Kimi Sato

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.

Prognostic value of paradoxical low-gradient severe aortic stenosis in Japan: Japanese Multicenter Aortic Stenosis Study, Retrospective (JUST-R) Registry.

BACKGROUND Whether the prognosis of paradoxical low-gradient severe aortic stenosis (PLG-SAS), especially due to paradoxical low-flow low-gradient SAS (PLFLG-SAS), is malignant in any specific ethnicity, including Japanese, remains unclear. METHODS We retrospectively enrolled 385 consecutive Japanese patients (age, 76±8 years; 148 men) with moderate AS [MAS: 0.6≤indexed aortic valve area (iAVA)<0.85cm(2)/m(2)] or SAS (iAVA <0.6cm(2)/m(2)) with preserved left ventricular ejection fraction (≥50%). SAS patients were divided into PLG-SAS and high-gradient (HG)-SAS according to the transvalvular mean gradient (40mmHg). PLG-SAS was categorized into 2 groups: normal-flow (NF) LG-SAS [stroke volume index (SVi) ≥35mL/m(2)] and PLFLG-SAS (SVi <35mL/m(2)). Endpoints were all-cause death and major adverse cardio-cerebrovascular events (MACE). RESULTS During a median follow-up of 15 months, 31 patients died and 48 suffered MACE. All-cause death and MACE rates in PLG-SAS and PLFLG-SAS were significantly lower than those in HG-SAS and similar to those in MAS. On multivariate analysis, neither PLG-SAS nor PLFLG-SAS were independent determinants for all-cause death compared with MAS [MAS as reference, PLG-SAS: hazard ratio (HR) 0.47, p=0.32; PLFLG-SAS: HR 0.01, p=0.20; HG-SAS: HR 3.37, 95% confidence interval 1.24-9.74, p=0.02]. CONCLUSIONS In Japanese patients, the prognoses of PLG-SAS and PLFLG-SAS were better than that of HG-SAS and similar to that of MAS, being better than that in Western populations.

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).

Prognostic implications in patients with symptomatic aortic stenosis and preserved ejection fraction: Japanese multicenter aortic stenosis, retrospective (JUST-R) registry.

BACKGROUND Current prognostic implication of symptomatic patients with aortic stenosis (AS) remains undetermined. This study investigated the current prognostic implications of AS-related symptoms and the effect of aortic valve replacement (AVR) on outcome. METHODS We enrolled 586 consecutive patients with severe AS (aortic valve area <1.0cm2) with preserved left ventricular ejection fraction (≥50%). All patients were stratified into the following four groups based on the predominant symptoms: Group 1, asymptomatic (n=316); Group 2, chest pain (n=41); Group 3, heart failure (n=192); or Group 4, syncope (n=37). RESULTS AS-related symptoms were diagnosed in 270 patients (46.1%), among whom 182 patients (32.2%) received AVR. Thirty-nine patients (6.7%) had cardiac death during the mean follow-up of 16±14 months. AVR was associated with significant reduction in cardiac death in Groups 3 (p<0.001) and 4 (p=0.004) whereas no significant prognostic advantage of AVR was observed in Groups 1 or 2. Cox proportional-hazard multivariate analysis revealed that age, heart failure, and mean pressure gradient (PG) were associated with increased risk of cardiac death in all patients regardless of AVR [hazard ratio (HR): 1.079, 2.090, and 1.008 respectively, all p<0.05]. In the patients without AVR, age, heart failure, syncope, and mean PG were independently associated with cardiac death (HR: 1.130, 3.639, 4.638, and 1.008, all p<0.05). CONCLUSION This retrospective study demonstrated the current associations between the types of AS symptoms and prognosis in Japanese patients with severe AS.

Utility of Nutritional Screening in Predicting Short-Term Prognosis of Heart Failure Patients

Controlling nutritional status (CONUT) uses 2 biochemical parameters (serum albumin and cholesterol level), and 1 immune parameter (total lymphocyte count) to assess nutritional status. This study examined if CONUT could predict the short-term prognosis of heart failure (HF) patients.A total of 482 (57.5%) HF patients from the Ibaraki Cardiovascular Assessment Study-HF (n = 838) were enrolled (298 men, 71.7 ± 13.6 years). Blood samples were collected at admission, and nutritional status was assessed using CONUT. CONUT scores were defined as follows: 0-1, normal; 2-4, light; 5-8, moderate; and 9-12, severe degree of undernutrition. Accordingly, 352 (73%) patients had light-to-severe nutritional disturbances. The logarithmically transformed plasma brain natriuretic peptide (log BNP) concentration was significantly higher in the moderate-severe nutritional disturbance group (2.92 ± 0.42) compared to the normal group (2.72 ± 0.45, P < 0.01). CONUT scores were significantly higher in the in-hospital death patients [4 (3-8), n = 14] compared with patients who were discharged following symptom alleviation [3 (1-5), n = 446, P < 0.05]. With the exception of transferred HF patients (n = 22), logistic regression analysis that incorporated the CONUT score and the log BNP, showed that a higher CONUT score (P = 0.019) and higher log BNP (P = 0.009) were predictors of in-hospital death, and the median duration of hospital stay was 20 days.Our results demonstrate the usefulness of CONUT scores as predictors of short-term prognosis in hospitalized HF patients.

Effect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Outcome and Cardiac Function in Patients With Diabetes and Heart Failure ― Insights From the Ibaraki Cardiac Assessment Study-Heart Failure (ICAS-HF) Registry ―

BACKGROUND Although experimental animal studies report many pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), their prognostic value has not been demonstrated in clinical trials.Methods and Results:Among 838 prospectively enrolled heart failure (HF) patients hospitalized for acute decompensated HF, 79 treated with DPP-4i were compared with 79 propensity score-matched non-DPP-4i diabetes mellitus (DM) patients. The primary endpoint was all-cause mortality; the secondary endpoint was a composite of cardiovascular death and hospitalization. During follow-up (423±260 days), 8 patients (10.1%) in the DPP-4i group and 13 (16.5%) in the non-DPP-4i group died (log-rank, P=0.283). The DPP-4i group did not have a significantly higher rate of all-cause mortality (log-rank, P=0.283), or cardiovascular death or hospitalization (log-rank, P=0.425). In a subgroup analysis of HF with preserved ejection fraction (HFpEF; n=75), the DPP-4i group had a significantly better prognosis than the non-DPP-4i group regarding the primary endpoint (log-rank, P=0.021) and a tendency to have better prognosis regarding the secondary endpoint (log-rank, P=0.119). In patients with HF with reduced EF (n=83), DPP-4i did not result in better prognosis. CONCLUSIONS DPP-4i did not increase the risk of adverse clinical outcomes in patients with DM and HF. DPP-4i may be beneficial in HFpEF.

Direct Comparison of Severity Grading Assessed by Two-Dimensional, Three-Dimensional, and Doppler Echocardiography for Predicting Prognosis in Asymptomatic Aortic Stenosis

Background: Reliable assessment of aortic stenosis (AS) severity relies on stroke volume (SV) determination using Doppler echocardiography, but it can also be estimated with two‐dimensional/three dimensional echocardiography (2DE/3DE). The aim of this study was to compare SV measurements and AS subgroup classifications among the three modalities and determine their prognostic strength in asymptomatic AS. Methods: We prospectively enrolled 359 patients with asymptomatic AS. SV was determined using three methods, and the patients were divided into four AS subgroups according to indexed aortic valve area (iAVA) and SV index (SVI) determined by each method and mean pressure gradient. The primary end point was major adverse cardiovascular events (MACEs), which included cardiac death, ventricular fibrillation, heart failure, and aortic valve replacement. We also assessed the presence or absence of upper septal hypertrophy. Results: Doppler‐derived SVI was significantly larger than that derived from 2DE/3DE with modest correlations (r = 0.33 and 0.47). Thus, group classification varied substantially by modality. During the median follow‐up period of 17 months, 112 patients developed a major adverse cardiovascular event. Although iAVA assessed by Doppler echocardiography had a significantly better net reclassification improvement compared with iAVA by 2DE or 3DE, prognostic values were nearly identical among the three methods. Ventricular septal geometry affected the accuracy of risk stratification. Conclusions: AS severity grading varied considerably according to the methods applied for calculating SV. Thus, SV measurements are not interchangeable, even though their prognostic power is similar. Hence, examiners should select one of the three methods to assess AS severity and should use the same method in longitudinal examinations. Highlights:Doppler‐derived SV was larger than SV by 2D and 3D echocardiography.AS severity group classification among the three methods was significantly different.The prognostic value of AS severity grading among the three methods was identical.The prognosis of asymptomatic paradoxical LF/LG severe AS was intermediate.

Pertuzumab/Trastuzumab Breast Cancer Therapy Is Associated With Complex Hemodynamic Abnormalities

Whereas breast cancer therapy may target cardiovascular system through side effects of surgery, chemotherapy, and radiation, interest has been focused on the impact of trastuzumab [(1)][1], a human epidermal growth factor receptor-2 (HER2) blocker, on left ventricular (LV) function. Maximizing HER2

Hemodynamic durability of transcatheter aortic valves using the updated Valve Academic Research Consortium-2 criteria

We investigated the hemodynamic durability of the transcatheter aortic valves (TAVs) using the updated Valve Academic Research Consortium‐2 (VARC‐2) criteria.

Is universal grading of diastolic function by echocardiography feasible

Quantitation of diastolic function centers on the assessment of active and passive ventricular properties, and involves measurement estimates of ventricular relaxation, and chamber and myocardial stiffness. Diastolic dysfunction is a propensity to develop increased left ventricular (LV) end-diastolic pressure. Recently American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) proposed a new grading system. While the new guidelines are ambiguous and with cutoff points that may misclassify patients as both sicker and healthier than they are. This article outlines the pathophysiology behind the diastolic dysfunction and role and limitation of echocardiographic assessment in predicting LV diastolic dysfunction.