in 3Q, 2% in 4Q; 1Q vs. 3Q, p=0.0035; 1Q vs. 4Q, p=0.0003; 2Q vs. 4Q, p=0.013) and 15 (7%) periprocedural complications (12% in 1Q, 8% in 2Q, 6% in 3Q, 4% in 4Q), both of which declined progressively over time. Multiple logistic regression analysis revealed that 1Q, but not any other patient background parameters, was an independent predictor of the incidence of AF recurrence or periprocedural complications (odds ratio, 2.45; 95% confidence interval, 1.19-5.20; p=0.015). CONCLUSIONS The time period when the procedure was performed significantly influenced the AF ablation outcome, indicating that operators in medium-volume centers should be committed to providing gratifying outcomes particularly early in the institutional experience with AF ablation.

Risk stratification of ventricular fibrillation in Brugada syndrome using noninvasive scoring methods

BACKGROUND Risk stratification for ventricular fibrillation (VF) in patients with Brugada syndrome (BrS) remains controversial. OBJECTIVE The purpose of this study was to construct a novel prediction model for VF risk in BrS patients using noninvasive parameters. METHODS A total of 143 Japanese BrS patients with VF (n = 35) and without VF (n = 108) were retrospectively enrolled. We built a logistic regression model predicting VF occurrence and evaluated it by cross-validation. RESULTS Frequencies of history of syncope and spontaneous type 1 ECG, r-J interval in V1, QRS duration in V6, and LAS40, Tpeak-Tend dispersion, and max T-wave alternans were significantly associated with VF occurrence in univariate analyses. The history of syncope, r-J interval in V1, QRS duration in V6, and Tpeak-Tend dispersion were identified as independent predictors by multivariate logistic regression analysis. The predictive model was constructed using all these parameters with good discrimination of VF occurrence (area under the curve 0.869 with 97.1% sensitivity and 65.7% specificity). The area under the curve based on leave-one-out cross-validation was 0.845, with 97.1% sensitivity and 63.0% specificity suggesting good performance of the model. Retrospective survival analysis revealed that the cumulative VF event rate was significantly higher in patients at high risk than in those with low risk using the log rank test (P = 2.97 × 10(-8)). Notably, no BrS patient below the cutoff value developed a subsequent VF event. CONCLUSION This novel prediction method may effectively assesses VF risk in BrS patients, especially when determining implantable cardioverter-defibrillator placement for asymptomatic BrS patients.

Exogenous adenosine triphosphate disodium administration during primary percutaneous coronary intervention reduces no-reflow and preserves left ventricular function in patients with acute anterior myocardial infarction: A study using myocardial contrast echocardiography

BACKGROUND It is unknown whether adenosine triphosphate disodium (ATP) administration during primary percutaneous coronary intervention (PCI) is useful in anterior acute myocardial infarction (AMI). METHODS The study was a prospective, non-randomized, open-label trial. Primary PCI was successfully performed in 204 consecutive patients with first anterior AMI. ATP at a mean dose of 117 microg/kg/min for 45 min on an average was infused intravenously during PCI in 100 patients (Group 1). In the other 104 patients, normal saline was administered (Group 2). ST-segment resolution (STR) was estimated 90 min after recanalization. The no-reflow ratio was measured 2 weeks later, using intravenous myocardial contrast echocardiography. Left ventricular ejection fraction (LVEF), LV regional wall motion (LVRWM), and LV end-diastolic volume index (LVEDVI) were measured 6 months later. RESULTS Baseline patient characteristics of the two groups were similar, including TIMI risk scores. Significant STR (> or =50% resolution compared to baseline) (66% versus 50%; Group 1 versus Group 2, p=0.02), no-reflow ratio (24% versus 34%, indicated by mean values, p=0.02), LVEF (61% versus 55%, p=0.0007), LVRWM (-1.56 versus -2.05, using the SD/chord, p=0.0001), and LVEDVI (60 ml/m(2) versus 71 ml/m(2), p=0.0007) were significantly better in Group 1, and the no-reflow ratio, LVEF, LVRWM and LVEDVI were significantly better in ATP-administered patients, regardless of antecedent angina or advanced age. ATP Administration was consistently identified as a significant determinant for STR, no-reflow ratio, LVEF, LVRWM, and LVEDVI. CONCLUSIONS Intravenous ATP administration during reperfusion is an independent determinant of STR and the no-reflow ratio, and LVEF, LVRWM, and LVEDVI at 6 months after primary PCI.

A spontaneous Type 1 electrocardiogram pattern in lead V2 is an independent predictor of ventricular fibrillation in Brugada syndrome.

AIM Risk stratification for Brugada syndrome remains controversial. We investigated the relationships between episodes of ventricular fibrillation (VF) and various clinical, electrocardiographic, electrophysiologic, and genetic parameters both retrospectively and prospectively. METHODS AND RESULTS Fifty-two patients with Brugada syndrome (49 men, average age 42 +/- 3 years) were studied. In the Brugada patients with a VF history, the frequency of a spontaneous Type 1 electrocardiogram (ECG) pattern in lead V2 was significantly higher and the STJ amplitude in the V1 and V2 leads was also higher than in those without a VF history. Multivariate analyses revealed that the spontaneous Type 1 ECG pattern in lead V2 (but not lead V1) was the only independent predictor of a VF history. During a mean follow-up period of 39 +/- 4 months, 38.8% of the patients with a VF history and 2.9% of those without experienced an appropriate implantable cardioverter-defibrillation owing to VF. A multivariate analysis using a Coxs proportional hazard model showed that a VF history and spontaneous Type 1 ECG pattern in lead V2 were independent predictors of subsequent VF events. CONCLUSION A spontaneous Type 1 Brugada ECG pattern in lead V2 (but not lead V1) was both a prospective and retrospective independent predictor of VF episodes in Brugada syndrome.

Mechanical and substrate abnormalities of the left atrium assessed by 3-dimensional speckle-tracking echocardiography and electroanatomic mapping system in patients with paroxysmal atrial fibrillation.

BACKGROUND Left atrial (LA) remodeling progresses to electrical remodeling, contractile remodeling, and subsequently structural remodeling. Little is known about the relationship between LA electrical and anatomical remodeling and LA mechanical function. OBJECTIVES We aimed to clarify the relationship between LA mechanical function using 3-dimensional speckle-tracking echocardiography (3D-STE) and LA electrical remodeling using an electroanatomic mapping system (CARTO 3) and to estimate atrial fibrillation (AF) substrate in patients with paroxysmal AF (PAF). METHODS A total of 52 patients with PAF (41 (79%) men; mean age 61 ± 11 years) undergoing their initial pulmonary vein isolation (PVI) were examined. The standard deviation of the time to peak strain in each LA segment (%SD-TPS) was analyzed as an index of LA dyssynchrony using 3D-STE before PVI. Contact LA bipolar voltage and activation maps were constructed during sinus rhythm before PVI using CARTO 3. The LA total activation time was measured and low-voltage zones (LVZs) were determined with a local bipolar electrogram amplitude of <0.5 mV. The patients were divided into those with an LVZ (LVZ group; n = 23) and those without an LVZ (non-LVZ group; n = 29). RESULTS The %SD-TPS was significantly higher (14.1 ± 5.7 vs 8.0 ± 5.1; P=.0002) in the LVZ group than in the non-LVZ group and was an independent determinant of the LVZ (odds ratio 1.21; 95% confidence interval 1.04-1.49; P=.01). In addition, the LA total activation time was weakly correlated with the %SD-TPS. CONCLUSION LA dyssynchrony and conduction delay exist in patients with PAF. The 3D-STE enabled noninvasive estimation of LA electrical remodeling and AF substrate.

Prediction of sinus node dysfunction in patients with long-standing persistent atrial fibrillation using the atrial fibrillatory cycle length ☆

BACKGROUND Sinus node dysfunction (SND) occasionally coexists with long-standing atrial fibrillation (AF) but is unidentifiable during AF. We aimed to identify the predictors of underlying SND when deciding the indications for long-standing persistent AF ablation. METHODS We included 105 patients undergoing ablation of long-standing persistent AF to assess the frequency of a permanent pacemaker implantation (PMI) for SND that manifested after sinus conversion and to determine the relationship between the corrected sinus node recovery time (CSNRT) and other clinical parameters obtained before the ablation including the atrial fibrillatory cycle length (AFCL). RESULTS We identified 7 patients (7%) requiring a PMI for SND after AF termination. The patients with a PMI were nearly all females (6/7) and had a significantly longer CSNRT (1197 ± 647 vs 612 ± 349 milliseconds; P = .0046) and more prolonged AFCL (179 ± 19 vs 153 ± 22 milliseconds; P = .0028) than those without. The age (r = 0.26; P = .011), female sex (r = 0.25; P = .012), hypertension (r = 0.22; P = .038), and AFCL (r = 0.4; P < .0001) were significantly correlated with the CSNRT. A stepwise multivariate linear regression analysis including these parameters revealed that the AFCL was the only independent determinant of the CSNRT (β = 0.38; P = .0012). A receiver operating characteristic curve identified an AFCL of more than 162 milliseconds as the optimal cutoff value for predicting SND requiring a PMI (area under the curve, 0.84; sensitivity, 86%; specificity, 74%; P = .0066). CONCLUSIONS A prolonged AFCL was significantly associated with SND. Thus, assessing the AFCL in the patients with long-standing persistent AF may be helpful for the risk stratification of underlying SND.

How many electrical cardioversions should be applied for repetitive recurrences of atrial arrhythmias following ablation of persistent atrial fibrillation

AIMS We aimed to determine how many electrical cardioversions (ECs) should be applied to treat repetitive persistent recurrences of atrial fibrillation (AF) following ablation of persistent AF within the early post-procedural period. METHODS AND RESULTS A total of 40 patients with >1 episode of recurrent AF in the form of persistent atrial arrhythmias within 3 months following the ablation were recruited from 108 patients who underwent ablation for persistent or long-standing persistent AF. Electrical cardioversions were applied up to six times, if necessary, to restore sinus rhythm at clinical visits at 2-week intervals until 3 months after the ablation. Fourteen (35%) ablation failures defined as recurrences of AF identified from the 3rd month after the ablation procedure were finally diagnosed during the follow-up period (14 ± 4 month). The patients with an ablation failure more frequently required ECs than those without (3.7 ± 0.3 vs. 1.2 ± 0.2 times; P < 0.0001). A receiver-operating characteristic curve identified a number of ECs of ≥3 as the optimal cut-off value for predicting an ablation failure (area under the curve 0.91; sensitivity, 86%, and specificity, 96%; P = 0.0007). In the multivariate logistic regression analysis, a number of ECs of ≥3 was the only independent predictor of an ablation failure (odds ratio, 11.32; 95% confidence interval, 3.83-58.22; P = 0.0019). CONCLUSION It was difficult to maintain sinus rhythm in patients with persistent AF who required several ECs for recurrences of AF within the early post-ablation period.

Prediction of sinus node dysfunction in patients with persistent atrial flutter using the flutter cycle length

AIMS Sinus node dysfunction (SND) occasionally coexists with atrial flutter (AFL). However, the identification of SND during AFL is difficult. We investigated whether we could predict underlying SND in patients with persistent AFL using the flutter cycle length (FCL). METHODS AND RESULTS We retrospectively studied 211 successfully ablated patients with persistent cavotricuspid isthmus (CTI)-dependent AFL and measured the FCL before the ablation and corrected sinus node recovery time (CSNRT) after the ablation. Twenty-four patients (11%) required a permanent pacemaker implantation (PMI) for significant SND after AFL termination and had a longer FCL (295 ± 37 vs. 236 ± 34 ms; P< 0.0001) and greater CSNRT (1727 ± 1014 vs. 603 ± 733 ms; P< 0.0001) than those not requiring a PMI. A receiver-operating characteristic curve identified an FCL of >273 ms as the optimal cut-off value for predicting SND requiring a PMI (area under the curve 0.91; sensitivity, 83% and specificity, 89%; P< 0.0001). Multiple linear and logistic regression analyses revealed that the left ventricular ejection fraction (LVEF) (β = -0.2; P= 0.0016) and FCL (β = 0.46; P< 0.0001) were independently associated with the CSNRT, and that females [odds ratio (OR), 2.43; 95% confidence interval (CI), 1.32-4.62; P= 0.0046], an LVEF < 50% (OR, 2.10; 95% CI, 1.20-3.87; P= 0.012), and an FCL of >273 ms (OR, 5.34; 95% CI, 3.08-10.08; P< 0.0001) were independent predictors of SND requiring a PMI. CONCLUSION Although this study was based on a review of a database, the results suggest that assessing the FCL in patients with persistent CTI-dependent AFL could be helpful in the risk stratification of underlying SND.