Transcatheter Aortic Valve Implantation in Japanese Patients With Large Annulus: The OCEAN-TAVI Registry.

Background: East Asians have smaller aortic valve complexes than individuals from Western countries, and few studies have reported transcatheter aortic valve implantation (TAVI) outcomes in Asian patients with a large annulus. Objectives: This study aimed to compare the short- and long-term outcomes of TAVI using balloon-expandable valves (BEVs) and self-expandable valves (SEVs) in Asian patients with a large annulus. Methods: The study retrospectively analyzed the data from the OCEAN-TAVI (Optimized Transcatheter Valvular Intervention Transcatheter Aortic Valve Implantation) registry. A large annulus was defined by an annular area ≥500 mm2 and an average diameter ≥25 mm as measured by computed tomography. The primary endpoint was 3-year all-cause mortality. Secondary endpoints were 3-year heart failure rehospitalization (HFR) after TAVI, short-term outcomes of TAVI, and changes in valve function 2 years after TAVI. Results: Among 773 patients, 671 underwent BEV TAVI. The SEV TAVI group showed a significantly higher incidence of greater than moderate paravalvular leakage (PVL) (P < 0.001), and an increased pacemaker implantation rate (P = 0.035). The incidence of prosthesis-patient mismatch did not differ between the 2 groups. The Kaplan-Meier curve showed no significant differences in 3-year all-cause mortality and HFR rates (log-rank P = 0.900), and echocardiographic valve function at 2 years post-TAVI did not differ between the 2 groups. Conclusions: The lack of differences in postoperative valve performance and long-term prognosis between BEV TAVI and SEV TAVI highlights the importance of selecting valves that can reduce the pacemaker implantation rate and PVL grade in the acute phase in patients with a large annulus. (Optimized Transcatheter Valvular Intervention Transcatheter Aortic Valve Implantation [OCEAN-TAVI]; UMIN000020423).

Impact of beta-blocker uptitration on patients after transcatheter edge-to-edge mitral valve repair for secondary mitral regurgitation: The OCEAN-mitral registry.

BACKGROUND: Optimal medical therapy for patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER) remains unclear. This study aimed to investigate the association between beta-blocker uptitration and clinical outcomes after M-TEER. METHODS: Using data from the Japanese multicenter registry, we examined 1474 patients who underwent M-TEER for SMR between April 2018 and June 2021. Beta-blocker uptitration was defined as an increased dose of beta-blockers 1 month after M-TEER compared with that before M-TEER. The 2-year clinical outcomes were compared between patients with and without beta-blocker uptitration, utilizing multivariable Cox regression analyses and propensity score matching (PSM). RESULTS: Of the 1474 patients who underwent M-TEER, 272 (18.4 %) were receiving increasing doses of beta-blockers at the 1-month follow-up. These patients had lower left ventricular ejection fraction (LVEF) and higher B-type natriuretic peptide levels. Most patients in the beta-blocker uptitration group received less than the target dose of beta-blockers. Multivariable Cox regression analyses showed that beta-blocker uptitration was significantly associated with a lower risk of all-cause (adjusted hazard ratio [HR]: 0.55; 95 % confidence interval [CI]: 0.36-0.84; P = 0.006) and cardiovascular mortalities (adjusted HR: 0.45, 95 % CI: 0.26-0.79, P = 0.006). PSM analyses revealed consistent findings. Subgroup analyses revealed a significant interaction between beta-blocker uptitration and LVEF≤40 % (interaction P = 0.018). CONCLUSIONS: In patients with SMR, beta-blocker uptitration after M-TEER was associated with better clinical outcomes, especially in the group with an LVEF≤40 %. Efforts to uptitrate guideline-directed medical therapy after M-TEER for SMR may be necessary, even if reaching the target dose proves challenging.

Lipid profile and risk factors for neoatherosclerosis after drug-eluting stent implantation in acute coronary syndrome.

BACKGROUND: Predictors of neoatherosclerosis in patients who received primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. OBJECTIVE: The aim of this study is to investigate the frequency and risk factors of neoatherosclerosis 1-year after the onset of ACS. METHODS: This study investigated 83 patients who underwent PCI for ACS followed by 1-year follow-up optical coherence tomography. The patients were categorized into the neoatherosclerosis (n = 11) and non-neoatherosclerosis groups (n = 72). Baseline characteristics, PCI procedures, medical therapies, and blood tests at 1-year, including detailed lipid profiles, were compared between the two groups. RESULTS: Diabetes mellitus was more prominent in the neoatherosclerosis than in the non-neoatherosclerosis group (45% vs. 17 %, respectively, p = 0.03). Total cholesterol (171 ± 37 mg/dL vs. 145 ± 25 mg/dL, respectively, p < 0.01), non-high-density lipoprotein cholesterol (HDL-C) (124 ± 36 mg/dL vs. 94 ± 24 mg/dL, respectively, p < 0.01), low-density lipoprotein cholesterol (94 ± 36 mg/dL vs. 72 ± 19 mg/dL, respectively, p < 0.01), and lipoprotein (a) (Lp[a]) (70 [19-112] mg/dL vs. 10 [3-25] mg/dL, respectively, p = 0.03) at follow-up were significantly higher in the neoatherosclerosis group. Multivariate analysis revealed that neoatherosclerosis was associated with high serum non-HDL-C (odds ratio [OR]: 1.075; 95 % confidence interval [CI]: 1.011-1.144; p < 0.01) and high serum Lp(a) levels (>30 mg/dL) (OR: 11.0; 95 % CI: 1.492-81.02; p = 0.02). CONCLUSION: Poorly controlled non-HDL-C and Lp(a) would be risk factors of neoatherosclerosis in patients 1-year after ACS.

Prognostic impact of being underweight in patients undergoing mitral TEER: The OCEAN-Mitral registry.

AIMS: Mitral transcatheter edge-to-edge repair (M-TEER) is a valid treatment option for severe mitral regurgitation (MR), necessitating accurate risk stratification of M-TEER candidates for effective patient selection, optimal periprocedural care and improved long-term outcomes. The body mass index (BMI) is a simple and practical prognostic index, and the obesity paradox has been widely reported. METHODS AND RESULTS: Between April 2018 and June 2021, 2149 patients undergoing M-TEER were registered in the prospective multicentre registry and classified into three groups: underweight (BMI < 18.5 kg/m2), normal weight (18.5 â‰¦ BMI < 25 kg/m2) and overweight and obese (25 kg/m2 â‰¦ BMI). The impact of underweight on the all-cause, cardiovascular and non-cardiovascular mortality following M-TEER was evaluated [follow-up duration: 436 (363-733) days]. The participants (median BMI: 21.1 kg/m2) were categorized as underweight (n = 450, 20.9%), normal weight (n = 1409, 65.6%) and overweight and obese (n = 290, 13.5%). Compared with the other two groups, the underweight group exhibited several negative prognostic factors, including older age, frailty, no dyslipidaemia, hypoalbuminaemia, residual MR and non-home discharge. Underweight patients had the highest rate of all-cause, cardiovascular and non-cardiovascular mortality, whereas those in the other two groups were similar. As per the multivariate analysis, underweight itself was associated with all-cause mortality (hazard ratio: 1.52, 95% confidence interval: 1.17-1.97, P = 0.009) and cardiovascular mortality (hazard ratio: 1.45, 95% confidence interval: 1.04-2.01, P = 0.028). CONCLUSIONS: Underweight patients had the highest mortality rate after M-TEER. Comorbidities, residual MR, discharge disposition and underweight status were correlated with postprocedural outcome.

Difference in Cardiac Response after Transcatheter Aortic Valve Implantation according to Flow and Gradient Pattern.

BACKGROUND: In patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS), data on the differences in subsequent cardiac structure and function among stratified groups with flow gradient patterns through the aortic valve are insufficient. METHODS: In this large multicenter study, 4,523 patients undergoing TAVI for severe AS between 2013 and 2019 were divided into 3 groups according to the following criteria: (1) high-gradient AS (HG-AS) (mean pressure gradient [MPG] ≥40 mmHg), (2) classical low-flow low-gradient AS (cLFLG-AS) (MPG <40 mmHg, left ventricular [LV] ejection fraction [LVEF] <50%), and (3) paradoxical low-flow low-gradient AS (pLFLG-AS) (MPG <40 mmHg, LVEF ≥50% but stroke volume index [SVi] <35 mL/m2). Echocardiography was performed at baseline, post-procedure, and 1 year post-TAVI. RESULTS: 3,697, 507, and 319 patients had HG-AS, cLFLG-AS, and pLFLG-AS, respectively. After adjusting for clinical factors, cLFLG-AS and pLFLG-AS had an approximately 1.5-fold higher 2-year all-cause mortality compared with HG-AS. During 1 year following TAVI, compared with HG-AS, cLFLG-AS showed greater reduction of LV systolic diameter (LVDs) and LV diastolic diameter (LVDd) and greater increase of LVEF (p<0.001 for all), and changes in LV mass index (LVMi) and SVi were comparable (p=0.915 and p=0.821, respectively). However, pLFLG-AS demonstrated less reduction of LVDs and LVDd (p=0.039 and p=0.001, respectively), less improvement of LVEF and LVMi (p=0.045 and p<0.001, respectively), and comparable change in SVi (p=0.364). CONCLUSIONS: During 1 year post-TAVI, compared with HG-AS, cLFLG-AS achieves smaller LV diameters, greater increase in LVEF, and comparable regression of LVMi, whereas pLFLG-AS does not.

Mismatch Between Residual Mitral Regurgitation and Left Atrial Pressure Predicts Prognosis After Transcatheter Edge-to-Edge Repair.

BACKGROUND: The mechanism and impact of mismatch between residual mitral regurgitation (MR) and postprocedural left atrial pressure (LAP) after transcatheter edge-to-edge repair (TEER), which may adversely affect clinical outcome, is of great interest. OBJECTIVES: This study aimed to examine the effect of hemodynamic mismatch after TEER on clinical outcomes in patients with heart failure due to severe MR and investigate the predictive factors for the mismatch using a prospective multicenter registry. METHODS: We categorized 1,477 patients into optimal (residual MR grade ≤1 and postprocedural LAP ≤15 mm Hg), mismatched (residual MR grade >1 or postprocedural LAP >15 mm Hg), and poor (residual MR grade >1 and postprocedural LAP >15 mm Hg) groups and examined their prognosis. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization. RESULTS: There were 927 (62.7%), 459 (31.1%), and 91 (6.2%) patients categorized into optimal, mismatched, and poor groups, respectively. Cox regression analysis, referenced to the optimal group, revealed that the mismatched and poor groups exhibited a higher risk for the primary endpoint (HR: 1.55; 95% CI: 1.28-1.88; and HR: 1.95; 95% CI: 1.38-2.74, respectively). Six risk factors were identified as predictors of hemodynamic mismatch after TEER: body mass index, baseline left atrial volume index, atrial fibrillation, tricuspid annular plane systolic excursion value, preprocedural mean left atrial pressure, and postprocedural mean mitral valve pressure gradient. CONCLUSIONS: Post-TEER hemodynamic mismatch between residual MR and postprocedural LAP was associated with a poor prognosis. Six readily accessible perioperative parameters predict the hemodynamic mismatch. (OCEAN-Mitral registry; UMIN000023653).

Long-term effect of biodegradable vs durable polymer everolimus-eluting stents on neoatherosclerosis in ST-segment elevation myocardial infarction: the CONNECT trial.

BACKGROUND AND AIMS: Neoatherosclerosis is a leading cause of late (>1 year) stent failure following drug-eluting stent implantation. The role of biodegradable (BP) versus durable polymer (DP) drug-eluting stents on long-term occurrence of neoatherosclerosis remains unclear. Superiority of biodegradable against durable polymer current generation thin-strut everolimus-eluting stent (EES) was tested by assessing the frequency of neoatherosclerosis 3 years after primary percutaneous coronary intervention (pPCI) among patients with ST-segment elevation myocardial infarction (STEMI). METHODS: The randomized controlled, multicentre (Japan and Switzerland) CONNECT trial (NCT03440801) randomly (1:1) assigned 239 STEMI patients to pPCI with BP-EES or DP-EES. The primary endpoint was the frequency of neoatherosclerosis assessed by optical coherence tomography (OCT) at 3 years. Neoatherosclerosis was defined as fibroatheroma or fibrocalcific plaque or macrophage accumulation within the neointima. RESULTS: Among 239 STEMI patients randomized, 236 received pPCI with stent implantation (119 BP-EES; 117 DP-EES). A total of 178 patients (75%; 88 in the BP-EES group and 90 in the DP-EES group) underwent OCT assessment at 3 years. Neoatherosclerosis did not differ between the BP-EES (11.4%) and DP-EES (13.3%; odds ratio 0.83, 95% confidence interval 0.33-2.04, p=0.69). There were no differences in the frequency of fibroatheroma (BP-EES 9.1% vs DP-EES 11.1%, p=0.66) or macrophage accumulation (BP-EES 4.5% vs DP-EES 3.3%, p=0.68), and no fibrocalcific neoatherosclerosis was observed. Rates of target lesion failure did not differ between groups (BP-EES 5.9% vs DP-EES 6.0%, p=0.97). CONCLUSIONS: Use of BP-EES for primary PCI in patients presenting with STEMI was not superior to DP-EES regarding frequency of neoatherosclerosis at 3 years.

Transcatheter aortic valve implantation for combined aortic and mitral stenoses: Insights from the OCEAN-TAVI Registry.

AIMS: Mitral stenosis (MS) occasionally coexists with aortic stenosis (AS). Limited data are available regarding the functional class and clinical outcomes of patients who undergo transcatheter aortic valve implantation (TAVI) for combined AS and MS. This study compared the clinical outcomes in patients with and without MS who underwent TAVI for severe AS and assessed the impact of mitral annulus calcification (MAC) severity, transmitral gradient (TMG) and mitral valve area (MVA) on outcomes in patients with combined AS and MS. METHODS: We investigated patients in the OCEAN-TAVI registry who underwent TAVI. MS was defined as an MVA ≤ 1.5 cm2 or TMG ≥ 5 mmHg. The composite of all-cause death and admission for heart failure was compared between patients with and without MS. The impact of MAC, TMG and MVA on outcomes was assessed in patients with combined AS and MS. RESULTS: We identified 106 patients with MS (MAC 84%; TMG 6.4 ± 2.6 mmHg; MVA 1.10 ± 0.31 cm2) and 6570 without MS as controls. The MS group was older (85 ± 5 vs. 84 ± 5 years, P = 0.033), more of women (85 vs. 67%, P < 0.01), and had a higher risk of surgery (the Society of Thoracic Surgeons Mortality Score 8.7 ± 5.1 vs. 7.6 ± 5.9, P = 0.047) than the controls. In the MS group, the New York Heart Association Functional Class was 3 or 4 in 56% of the patients at baseline and 6% at 1 year after TAVI. Thirty-day mortality (2.8% vs. 1.3%, P = 0.18) and early composite outcomes (17% vs. 15%, P = 0.56) were comparable between patients with and without MS. During a median follow-up of 2.1 years, the presence of MS was associated with a higher incidence of adverse events compared with controls (adjusted hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.34-2.51, P < 0.01), even on propensity score matched analysis (adjusted HR 1.91; 95% CI 1.14-3.22, P < 0.01). Moderate or severe MAC contributed to increased risk of adverse events in patients with MS (adjusted HR 2.89; 95% CI 1.20-6.99, P = 0.018), but TMG and MVA did not. CONCLUSIONS: In patients undergoing TAVI for severe AS, those with moderate or severe MS experienced worse outcomes after TAVI compared with those without MS. Patients with combined AS and MS sustained symptom improvement at 1-year post-TAVI. MAC severity was a useful predictor of adverse events compared with MS haemodynamics such as TMG and MVA in patients with combined AS and MS.

Initial Results of Intra-Annular Self-Expandable Valves: Insights From the OCEAN-TAVI Registry.

Background: Navitor, an intra-annular self-expanding heart valve (IA-SEV), is the third transcatheter heart valve introduced in Japan (in April 2022) as the next generation of the Portico valve ahead of other Asian countries. Objectives: The purpose of this study was to assess the patient-prosthesis mismatch (PPM) after IA-SEV implantation in Asian patients. Methods: All clinical data were collected from the database of an ongoing prospective Japanese multicenter registry (OCEAN-TAVI [Optimised Catheter Valvular Intervention transcatheter aortic valve implantation]). The primary endpoint was the rate of no PPM; the secondary endpoint included the rate of in-hospital mortality and hemodynamics after IA-SEV implantation. Results: A total of 463 patients (median age 86; 69.7% female) were enrolled in the registry. The percentages of implanted valves sized 23 mm, 25 mm, 27 mm, and 29 mm were 26.1% (n = 121), 41.7% (n = 193), 22.9% (n = 106), and 9.3% (n = 43), respectively. The primary endpoint of no PPM was achieved in 91.7% of the entire cohort and in 87.3%, 94.2%, 91.4%, and 93.0% of each valve size. The rate of in-hospital mortality was 1.9%. Postprocedural mean pressure gradient was 8.3 ± 4.3 mm Hg. The overall rate of pacemaker implantation was 9.7%; the incidence of pacemaker rate tended to be reduced when dividing the first and second half of operator experiences (13.0% vs. 8.0%; P = 0.08). Conclusions: The initial results for the IA-SEV were excellent regarding hemodynamics and reduction of paravalvular leakage regardless of valve size. The IA-SEV is a useful transcatheter heart valve, especially for Asian patients with a high prevalence of small annulus.

Pathological evaluation of predictors for delayed endothelial coverage after currently available drug-eluting stent implantation in coronary arteries: Impact of lesions with acute and chronic coronary syndromes.

BACKGROUND: The optimal duration of dual antiplatelet therapy after currently available drug-eluting stent (DES) implantation to prevent stent thrombosis (ST) remains controversial. Delayed healing is frequently identified as a leading cause of ST in the early phase. However, a thorough pathological investigation into strut coverage after currently available DES implantation is lacking-a gap addressed in the current study. METHODS: From our autopsy registry of 199 stented lesions, 4,713 struts from 66 currently available DES-stented lesions with an implant duration ≤370 days were histologically evaluated. Endothelial coverage was defined as the presence of luminal endothelial cells overlying struts and an underlying smooth muscle cell layer. The stented lesions were classified into acute coronary syndrome (ACS) (n = 40) and chronic coronary syndrome (CCS) (n = 26) groups and were compared. Endothelial coverage predictors were identified through logistic analysis. RESULTS: Although ACS and CCS lesions presented comparable clinical characteristics, including age, sex, and cause of death, the latter exhibited a significantly higher prevalence of chronic kidney disease and hemodialysis than the former (33.3% vs. 65.2%; P = .02, 7.7% vs. 30.4%; P = .02). The poststent implant median duration was significantly shorter in ACS lesions than in CCS lesions (13 [IQR 5-26 days] vs. 40 [IQR 16-233 days]; P < .01). The endothelial coverage percentage was 3.5% at 30 days and 27.7% at 90 days after currently available DES implantation. Multivariable logistic regression analysis implicated implant duration of ≤90 days (odds ratio [OR], 0.009; 95% confidence interval [CI], 0.006-0.012; P < .01), superficial calcification (OR, 0.11; 95% CI, 0.07-0.17; P < .01), ACS culprit site (OR, 0.29; 95% CI, 0.09-0.94; P = .039), and circumferentially durable polymer-coated DES (OR, 0.32; 95% CI, 0.24-0.41; P < .01) as delayed endothelial coverage predictors. CONCLUSIONS: Endothelial coverage was limited at 90 days after currently available DES implantation, and the ACS culprit site and circumferentially durable polymer-coated DES were identified as independent predictors of delayed endothelial coverage. Our findings suggest the importance of underlying plaque morphology and stent technology for vessel healing after such implantation.

Clinical Outcomes of Mitral Valve Surgery in Atrial Functional Mitral Regurgitation in the REVEAL-AFMR Registry.

Importance: The characteristics and treatment strategies of atrial functional mitral regurgitation (AFMR) are poorly understood. Objective: To investigate the prevalence, clinical characteristics, and outcomes of mitral valve (MV) surgery in AFMR. Design, Setting, and Participants: This retrospective cohort study, called the Real-World Observational Study for Investigating the Prevalence and Therapeutic Options for Atrial Functional Mitral Regurgitation (REVEAL-AFMR), was conducted across 26 Japanese centers (17 university hospitals, 1 national center, 3 public hospitals, and 5 private hospitals). All transthoracic echocardiography procedures performed from January 1 to December 31, 2019, were reviewed to enroll adult patients (aged ≥20 years) with moderate or severe AFMR, defined by preserved left ventricular function, a dilated left atrium, and an absence of degenerative valvular changes. Data were analyzed from May 8, 2023, to May 16, 2024. Exposures: Mitral valve surgery, with or without tricuspid valve intervention. Main Outcomes and Measures: The primary composite outcome included heart failure hospitalization and all-cause mortality. Results: In 177 235 patients who underwent echocardiography, 8867 had moderate or severe MR. Within this group, 1007 (11.4%) were diagnosed with AFMR (mean [SD] age, 77.8 [9.5] years; 55.7% female), of whom 807 (80.1%) had atrial fibrillation. Of these patients, 113 underwent MV surgery, with 92 (81.4%) receiving concurrent tricuspid valve surgery. Patients who underwent surgery were younger but had more severe MR (57.5% [n = 65] vs 9.4% [n = 84]; P < .001), a larger mean (SD) left atrial volume index (152.5 [97.8] mL/m2 vs 87.7 [53.1] mL/m2; P < .001), and a higher prevalence of heart failure (according to the New York Heart Association class III [marked limitation of physical activity] or class IV [symptoms of heart failure at rest], 26.5% [n = 30] vs 9.3% [n = 83]; P < .001) than those who remained under medical therapy. During a median follow-up of 1050 days (IQR, 741-1188 days), 286 patients (28.4%) experienced the primary outcome. Despite a more severe disease status, only the surgical group showed a decrease in natriuretic peptide levels at follow-up and had a significantly lower rate of the primary outcome (3-year event rates were 18.3% vs 33.3%; log-rank, P = .03). Statistical adjustments did not alter these findings. Conclusions and Relevance: The findings of this cohort study suggest that in patients with AFMR, who were typically older and predominantly had atrial fibrillation, MV surgery was associated with lower rates of adverse clinical outcomes. Future studies are warranted to investigate a possible causal relationship to better regulate cardiovascular medicine.

Takotsubo syndrome complicated by cardiogenic shock due to left ventricular outflow tract obstruction, acute mitral regurgitation, and atrial fibrillation: a case report.

Background: Although Takotsubo syndrome (TTS) is generally considered a benign disease, recent reports showed the incidence of cardiogenic shock due to left ventricular outflow tract obstruction (LVOTO), mitral regurgitation (MR), and primary pump failure was estimated to be 6-20%. Case summary: A 78-year-old woman presented with chest pain and cold sweats 2 days after surgery for lung cancer. Acute coronary syndrome was suspected based on her symptoms, electrocardiography, transthoracic echocardiography (TTE), and laboratory data; thus, emergency catheterization was performed. Normal coronaries were observed, with hyperkinesis at the base of the left ventricle and akinesis at its apex, leading to the diagnosis of the apical ballooning type of TTS. Pressure differences between the apex of the left ventricle (168/8/28 mmHg) and aorta (94/50/64 mmHg) indicated the presence of LVOTO. Two days after TTS onset, she developed cardiogenic shock (blood pressure was 54/38 mmHg). Transthoracic echocardiography showed acute MR due to systolic anterior motion of the mitral valve caused by LVOTO, which was further exacerbated by paroxysmal atrial fibrillation. Fluid resuscitation, intravenous ß-blockers, and amiodarone were administered for reduction of the pressure gradient in the left ventricular outflow, rate control, and sinus rhythm maintenance. Her condition improved along with the MR, thereby improving LVOTO and maintaining sinus rhythm. Discussion: Takotsubo syndrome should be kept in mind as a potential cause of acute MR due to LVOTO. Catheterization and multiple follow-up TTE play a major role in early detection for this condition.

Prognostic impact of increase in left atrial volume following left atrial appendage closure: Insights from the OCEAN-LAAC registry.

Background: Percutaneous left atrial appendage closure (LAAC) is an effective therapy to prevent thromboembolic events among patients with atrial fibrillation (AF). However, since the left atrial appendage (LAA) contributes to left atrial volume and serves as a buffer for increasing left atrial pressure, this procedure may impair left atrium (LA) compliance, enlarge LA, and deteriorate diastolic function. In this study, we sought to investigate the change in left atrial volume index (LAVI) following LAAC and its effect on prognosis. Methods and Results: We analyzed 225 patients from the OCEAN-LAAC registry, an ongoing, multicenter Japanese study. Comparing LAVI measurements at baseline and 6 months after LAAC, no significant increase was observed (55.0 [44.0, 70.0] ml/m2 vs. 55.0 [42.0, 75.6] ml/m2; P = 0.31). However, some patients underwent LAVI increase. Particularly, a smaller LAVI (odds ratio [OR]: 0.98 [95 % confidence interval (CI): 0.97-0.996]) and elevated tricuspid regurgitation pressure (TRPG) at baseline (OR: 1.04 [95 % CI: 1.00 - 1.08]) were significantly related to the increase in LAVI at 6-month follow-up. In addition, a 5 ml/m2 increase in LAVI was significantly associated with subsequent heart failure hospitalization (HFH) (hazard ratio: 3.37 [95 % CI: 1.18-9.65]). This association, however, was not observed in patients with lower baseline LAVI (≤55 ml/m2) but was only seen in those with a baseline LAVI over 55 ml/m2. Conclusion: Our study demonstrated an increase in LAVI after LAAC was related to smaller LAVI or elevated TRPG at baseline. The LAVI increase was significantly associated with subsequent HFH.

Performance and outcomes of the SAPIEN 3 Ultra RESILIA transcatheter heart valve in the OCEAN-TAVI registry.

BACKGROUND: Data on the performance of the latest-generation SAPIEN 3 Ultra RESILIA (S3UR) valve in patients who undergo transcatheter aortic valve replacement (TAVR) are scarce. AIMS: We aimed to assess the clinical outcomes, including valve performance, of the S3UR. METHODS: Registry data of 618 consecutive patients with S3UR and of a historical pooled cohort of 8,750 patients who had a SAPIEN 3 (S3) valve and underwent TAVR were collected. The clinical outcomes and haemodynamics, including patient-prosthesis mismatch (PPM), were compared between the 2 groups and in a propensity-matched cohort. RESULTS: The incidence of in-hospital death, vascular complications, and new pacemaker implantation was similar between the S3UR and the S3 groups (allp>0.05). However, both groups showed significant differences in the degrees of paravalvular leakage (PVL) (none-trivial: 87.0% vs 78.5%, mild: 12.5% vs 20.5%, ≥moderate: 0.5% vs 1.1%; p<0.001) and the incidence of PPM (none: 94.3% vs 85.1%, moderate: 5.2% vs 12.8%, severe: 0.5% vs 2.0%; p<0.001). The prevalence of a mean pressure gradient ≥20 mmHg was significantly lower in the S3UR group (1.6% vs 6.2%; p<0.001). Better haemodynamics were observed with the smaller 20 mm and 23 mm S3UR valves. The results were consistent in a matched cohort of patients with S3UR and with S3 (n=618 patients/group). CONCLUSIONS: The S3UR has equivalent procedural complications to the S3 but with lower rates of PVL and significantly better valve performance. The better valve performance of the S3UR, particularly in smaller valve sizes, overcomes the remaining issue of balloon-expandable valves after TAVR.

Defining high bleeding risk in patients undergoing transcatheter aortic valve implantation: a VARC-HBR consensus document.

The identification and management of patients at high bleeding risk (HBR) undergoing transcatheter aortic valve implantation (TAVI) are of major importance, but the lack of standardised definitions is challenging for trial design, data interpretation, and clinical decision-making. The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) is a collaboration among leading research organisations, regulatory authorities, and physician-scientists from Europe, the USA, and Asia, with a major focus on TAVI-related bleeding. VARC-HBR is an initiative of the CERC (Cardiovascular European Research Center), aiming to develop a consensus definition of TAVI patients at HBR, based on a systematic review of the available evidence, to provide consistency for future clinical trials, clinical decision-making, and regulatory review. This document represents the first pragmatic approach to a consistent definition of HBR evaluating the safety and effectiveness of procedures, devices and drug regimens for patients undergoing TAVI..

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.

Size of Self-Expandable Transcatheter Heart Valve and Mid-Term Adverse Events After Transcatheter Aortic Valve Replacement.

The hemodynamic performance of self-expandable valves (SEVs) is a preferable choice for small aortic annuli in transcatheter aortic valve replacement (TAVR). However, no data are, so far, available regarding the relation between the size of SEVs and clinical outcomes. This study aimed to evaluate the impact of prosthesis size on adverse events after TAVR using SEVs. We retrospectively analyzed 1,400 patients (23-mm SEV: 13.6%) who underwent TAVR using SEVs at 12 centers. The impact of SEV size on all-cause death and heart failure (HF) after TAVR was evaluated by multivariate Cox regression and propensity score (PS) matching analysis. During the follow-up period (median 511 days), 201 all-cause deaths and 87 HF rehospitalizations were observed. The incidence of all-cause death was comparable between small- (23-mm SEV) and larger-sized (26- or 29-mm SEV) (16.8% vs 13.9%, log-rank p = 0.29). The size of SEV was not associated with a higher incidence of all-cause death (hazard ratio [HR] 1.21, 95% confidence interval [CI] 0.79 to 1.86 in Cox regression; HR 1.31, 95% CI 0.77 to 2.23 in PS matching) and HF after TAVR (subdistribution HR 0.79, 95% CI 0.37 to 1.72 in Cox regression; subdistribution HR 1.00, 95% CI 0.44 to 2.30 in PS matching). The multivariate model including postprocedural prosthesis-patient mismatch showed consistent results. In conclusion, small SEVs had comparable midterm clinical outcomes to larger-sized SEVs, even if the prosthesis-patient mismatch was observed after TAVR.

Pre-Existing Left Bundle Branch Block and Clinical Outcomes After Transcatheter Aortic Valve Replacement.

Background: Few reports on pre-existing left bundle branch block (LBBB) in patients undergoing transcatheter aortic valve replacement (TAVR) are currently available. Further, no present studies compare patients with new onset LBBB with those with pre-existing LBBB. Objectives: This study aimed to investigate the association between pre-existing or new onset LBBB and clinical outcomes after TAVR. Methods: Using data from the Japanese multicenter registry, 5,996 patients who underwent TAVR between October 2013 and December 2019 were included. Patients were classified into 3 groups: no LBBB, pre-existing LBBB, and new onset LBBB. The 2-year clinical outcomes were compared between 3 groups using Cox proportional hazards models and propensity score analysis to adjust the differences in baseline characteristics. Results: Of 5,996 patients who underwent TAVR, 280 (4.6%) had pre-existing LBBB, while 1,658 (27.6%) experienced new onset LBBB. Compared with the no LBBB group, multivariable Cox regression analysis showed that pre-existing LBBB was associated not only with a higher 2-year all-cause (adjusted HR: 1.39; 95% CI: 1.06-1.82; P = 0.015) and cardiovascular (adjusted HR: 1.60; 95% CI: 1.04-2.48; P = 0.031) mortality, but also with higher all-cause (adjusted HR: 1.43, 95% CI: 1.07-1.91; P = 0.016) and cardiovascular (adjusted HR: 1.81, 95% CI:1.12-2.93; P = 0.014) mortality than the new onset LBBB group. Heart failure was the most common cause of cardiovascular death, with more heart failure deaths in the pre-existing LBBB group. Conclusions: Pre-existing LBBB was independently associated with poor clinical outcomes, reflecting an increased risk of cardiovascular mortality after TAVR. Patients with pre-existing LBBB should be carefully monitored.

Cardiac Damage in Degenerative Mitral Regurgitation Treated With Transcatheter Mitral Edge-to-Edge Repair.

BACKGROUND: The extent of cardiac damage and its association with clinical outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) for degenerative mitral regurgitation remains unclear. This study was aimed to investigate cardiac damage in patients with degenerative mitral regurgitation treated with TEER and its association with outcomes. METHODS: We analyzed patients with degenerative mitral regurgitation treated with TEER in the Optimized Catheter Valvular Intervention-Mitral registry, which is a prospective, multicenter observational data collection in Japan. The study subjects were classified according to the extent of cardiac damage at baseline: no extravalvular cardiac damage (stage 0), mild left ventricular or left atrial damage (stage 1), moderate left ventricular or left atrial damage (stage 2), or right heart damage (stage 3). Two-year mortality after TEER was compared using Kaplan-Meier analysis. RESULTS: Out of 579 study participants, 8 (1.4%) were classified as stage 0, 76 (13.1%) as stage 1, 319 (55.1%) as stage 2, and 176 (30.4%) as stage 3. Two-year survival was 100% in stage 0, 89.5% in stage 1, 78.9% in stage 2, and 75.3% in stage 3 (P=0.013). Compared with stage 0 to 1, stage 2 (hazard ratio, 3.34 [95% CI, 1.03-10.81]; P=0.044) and stage 3 (hazard ratio, 4.51 [95% CI, 1.37-14.85]; P=0.013) were associated with increased risk of 2-year mortality after TEER. Significant reductions in heart failure rehospitalization rate and New York Heart Association functional scale were observed following TEER (both, P<0.001), irrespective of the stage of cardiac damage. CONCLUSIONS: Advanced cardiac damage is associated with an increased risk of mortality in patients undergoing TEER for degenerative mitral regurgitation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023653.