Guidelines for cadaver dissection in education and research of clinical medicine (The Japan Surgical Society and The Japanese Association of Anatomists).

This article translates the guidelines for cadaver surgical training (CST) published in 2012 by Japan Surgical Society (JSS) and Japanese Association of Anatomists from Japanese to English. These guidelines are based on Japanese laws and enable the usage of donated cadavers for CST and clinical research. The following are the conditions to implement the activities outlined in the guidelines. The aim is to improve medicine and to contribute to social welfare. Activities should only be carried out at medical or dental universities under the centralized control by the department of anatomy under the regulation of Japanese law. Upon the usage of cadavers, registered donors must provide a written informed-consent for their body to be used for CST and other activities of clinical medicine. Commercial use of cadavers and profit-based CST is strongly prohibited. Moreover, all the cadaver-related activities except for the commercial-based ones require the approval of the University's Institutional Review Board (IRB) before implementation. The expert committee organized at each university for the implementation of CST should summarize the implementation of the program and report the details of the training program, operating costs, and conflicts of interest to the CST Promotion Committee of JSS.

A novel approach for the complete extraction of large tumours in video-assisted thoracoscopic surgery.

BACKGROUND: Video-assisted thoracoscopic (VATS) lobectomy has recently become the standard for treating lung cancer. However, the complete removal of large tumours from the chest cavity is often difficult. Therefore, we developed a novel approach to extract large tumours from the wound without rib resection or fracture (the eXtraction of resected specimens through the Lower INterCostal route [XLINC] method). SUBJECTS AND METHODS: In XLINC, a skin incision is made on the tenth intercostal space, and the resected lung tissue is extracted. This retrospective study included patients who underwent VATS lobectomy using XLINC in our institution from 2016 to 2018. As a control group, six patients who had undergone thoracotomy during VATS surgery due to a large tumour diameter were included in the conversion group. RESULTS: Four men and six women (median age = 66 years, maximum median tumour diameter = 59 mm) were included in the study. The median length of the wound incision for XLINC was 4.5 (range: 4-8) cm. The median operative time was 183 min, and the estimated blood loss was 50 ml. Rib resection was not required, and no fractures were noted. The median length of hospital stay was 8 days. No patients developed major complications caused by XLINC. There were no significant differences, except in operation time and amount of blood loss, between the two groups. However, the XLINC group used fewer post-operative analgesics. CONCLUSION: Our report suggests that XLINC might be a simpler, less invasive procedure that could be used in patients with large tumours.

Bridge-to-Bridge Left Ventricular Assist Device Implantation Strategy vs. Primary Left Ventricular Assist Device Implantation Strategy.

BACKGROUND: The bridge-to-bridge (BTB) strategy, a conversion to durable left ventricular assist device (LVAD) after stabilization using surgical temporary mechanical circulatory supports for a couple of months, is not uncommon in Japan. However, its effect on clinical outcomes in comparison with a primary durable LVAD implantation strategy remains unknown.Methods and Results:Data of 837 consecutive patients (median age 45, 73% males) who underwent durable LVAD implantation as BTB (n=168) or primary implant (n=669) between April 2011 and April 2019 were retrospectively reviewed from the prospective multicenter Japanese mechanically assisted circulatory support registry. The BTB group was younger and had comparable end-organ function, better hemodynamic profile, and longer operative time compared with the primary implant group at baseline. The 3-year survival was 80% vs. 87% (P=0.007) for the BTB and primary implant groups respectively, with greater observed rates of stroke and infection as the predominant causes of death. The BTB strategy was independently associated with increased 3-year mortality (hazard ratio 2.69 [1.43-5.07], P=0.002) in addition to other significant risk factors. CONCLUSIONS: The BTB cohort had comparable baseline characteristics to the primary implant cohort at the time of durable LVAD conversion, but had lower 3-year survival. Detailed analysis clarifying the causality of this finding should improve outcomes with the BTB strategy.

Forns Index is a predictor of cardiopulmonary bypass time and outcomes in Fontan conversion.

Recent reports suggested that cardiopulmonary bypass (CPB) time is one of the risk factors for postoperative complications after Fontan conversion. Although Fontan conversion may be performed for the patients with hepatic fibrosis after initial Fontan procedure, there is no predictive indicator regarding the liver function associated with hemostasis which can affects CPB time. Thirty-one patients who underwent Fontan conversion using the same surgical procedure (extracardiac conduit conversion with right atrium exclusion) were enrolled. In multivariate analyses including age at Fontan conversion, interval from initial Fontan to conversion, hemodynamic data such as right atrial pressure, ventricular end-diastolic pressure, and cardiac index, hepatic data such as platelet count, prothrombin time international normalized ratios, serum total bilirubin, hyaluronic acid levels, five known indices for hepatic fibrosis (Forns Index, APRI, FIB4, FibroIndex, and MELD-XI), and liver stiffness measured by ultrasound elastography, only the Forns Index remained independently associated with the CPB time (P < 0.01) and blood transfusions (plasma transfusions and platelet concentrations: P < 0.01 for both). The cutoff level for Forns Index to predict the prolonged CPB time (exceeding 240 min) was 4.85 by receiver-operating characteristic curve (area under the curve 0.823, sensitivity 76.9%, and specificity 72.2%). Three patients with Forns Index > 7.0 had poor outcomes with long CPB time and massive blood transfusions in contrast with the other 28 patients. In conclusion, Forns Index could serve as a practical predictor of CPB time and is associated with blood transfusion volume in Fontan conversion.

Hemocompatibility-related Adverse Events Following HeartMate II Left Ventricular Assist Device Implantation between Japan and United States.

Background: Left ventricular assist device (LVAD) therapy has improved the clinical outcomes in advanced heart failure patients, however, this may differ between countries. We aimed to compare outcomes between Japanese and US LVAD cohorts. Methods: For 416 consecutive LVAD patients who received HeartMate II LVAD implantation and completed a one-year follow-up, age-matched Japanese patients (the Japanese registry for mechanically assisted circulatory support (J-MACS) group) and the US patients were compared for their clinical outcomes. Results: 154 J-MACS patients and 77 US patients were compared. Survival, free from hemocompatibility-related adverse events (HRAEs) in the J-MACS was statistically comparable with the US (75% vs. 63%, p = 0.79). J-MACS had more disabling strokes than the US (0.221 vs. 0.052/patient-year, p = 0.005), whereas there was less nonsurgical bleeding (0.045 vs. 0.117/patient-year, p = 0.024). The net hemocompatibility score was statistically comparable between the groups (1.54 vs. 1.19 points/patient, p = 0.99). Post-LVAD prothrombin time with international normalized ratio (INR) <1.5 (odds ratio 4.07) was a risk factor for HRAEs in J-MACS, whereas INR >3.0 (odds ratio 5.71) was a risk factor in the US (p < 0.05 for both). Conclusion: In the age-matched cohorts, the J-MACS group experienced more strokes, while the US group had more bleedings. "Tailor-made" therapeutic strategy might be required for each country, given the unique variation of HRAE incidence among each country.

Implication of Preoperative Existence of Atrial Fibrillation on Hemocompatibility-Related Adverse Events During Left Ventricular Assist Device Support.

BACKGROUND: Hemocompatibility-related adverse events (HRAEs) are substantial issues in patients with left ventricular assist devices (LVADs). Atrial fibrillation (AF) is associated with worse prognosis in patients with heart failure (HF), but its effect on HRAEs following LVAD implantation remain uncertain.Methods and Results:Data from the Japanese Mechanically Assisted Circulatory Support registry of consecutive patients who received HeartMate II LVADs and were followed for 1 year were retrospectively reviewed. Among 190 patients, 23 had AF and 167 had sinus rhythm. The AF group had comparable baseline characteristics with the non-AF group except for their higher age (53 vs. 42 years, P<0.001). Following LVAD implantation, most cases of AF (73%) persisted. Antiplatelet therapy, anticoagulation therapy, and LVAD speed following LVAD implantation were comparable between groups (P>0.05 for all). The 1-year survival free from HRAEs was comparable between groups (83% vs. 76%, P=0.52). Event rates of the breakdown of HRAEs were comparable between groups except for a relatively higher rate of surgically managed pump thrombosis in the AF group (0.16 vs. 0.04, incidence rate ratio 3.75, 95% confidence interval 0.87-16.1, P=0.075). These trends still remained with propensity score-matched comparison. CONCLUSIONS: Existence of AF had no effect on the development of HRAEs following LVAD implantation. The need to aggressively treat AF before or after LVAD implantation needs further investigation.

Mechanical properties of a new thermally deformable mitral valve annuloplasty ring and its effects on the mitral valve.

Ideally, an annuloplasty ring's shape should be changed intraoperatively if mitral valve repair is unsuccessful because of a short coaptation length or systolic anterior motion. Several post-implantation adjustable rings have been developed, but they are not freely deformable and are unsuitable for asymmetric repair of the valvular annulus. We developed a novel thermally deformable mitral annuloplasty ring to address these problems and assessed the ring's mechanical properties and its effect on the mitral valve anatomy. This ring was made of polycaprolactone. Tensile and bending tests were performed to evaluate the ring's mechanical properties. The ratio of the transverse and septal-lateral length was determined as 4:3. Using 10 pig hearts, we measured the post-deformation coaptation length and minimum distance from the coaptation to the ventricular septum, which is a factor of abnormal systolic anterior motion of the mitral valve. In the mechanical tests, the ring's yield point was greater than the deformation force of the annulus in humans. In pigs with deformation from "4:3" to "4:2", the coaptation length was significantly increased in each mitral valve part. In pigs with deformation from "4:3" to "4:4", the minimum distance from the coaptation to the ventricular septum was significantly increased. Asymmetrical ring deformation increased the coaptation length only at the deformed area. In conclusion, this new thermally deformable mitral annuloplasty ring could be "order-made" to effectively change the coaptation length in all parts of the mitral valve and the distance from the coaptation to septum post-deformation via intraoperative heating.

Re-do mitral valve replacement for a bioprosthetic valve with central transvalvular leakage in a patient with ischemic cardiomyopathy: a case report.

Transvalvular leakage (TVL) of a prosthetic heart valve is not negligible regurgitant flow in patients with critically low contractile function. Although the opening function of prosthetic valves has been reported, its closing function is not well understood. A man in his 70 s had a history of mitral valve replacement (MVR) with a Magna Mitral® valve for ischemic mitral valve regurgitation. He presented with dyspnea 2 years postoperatively. Echocardiography showed moderate TVL. The pulmonary capillary wedge pressure and cardiac index were 37 mmHg and 1.65 L/min/m2, respectively. Because we considered his TVL relevant, we performed re-do MVR with a mechanical valve and papillary muscle approximation and suspension ("papillary muscle tugging approximation"). His cardiac function improved postoperatively; he was discharged with New York Heart Association class I. For MVR in patients with critically low contractile function, prosthetic valves, such as mechanical valves, with small TVL are recommended.

Clinical Results, Adverse Events, and Change in End-Organ Function in Elderly Patients With HeartMateII Left Ventricular Assist Device　- Japanese Multicenter Study.

BACKGROUND: Advanced age has an adverse impact on clinical results in left ventricular assist device (LVAD) patients. We compared the clinical results of patients aged >60 years with younger patients using a national Japanese database.Methods and Results:Between April 2013 and December 2016, 300 patients underwent HeartMateII implantation. Of these, 37 patients were ≥60 years at LVAD implantation, and the clinical results of these patients were compared with the other younger 263 patients. At 1 and 3 years the on-device survival was 95%, 91% in younger patients, and 85%, 75% in older patients, respectively (P=0.016), although age was not a risk factor on the multivariate analysis. There was no significant difference between the groups in incidence of various adverse events except stroke. In the propensity-matching cohort, the incidence of stroke was significantly higher in patients aged >60 years (P=0.047). In patients aged >60 years, improvement of renal function was transient and there was no improvement later than 3 months, and recovery of serum albumin level to preoperative value was delayed. CONCLUSIONS: There were significant differences in the stroke incidence and recovery of end-organ functions after LVAD implantation. This may have important implications for patient selection in future destination therapy in Japan, where quality of life is an important issue in LVAD support.

Surgery for Left Ventricular Outflow Tract Obstruction with a Relatively Thin Interventricular Septum.

BACKGROUND: To examine the results of myectomy and mitral valve surgery for systolic anterior motion (SAM) of the mitral valve and left ventricular outflow tract obstruction (LVOTO) with a relatively thin interventricular septum. METHODS: The subjects were 12 patients with SAM and LVOTO. Eight had hypertrophic obstructive cardiomyopathy (HOCM) with a mean interventricular septal thickness of 16 mm. Three had sigmoid septum and one had an unknown etiology. For HOCM, isolated extended myectomy was performed when mitral regurgitation was mild (n = 1) and extended myectomy plus mitral valve surgery was performed when mitral regurgitation was more than mild (n = 4) or primary valve etiologies existed (n = 3). Myectomy was performed for the three cases with sigmoid septum. Myectomy plus height reduction of the posterior mitral leaflet was performed for the one case with the unknown etiology of SAM. RESULTS: In the patients with HOCM, the maximum LVOT pressure gradient significantly decreased from 140 ± 18 to 16 ± 6 and 3 ± 3 mm Hg, while mitral regurgitation significantly decreased from 2.3 ± 0.5 to 0.5 ± 0.3 and 0.4 ± 0.2 at pre-op, early post-op, and last follow-up (3 ± 1 years), respectively. In the other etiologies, the maximum LVOT pressure gradient changed from 56 ± 15 to 25 ± 15 and 5 ± 4 mm Hg; mitral regurgitation changed from 2.0 ± 0.6 to 1.3 ± 0.3 and 1.3 ± 0.8, at pre-op, early post-op, and the last follow-up (3 ± 2 years), respectively. CONCLUSION: Myectomy with mitral valve surgery is an option for SAM and LVOTO in patients with a relatively thin interventricular septum.

Anticoagulation management during cardiopulmonary bypass in patients with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a complex autoimmune disease often related to systemic lupus erythematosus. Although adequate anticoagulation is important for APS patients during cardiopulmonary bypass, clotting tests can be potentially misleading due to antiphospholipid antibodies. We performed cardiac surgery safely in two APS patients under anticoagulation monitoring determined using preoperative heparin titration. We performed heparin titration for activated clotting time to determine the appropriate heparin concentration during cardiac surgery. We changed the targeted heparin concentration considering each patient's thrombotic risks: 3 U/ml of heparin for a normal-risk APS patient and 5 U/ml for a high-risk APS patient with a history of antiphospholipid-antibody-associated thrombocytopenia. A higher targeted heparin concentration might be necessary for patients with high thrombotic risks.

Vasoactive-inotropic score as a predictor of morbidity and mortality in adults after cardiac surgery with cardiopulmonary bypass.

PURPOSE: The vasoactive-inotropic score (VIS) is a scale showing the amount of vasoactive and inotropic support. Recently, it was suggested that the VIS after cardiac surgery predicts morbidity and mortality in infants. The purpose of this study was to evaluate the VIS at the end of surgery as a predictor of morbidity and mortality in adult cardiac surgery. METHODS: A retrospective cohort study of 129 adult cardiac surgery patients was performed at a university hospital. The primary outcome was termed "poor outcome", which was a composite of morbidity and mortality. The secondary outcomes were the duration of intensive care unit (ICU) stay and time to first extubation. Multivariate logistic regression analysis was performed to evaluate the association between the VIS and poor outcomes. A proportional hazards model was used to evaluate the duration of the ICU stay and time to first extubation. RESULTS: After adjusting for the EuroSCORE, preoperative ejection fraction, and bypass time, a high VIS at the end of surgery was associated with a poor outcome with an adjusted odds ratio of 4.87 (95% confidence interval 1.51-18.94; p = 0.007). After controlling for the EuroSCORE and bypass time, patients with a high VIS experienced longer ICU stay (hazard ratio 1.62; 95% confidence interval 1.10-2.39; p = 0.015) and needed longer ventilation (hazard ration 1.87; 95% confidence interval 1.28-2.74, p = 0.001). CONCLUSIONS: The amount of cardiovascular support at the end of cardiac surgery may predict morbidity and mortality in adults.

[Surgical Options for Refractory Heart Failure Patients with Non-ischemic Dilated Cardiomyopathy].

Surgical strategy for non-ischemic dilated cardiomyopathy (NIDCM) is currently controversial. Subjects were 20 patients who underwent left ventriculoplasty(LVP) from 2006 to 2013 and 6 patients who underwent papillary muscle tugging approximation (PMTA) after 2015. PMTA is a new trans-mitral approach combined with valve replacement without left ventriculotomy. Another group of patients( n=14)who were registered for heart transplantation( HTx) after 2013 was also analyzed for left ventricular assist device(LVAD) free survival. Mw( slope in the preload recruitable stroke work relationship) calculated by single beat technique using echocardiography was employed as a load-independent cardiac functional parameter. The baseline characteristics and Mw were not different between the LVP and PMTA groups. One-year survival was significantly lower in the LVP group(53%)than in the PMTA group(100%)[log-rank:p=0.024]. In the HTx group, early LVAD implantation was necessary in the patients who had low Mw(<20)at the time of registration. In conclusion, PMTA would be one option for NIDCM patients( non-HTx candidates) with severe mitral regurgitation. Early LVAD implantation might be predicted in HTx candidates with low Mw(<20).

Left-Ventricular Plication Reduces Wall Stress and Cardiomyocyte Hypertrophy in a Rat Model of Ischemic Cardiomyopathy.

BACKGROUND: The indications of left-ventricular plication (LVP) are controversial, although several studies have reported favorable outcomes in heart failure patients. The aim of this study was to assess left-ventricular (LV) wall stress and myocardial remodeling after LVP in a rat model of myocardial infarction (MI). METHODS: Sixteen rats underwent LVP by excluding the LV anterior wall scar 4 weeks after ligation of the left anterior descending artery. After 4 weeks, LV wall stress was assessed using transthoracic echocardiography and an LV catheter. Gene expression of the wall stress markers, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), were evaluated via reverse transcription polymerase chain reaction. Cardiomyocyte area and myocardial fibrosis were also examined through histological examinations. These parameters were compared to those in 16 rats that underwent coronary artery ligation but not LVP. RESULTS: We noted that the LV end-diastolic dimension was smaller (9.9 ± 0.3 vs. 11.2 ± 0.2 mm, p < 0.05) and fractional shortening was greater (25 ± 2 vs. 15 ± 1%, p < 0.05) in LVP rats than in sham rats. Moreover, systolic wall stress was lower in LVP rats (71 ± 7 vs. 111 ± 9 × 103 dyn/cm2, p < 0.05). Myocardial ANF and BNP expression levels were lower in LVP rats (2.6 ± 0.3 vs. 4.4 ± 0.5 and 1.0 ± 0.1 vs. 1.5 ± 0.2 arbitrary units, respectively; p < 0.05). Cardiomyocyte area was significantly decreased in LVP rats (556 ± 15 vs. 670 ± 28 µm2, p = 0.003) and was correlated with LV wall stress (r = 0.669, p = 0.002). The reduction in myocardial fibrosis after LVP was not significant. CONCLUSION: LVP reduced LV wall stress and cardiomyocyte hypertrophy in a rat model of MI.

[Perioperative Care of Low Cardiac Output Syndrome].

Low cardiac syndrome( LOS) is the imbalance of the oxygen supply and demand at the tissue due to reduced oxygen supply by decreased cardiac function. The causes of the cardiac dysfunction are insufficient cardioplegia, elongation of aortic clamp or cardiopulmonary bypass (CPB) duration, incomplete revascularization, and so on. The preventions of LOS are myocardial protections intraoperatively. The most important myocardial protection is to accomplish more quickly, accurately and safety to operation. And today, cardioplegia is essential for surgery requiring CPB. The integrated myocardia protection is likely to be effective to the patients who suffer low cardiac function. LOS is commonly defined the decreased cardiac index (CI)[<2.0~2.2 l/min/m2], systolic blood pressure (<80~90 mmHg) and the signs of tissue malperfusion, in the absence of hypovolemia. The treatment of LOS is, at first, the correction of hypovolemia, then rhythm control, adjustment of preload and afterload. When it does not recover from LOS despite adequate treatment, the mechanical circulatory assist devices should be introduced without hesitation.

Japanese Multicenter Outcomes With the HeartMate II Left Ventricular Assist Device in Patients With Small Body Surface Area.

BACKGROUND: The HeartMate II (HMII) continuous-flow LVAD was approved for Japanese health insurance coverage in April 2013 as a bridge to transplantation (BTT). We report on post-approval Japanese multicenter outcomes, and a comparison between patients with low and high body surface area (BSA). METHODS AND RESULTS: HMII LVAD was implanted in 104 consecutive patients at 15 Japanese centers between April 2013 and July 2014. Perioperative data were submitted to the Japanese Registry for Mechanically Assisted Circulatory Support. Patients were divided into 2 groups on the basis of BSA less or greater than 1.5 m(2). Survival outcomes, New York Heart Association functional class, and adverse event rates were compared between the 2 groups. Preoperative hemodynamics and INTERMACS profiles were similar between groups. There were more females and younger patients in the low BSA group. The respective 6-month and 1-year death- or pump exchange-free survival rates were excellent: 90% and 90% in the BSA <1.5 group vs. 90% and 85% in the BSA ≥1.5 group. In the BSA <1.5 group, occurrence of hemorrhagic stroke was 10% and occurrence of embolic stroke was 0%, vs. 12% and 8% in BSA ≥1.5 group. Driveline infection was encountered more frequently in the BSA <1.5 group. CONCLUSIONS: Results for HMII LVAD as BTT in the post-approval era showed excellent survival and functional capacity improvement. Of particular interest to the Japanese patient population are the excellent results in patients with small BSA. (Circ J 2016; 80: 1931-1936).

The significance of the analysis on scalographic pattern for detecting malfunctioning bileaflet valve with the wavelet analysis.

The authors developed the wavelet analysis system which can detect the splitting of bileaflet mechanical heart valve (BLV) into two spikes on the scalogram, and reported that either consecutive single spike or the split behavior can detect malfunctioning BLV (MBV). The latest study on 12 BLVs suggested that the comparison between two spike areas showed higher potential to detect MBV than the split behavior. The aim of the current study is to review 226 files of BLV sound and to select the suitable scalographic property to differentiate the function of BLV with the split. Eight of 30 MBV files showed consecutive single spike, and the rest of 22 MBV files showed two spikes. Two spike areas can be compared by the following three ratios; the anterior spike area/posterior spike area (Aa/La), its reverse ratio (Pa/Aa) and the smaller spike area/the larger spike ratio (Sa/La). Therefore, the current study compared those three ratios to pursue the suitable ratio to compare two spike areas and its sensitivity to differentiate valve function by the ROC analysis. As a result, the Sa/La was suitable for comparing two spike areas, and only this ratio showed high accuracy to differentiate the function of BVL with the split, and its cutoff value was <0.665. Conclusively, the key for detecting MBV was either consecutive single spike or the mean of Sa/La < 0.665. However, this cutoff point is still tentative due to small number of malfunctioning valves, and other key might be available in future.

[Uniquely Shaped Giant Thrombus in the Right Atrium after Long-term Insertion of Central Venous Catheters].

Thrombosis around intravenous catheters are often found in daily practice, and their treatment must be considered if they are mobile or large. However, in such giant thrombosis cases as this one, it is considered that thrombolytic therapy is ineffective and that immediate surgical resection is the best choice of treatment. The patient had a very uniquely-shaped right atrial thrombus.