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 .

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.

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.

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.

[Repeat Mitral Valve Repair].

The keys to successful repeat mitral valve repair are careful selection of eligible patients and the use of high-quality surgical techniques. Regarding patient selection, patients with soft leaflet tissue, redundant rough-zone areas, and posterior mitral leaflet regions are good candidates for repeat repair. Autologous pericardial patch reinforcement for sutured dehiscence line, triangular resection for residual excess tissue, and sophisticated neo-chord reconstruction are high-quality techniques that increase the durability of repeat repair.

[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.

Impact of sarcopenia on the progress of cardiac rehabilitation and discharge destination after cardiovascular surgery.

[Purpose] To investigate the factors that affect the progress of cardiac rehabilitation, length of stay in the hospital, and discharge destination after cardiovascular surgery. [Participants and Methods] This was a prospective observational study. Sixty-seven patients scheduled to undergo open-heart surgery were included in the study. We evaluated physical and psychiatric functions pre- and post-surgery. Sarcopenia was defined as a short physical performance battery score of <9.5. [Results] Sarcopenia was a significant factor of delay of the day of the first rehabilitation, independence in 100-m walking, and exercise training at the rehabilitation gym. Comparisons between pre- and post-surgery were performed in the sarcopenia group. No significant decreases in physical and psychiatric functions were found. The discharge transfer rate was significantly different between the sarcopenia and non-sarcopenia groups. Sarcopenia and the decline in balance score significantly correlated with discharge transfer. [Conclusion] Cardiac rehabilitation can achieve recovery of physical and psychiatric functions even in patients with sarcopenia; however, the discharge transfer rate among the patients with sarcopenia was high. Improving balance ability may result in early home discharge.

Association between Enterocyte Injury and Mortality in Patients on Hemodialysis Who Underwent Cardiac Surgery: An Exploratory Study.

BACKGROUND: Intestinal ischemia and enterocyte injury are significant causes of death after cardiac surgery. Hemodialysis is a well-known risk factor for intestinal ischemia. However, the relationship between enterocyte injury and mortality is unclear. This exploratory study assessed the association between intestinal fatty acid-binding protein (I-FABP), a specific marker of enterocyte injury, at intensive care unit (ICU) admission and in-hospital mortality in patients on hemodialysis who underwent cardiac surgery with cardiopulmonary bypass. MATERIALS AND METHODS: Forty-seven consecutive patients on long-term hemodialysis who underwent elective cardiac surgery (median age, 70 y; men, 27 [57%]) were prospectively enrolled. The association between serum I-FABP levels at ICU admission and in-hospital mortality was compared with the associations between serum I-FABP levels and prognostic severity scores, vasoactive-inotropic scores, and lactate levels. RESULTS: Only I-FABP levels at ICU admission were significantly related to in-hospital mortality (odds ratio, 5.54; 95% confidence interval [CI], 1.08-28.43) in the simple logistic regression analysis. Univariate and multiple linear regression analyses indicated prolonged cardiopulmonary bypass (ρ, 0.49; 95% CI, 0.15-0.83), higher mean norepinephrine dose (ρ, 0.07; 95% CI, 0.02-0.12), lower mean dopamine dose (ρ, -0.51; 95% CI, -0.94 to -0.08), and intra-aortic balloon pump use (ρ, 3.63; 95% CI, 1.68-5.59) were significant risk factors for high I-FABP levels. CONCLUSIONS: Enterocyte injury at ICU admission was associated with in-hospital mortality after cardiac surgery for patients on hemodialysis. Intraoperative hidden hypoperfusion of the intestine may impact prognoses. Enterocyte injury prevention, early diagnosis, and intervention for intestinal ischemia might be required to improve outcomes.

Intestinal fatty acid-binding protein levels in patients with chronic renal failure.

BACKGROUND: Intestinal fatty acid-binding protein (I-FABP), a biomarker of enterocyte injury, has been reported to be a diagnostic marker of intestinal ischemia and a prognostic marker in critically ill patients. However, the kinetics of I-FABP in renal failure patients is unknown. We sought to identify I-FABP levels in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) on hemodialysis (HD) and to identify the manner in which the I-FABP levels change. MATERIALS AND METHODS: Adult patients who were admitted for elective cardiac surgery with either normal renal function (NRF), CKD, or ESKD on HD were enrolled. Serum I-FABP levels in NRF and CKD patients and in ESKD patients before and after HD were determined. RESULTS: A total of 124 patients were evaluated: 47 NRF, 53 CKD, and 24 ESKD. The I-FABP levels of the CKD patients and pre-HD ESKD patients were significantly higher than those of the NRF patients (P = 0.018 and P <0.001, respectively). I-FABP levels were significantly negatively correlated with the estimated glomerular filtration rate in NRF and CKD patients (Spearman's ρ = -0.313, P = 0.002). In addition, I-FABP levels in ESKD patients were significantly lower after HD than those before HD (P <0.001). CONCLUSIONS: I-FABP levels in CKD and pre-HD ESKD patients were significantly higher than those in NRF patients. In addition, I-FABP was significantly eliminated by HD in patients with ESKD. Clinicians and researchers should consider this aspect of I-FABP when using it as a diagnostic and prognostic marker in patients with renal insufficiency.

Early Diagnosis of Infective Endocarditis by Brain T2*-Weighted Magnetic Resonance Imaging.

BACKGROUND: Because infective endocarditis (IE) carries a high risk of morbidity and mortality, rapid diagnosis and effective treatment are essential to achieving a good patient outcome. However, the diagnosis of IE is often difficult in patients presenting with nonspecific clinical manifestations. An association between IE and hypointense signal spots on brain T2*-weighted magnetic resonance imaging (MRI) has been reported, but the clinical significance remains unclear.Methods and Results:To assess the clinical importance of silent lesions in the brains of IE patients, hypointense signal spots detected on their brain T2*-weighted MRI scans were investigated in a retrospective review of 44 consecutive patients with definite or suspected IE evaluated by MRI between June 2006 and January 2014. Hypointense signal spots on T2*-weighted MRI were detected in 37 (84%) patients; of these, 21 (46%) had ischemic lesions, 10 (22%) had subarachnoid hemorrhage, 4 (9%) had intraparenchymal hemorrhage, and 4 (9%) had infectious aneurysm. The hypointense signal spots on T2*-weighted images were preferentially distributed in cortical areas. CONCLUSIONS: T2*-weighted hypointense signal spots are highly frequent in patients with IE and their presence may be informative in the monitoring of IE-associated brain lesions, even those that are neurologically asymptomatic. The strong association between IE and T2*-weighted hypointense signal spots supports the need to consider additional criteria in the diagnosis of IE.

Incidence of orthostatic hypotension and cardiovascular response to postoperative early mobilization in patients undergoing cardiothoracic and abdominal surgery.

BACKGROUND: In cardiothoracic and abdominal surgery, postoperative complications remain major clinical problems. Early mobilization has been widely practiced and is an important component in preventing complications, including orthostatic hypotension (OH) during postoperative management. We investigated cardiovascular response during early mobilization and the incidence of OH after cardiothoracic and abdominal surgery. METHODS: In this prospective observational study, we consecutively analyzed data from 495 patients who underwent elective cardiothoracic and abdominal surgery. We examined the incidence of OH, and the independent risk factors associated with OH during early mobilization after major surgery. Multivariate logistic regression was performed using various characteristics of patients to identify OH-related independent factors. RESULTS: OH was observed in 191 (39%) of 495 patients. The incidence of OH in cardiac, thoracic, and abdominal groups was 39 (33%) of 119, 95 (46%) of 208, and 57 (34%) of 168 patients, respectively. Male sex (OR 1.538; p = 0.03) and epidural anesthesia (OR 2.906; p < 0.001) were independently associated with OH on multivariate analysis. CONCLUSIONS: These results demonstrate that approximately 40% patients experience OH during early mobilization after cardiothoracic and abdominal surgery. Sex was identified as an independent factor for OH during early mobilization after all three types of surgeries, while epidural anesthesia was only identified after thoracic surgery. Therefore, the frequent occurrence of OH during postoperative early mobilization should be recognized. TRIAL REGISTRATION: University hospital Medical Information Network Center (UMIN-CTR) number UMIN000018632 . (Registered on 1st October, 2008).

[Successful Treatment of Ascending Aortic Graft Infection with a Rifampicin-soaked Vascular Prosthesis and Continuous Irrigation].

A 68-year-old woman underwent replacement of the ascending aorta for acute type A aortic dissection. She was then diagnosed with postoperative methicillin-resistant Staphylococcus aureus (MRSA) infection, and the infected aortic graft was replaced with a rifampicin-soaked vascular prosthesis, which was followed by continuous irrigation using a 0.1% povidone-iodine solution. The postoperative course was uneventful, and she has been doing well for 5 years with no recurrence of infection. Prosthetic graft replacement using a rifampicin-soaked graft followed by continuous irrigation with povidone-iodine is useful for treatment of an MRSA-infected prosthetic vascular graft.

[Risk Factors for Post-operative Respiratory Failure and Respiratory Tract Infections Following Cardiovascular Surgery].

INTRODUCTION: Respiratory failure and respiratory tract infections are frequently observed as post-operative pulmonary complications, and significantly contribute to morbidity and mortality. However, the risk factors of post-operative respiratory failure and respiratory tract infections are controversial, and how these factors affect on incidence of complications is still unclear. OBJECTIVE: To identify risk factors of post-operative respiratory failure and respiratory tract infections, and evaluate its impact on incidences after cardiovascular surgery. METHODS: From June 2013 to May 2015, adult patients undergoing cardiovascular surgery in the department of cardiovascular surgery and post-operative rehabilitation of Nagasaki University Hospital (Nagasaki, Japan) were retrospectively investigated. RESULTS: Fifty-two of 416 patients(12.5%)suffered from post-operative respiratory failure and respiratory tract infections. Identified risk stratification indicates the relevant operative factors were more important than pre-operative factors. The operative time (OR 1.696, 95% CI 1.302~2.211), post-operative water balance( OR 1.025, 95% CI 1.004~1.046)and emergency operation( OR 3.607, 95% CI 1.492~8.716)were significant independent risk factors in the development of post-operative respiratory failure and respiratory tract infections. CONCLUSIONS: These results indicated that the operative factors are more important as onset of post-operative respiratory failure and respiratory tract infections after cardiovascular surgery.

[Native Valve Endocarditis due to Corynebacterium Striatum; Report of a Case].

We recently encountered a case of native valve endocarditis caused by Corynebacterium striatum (C. striatum) in the absence of immunosuppression and a prosthetic valve. A 49-year-old woman was urgently admitted for disturbance of consciousness and nosebleeds. Careful clinical examination revealed infective endocarditis caused by C. striatum, for which replacement of aortic and mitral valves was performed. The postoperative course was favorable, and we were able to save the patient with no postoperative complications. Detection of C. striatum may be recognized as contamination because this organism is a rare pathogen. However, elderly patients and patients with immunosuppression are rapidly increasing, and it is important to keep C. striatum in mind when Gram-positive bacilli are detected in the clinical examination.

[Surgical Procedure Using the Elephant Trunk Technique at All Anastomotic Sites for Acute Type A Aortic Dissection].

OBJECTIVE: We report the use of the elephant trunk technique at all anastomotic sites in acute type A aortic dissection surgery. METHODS: Artificial graft carrying a 2-mm short elephant trunk were prepared for both distal and proximal anastomotic sites. Subjects were 82 patients with acute type A aortic dissection who underwent surgery using this procedure between March 2009 and August 2015. The mean age was 69.6 ±10.7 years( range, 43~89 years). Seventeen patients( 20.7%) had cardiac tamponade or shock, while 8 cases( 9.8%) had organ ischemia due to malperfusion. RESULTS: Total aortic arch replacement was performed in 22 patients (26.8%), while replacement of the ascending aorta was performed in 60( 73.2%). The mean durations of surgery, extracorporeal circulation, and cardiac ischemia were 352 ± 64, 199 ± 37, and 123 ± 26 min, respectively. Five in-hospital deaths( 6.1%) occurred. With respect to early complications, 5 patients( 6.1%) had permanent encephalopathy. Nine (11.0%) had respiratory failure, and 4 (4.9%) required tracheotomy. None of the patients had bleeding requiring additional thoracotomy for hemostasis and none had complications attributed to preparation of the artificial vessels. CONCLUSION: Artificial graft were prepared using the elephant trunk technique for use at all anastomotic sites in acute type A aortic dissection surgery. This procedure, involving stepwise proximal anastomosis, is highly effective for hemostasis and safe.

[Repair of Cardiac and Pulmonary Damage caused by Stabbing with a Kitchen Knife;Report of a Case].

A 51-year-old woman was stabbed in the chest with a kitchen knife. Twenty minutes after arrival at our hospital by ambulance, she was transferred to the operating room, and a cardiopulmonary bypass was established from the right femoral artery and vein, and a median sternotomy was performed. The knife had damaged the surface of the heart and penetrated the lingular segment of the left lung. Both wounds were directly sutured. Chest X-rays taken after closing the chest showed bleeding in the left lung probably because of the administration of heparin. Bleeding was controlled by lingulectomy. The postoperative course was uneventful.

Computed tomography evaluation of aortic remodeling after endovascular treatment for complicated ulcer-like projection in patients with type B aortic intramural hematoma.

OBJECTIVE: The purpose was to investigate changes of the affected aorta after endovascular treatment for complicated ulcer-like projection (ULP), including aneurysmal change or rupture of ULP, or both, in patients with type B aortic intramural hematoma (IMH). METHODS: The study evaluated 18 patients (nine men) undergoing thoracic endovascular aortic repair for progressive aneurysmal formation of ULP (n = 17), rupture of ULP (n = 5), or both. Patients were a median age of 72 years (range, 45-83 years). Regular follow-up computed tomography studies were performed after treatment (mean follow-up, 61.2 months). A workstation was used to calculate changes on computed tomography images in the size or volume of ULP, affected aorta, and IMH. The growth rate of the volume of the affected aorta and IMH was also calculated before and after treatment. We evaluated the data using the paired t-test. RESULTS: A stent graft was successfully deployed and ULPs disappeared in all patients. IMH disappeared in 16 or decreased in two after treatment. There were significant differences in the mean maximum aortic diameter (37.8 ± 5.2 vs 34.5 ± 5.2 mm; P = .0006), mean IMH volume (39.4 ± 12.1 vs 2.0 ± 6.0 mL; P < .0001), and total volume of the aorta with IMH (158.1 ± 40.2 vs 128.9 ± 28.0 mL; P < .0001) before and after treatment. CONCLUSIONS: Endovascular treatment is a useful treatment for complicated ULP in patients with IMH. Endovascular treatment also contributes to ideal remodeling of the affected aorta.