Impact of the MitraClip G4 System on Routine Practice and Outcomes in Patients With Secondary Mitral Regurgitation.

BACKGROUND: The MitraClip G4 system is a new iteration of the transcatheter edge-to-edge repair system. We assessed the impact of the G4 system on routine practice and outcomes in secondary mitral regurgitation (2°MR).Methods and Results: Consecutive patients with 2°MR treated with either the MitraClip G2 (n=89) or G4 (n=63) system between 2018 and 2021 were included. Baseline characteristics, procedures, and outcomes were compared. Inverse probability of treatment weighting and Cox regression were used to adjust for baseline differences. Baseline characteristics were similar, except for a lower surgical risk in the G4 group (Society of Thoracic Surgeons Predicted Risk of Mortality ≥8: 38.1% vs. 56.2%; P=0.03). In the G4 group, more patients had short (≤2 mm) coaptation length (83.7% vs. 54.0%; P<0.001) and fewer clips were used (17.5% vs. 36.0%; P=0.02). Acceptable MR reduction was observed in nearly all patients, with no difference between the G4 and G2 groups (100% vs. 97.8%, respectively; P=0.51). The G4 group had fewer patients with high transmitral gradients (>5mmHg; 3.3% vs. 13.6%; P=0.03). At 1 year, there was no significant difference between groups in the composite endpoint (death or heart failure rehospitalization) after baseline adjustment (10.5% vs. 20.2%; hazard ratio 0.39; 95% confidence interval 0.11-1.32; P=0.13). CONCLUSIONS: The G4 system achieved comparable device outcomes to the early-generation G2, despite treating more challenging 2°MR with fewer clips.

Impact of Renal Congestion in Patients With Secondary Mitral Regurgitation After Mitral Transcatheter Edge-to-Edge Repair.

BACKGROUND: Renal congestion is a potential prognostic factor in patients with heart failure and recently, assessment has become possible with intrarenal Doppler ultrasonography (IRD). The association between renal congestion assessed by IRD and outcomes after mitral transcatheter edge-to-edge repair (TEER) is unknown, so we aimed to clarify renal congestion and its prognostic implications in patients with mitral regurgitation (MR) who underwent TEER using MitraClip system.Methods and Results: Patients with secondary MR who underwent TEER and were assessed for intrarenal venous flow (IRVF) by IRD were classified according to their IRVF pattern as continuous or discontinuous. Of the 105 patients included, 78 patients (74%) formed the continuous group and 27 (26%) were the discontinuous group. Kaplan-Meier analysis revealed significant prognostic power of the IRVF pattern for predicting the composite outcome of all-cause death and heart failure rehospitalization (log-rank P=0.0257). On multivariate Cox regression analysis, the composite endpoint was independently associated with the discontinuous IRVF pattern (hazard ratio, 3.240; 95% confidence interval, 1.300-8.076; P=0.012) adjusted using inverse probability of treatment weighting. CONCLUSIONS: IRVF patterns strongly correlated with clinical outcomes without changes in renal function. Thus, they may be useful for risk stratification after mitral TEER for patients with secondary MR.

Comparative Data of Procedural and Midterm Outcomes in Patients Who Underwent Percutaneous Left Atrial Appendage Closure Between the WATCHMAN FLX and WATCHMAN 2.5 Devices　- Insight From the OCEAN-LAAC Registry.

BACKGROUND: Limited data are available regarding clinical outcomes after percutaneous left atrial appendage closure using WATCHMAN FLX (WM-FLX) and WATCHMAN-2.5 (WM2.5) devices in Asian patients. METHODS AND RESULTS: Data of 1,464 consecutive patients (WM-FLX, n=909; WM2.5, n=555) were extracted from a Japanese multicenter registry, and clinical data were compared between the 2 groups. No in-hospital deaths, periprocedural stroke, or device embolization occurred. Procedural success was significantly higher in the WM-FLX than WM2.5 group (95.8% vs. 91.9%; P=0.002) owing to the lower incidence of periprocedural pericardial effusion (0.55% vs. 1.8%; P=0.021). No significant differences in all-cause death, postprocedural stroke, and device-related thrombus were observed between the 2 groups. However, the cumulative bleeding rate at 1 year was substantially lower in the WM-FLX group (7.8% vs. 16.4%; P<0.001). Landmark analysis of bleeding events highlighted lower bleeding rates in the WM-FLX than WM2.5 group within the first 6 months (6.4% vs. 14.8%; P<0.001), with comparable bleeding rates over the 6- to 12-month period (1.5% vs. 3.2%, respectively; P=0.065). CONCLUSIONS: This study demonstrated higher early safety and lower 1-year bleeding rates in the WM-FLX than WM2.5 group. The lower bleeding events with WM-FLX are likely due to multiple factors other than purely difference in devices, such as postprocedural drug regimen.

Clinical efficacy of tolvaptan in acute decompensated heart failure patients with severe aortic stenosis and atrial fibrillation: a sub-analysis from the LOHAS registry.

BACKGROUND: Severe aortic valve stenosis (AS) and atrial fibrillation (AF) are risk factors of hemodynamic instability in heart failure (HF) management due to low cardiac output, respectively. Therefore, the treatment of HF due to severe AS complicated with AF is anticipated to be difficult. Tolvaptan, a vasopressin V2 receptor inhibitor, is effective in controlling acute decompensated heart failure (ADHF) with hemodynamic stability. However, its clinical efficacy against ADHF caused by AS with AF remains to be determined. METHODS: Clinical information (from September 2014 to December 2017) of 59 patients diagnosed with ADHF due to severe AS (20 patients with AF; 39 patients with sinus rhythm [SR]) was obtained from the LOHAS registry. The registry collected data from seven hospitals and assessed the short-term effects of tolvaptan in patients hospitalized for ADHF with severe AS. We attempted to identify clinical differences from baseline up to 4 days, comparing patients with AF (AF group) versus those with SR (SR group). RESULTS: There were no significant differences between the groups in age (83.7 ± 4.5 vs. 85.8 ± 6.9 years, respectively; p = 0.11) and aortic valve area (0.60 [0.46-0.73] vs. 0.56 [0.37-0.70] cm2, respectively; p = 0.50). However, left atrial volume was larger (104 [85-126] vs. 87 [64-103] mL, respectively; p < 0.01), whereas stroke volume was lower (51.6 ± 14.8 vs. 59.0 ± 18.7 mL, respectively; p = 0.08) in the AF group versus the SR group. Body weight decreased daily from baseline up to day 4 in both groups (from 55.4 to 53.2 kg [p < 0.01] and from 53.5 to 51.0 kg [p < 0.01], respectively) without change in heart rate. Notably, the systolic blood pressure decreased slightly in the AF group after 2 days of treatment with tolvaptan. CONCLUSIONS: Short-term treatment with tolvaptan improved HF in patients hospitalized for severe AS, regardless of the presence of AF or SR. After achieving sufficient diuresis, a slight decrease in blood pressure was observed in the AF group, suggesting an appropriate timeframe for safe and effective use of tolvaptan.

Prognostic value of transvalvular flow rate in patients with low-gradient severe aortic stenosis: A dobutamine stress echocardiography study.

BACKGROUNDS: There are limited data on the clinical relevance of transvalvular flow rate (Qmean ) at rest (Qrest) and at peak stress (Qstress ) during dobutamine stress echocardiography (DSE) in patients with low-gradient severe aortic stenosis (LG-SAS). METHODS: We retrospectively analyzed the clinical data of patients with LG-SAS who underwent DSE. LG-SAS was defined as an aortic valve (AV) area index of < .6 cm2 /m2 and a mean AV pressure gradient (AVPG) of < 40 mm Hg. The primary endpoint included all-cause death and heart failure hospitalization. RESULTS: Of 100 patients (mean age 79.5 ± 7.3 years; men, 45.0%; resting left ventricular ejection fraction [LVEF] 52.1% ± 15.9%; resting stroke volume index 35.8 ± 7.7 mL/m2 ; Qrest 171.8 ± 34.9 mL/s), the primary endpoint occurred in 51 patients during a median follow-up of 2.84 (interquartile range 1.01-5.21) years. When the study patients were divided into three subgroups based on Qrest and Qstress , the multivariate analysis showed that Qrest < 200 mL/s and Qstress ≥200 mL/s (hazard ratio 3.844; 95% confidence interval 1.143-12.930; p = .030), as well as Qrest and Qstress < 200 mL/s (hazard ratio 9.444; 95% confidence interval 2.420-36.850; p = .001), were significantly associated with unfavorable outcomes with Qrest and Qstress ≥200 mL/s as a reference after adjusting for resting LVEF, resting mean AVPG, chronic kidney disease, New York Heart Association functional class III/IV, and AV replacement. CONCLUSIONS: Flow conditions based on the combination of Qrest and Qstress are helpful for risk stratification in LG-SAS patients.

Prognostic value of extraaortic-valvular cardiac damage in patients with moderate aortic stenosis and reduced left ventricular ejection fraction.

PURPOSE: The extraaortic-valvular cardiac damage (EVCD) Stage has shown potential for risk stratification for patients with aortic stenosis (AS). This study aimed to examine the usefulness of the EVCD Stage in risk stratification of patients with moderate AS and reduced left ventricular ejection fraction (LVEF). METHODS: Clinical data from patients with moderate AS (aortic valve area, .60-.85 cm2/m2; peak aortic valve velocity, 2.0-4.0 m/s) and reduced LVEF (LVEF 20%-50%) were analyzed during 2010-2019. Patients were categorized into three groups: EVCD Stages 1 (LV damage), 2 (left atrium and/or mitral valve damage), and 3/4 (pulmonary artery vasculature and/or tricuspid valve damage or right ventricular damage). The primary endpoint included a composite of cardiac death and heart failure hospitalization, with non-cardiac death as a competing risk. RESULTS: The study included 130 patients (mean age 76.4 ± 6.8 years; 62.3% men). They were categorized into three groups: 26 (20.0%) in EVCD Stage 1, 66 (50.8%) in Stage 2, and 48 (29.2%) in Stage 3/4. The endpoint occurred in 54 (41.5%) patients during a median follow-up of 3.2 years (interquartile range, 1.4-5.1). Multivariate analysis indicated EVCD Stage 3/4 was significantly associated with the endpoint (hazard ratio 2.784; 95% confidence interval 1.197-6.476; P = .017) compared to Stage 1, while Stage 2 did not (hazard ratio 1.340; 95% confidence interval .577-3.115; P = .500). CONCLUSION: The EVCD staging system may aid in the risk stratification of patients with moderate AS and reduced LVEF.

Usefulness of Vena Contracta for Identifying Severe Secondary Mitral Regurgitation: A Three-Dimensional Transesophageal Echocardiography Study.

Background: In secondary mitral regurgitation (SMR), effective regurgitant orifice area by the proximal isovelocity surface area method ( EROA PISA ) evaluation might cause an underestimation of regurgitant orifice area because of its ellipticity compared with vena contracta area (VCA). We aimed to reassess the SMR severity using VCA-related parameters and EROA PISA . Methods: The three-dimensional transesophageal echocardiography data of 128 patients with SMR were retrospectively analyzed; the following parameters were evaluated: EROA PISA , anteroposterior and mediolateral vena contracta widths (VCWs) of VCA (i.e., VCW AP and VCW ML ), VCW Average calculated as ( VCW AP + VCW ML )/2, and VCA Ellipse calculated as π × ( VCW AP /2) × ( VCW ML /2). Severe SMR was defined as ≥ 0.39 cm 2 . Results: The mean age of the patients was 77.0 ± 8.9 years, and 78 (60.9%) were males. Compared with EROA PISA (r = 0.801), VCW Average (r = 0.940) and VCA Ellipse (r = 0.980) were strongly correlated with VCA. On receiver-operating characteristic curve analysis, VCW Average and VCA Ellipse had C-statistics of 0.981 (95% confidence interval [CI], 0.963-1.000) and 0.985 (95% CI, 0.970-1.000), respectively; these were significantly higher than 0.910 (95% CI, 0.859-0.961) in EROA PISA (p = 0.007 and p = 0.003, respectively). The best cutoff values for severe SMR of VCW Average and VCA Ellipse were 0.78 cm and 0.42 cm 2 , respectively. The prevalence of severe SMR significantly increased with an increase in EROA PISA (38 of 88 [43.2%] patients with EROA PISA < 0.30 cm 2 , 21 of 24 [87.5%] patients with EROA PISA = 0.30-0.40 cm 2 , and 16 of 16 [100%] patients with EROA PISA ≥ 0.40 cm 2 [Cochran-Armitage test; p < 0.001]). Among patients with EROA PISA < 0.30 cm 2 , SMR severity based on VCA was accurately reclassified using VCW Average (McNemar's test; p = 0.505) and VCA Ellipse (p = 0.182). Conclusions: Among patients who had SMR with EROA PISA of < 0.30 cm 2 , suggestive of moderate or less SMR according to current guidelines, > 40% had discordantly severe SMR based on VCA. VCW Average and VCA Ellipse values were useful for identifying severe SMR based on VCA in these patients.

Newer versus Early Generation of the MitraClip for Primary Mitral Regurgitation: A Japanese Single-Center Experience.

Background: The MitraClip G4 system is the latest version of the transcatheter edge-to-edge repair (TEER) system for mitral regurgitation (MR). We aimed to investigate the impact of the new system on routine clinical practice and patient outcomes in the treatment of primary MR. Methods: Consecutive patients with primary MR who underwent TEER with either the MitraClip G2 or G4 between 2018 and 2021 were enrolled from a single center registry. Baseline clinical and echocardiographic characteristics as well as procedural and clinical outcomes up to 1 year were compared between groups. Technical and device success were defined in accordance with the Mitral Valve Academic Research Consortium criteria. Results: Among 71 patients with primary MR, 34 were treated with G2 and 37 were treated with G4. Patients treated with G4 had lower surgical risk (7.74 [5.04, 14.97] vs. 5.26 [3.98, 6.40]; p < 0.01) than those with G2. There were no significant differences in other baseline clinical variables between groups. On baseline echocardiography, MR volume and flail gap were significantly greater in the G4 group than in the G2 group (regurgitant volume: 63 [41-76] mL vs. 68 [62-84] mL; p = 0.04, flail gap: 4.5 [3.5-5.5] mm vs. 5.4 [4.5-7.1] mm; p = 0.04). Technical success was achieved in over 95% of both groups with no significant difference (p > 0.99). Device success was achieved in 61.8% of the G2 group, while in 70.3% of the G4 group (p = 0.47). Post-procedural MR severity was comparable (p = 0.42) and there was no significant difference in the occurrence of mitral stenosis (p = 0.61) between groups. Among patients who reached 1-year follow-up (n = 54), there was no significant difference between groups in a composite endpoint of death or heart failure rehospitalization (10.5% vs. 20.2%; HR 0.61; 95% CI 0.17-2.22; p = 0.45). Residual heart failure symptoms (NYHA ≥ 3) at 1 year were observed in 3.7% of the G2 group, while no patient in the G4 group (p > 0.99). Conclusions: The MitraClip G4 system achieved comparable device outcomes to the early-generation device (G2), despite treating more severe primary MR with a larger flail gap.

MitraClip Treatment of Moderate-to-Severe and Severe Mitral Regurgitation in High Surgical Risk Patients　- Real-World 1-Year Outcomes From Japan.

BACKGROUND: The MitraClip NT System was approved for marketing in Japan on October 31, 2017, and a prospective, multi-center, single-arm Post-Marketing use Surveillance (PMS) study was launched in 2018. This is the first report of the Japan PMS study with 1-year subject outcomes.Methods and Results:A total of 500 patients were registered between April 2018 and January 2019. Patients with symptomatic chronic moderate-to-severe (3+) or severe mitral regurgitation (MR; 4+), MR with a Society of Thoracic Surgery (STS) replacement score of ≥8%, or presence of 1 pre-defined risk factor were enrolled. Primary outcome measures included acute procedural success (APS), and rate of Single Leaflet Device Attachment (SLDA) at 30 days. The overall cohort was elderly (77.9±9.48 years) with functional MR etiology in 71.6% of the subjects. The majority of subjects were New York Heart Association (NYHA) class III/IV (68.9%), with mean STS replacement score of 11.95±9.66%. The APS rate was 91.13% and the 30-day SLDA rate was 1.21%. Durable MR reduction was achieved with 88.1% of subjects at MR ≤2+ at 1 year. Significant improvement in the functional capacity was observed, with 93% of subjects at NYHA class I/II at 1 year. CONCLUSIONS: In the Japan PMS experience, the MitraClip procedure resulted in improvements in MR severity, with significantly improved functional outcomes. These results demonstrate safety and efficacy of MitraClip therapy in the eligible Japanese population.

Antithrombotic Therapy for Patients With Atrial Fibrillation and Bioprosthetic Valves　- Real-World Data From the Multicenter, Prospective, Observational BPV-AF Registry.

BACKGROUND: Although bioprosthetic valve (BPV) replacements are becoming more common within our aging society, there are limited prospective data on the appropriate antithrombotic therapy for East Asian patients with atrial fibrillation (AF) and BPV replacement. Antithrombotic therapy and thrombotic and hemorrhagic event rates in Japanese patients with AF and BPV replacement are investigated.Methods and Results:This multicenter, prospective, observational study enrolled patients with BPV replacement and AF. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. Of the 894 patients analyzed, 54.7%, 29.4%, and 9.6%, were treated with warfarin-based therapy, direct oral anticoagulant (DOAC)-based therapy, or antiplatelet therapy without anticoagulants, respectively; 6.3% did not receive any antithrombotic drugs. The mean observation period was 15.3±4.0 months. The event rates for stroke or systemic embolism and major bleeding were 1.95%/year and 1.86%/year, respectively. The multivariate adjusted hazard ratios for DOAC vs. warfarin were 1.02 (95% confidence intervals [CI], 0.30-3.41 [P=0.979]) for systemic embolic events and 0.96 (95% CI, 0.29-3.16 [P=0.945]) for major bleeding. CONCLUSIONS: Approximately 30% of patients with AF and BPV replacement were treated with DOAC. The risks of major bleeding and stroke or systemic embolism were similar between warfarin- and DOAC-treated patients with AF who had BPV replacement. Treatment with DOACs could be an alternative to warfarin in this population.

Edoxaban vs. Vitamin K Antagonist for Atrial Fibrillation After Transcatheter Aortic Valve Replacement in Japanese Patients　- A Subanalysis of the ENVISAGE-TAVI AF Trial.

BACKGROUND: Japanese patients undergoing transcatheter aortic valve replacement (TAVR) are often female and have a small body size, potentially impacting bleeding risk with antithrombotic therapy. Outcomes of direct oral anticoagulant use in these patients with atrial fibrillation (AF) need to be clarified.Methods and Results: This prespecified analysis included Japanese patients from ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial that compared treatment with edoxaban and vitamin K antagonists (VKAs) in patients with AF after TAVR. The primary efficacy and safety outcomes were net adverse clinical events (NACE; composite of all-cause death, myocardial infarction, ischemic stroke, systemic embolic event, valve thrombosis, and International Society on Thrombosis and Haemostasis [ISTH]-defined major bleeding) and ISTH-defined major bleeding, respectively. Intention-to-treat (ITT) and on-treatment analyses were performed. Overall, 159 Japanese patients were enrolled (edoxaban group: 82, VKA group: 77) and followed for on average 483 days. Mean patient age was 83.8 years; 52.2% were female. In the ITT analysis, NACE rates were 10.9%/year with edoxaban and 12.5%/year with VKA (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.38-1.90); major bleeding occurred in 8.9%/year and 7.3%/year, respectively (HR, 1.17; 95% CI, 0.45-3.05). In edoxaban- and VKA-treated patients, rates of ischemic stroke were 1.8%/year and 1.0%/year, respectively; fatal bleeding rates were 0.9%/year and 2.0 %/year. On-treatment results were similar to ITT. CONCLUSIONS: In Japanese patients with AF after successful TAVR, edoxaban and VKA treatment have similar safety and efficacy profiles.

Comparison of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and an Aortic Bioprosthetic Valve.

BACKGROUND: Current guidelines equally recommend direct oral anticoagulants (DOACs) and warfarin for atrial fibrillation (AF) patients with a bioprosthetic valve (BPV); however, there are limited data comparing DOACs and warfarin in AF patients with an aortic BPV.Methods and Results: This post-hoc subgroup analysis of a multicenter, prospective, observational registry (BPV-AF Registry) aimed to compare DOACs and warfarin in AF patients with an aortic BPV. The primary outcome was a composite of stroke, systemic embolism, major bleeding, heart failure requiring hospitalization, all-cause death, or BPV reoperation. The analysis included 479 patients (warfarin group, n=258; DOAC group, n=221). Surgical aortic valve replacement was performed in 74.4% and 36.7% of patients in the warfarin and DOAC groups, respectively. During a mean follow up of 15.5 months, the primary outcome occurred in 45 (17.4%) and 32 (14.5%) patients in the warfarin and DOAC groups, respectively. No significant difference was found in the primary outcome between the 2 groups (adjusted hazard ratio: 0.88, 95% confidence interval: 0.51-1.50). No significant multiplicative interaction was observed between the anticoagulant effects and type of aortic valve procedure (P=0.577). CONCLUSIONS: Among AF patients with an aortic BPV, no significant difference was observed in the composite outcome of adverse clinical events between patients treated with warfarin and those treated with DOACs, suggesting that DOACs can be used as alternatives to warfarin in these patients.

Medical student medium-term skill retention following cardiac point-of-care ultrasound training based on the American Society of Echocardiography curriculum framework.

BACKGROUND: No studies have demonstrated medium- or long-term skill retention of cardiac point-of-care ultrasound (POCUS) curriculum for medical student. Based on the American Society of Echocardiography (ASE) curriculum framework, we developed a blended-learning cardiac POCUS curriculum with competency evaluation. The objective of this study was to investigate the curriculum impact on image acquisition skill retention 8 weeks after initial training. METHODS: This study was a prospective, pre-post education intervention study for first- and second-year medical students, with blinded outcome assessment. The curriculum included a pre-training ASE online module and healthy volunteer hands-on training to obtain 5 views: parasternal long-axis (PLAX), parasternal short-axis (PSAX), apical 4-chamber (A4C), subcostal 4-chamber (S4C), and subcostal inferior vena cava (SIVC) views. Students took 5-view image acquisition skill tests at pre-, immediate post-, and 8-week post-training, using a healthy volunteer. Three blinded assessors rated the image quality using a validated 10-point maximum scoring system. Students used a hand-held ultrasound probe (Butterfly iQ). RESULTS: Fifty-four students completed hands-on training, and pre- and immediate post-training skill tests. Twenty-seven students completed 8-week post-training skill tests. Skill test score improvement between pre- and 8-week post-training was 2.11 points (95% CI, 1.22-3.00; effect size, 1.13). CONCLUSION: The cardiac POCUS curriculum demonstrated medium-term skill retention. The curriculum was sufficient for S4C and SIVC skill retention, but inadequate for PLAX, PSAX, and A4C. Therefore, instructional design modifications or re-training for PLAX, PSAX, and A4C are needed to make the curriculum more effective for clinically relevant skill retention.

Additive value of the right parasternal view for the assessment of aortic stenosis.

BACKGROUND: Although Doppler evaluation using a multiplanar method is recommended to assess the severity of aortic stenosis (AS) with transthoracic echocardiography, evidence on the diagnostic significance of a non-apical method is limited. This study aimed to compare the use of the apical with the use of the right parasternal view (RPV) method to evaluate AS severity and to examine the diagnostic significance of performing the RPV method in addition to the apical method during the evaluation. METHODS: This retrospective observational study included 276 consecutive patients (mean age: 79 ± 10 years; women, 56%) with severe AS (aortic valve area [AVA] ≤1.0cm2 ). The severity of AS according to the apical method and that according to the RPV for all subjects were compared, and the significance of performing the RPV method in addition to the apical method was examined. Furthermore, we compared the concordance group, in which the apical and RPV methods indicated matching in severity, and the discordant group, in which the apical and RPV methods did not indicate matching severity. RESULTS: Peak velocity (Vmax ), mean pressure gradient (MG) were significantly higher and the AVA, AVAi, and Doppler velocity index (DVI) were significantly smaller when the RPV was added to the apical view. Performing the RPV method in addition to the apical method significantly decreased the number of low PG AS cases (MG < 40 mmHg) from 69.9% to 65.0% and it increased the number of very severe AS cases (Vmax ≥ 5 m/s) from 8.7% to 14.5%. Deviation of Doppler angle was significantly greater in the discordant group compared to the concordant group (22.5 ± .6 vs. 31.8 ± 1.7, p < .001). CONCLUSIONS: By performing the RPV method in addition to the apical method to determine AS severity, the diagnosis of AS to be resolved in approximately 10% of cases. These results suggest that AS severity may be underestimated by using the apical method alone.

Prognostic Value of Apical Sparing of Longitudinal Strain in Patients with Symptomatic Aortic Stenosis.

Background: Older patients with aortic stenosis (AS) have a higher incidence of wild-type transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to determine whether apical sparing of longitudinal strain (LS) could help diagnose ATTR-CA and provide useful prognostic information in symptomatic AS. Methods: We performed vendor-independent two-dimensional speckle-tracking analysis of regional and global left ventricular LS in 16 patients with ATTR-CA and 31 patients with non-obstructive hypertrophic cardiomyopathy to determine the best cutoff value of the apical sparing ratio (APSR) for diagnosing ATTR-CA. We then determined the prevalence in patients who had an APSR higher than the best cutoff value and investigated its prognostic value in 230 patients with symptomatic AS. To determine the natural history of symptomatic AS, patients who had aortic valve replacement were censored at the time of surgery. Results: The best cutoff value of APSR was 0.76. APSR ≥ 0.76 was observed in 108 patients with symptomatic AS (48%). The prevalence was not different among the four AS subgroups. During a median follow-up period of 5.7 months, 47 patients had cardiac events. Cox proportional hazards analysis revealed that neither APSR nor APSR ≥ 0.76 was significantly associated with future cardiac events. Conclusions: Apical sparing was frequently observed in patients with symptomatic AS, and it was not a useful predictor of future adverse outcomes. Our results suggest that the underlying cause of apical sparing in AS may not be related to the presence of ATTR-CA.

Effect of Diastolic Flow Reversal Patterns on Clinical Outcomes Following Transcatheter Aortic Valve Implantation　- An Intraprocedural Echocardiography Study.

BACKGROUND: Although diastolic flow reversal (DFR) in the descending aorta, assessed via transesophageal echocardiography (TEE), is a simple and easy indicator for evaluating aortic regurgitation, the association between DFR pattern and clinical outcomes following transcatheter aortic valve implantation (TAVI) is unclear. The purpose of this study was to evaluate the effect of DFR patterns on clinical outcomes following TAVI.Methods and Results:Two-hundred and eleven patients (mean age, 83.6±5.7 years; 69% female) who underwent TAVI were retrospectively assessed via intraprocedural TEE. DFR was evaluated using pulsed-wave Doppler in the descending aorta before and after TAVI. The primary endpoint was major adverse cardio-cerebrovascular events (MACCEs). Although only 7 patients (3.3%) had moderate or severe paravalvular leak, as assessed by color Doppler echocardiography, holo-DFR (HDFR) was observed in 33 patients (16.0%) after TAVI. MACCEs occurred in 40 patients during the median follow up of 282 days (interquartile range: 160-478 days). The estimated cumulative MACCE-free survival at 1 year was significantly lower in patients with HDFR than in those without HDFR. A Cox proportional hazards analysis revealed that HDFR after TAVI was independently associated with MACCEs. CONCLUSIONS: HDFR was associated with an increased risk of MACCEs after TAVI. DFR evaluated by intraprocedural echocardiography could serve as a simple and easy method for predicting clinical outcomes.

Usefulness of velocity ratio in patients with moderate aortic stenosis and reduced left ventricular ejection fraction.

Background. Moderate aortic stenosis (AS) increases left ventricular afterload and results in unfavorable outcomes in patients with reduced left ventricular ejection fraction (LVEF). Velocity ratio (VR) may be appropriate for the evaluation of aortic valve (AV) hemodynamics because of the low dependence on flow. Therefore, this study investigated the usefulness of VR on the clinical outcomes of such patients. Method. Clinical data of patients with moderate AS (AV area, 0.60-0.85 cm2/m2; peak AV velocity, 2.0-4.0 m/s) and reduced LVEF (LVEF 20-50%) were analyzed during 2010-2018. VR was calculated as peak left ventricular outflow tract velocity/peak AV velocity. The primary endpoint included all-cause death, heart failure hospitalization, and AV replacement. Results. In total, 104 patients (mean age, 75.9 ± 7.0 years; 62.5% men) were included. LVEF was 39.5% ± 7.8%. The AV area was 0.72 ± 0.08 cm2/m2, peak AV velocity was 2.59 ± 0.40 m/s, and VR was 0.30 ± 0.07. The follow-up period was 1.7 (0.5-3.5) years. Kaplan-Meier estimates for the endpoint were 59.9% at 3 years. Multivariable analysis revealed that VR (hazard ratio, 0.947; 95% confidence interval, 0.905-0.990; p = .018) was significantly related to this endpoint. Patients with a VR <0.25 had significantly higher incidence rates of the endpoint than those with a VR ≥0.25 (85.6% versus 47.8% at 3 years; p < .001). Conclusions. Patients with moderate AS and reduced LVEF have unfavorable clinical outcomes, particularly those with low VR.

Impact of perioperative change in physical function on midterm outcomes after transcatheter aortic valve implantation.

Preoperative frailty diminishes the potential for functional recovery after transcatheter aortic valve implantation (TAVI). However, perioperative changes in physical status and their impact on prognosis after TAVI have not previously been reported. Therefore, this study aimed to investigate whether perioperative changes in physical function affect prognosis in patients undergoing TAVI. We retrospectively reviewed 257 patients who underwent TAVI. The Short Physical Performance Battery (SPPB), an objective physical status assessment tool, was evaluated pre- and post-TAVI. Patients were divided into two groups: (i) patients whose SPPB score declined in the perioperative period (the decline group) and (ii) patients whose SPPB score did not decline in the perioperative period (the non-decline group). The primary endpoint was unplanned hospitalization owing to heart failure or cardiovascular death following TAVI. The mean follow-up period was 385 ± 151 days, mean age was 83.2 ± 5.8 years, and 67% of the patients were women. Sixteen patients required readmission owing to heart failure, and seven experienced cardiovascular-related death. Kaplan-Meier analysis revealed that the event-free rate was significantly lower in the decline group (log-rank, p = 0.006). A stepwise multivariate logistic regression analysis showed that a perioperative change in SPPB was significantly associated with primary endpoints (odds ratio, 1.51; 95% confidence interval, 1.12-2.04). Perioperative change in physical function was an independent risk factor for heart failure, hospitalization, or cardiovascular death following TAVI.

Prognostic significance of right ventricular function during exercise in asymptomatic/minimally symptomatic patients with nonobstructive hypertrophic cardiomyopathy.

BACKGROUND: The risk stratification of hypertrophic cardiomyopathy (HCM) without left ventricular outflow tract (LVOT) obstruction and the utility of exercise stress echocardiography (ESE) remains unclear. We investigated the value of right ventricular (RV) function and RV-pulmonary artery (PA) coupling during exercise in asymptomatic/minimally symptomatic patients with nonobstructive HCM (nHCM). METHOD AND RESULTS: This retrospective study evaluated 74 HCM patients (age 63 ± 13 years, 65% men) without LVOT obstruction (≥30 mmHg) who underwent​ ESE. Eight patients (11%) suffered from HCM-related cardiac events during a median 2.5 years follow-up. During exercise, tricuspid annular plane systolic excursion (Ex-TAPSE) and Ex-TAPSE/systolic pulmonary artery pressure [SPAP] ratio were more impaired in patients with than in those without events (22 ± 4 vs 26 ± 4 mm, P = .005; and 0.45 [0.41, 0.47] vs 0.56 [0.47, 0.82] mm/mmHg, P = .002). In Cox regression analysis, Ex-TAPSE (HR: 1.397, P = .002) and the Ex-TAPSE/SPAP ratio (HR: 2.737, P = .006) were associated with cardiac events. In Kaplan-Meier analysis, patients with a low Ex-TAPSE (<24 mm) and Ex-TAPSE/SPAP ratio (<0.50 mm/mmHg) had a higher incidence of adverse outcomes than those with high Ex-TAPSE (Log rank, P < .001 and =.001, respectively). CONCLUSIONS: A low Ex-TAPSE and Ex-TAPSE/SPAP ratio were associated with adverse outcomes in nHCM. Evaluation of RV functional performance during exercise may play a crucial role in the risk stratification of nHCM.

Resting echocardiographic predictors for true-severe aortic stenosis in patients with low-gradient severe aortic stenosis: A dobutamine stress echocardiography study.

OBJECTIVE: Dobutamine stress echocardiography (DSE) is not always feasible in patients with low-gradient severe aortic stenosis (LG-SAS), and there are limited data available on the resting echocardiographic predictors for true-severe aortic stenosis (TSAS). This study investigated resting echocardiographic predictors for TSAS. METHODS: Clinical data of 106 LG-SAS patients who underwent DSE were retrospectively analyzed. LG-SAS was defined as an aortic valve area index (AVAi) < .6 cm2 /m2 , and a mean AV pressure gradient < 40 mm Hg. The velocity ratio (VR) was calculated as the peak left ventricular outflow tract velocity/peak AV velocity. TSAS was defined as a projected AVAi < .6 cm2 /m2 . RESULTS: The mean age was 79.3 ± 7.3 years, and 45 (42.5%) were men. The resting AV data were as follows: AVAi, .50 ± .07 cm2 /m2 ; mean AV pressure gradient, 23.0 ± 7.4 mm Hg; and VR, .25 ± .05. The projected AVAi was .58 ± .09 cm2 /m2 , and TSAS was documented in 65 (61.3%) patients. In multivariate analysis, the independent predictors of TSAS were AVAi (p = 0.012) and VR (p = 0.004) with respective best cut-off values of .52 cm2 /m2 and .25 on receiver-operating characteristic curve analysis. According to incremental numbers of the predictors, correct classification percentages of TSAS significantly increased with the Cochran-Armitage trend test (16.2% in no predictors, 65.2% in one predictor, and 95.7 % in two predictors; p < 0.001). CONCLUSIONS: Resting AVAi and VR were independent predictors of TSAS in LG-SAS patients. The true severity might be predictable using the combination of resting parameters.