Noboru Oda

Strain rate imaging would predict sub-clinical acute rejection in heart transplant recipients

OBJECTIVE Non-invasive diagnosis of rejection is a major objective in the management of heart transplant recipients. The ability of strain rate (SR) imaging on echocardiograms to detect rejection in heart transplant recipients was investigated. METHODS A total of 396 endomyocardial biopsies, right-heart catheterisation and echocardiograms were performed in 35 heart transplant recipients. Mean values of systolic strain (epsilon(sys)), peak systolic SR (SR(sys)), and peak early diastolic SR (SR(dia)) obtained from eight left ventricular segments were calculated. RESULTS According to the conventional International Society for Heart and Lung Transplantation criteria, 351 biopsies showed a rejection grade (acute rejection, AR) of 0 or 1a (group AR(-)) whereas 45 biopsies showed a grade of 1b or higher (group AR(+)). The epsilon(sys), SR(sys) and SR(dia) were significantly different between group AR(+) and group AR(-) (-20.7+/-8.0 vs -32.6+/-6.3%, p<0.0001, 2.5+/-1.8 vs 3.6+/-1.1/s, p<0.0001, and -1.9+/-1.6 vs -3.5+/-1.3/s, p<0.001, respectively). Multivariate analysis identified epsilon(sys) (p<0.0001) as a strong predictor for group AR(+), and epsilon(sys) cut-off value of -27.4% was associated with a predictive accuracy of 82.3%. The combination of epsilon(sys) and SR(dia) discriminated group AR(+) from group AR(-) with a predictive accuracy of 84.8%. The pulmonary artery wedge pressure was higher in group AR(+) than that in group AR(-) (7.4+/-3.0 vs 9.4+/-4.4 mm Hg, p<0.05). CONCLUSION SR imaging is of potential clinical value for monitoring acute rejection in heart transplant recipients.

Utility of left ventricular systolic torsion derived from 2-dimensional speckle-tracking echocardiography in monitoring acute cellular rejection in heart transplant recipients

BACKGROUND Reduced left ventricular torsion (LV-tor) has been reported to be associated with acute rejection in heart transplant (HTx) recipients. We investigated the utility of LV-tor analysis derived from 2-dimensional speckle-tracking echocardiography (2D-STE) for detecting allograft rejection. METHODS A total of 301 endomyocardial biopsies (EMBs), right heart catheterizations and echocardiograms were performed in 32 HTx recipients. Echocardiography was done within 3 hours from EMB or simultaneously with the procedures. The LV-tor was defined as the difference between apical and basal end-systolic rotations. The LV-tor values with and without cellular rejection were compared. In addition, we investigated whether the change in LV-tor values predicts the change in rejection grade in each patient. The baseline LV-tor value in each patient was defined as a mean value of the first 3 LV-tor measurements obtained when the patient was free from rejection. RESULTS According to the conventional International Society for Heart and Lung Transplantation criteria, 274 biopsies showed a rejection Grade of 0, 1a or 1b (Group AR(-)), whereas 27 biopsies were Grade 2 or higher (Group AR(+)). LV-tor decreased more in Group AR(+) than in Group AR(-) (9.3 ± 0.7 vs 12.2 ± 0.2 degrees, p < 0.0001). In the LV-tor measurement for each patient, the 25% reduction in LV-tor value from baseline predicted Grade 2 or higher rejection with a predictive accuracy of 92.9%. CONCLUSION LV-tor derived from 2D-STE could be of clinical value for non-invasive monitoring of acute rejection in HTx recipients.

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.

Which factors predict the recovery of natural heart function after insertion of a left ventricular assist system

BACKGROUND Recent reports have demonstrated that use of a left ventricular assist system (LVAS) can initiate recovery of cardiac function, and subsequent weaning from the LVAS has attracted considerable interest. In this study we investigated reliable predictors of LVAS weaning. METHODS Eighty-two patients underwent LVAS implantation between April 1994 and July 2006 at our institution. Cardiac function was restored in 8 patients, who were weaned from LVAS after a mean of 5 months (Group R). Thirty-three patients remained on LVAS support for >1 year (Group N) because natural heart function did not show adequate improvement. We retrospectively evaluated the differences between these two groups. Group R was younger, and had a shorter duration of heart failure than Group N (23.4 vs 36.7 years and 13.3 vs 56.1 months, p < 0.01, respectively). Pathologic findings showed that the interstitial fibrosis score was lower in Group R (p < 0.01). Three months after LVAS insertion, B-type natriuretic peptide (BNP) and fractional shortening (FS) were more favorable (66.6 +/- 46 vs 264.5 +/- 170 pg/ml, p < 0.01, and 23 +/- 17.1 vs 12 +/- 9.1%, p < 0.05, respectively) in Group R. Furthermore, Group R received a higher dose of beta-blocker (15.4 +/- 8.4 vs 5.8 +/- 3.9 mg, p < 0.05). CONCLUSIONS Younger age, shorter history of heart failure, and less interstitial fibrosis were effective predictors of weaning from LVAS. Restoration of natural heart function was more rapid and more persistent in candidates for LVAS explantation, and presence of beta-blocker played a prominent role in improving cardiac function after LVAS implantation.

Time‐Domain T‐Wave Alternans is Strongly Associated with a History of Ventricular Fibrillation in Patients with Brugada Syndrome

T‐wave alternans (TWA) is an indicator of vulnerability to ventricular arrhythmias and is useful for predicting sudden cardiac death (SCD) in patients with various structural heart diseases. We evaluated whether high levels of time‐domain TWA on ambulatory ECG (AECG) are associated with a history of ventricular fibrillation (VF) in Brugada syndrome (BrS) patients.

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.

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.