Tomoko Machino-Ohtsuka

Complex Left Atrial Appendage Morphology and Left Atrial Appendage Thrombus Formation in Patients With Atrial Fibrillation

Background—In patients with atrial fibrillation (AF), most thrombus forms in the left atrial appendage (LAA). However, the relation of LAA morphology with LAA thrombus is unknown. Methods and Results—We prospectively enrolled 633 consecutive patients who were candidates for catheter ablation for symptomatic drug-resistant AF. Transesophageal echocardiography (TEE) was performed to assess LAA thrombus. LAA structure was assessed by 3-dimensional TEE. LAA orifice area, depth, volume, and number of lobes were measured on reconstructed 3-dimensional images. Clinical characteristics and echocardiographic measures were compared to determine variables predicting LAA thrombus. Excluded were 69 (10.9%) patients who met the exclusion criteria. Finally, this study comprised 564 patients, of whom LAA thrombus was observed in 36 (6.4%) patients. Multivariate analysis revealed CHADS2 (Congestive heart failure, Hypertension Age>75, Diabetes mellitus and prior Stroke or transient ischemic attack) score (P=0.002), left ventricular ejection fraction (P=0.01), degree of spontaneous echo contrast (P=0.02), left atrial volume (P=0.02), and number of LAA lobes (P<0.001) to be independently associated with thrombus formation. Most patients with LAA thrombus (32/34, 94.4%) had ≥3 LAA lobes, whereas LAA thrombus was observed in only 2 (0.7%) of 296 patients with 1 or 2 lobes. LAA volume significantly decreased in patients maintaining sinus rhythm after catheter ablation (P=0.0009). Number of LAA lobes did not change in any patient. Conclusions—Complex LAA morphology characterized by an increased number of LAA lobes was associated with the presence of LAA thrombus independently of clinical risk and blood stasis. This study suggests that LAA morphology might be a congenital risk factor for LAA thrombus formation in patients with AF.

Left Atrial Stiffness Relates to Left Ventricular Diastolic Dysfunction and Recurrence After Pulmonary Vein Isolation for Atrial Fibrillation

Left Atrial Stiffness and Atrial Fibrillation. Introduction: An increased left atrial (LA) stiffness reflects the structural remodeling and deterioration of the LA function. This study was designed to estimate LA stiffness by measuring a combination of the strain and LA pressure in patients undergoing pulmonary vein isolation (PVI) of atrial fibrillation (AF) and to evaluate the influence of the LA stiffness on the cardiac function, serum markers, and recurrence of AF after PVI.

Transmural Compensation of Myocardial Deformation to Preserve Left Ventricular Ejection Performance in Chronic Aortic Regurgitation

BACKGROUND In patients with chronic aortic regurgitation (AR), systolic wall stress and volume overload affects left ventricular (LV) systolic function and remodeling. The aim of this study was to assess transmural rearrangements of myocardial deformation to preserve LV ejection performances using speckle-tracking echocardiography in patients with chronic AR. METHODS Ninety patients with AR were enrolled. On LV short-axis images, total, inner, and outer radial strain and circumferential strain at the inner, mid, and outer layers were calculated. On apical four-chamber images, endocardial longitudinal strain was calculated. End-systolic wall stresses were calculated using previous methods. RESULTS AR severities were classified as moderate in 31 patients, severe and preserved LV ejection fraction (LVEF) (≥50%) in 42 patients, and severe and reduced LVEF (<50%) in 17 patients. Longitudinal strain was decreased even in the moderate AR group, despite normal end-systolic wall stress. Inner radial strain progressively decreased with increasing end-systolic wall stress, whereas outer radial strain in the moderate and severe AR and preserved LVEF groups was higher than in the control group. Consequently, total radial strain was preserved even in the severe AR and preserved LVEF groups with increased end-systolic wall stress. Similarly, despite reduced inner circumferential strain, outer circumferential strain was higher in the severe AR and preserved LVEF group than in the control group. All strain parameters were lower in the severe AR and reduced LVEF group with dramatically increased end-systolic wall stress than in other groups. CONCLUSIONS Transmural strain analysis revealed that subendocardial dysfunction accompanied by increased wall thickening at the subepicardium may be a compensatory mechanism of wall thickening to preserve LVEF in patients with chronic AR.

Tenascin‐C Aggravates Autoimmune Myocarditis via Dendritic Cell Activation and Th17 Cell Differentiation

Background Tenascin‐C (TN‐C), an extracellular matrix glycoprotein, appears at several important steps of cardiac development in the embryo, but is sparse in the normal adult heart. TN‐C re‐expresses under pathological conditions including myocarditis, and is closely associated with tissue injury and inflammation in both experimental and clinical settings. However, the pathophysiological role of TN‐C in the development of myocarditis is not clear. We examined how TN‐C affects the initiation of experimental autoimmune myocarditis, immunologically. Methods and Results A model of experimental autoimmune myocarditis was established in BALB/c mice by immunization with murine α‐myosin heavy chains. We found that TN‐C knockout mice were protected from severe myocarditis compared to wild‐type mice. TN‐C induced synthesis of proinflammatory cytokines, including interleukin (IL)‐6, in dendritic cells via activation of a Toll‐like receptor 4, which led to T‐helper (Th)17 cell differentiation and exacerbated the myocardial inflammation. In the transfer experiment, dendritic cells loaded with cardiac myosin peptide acquired the functional capacity to induce myocarditis when stimulated with TN‐C; however, TN‐C‐stimulated dendritic cells generated from Toll‐like receptor 4 knockout mice did not induce myocarditis in recipients. Conclusions Our results demonstrated that TN‐C aggravates autoimmune myocarditis by driving the dendritic cell activation and Th17 differentiation via Toll‐like receptor 4. The blockade of Toll‐like receptor 4‐mediated signaling to inhibit the proinflammatory effects of TN‐C could be a promising therapeutic strategy against autoimmune myocarditis.

Feasibility of left ventricular volume measurements by three-dimensional speckle tracking echocardiography depends on image quality and degree of left ventricular enlargement: Validation study with cardiac magnetic resonance imaging

BACKGROUND Novel 3-dimensional echocardiography with speckle tracking imaging (3D-STE) may have advantages in assessing left ventricular (LV) volume through a cardiac cycle. The feasibility of 3D-STE may be affected by image quality and LV morphology. METHODS AND RESULTS We studied 64 patients (38 men, age 55±12 years) who underwent cardiac magnetic resonance imaging (CMRI) and 3D-STE on the same day. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were measured by both modalities. Imaging qualities were quantified in each of 6 LV segments by an imaging quality score (IQS) of 1-3, and scores were averaged (mean IQS) at end-diastole and end-systole. Compared to CMRI, 3D-STE showed a tendency to underestimate LV volume measurements, but not significantly (EDV: bias=-18±37ml; ESV: bias=-10±34ml), and measurements correlated well with those by CMRI (EDV: R=0.80, ESV: R=0.86, ejection fraction: R=0.75, p<0.001). The absolute differences of LVEDV and ESV between 3D-STE and CMRI correlated significantly with mean IQS (LVEDV, R=-0.35, p=0.005; LVESV, R=-0.30, p=0.02). Based on the medium value of LVEDV by CMRI (127ml), subjects were classified into the small (<127ml) and large LVEDV (≧127ml) groups. In the large LVEDV group, mean IQS significantly correlated with the absolute differences of LVEDV (mean IQS, r=-0.45, p=0.01), despite no significant correlation in the small LVEDV group. CONCLUSION 3D-STE could measure LV volume as well as CMRI, however, its accuracy depends on the quality of the acquired image and particularly on enlargement of the left ventricle.

Novel Mechanistic Insights Into Atrial Functional Mitral Regurgitation – 3-Dimensional Echocardiographic Study –

BACKGROUND Left atrial remodeling caused by persistent atrial fibrillation (AF) causes atrial functional mitral regurgitation (MR), even though left ventricular (LV) remodeling and organic changes of the mitral leaflets are lacking. The detailed mechanism of atrial functional MR has not been fully investigated. METHODSANDRESULTS Of 1,167 patients with AF who underwent 3D transesophageal echocardiography, 75 patients were retrospectively selected who developed no, mild, or moderate-to-severe atrial functional MR (n=25 in each group) despite an LV ejection fraction ≥50% and LV volumes within the normal range. Mitral valve morphology and dynamics were analyzed. Patients with moderate-to-severe MR had a larger mitral annulus (MA) area, smaller MA area fraction, and greater nonplanarity angle and tethering angle of the posterior mitral leaflet (PML) compared with other groups (all P<0.001). In the multiple regression analysis, the MA area, MA area fraction, nonplanarity angle, and PML angle were independent determinants of the effective regurgitant orifice area of MR after adjusting for LV parameters (adjusted R(2)=0.725, P<0.001). The PML angle and MA area had a higher standardized regression coefficient (β=0.403, P<0.001, β=0.404, P<0.001, respectively) than the other variables. CONCLUSIONS Functional atrial MR in persistent AF is caused by not only MA dilatation, but also by multiple factors including the MA contractile dysfunction, disruption of the annular saddle shape, and atriogenic PML tethering. (Circ J 2016; 80: 2240-2248).

Estimation of Central Venous Pressure Using the Ratio of Short to Long Diameter from Cross-Sectional Images of the Inferior Vena Cava

Background: Long‐axis images of the inferior vena cava (IVC) have limitations as surrogates for IVC morphology in grading central venous pressure (CVP) by two‐dimensional echocardiography (2DE), because of the various cross‐sectional morphologies and the translational motion of the IVC induced by sniffing. On the basis of the relationship between venous pressure and compliance, it was hypothesized that the cross‐sectional morphology of the IVC, which was obtained using three‐dimensional echocardiography, might estimate CVP more accurately compared with standard grading by 2DE. Methods: Sixty consecutive patients who underwent right‐heart catheterization studies were prospectively enrolled. Echocardiography was performed <24 hours before catheterization. From three‐dimensional data sets, a cross‐section of the IVC was determined that was perpendicular to the long‐axis reference of the IVC. Short diameter (SD), long diameter (LD), the ratio of SD to LD (S/L) as the sphericity index, and area were measured on this cross‐sectional IVC image. Results: CVP correlated moderately with SD (r = 0.69, P < .001), strongly with S/L (r = 0.75, P < .001), and modestly with area (r = 0.47, P < .001) but not with LD (r = 0.24, P = .17). The largest areas under the curve by receiver operating characteristic analyses to detect CVP ≥ 10 mm Hg were 0.98 (95% CI, 0.97–1.0; P < .001) for S/L, 0.83 for SD (95% CI, 0.74–0.94; P < .001), and 0.70 for area (95% CI, 0.56–0.84; P = .02). If a cutoff value of 0.69 for S/L was used, the sensitivity, specificity, and accuracy to detect CVP ≥ 10 mm Hg were 0.94, 0.95, and 0.95 and for CVP grading by 2DE were 0.59, 0.98, and 0.85, respectively. Estimations of CVP were more accurately reclassified using S/L rather than grading by 2DE (net reclassification improvement, 0.38; 95% CI, 0.31–0.44; P < .001). Conclusions: S/L of an IVC cross‐section measured using three‐dimensional echocardiography may be a reliable parameter to estimate CVP compared with standard grading by 2DE.

Novel dyssynchrony evaluation by M-mode imaging in left bundle branch block and the application to predict responses for cardiac resynchronization therapy

BACKGROUND To determine an appropriate M-mode method in assessing left ventricular (LV) dyssynchrony in left bundle branch block (LBBB), and to assess feasibility of the method to predict cardiac resynchronization therapy (CRT) responses. METHODS AND RESULTS Fifty-one patients with LBBB were enrolled. Among them 31 patients underwent CRT. In addition to original septal to posterior wall motion delay (SPWMD), first peak-SPWMD was proposed as time of difference between the first septal displacement and the maximum displacement of the posterior. If an early septal point was not present, anatomical M-mode was used to visualize an early septal displacement spreading scan-area until inferoseptal wall. CRT responders were defined as LV end-systolic volume reduction (>15%) at 6 months after CRT. Twenty patients (65%) were identified as CRT responders. First peak-SPWMD in responders was significantly higher than those in nonresponders, although SPWMD did not differ between groups. Strong predicting ability of first peak-SPWMD was revealed (first peak-SPWMD: 80/90/83%; SPWMD: 35/100/58%), and area under the curve in receiver operating characteristic analysis of first peak-SPWMD (0.88) was significantly higher than that of SPWMD (0.61) (p<0.05). CONCLUSION In patients with LBBB, time differences between early septal and delayed displacement of posterolateral wall on M-mode images were the appropriate dyssynchrony parameter, and could improve the predictive ability for CRT responses.

Incremental Value of Speckle Tracking Echocardiography to Predict Cardiac Resynchronization Therapy (CRT) Responders.

Background Speckle tracking echocardiography (STE) is reported as a useful method to predict cardiac resynchronization therapy (CRT) responders. This study aimed to identify the incremental value of a STE parameter to predict CRT responders. Methods and Results We enrolled 171 patients from the Speckle Tracking imaging for the Assessment of cardiac Resynchronization Therapy (START) study. CRT responders were defined as patients with ≥15% reduction of left ventricular (LV) end‐systolic volume at 6 months post‐CRT. Based on multivariable logistic regression analysis, incremental values of STE were assessed by c‐statistics, net reclassification improvement (NRI)/integrated discrimination improvement (IDI), and decision curve analysis. Six parameters (left bundle branch block or right ventricular pacing, use of beta‐blocker, blood urea nitrogen ≤3.0 mg/dL, LV end‐systolic diameter ≤50 mm, mitral regurgitation index ≤40%, and STE parameter standard deviation of time from QRS onset to first peak on the circumferential strain curves [TSD] ≥116 ms) were identified as the determinants. Compared to the multivariable logistic regression model without TSD (model 1), that with TSD (model 2) showed significant improvement to predict CRT responders: c‐statistic (0.86 vs 0.77; P<0.001), NRI=0.19, P<0.001, and IDI=0.17, P<0.001. The decision curve of model 2 was higher than that of model 1 at threshold probabilities ≥0.2. Based on model 2, a START score was constructed. Compared to the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT‐CRT) score, the decision curve of the START score was higher than that of the MADIT‐CRT score at threshold probabilities ≥0.2. Conclusions Based on various statistical methods, this study revealed that STE had an incremental value to predict CRT responders.

Noninvasive Localization of Accessory Pathways in Wolff-Parkinson-White Syndrome by Three-Dimensional Speckle Tracking Echocardiography.

Background—We have developed a noninvasive isochrone activation imaging (AI) system with 3-dimensional (3D) speckle tracking echocardiography (STE), which allows visualization of the wavefront image of mechanical propagation of the accessory pathway (ACP) in Wolff–Parkinson–White syndrome. Methods and Results—Patients with manifest Wolff–Parkinson–White syndrome were imaged in 3D-STE AI mode, which quantified the time from QRS onset to regional endocardial deformation. In 2 patients with left- and right-side ACP, we confirmed that intraoperative contact endocardial electric mapping and the 3D-STE AI system showed comparable images pre- and postablation. In normal heart assessment by 3D-echo AI, the earliest activation sites were found at the attachment of the papillary muscles in the left ventricle and midseptum in the right ventricle, and none showed earliest activation at the peri-atrioventricular valve annuli. An analyzer who was unaware of the clinical information assessed 39 ACP locations in 38 Wolff–Parkinson–White syndrome patients using 3D-STE. All showed abnormal perimitral or tricuspid annular activations, and the location of 34 ACP (87%) showed agreement with the successful ablation sites within a 2-o’clock range. Especially for left free wall ACP, 17/18 (94%) showed consistency with the ablation site within a 2 o’clock range. Among 15 ACP at the ventricular septum, 9 (60%) showed early local activation in both right and left sides of the septum. Conclusions—Isochrone AI with 3D-STE may be a promising noninvasive imaging tool to assess cardiac synchronized activation in normal hearts and detect abnormal breakthrough of mechanical activation from both atrioventricular annuli in Wolff–Parkinson–White syndrome.