R2-CHA2DS2-VASc Score for Cardiovascular Event Prediction After Bioprosthetic Valve Replacement　- Subanalysis From the BPV-AF Registry.

Background: There are few studies evaluating the prognostic prediction method in atrial fibrillation (AF) patients after bioprosthetic valve (BPV) replacement. The R2-CHA2DS2-VASc score is increasingly used for the prediction of cardiovascular (CV) events in patients with AF, device implantation, and acute coronary syndrome. We aimed to evaluate the predictive value of the R2-CHA2DS2-VASc score for future CV events in AF patients after BPV replacement. Methods and Results: The BPV-AF, an observational, multicenter, prospective registry, enrolled AF patients who underwent BPV replacement. The primary outcome measure was a composite of stroke, systemic embolism, CV events including heart failure requiring hospitalization, and cardiac death. A total of 766 patients was included in the analysis. The mean R2-CHA2DS2-VASc score was 5.7±1.8. Low (scores 0-1), moderate (scores 2-4), and high (scores 5-11) R2-CHA2DS2-VASc score groups consisted of 12 (1.6%), 178 (23.2%), and 576 (75.2%) patients, respectively. The median follow-up period was 491 (interquartile range 393-561) days. Kaplan-Meier analysis showed a higher incidence of the composite CV events in the high R2-CHA2DS2-VASc score group (log rank test; P<0.001). Multivariate Cox proportional hazards regression analysis revealed that the R2-CHA2DS2-VASc score as a continuous variable was an independent predictor of composite CV outcomes (hazard ratio 1.36; 95% confidence interval 1.18-1.55; P<0.001). Conclusions: The R2-CHA2DS2-VASc score is useful for CV risk stratification in AF patients after BPV replacement.

Clinical effects of direct oral anticoagulants in elderly patients with a bioprosthetic valve and atrial fibrillation.

BACKGROUND: Current guidelines recommend direct oral anticoagulants (DOACs) and warfarin for patients with atrial fibrillation (AF) who have a bioprosthetic valve (BPV). However, the data related to elderly patients (aged ≥80 years) with BPV replacement and AF are limited. METHODS: This post-hoc subgroup analysis of a BPV-AF Registry enrolled 752 patients with BPV replacement and AF. The primary net outcome was a composite of cardiac death, stroke, systemic embolism, major bleeding, and cardiovascular events. RESULTS: Among 752 patients, 429 (57%) patients were ≥ 80 and 323 (43%) were < 80 years old. The higher risk in patients aged ≥80 than <80 years was significant for the net outcome (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.31-3.17; P = 0.001). After adjustment for confounders, there was no statistically significant difference between warfarin (reference) and DOAC users in the risk of net outcomes (adjusted HR, 1.26; 95% CI, 0.71-2.24; P = 0.44), stroke and systemic embolism (adjusted HR, 2.01; 95% CI, 0.48-8.38; P = 0.34), and major bleeding (adjusted HR, 0.73; 95% CI, 0.11-4.98; P = 0.75) in patients aged ≥80 years old as well as those aged <80 years. Among 489 warfarin users, the cumulative incidence of net outcomes tended to be higher in patients aged ≥80 than <80 years (12.2% vs. 5.7% at 1 year, log-rank P = 0.002). Among 263 DOAC users, however, it was similar between patients aged ≥80 and < 80 years. CONCLUSIONS: The present study demonstrated that DOAC showed similar efficacy and safety compared with warfarin even in elderly patients aged ≥80 years with BPV replacement and AF.

Gerbode defect resulting from Group B Streptococcus infective endocarditis: a case report.

BACKGROUND: Gerbode defect is an unusual abnormal communication between the left ventricle and the right atrium and is a serious complication of aortic infective endocarditis. Group B Streptococcus is an uncommon cause of infective endocarditis and has a markedly destructive effect on valvular tissue. Acute fistulation between the left ventricle and the right atrium associated with this form of infective endocarditis is a life-threatening, aggressive complication that often requires urgent surgical intervention. However, the identification of actual communication is often extremely difficult. Herein, we describe an unusual case of Gerbode defect resulting from Group B Streptococcus infective endocarditis and discuss the issues surrounding such a rare cardiac defect and such an infection. CASE PRESENTATION: A 60-year-old man with underlying uncontrolled diabetes mellitus underwent endoscopic retrograde biliary drainage for acute cholangitis. On the 10th postoperative day, the patient developed multiple acute cerebral embolisms. Transthoracic echocardiography demonstrated severe aortic regurgitation and a large mobile vegetation near the tricuspid annulus. No obvious fistula between the left ventricle and the right atrium could be demonstrated. The blood culture examination was positive for Group B Streptococcus. The patient was diagnosed with Group B Streptococcus infective endocarditis, and antibiotic therapy was initiated. Transesophageal echocardiogram performed after referral to our hospital confirmed detachment of the right coronary cusp of the aortic valve from the annulus and an abnormal cavity immediately below the right coronary cusp. Color Doppler imaging finally revealed systolic blood flows from the left ventricle into the right atrium through the cavity. Therefore, we diagnosed the patient with Gerbode defect resulting from Group B Streptococcus infective endocarditis. In addition to aortic valve replacement, defect closure and left ventricular outflow tract repair were successfully performed urgently for severely complicated and uncommon infective endocarditis. The patient was uneventfully discharged without any complications. CONCLUSIONS: We reported successful surgical treatment of unusual active IE and Gerbode defect caused by GBS. Careful preoperative echocardiographic work-up is imperative for accurate early diagnosis and successful repair.

Efficacy and Safety of Edoxaban in Anticoagulant Therapy Early After Surgical Bioprosthetic Valve Replacement: Rationale and Design of the ENBALV Trial.

BACKGROUND AND PURPOSE: Anticoagulant therapy with vitamin K antagonists is recommended within 3 to 6 months after bioprosthetic valve replacement to prevent thromboembolic events. However, data regarding whether direct oral anticoagulants can be an alternative to warfarin in such patients are limited. The purpose of this study is to compare the efficacy and safety of edoxaban versus warfarin within 3 months after bioprosthetic valve replacement. METHODS: The ENBALV trial is an investigator-initiated, phase 3, randomized, open-label, multicenter study. It involves patients aged 18 to 85 years undergoing bioprosthetic valve replacement at the aortic and/or mitral position. They are randomized 1:1 to receive either edoxaban or warfarin. Administration of edoxaban or warfarin is to be continued for 12 weeks after surgery. The primary outcome is the occurrence rate of stroke or systemic embolism at 12 weeks after surgery. The net clinical outcome is a composite of stroke, systemic embolism, or major bleeding, which is included in the secondary outcomes. CONCLUSION: The ENBALV trial demonstrates the efficacy and safety of edoxaban compared with warfarin in patients early after bioprosthetic valve replacement, including patients with sinus rhythm, which will bring a significant benefit to patients in clinical practice. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) 2051210209. 30 Mar 2022 https://jrct.niph.go.jp/latest-detail/jRCT2051210209 .

Current management of tricuspid regurgitation: a focus on the spiral suspension approach.

The indication for surgery for tricuspid regurgitation (TR) has reached a major turning point. It has become clear that the presence of moderate or severe TR alone worsens the prognosis of life, and the previous guidelines of Japanese Circulation Society, in which the indication for surgery was recommended at the timing of "right heart failure difficult to treat medically," now recommends surgery with a trigger of "repeated right heart failure" in the 2020 edition. In addition, a new repair technique targeting at subvalvular structure has been developed for end-stage TR to overcome a high TR recurrence rate that is associated with severe right ventricular enlargement and leaflet tethering. This review focuses on the spiral suspension technique, in which the papillary muscles are spirally suspended towards the septal leaflet annulus to correct tethering and enhances the understanding of its application in the context of TR management.

Association of Left Atrial Size With Stroke or Systemic Embolism in Patients With Atrial Fibrillation Having Undergone Bioprosthetic Valve Replacement From the BPV-AF Registry.

Background: The left atrial volume index (LAVI) is important for predicting thromboembolism in patients with non-valvular atrial fibrillation (AF), but the utility of LAVI for predicting thromboembolism in patients with both bioprosthetic valve replacement and AF remains unclear. Methods and Results: Of 894 patients from a previous multicenter prospective observational registry (BPV-AF Registry), 533 whose LAVI data had been obtained by transthoracic echocardiography were included in this subanalysis. Patients were divided into tertiles (T1-T3) according to LAVI as follows: T1 (n=177), LAVI=21.5-55.3 mL/m2; T2 (n=178), LAVI=55.6-82.1 mL/m2; T3 (n=178), LAVI=82.5-408.0 mL/m2. The primary outcome was defined as either stroke or systemic embolism for a mean (±SD) follow-up period of 15.3±4.2 months. Kaplan-Meier curves indicated that the primary outcome tended to occur more frequently in the group with the larger LAVI (log-rank P=0.098). Comparison of T1 with T2 plus T3 using Kaplan-Meier curves indicated that patients in T1 experienced significantly fewer primary outcomes (log-rank P=0.028). Furthermore, univariate Cox proportional hazard regression showed that 1.3- and 3.3-fold more primary outcomes occurred in T2 and T3, respectively, than in T1. Conclusions: Larger LAVI was associated with stroke or systemic embolism in patients who had undergone bioprosthetic valve replacement and with a definitive diagnosis of AF.

Minimally Invasive Valvular Surgery in the Elderly　- Safety, Early Recovery, and Long-Term Outcomes.

BACKGROUND: For elderly people, the benefit of minimally invasive cardiac surgery (MICS) is unclear, so we evaluated the safety, recovery, and long-term survival in elderly MICS patients.Methods and Results: 63 propensity score-matched pairs of 213 consecutive patients (≥70 years old) who underwent mitral and/or tricuspid valve surgery between 2010 and 2020 (121 right mini-thoracotomies vs. 92 full sternotomies) were compared. The primary outcome was safety (composite endpoint of in-hospital death or major complication). Secondary outcomes were early ambulation and discharge to home. There were no differences between the groups for in-hospital death (3.2% vs. 0.0%, P=0.157) and primary outcome (14.3% vs. 17.5%, P=0.617). The rate of early ambulation (73.0% vs. 55.6%, P=0.048) and discharge to home (66.7% vs. 49.2%, P=0.034) were significantly higher in the mini-thoracotomy group. Major complication was an independent negative predictor of early ambulation for mini-thoracotomy but not for a conservative approach. Survival was 87.8±4.4% vs. 86.8±4.7% at 5 years, which was not significantly different. CONCLUSIONS: Similar safety but better recovery were observed for mini-thoracotomy, and long-term survival was comparable between groups. Major complication was a negative predictor of early ambulation after mini-thoracotomy. Careful preoperative risk stratification would enhance the benefits of MICS in elderly patients.

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.

Clinical and microbiological characteristics and challenges in diagnosing infected aneurysm: a retrospective observational study from a single center in Japan.

BACKGROUND: It is challenging to diagnose infected aneurysm in the early phase. This study aimed to describe the clinical and microbiological characteristics of infected aneurysm, and to elucidate the difficulties in diagnosing the disease. METHODS: Forty-one cases of infected aneurysm were diagnosed in Nagasaki University Hospital from 2005 to 2019. Information on clinical and microbiological characteristics, radiological findings, duration of onset, and type of initial computed tomography (CT) imaging conditions were collected. Factors related to diagnostic delay were analyzed by Fisher's exact test for categorical variables or by the Wilcoxon rank-sum test for continuous variables. RESULTS: Pathogens were identified in 34 of 41 cases; the pathogens were Gram-positive cocci in 16 cases, Gram-negative rods in 13 cases, and others in five cases. Clinical characteristics did not differ in accordance with the identified bacteria. At the time of admission, 16 patients were given different initial diagnoses, of which acute pyelonephritis (n = 5) was the most frequent. Compared with the 22 patients with an accurate initial diagnosis, the 19 initially misdiagnosed patients were more likely to have been examined by plain CT. The sensitivities of plain CT and contrast-enhanced CT were 38.1% and 80.0%, respectively. CONCLUSIONS: In cases of infected aneurysm, diagnostic delay is attributed to non-specific symptoms and the low sensitivity of plain CT. Clinical characteristics of infected aneurysm mimic various diseases. Contrast-enhanced CT should be considered if infected aneurysm is suspected.

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.

David Operation for Insufficient Pulmonary Autograft After Ross-Konno Procedure.

We report the case of a 25-year-old woman who developed severe aortic regurgitation because of pulmonary autograft root dilatation late after Ross-Konno procedure. The geometric heights of all 3 cusps were relatively small, allowing for the David operation with a 24-mm straight graft. We carefully dissected the aortic root and, the dissection process was relatively straightforward, and the basal ring could be sutured properly. The latest follow-up transthoracic echocardiogram showed normal autograft valve function and mild aortic regurgitation. Even in the Ross-Konno procedure, valve-sparing root replacement is possible, as in the Ross procedure.

[Mitral Valve Plasty Late after Tetrology of Fallot Repair:Report of a Case].

The case was a 32-year-old man. Blalock-Taussig shunt was performed at five months-old for tetralogy of Fallot, and intracardiac repair was performed at four years-old. He was admitted with a diagnosis of infective endocarditis. Preoperative echocardiography showed vegetations on the mitral valve and severe mitral regurgitation. Severe right heart pressure load findings, pulmonary valve stenosis and regurgitation, and residual ventricular septal defect were also observed. The surgery included mitral valve repair, reconstruction of the right ventricular outflow tract, pulmonary valve replacement, and closure of the ventricular septal defect. The postoperative course was favorable. The cause of mitral regurgitation was an abnormal chordae tendineae attached to the interventricular septum and valve destruction by infective endocarditis.

Determining Factors for Independent Walking in Patients Undergoing Cardiovascular Surgery: Differences between Coronary Artery Bypass Grafting, Heart Valve Surgery, and Aortic Surgery.

Physical deconditioning often occurs during the acute phase after cardiovascular surgery, and unassisted walking is required to achieve independence, to manage cardiac diseases, and to prevent recurrences. This study aims to investigate the characteristics of independent walking after cardiovascular surgery. We conducted a retrospective cohort study in patients who underwent cardiovascular surgeries (total of 567 patients): 153 in the coronary artery bypass grafting (CABG) group, 312 in the heart valve surgery group, and 102 in the aortic surgery group. We evaluated the effect of each surgery group on the cardiac rehabilitation (CR) progression. The factors associated with independent walking were age, renal diseases, intensive care unit (ICU) length of stay, and post-operative respiratory complications in the CABG group. In the heart valve surgery group, the factors were New York Heart Association functional classification, renal and respiratory diseases, ICU length of stay, duration of mechanical ventilatory support, and post-operative cardiovascular and respiratory complications. In the aortic surgery group, these were ICU length of stay and acute kidney injury. The CR progression in patients who underwent aortic surgery was significantly longer than those who underwent CABG and heart valve surgery (p < 0.001). New intervention strategies are needed for patients with prolonged ICU stays.

Association between Serum Phosphate Levels and the Development of Aortic Stenosis in Patients Undergoing Hemodialysis.

We aimed to investigate the factors associated with the development of aortic stenosis (AS) in patients undergoing hemodialysis (HD), and to elucidate the prognosis of HD patients with AS. Patients on HD that had also undergone echocardiography at Nagasaki Renal Center between July 2011 and June 2012 were included. Patients with AS at the time of inclusion were excluded. The diagnosis of AS was based on an annual routine or additional echocardiography. The patients were followed up until June 2021. The association between patient background and AS was also evaluated. Of the 302 patients (mean age, 67.4 ± 13.3 years; male, 58%; median dialysis history, 4.7 years), 60 developed AS and 10 underwent aortic valve replacement. A Cox proportional hazards model revealed that age (hazard ratio (HR), 1.07; 95% confidential interval (CI), 1.04-1.10; p < 0.001) and serum phosphate levels (HR, 1.40; 95%CI, 1.16-1.67, p < 0.001) were independent risk factors for developing AS. Incidentally, there was no significant mortality difference between patients with AS and those without (p = 0.53). Serum phosphate levels are a risk factor for developing AS and should be controlled. Annual echocardiography may contribute to the early detection of AS and improves the prognosis of patients undergoing HD.