An insertion mutation in the Apoe gene associated with spontaneous hyperlipidemia in mice.

Introduction: Spontaneously hyperlipidemic (SHL) mice, a mouse strain derived from an inbred strain of Japanese wild (original)-type mice (KOR; Mus musculus molossinus), show high plasma cholesterol concentrations with disruption of the apolipoprotein E (Apoe) gene. However, the details of the Apoe gene of SHL mice have yet to be described. Material and methods: The DNA sequence of the Apoe gene of SHL mice was compared to that of control KOR mice in genomic DNA and cDNA analyses. Results: In the DNA analysis, a 4700-bp fragment was found to be inserted into exon 4 of the Apoe gene of SHL mice. The insertion contained two 365-bp repeats at each terminal and was flanked by a 6-bp target duplication at each side. The inserted fragment produced a frameshift of an early stop codon, resulting in a protein product that consisted of 87 amino acids in SHL mice compared to 311 amino acids in control KOR mice. Conclusions: These findings provide useful information about the molecular basis of SHL mice and related lipid disorders.

[Distal Stent Graft-induced New Entry after Total Arch Replacement for the Aortic Dissection:Report of a Case].

A 73-year-old man after total arch replacement with open stent graft (OSG) technique for Stanford type B aortic dissection was found to have expanding descending aortic aneurysm. Contrast-enhanced computed tomography (CT) showed distal stent graft-induced new entry (distal SINE). We successfully performed additional thoracic endovascular aortic repair (TEVAR). The determinants of distal SINE are reported to be excessive distal oversizing and spring back force on the distal end of the stent graft, which might make the stress for descending aorta. We also found that the angle between distal end of the stent graft and the horizontal line of the body was changed. The angle when distal SINE occurred was smaller than that of when it was placed. Appropriate size selection and positioning of stent graft might reduce the risk of distal SINE events.

Clinical assessment of efficacy of poly-L-lactide sternal pin on sternal stability and post-operative pain: a prospective randomized trial in cardiovascular surgery.

BACKGROUND: Although the incident rate is low, sternal dislocation and dehiscence due to unstable sternal fixation after cardiovascular surgery could cause potentially lethal complications. Thus, to enforce the stability of closed sternum, the sternal pins have been utilized at surgeon's discretion. However, there is no randomized clinical trial to test whether these pins are effective to stabilize a sternum. Hence, this study aimed to examine the clinical efficacy of bioabsorbable poly-L-lactide (PLLA) sternal pins in reinforcing sternal stability and preventing instability of the sternum after full sternotomy. METHODS: We conducted a single institutional, prospective, randomized, single-blinded clinical study involving 100 patients who underwent an initial cardiovascular surgery via sternotomy. Patients were randomly allocated into two groups: with (group P) and without (group N) PLLA sternal pins, at 1:1 ratio from November 2013 to April 2016. Sternal deviation and stability were assessed with postoperative computed tomography (CT) at two postures to put shear stress on the sternum. Additionally, information on patient demographic indices was obtained prospectively, and patient's pain intensity was assessed with numerical rating scoring system during rehabilitation. Furthermore, propensity score matching was performed for further comparative sub-analysis. RESULTS: Ninety-one patients (43 in group P and 48 in group N) were analyzed using the intention-to-treat method. Group N had a significantly higher proportion of males (P=0.015) and ischemic disease as a primary diagnosis (P=0.040) than group P. Postoperative CT showed that the degree of sternal deviation and stability were comparable between the groups. Similarly, the numerical rating score of pain during rehabilitation showed no difference between the groups. Even after adjusting for patient characteristics using propensity score matching method, no significant differences in sternal gaps, stability, and numerical rating score of pain were observed. Of note, no material-related adverse event such as wound infection was found. CONCLUSIONS: We could not identify the efficacy of the sternal pin in enforcing sternal stability based on CT measurements with mild shear stress on sternum after cardiovascular surgery. Nevertheless, our results with no adverse events might encourage further investigations with a more specific cohort who is susceptible to infection but requires an additional sternal fixation. TRIAL REGISTRATION: This study was registered in University Hospital Medical Information Network Clinical Trial Registry (UMIN000017357).

Perioperative Hemodynamic Changes in the Thoracic Aorta in Patients With Aortic Valve Stenosis: A Prospective Serial 4D-Flow MRI Study.

This study investigated hemodynamic changes in the thoracic aorta and aortic arch branches before and after aortic valve replacement (AVR) by 4D-flow MRI in patients with aortic valve stenosis (AS). Thoracic 4D-flow MRI was performed in 10 AS patients before and after AVR (mean 27 ± 1.9 days). Fifteen aortic planes and 3 aortic arch branches planes were set to evaluate the mean volume flow rate in each plane during a cardiac cycle and the angle between the main flow direction in a specified plane and the axial direction of the aorta. We also focused on the distribution and magnitude of helicity density to evaluate the flow complexity. A significant increase in the volume flow rate after AVR was found in the ascending aorta (before 59.2 ± 8.7 mL/s vs after 77.3 ± 6.2 mL/s, P < 0.05) and the aortic arch branches (before 26.5 ± 2.8 mL/s vs after 35.8 ± 3.3 mL/s, P < 0.001). The flow angle significantly decreased in the ascending aorta (before 39.2 ± 2.7 degree vs after 25.2 ± 1.7°, P < 0.0001) and the arch aorta (before 19.3 ± 2.0 degree vs after 13.4 ± 0.9°, P < 0.001). The volume flow rate in the ascending aorta and the arch branches increased within 1 month after AVR, showing an increased blood supply to the upper body, including to the brain. The postoperative change was accompanied with an increased blood flow in the ascending aorta and a decreased flow complexity proximal to the arch branches.

Temporary ventricular assist device implantation by sternotomy-avoiding technique for bridge-to-decision therapy: a comparison with conventional implantation.

OBJECTIVE: Temporary ventricular assist device (VAD) is a commonly used therapeutic option for cardiogenic shock. Patients requiring this treatment are often critical, and clinical outcomes remain unsatisfactory. This study evaluated the feasibility and efficacy of a sternotomy-avoiding technique for temporary VAD implantation to improve patient outcomes. METHODS: Between December 2012 and November 2018, seven patients underwent temporary VAD implantation by sternotomy-avoiding technique (SA group) and eight by median sternotomy technique (MS group). Pre- and intraoperative characteristics, postoperative 7-day hemodynamic parameters, 30-day mortality, and adverse events were compared between the groups. RESULTS: More than 50% of the patients were mechanically supported before temporary VAD implantation. Cardiopulmonary bypass time was significantly shorter in the SA than in the MS group (84 min vs 215 min; p = 0.011); surgical time tended to be shorter in the SA group (385 min vs 461 min; p = 0.064). Pump index, cardiac index, mixed venous oxygen saturation, and central venous pressure did not differ significantly during the first seven days of support. The 30-day incidence of any adverse event was not significantly different between the groups. No patients in the SA group needed re-exploration for surgical bleeding. Thirty-day all-cause mortality rates were 29% in the SA group and 0% in the MS group (p = 0.11). CONCLUSIONS: The sternotomy-avoiding and conventional techniques resulted in comparable short-term hemodynamic support. The sternotomy-avoiding technique was associated with a potential reduction in risk of re-exploration for bleeding. These results support the usefulness of the sternotomy-avoiding procedure for selected patients.

The incidence, risk factors, and outcomes of gastrointestinal bleeding in patients with a left ventricular assist device: a Japanese single-center cohort study.

Continuous flow-left ventricular assist devices (CF-LVADs) have become a therapeutic option in the management of advanced heart failure. Several studies show that patients with CF-LVAD are at an increased risk of gastrointestinal bleeding (GIB). However, few reports have presented the characteristics of GIB in Japanese populations. We investigated the incidence, etiology, and outcome of GIB in patients with CF-LVAD. Records of adult patients who received CF-LVADs between October 2008 and January 2017 were reviewed. GIB was defined as detection of bleeding sites by any type of diagnostic imaging. 54 patients received CF-LVAD, of which eight (14%) presented with overt GIB (12 events). GIB patients are significantly older (p = 0.04) and their pre-operative inferior vena cava diameter was larger (p = 0.02). Multivariate analysis revealed that the use of Jarvik 2000 (p = 0.003) was a risk factor for GIB. In total, 85.8% of patients were free from GIB at 1 year. The most common site was the small intestine (67%). The most common cause was angiodysplasia (50%). Six patients required blood transfusion (nine events) and four underwent endoscopic clippings (five events); however, no patients needed surgeries. The incidence of GIB in our cohort was similar to the global registry data. Double balloon endoscopy is useful for diagnosis and treatment of small intestinal lesions. Future efforts to further understand the incidence of GIB in Japanese populations by multicenter data are needed.

[Splenic Injury during Replacement of the Thoracoabdominal Aorta].

Extraperitoneal approach is commonly employed for thoracoabdominal aortic repair via Stoney incision. It is supposedly rare to encounter abdominal visceral bleeding during that procedure. However, the spleen may spontaneously adhere to the adjacent peritoneum, which could induce incidental injury to the spleen by its anterior mobilization during extraperitoneal approach. Unless we bare its potential risk in mind, bleeding from the spleen may be overlooked, which results in hemodynamic deterioration. We have experienced 3 cases of splenic injury that necessitated hemostatic maneuvers for bleeding during and just after the thoracoabdominal aortic repair.

Concomitant Valve-Sparing Aortic Root Replacement With Repair of Tetralogy of Fallot.

Valve-sparing aortic root replacement is one of the effective repairs for aortic regurgitation resulting from progressive dilatation of the aortic root late after surgical correction of conotruncal anomaly. However, feasibility and effectiveness of this procedure are unknown for unrepaired physiology. A 32-year-old man presented with unrepaired tetralogy of Fallot (TOF) and moderate aortic regurgitation with severe left ventricular dysfunction. Valve-sparing aortic root replacement and TOF repair were simultaneously performed. Six months after the surgical procedure, aortic regurgitation remained trivial. Concomitant valve-sparing aortic root replacement with TOF repair can be feasible and effective for unrepaired TOF with aortic regurgitation.

Differential selective hypothermic intercostal artery perfusion: a new method to probe spinal cord perfusion during thoracoabdominal aortic aneurysm repair.

OBJECTIVE: To prevent paraplegia in patients undergoing thoracoabdominal aortic aneurysm repair, the importance of preoperative identification of the Adamkiewicz artery and reconstruction of critical intercostal artery have been advocated. Conversely, significance of collateral network for spinal cord perfusion has been recognized. We invented a new system consisting of a direct monitoring of cerebrospinal fluid temperature (CSFT) and differential selective hypothermic intercostal artery perfusion (D-HIAP). METHODS: After exposing a critical intercostal artery, a 10-mm prosthetic graft was anastomosed in an end to side fashion. A balloon-tipped catheter was inserted into the graft to perfuse with 15 °C blood. Neighboring intercostal arteries were also perfused in the same fashion. Serial monitoring of CSFT was performed. Between January 2011 and January 2015, D-HIAP was employed in 50 patients with Adamkiewicz artery that located within a reconstructed area. RESULTS: Significant CSFT drop was recorded after initiation of D-HIAP in 42 (84%) patients. Of those, 34 (68%) patients showed significantly lowered CSFT with D-HIAP into a single critical intercostal artery. Perfusion into plural intercostal arteries was necessary for CSFT drop in 2 cases (4%), and plural intercostal artery perfusion further enhanced CSFT drop that had been modestly achieved by single intercostal artery perfusion in 6 cases (12%). Eight (16%) patients did not exhibit a significant drop in CSFT even when D-HIAP was employed for the critical and neighboring intercostal arteries. CONCLUSIONS: The detection of a disparity in temperature between the intrathecal space and blood generated by D-HIAP revealed individual variability in CSFT changes, which may imply a complexity in spinal cord perfusion. Intraoperative D-HIAP may help to identify a major blood supply for spinal cord perfusion and underlying collateral network.

Morphometrical and biomechanical analyses of a stentless bioprosthetic valve: an implication to avoid potential primary tissue failure.

OBJECTIVES: Stentless bioprosthetic valves provide hemodynamic advantages over stented valves as well as excellent durability. However, some primary tissue failures in bioprostheses have been reported. This study was conducted to evaluate the morphometrical and biomechanical properties of the stentless Medtronic Freestyle™ aortic root bioprosthesis, to identify any arising problem areas, and to speculate on a potential solution. METHODS: The three-dimensional heterogeneity of the stentless bioprosthesis wall was investigated using computed tomography. The ascending aorta and the right, left, and non-coronary sinuses of Valsalva were resected and examined by an indentation test to evaluate their biomechanical properties. RESULTS: The non-coronary sinus of Valsalva was significantly thinner than the right sinus of Valsalva (p < 0.01). Young's modulus, calculated as an indicator of elasticity, was significantly greater at the non-coronary sinus of Valsalva (430.7 ± 374.2 kPa) than at either the left (190.6 ± 70.6 kPa, p < 0.01) or right sinuses of Valsalva (240.0 ± 56.5 kPa, p < 0.05). CONCLUSIONS: Based on the morphometrical and biomechanical analyses of the stentless bioprosthesis, we demonstrated that there are differences in wall thickness and elasticity between each sinus of Valsalva. These differences suggest that the non-coronary sinus of Valsalva is the most vulnerable and at greater risk of tissue failure. The exclusion of the non-coronary sinus of Valsalva may be beneficial to mitigate the long-term risks of tissue failure in the stentless bioprosthesis.

Predictors of Heparin Resistance Before Cardiovascular Operations in Adults.

BACKGROUND: Heparin resistance (HR) is often encountered during cardiovascular operations that require cardiopulmonary bypass. Clinical risk factors and the mechanism underlying heparin resistance are yet to be determined. The aim of this study was to elucidate the clinically valid preoperative predictors related to HR. METHODS: The study evaluated 489 patients undergoing cardiovascular operations. Of these, 25 patients presented with HR and received antithrombin III for the initiation of cardiopulmonary bypass with an effective activated coagulation time. The remaining 464 patients, who did not receive antithrombin III, served as controls (NHR). Preoperative patient demographic and laboratory data were analyzed to identify risk factors for HR. RESULTS: The preoperative laboratory data showed platelet count, fibrinogen, D-dimer, creatinine, and C-reactive protein were significantly higher in the HR group than in the NHR group. As expected, the antithrombin III level was significantly lower overall in the HR group (86.0% vs 95.5%, p = 0.009); however, 80% of the patients in the HR group showed normal antithrombin III levels preoperatively. Multivariable logistic regression analysis identified chronic aortic dissection, chronic obstructive pulmonary disease, smoking, and elevated fibrinogen levels as independent predictors for HR. CONCLUSIONS: HR was shown to be associated with preoperative high fibrinogen levels, a smoking habit, and a preoperative diagnosis of chronic, but not acute, aortic dissection, with chronic obstructive pulmonary disease as comorbidity. Administration of antithrombin III resolved HR in all of the affected patients, even when their preoperative antithrombin III level was within the normal limit.

Modification of a Standard Thoracoabdominal Incision to Preserve Collaterals to Adamkiewicz Artery.

We report a case of a 35-year-old male who underwent thoracoabdominal aortic repair of a chronic dissecting aortic aneurysm, Crawford extent II. Preoperative computed tomography showed thrombosis of almost all intercostal arteries. Precise diagnostic assessment demonstrated the Adamkiewicz artery originating from the left lateral thoracic artery and subscapular artery, which would have been at risk after using a standard Stoney's incision, thus potentially causing paraplegia or paraparesis due to spinal cord ischemia. We modified the lateral thoracic incision anteriorly and successfully preserved the collateral arteries without impairing the spinal cord function.

Long-term results after physiologic repair for congenitally corrected transposition of the great arteries.

OBJECTIVE: We aimed to evaluate the long-term results of physiologic repair for associated lesions of congenitally corrected transposition of great arteries (ccTGA) and to provide a basis for comparison with anatomic repair for this entity. SUBJECTS AND METHODS: Sixteen ccTGA patients who underwent physiologic repair from 1970 to 2000 comprise this retrospective study. Conventional Rastelli procedure was performed in 12 patients with pulmonary stenosis or atresia (PS/PA). Ventricular septal defect closure was carried out in 2 patients, atrial septal closure in 1, and tricuspid valvuloplasty in 1 without PS/PA. Mean follow-up period was 19.4 years. Long-term survival rates were assessed with respect to the presence or the absence of preoperative PS/PA and specifically in relation with the magnitude of pre- and postoperative tricuspid regurgitation (TR). RESULTS: There has been no long-term mortality in the ccTGA patients without PS/PA. Twenty-year survival rate after conventional Rastelli was 71 %. Overall 20-year freedom from more than mild TR or tricuspid valve replacement was 44 %. The development of postoperative more than mild TR was significantly linked with pre-repair right ventricular enlargement (p = 0.019), but not with the magnitude of pre-repair TR (p = 0.85). CONCLUSION: Long-term outcomes of physiologic repair for ccTGA were equivalent to those of reported anatomic repair performed in several centers during the same era. Notably, significant TR was observed in more than half of physiologically repaired patients over the 20 years after repair. The degree of pre-repair TR cannot predict the long-term function of tricuspid valve after physiologic repair.

[Issues in Coronary Artery Bypass Grafting for Kawasaki Disease].

Progressive narrowing at the entrance and exit of coronary artery aneurysm can develop at late phase of Kawasaki disease (KD). Evaluation and prediction of progressive coronary lesions remain a challenge in the treatment of post-KD coronary artery disease. We aimed to elucidate long-standing issues imposed on the patients who underwent coronary artry bypass grafting (CABG) for coronary artery lesions associated with KD. Between January, 2000 and December, 2013, CABG for coronary artery lesions associated with KD were performed in 6 patients (male/female: 5/1, mean age 14.5±10.0). There was no operative mortality. Follow-up for the 6 patients has been performed with the average period of 5 years (1~9 years). Cardiac events occurred in 2 patients during follow-up. In 1 patient, left internal thoracic artery (LITA) occluded due to flow competition between the native artery and LITA graft after LITA to LAD bypass grafting. The other patient required a re-do CABG using the free right internal thoracic artery to the circumflex branch because of occlusion at the coronary artery aneurysms after 4 years postoperatively. Meticulous preoperative diagnostic evaluations of coronary artery aneurysm may further improve the long-term outcome after surgical intervention for coronary lesions in conjunction with an aneurysm.

[Early Postoperative Outcomes and Evaluation of Hemodynamics after Mitral Valve Replacement with Epic Mitral Bioprosthesis].

BACKGROUND: In Guideline for Surgical and Interventional Treatment of Valvular Heart Disease, revised by Japanese Circulation Society in 2012, mitral valve replacement (MVR) with bioprosthesis is class II b recommendation for patients aged 70 years or older who have no risk factors for thromboembolism. The aim of this study was to evaluate the early postoperative surgical outcomes and the hemodynamic performance with the Epic mitral bioprosthesis. METHODS: Twenty-six consecutive patients underwent MVR with Epic mitral bioprostesis at Tohoku University Hospital between April 2011 and July 2014. Twenty-five cases of 26 were evaluated their hemodynamics at discharge, and of which 19 cases of 26 were evaluated at the outpatient clinic during follow-up period. RESULTS: There was 1 hospital death. Long-term mortality or reoperation for any valve abnormality was not observed in the median follow-up of 23.9 ± 11.3 months. Hemodynamic date at discharge obtained by transthoracic echocardiography included mean hemodynamics of mitral valve bioprosthesis as below. Effective orifice area (EOA):2.44 ± 0.62 cm², peak mitral pressure gradient (pMPG):15.8 ± 5.3 mmHg, mean mitral pressure gradient(mMPG):7.2 ± 2.4 mmHg. Hemodynamic parameters at follow-up were found to be stable as EOA:2.25 ± 0.64 cm², pMPG:17.3 ± 5.7 mmHg, mMPG:6.2 ± 2.3 mmHg, respectively. CONCLUSION: We have attempted to elucidate our preliminary postoperative outcomes and hemodynamics after MVR with Epic mitral bioprosthesis. These in vivo hemodynamic data can serves a clinical reference.

Remediation of coastal marine sediments using granulated coal ash.

It is very important to reduce phosphorus flux from sediment as well as cutting down terrigenous loads in order to control eutrophication in semi-enclosed coastal seas. Hydrogen sulfide is also a noxious substance which is highly toxic and fatal to benthic organisms. The purpose of this study is to evaluate remediation efficiency of organically enriched sediments using granulated coal ash (GCA) in terms of reducing benthic phosphorus flux and hydrogen sulfide. A flow-through experimental system was used to simulate the semi-enclosed water bodies. The application of GCA decreased the concentration of PO4(3-) in the pore water effectively, and reduced phosphate releasing flux from the sediment into overlying water by 37-44% compared to the control. The hydrogen sulfide in the pore water was also decreased by 77-100%, due to adsorption onto the GCA and deactivation of sulfate-reducing bacteria due to increasing pH. Thus, GCA is a promising recycled material for reducing phosphate releasing flux from organically enriched sediment to alleviate eutrophication as well as reduce the concentration of hydrogen sulfide in pore water.

Tagged cine magnetic resonance imaging with a finite element model can predict the severity of retrosternal adhesions prior to redo cardiac surgery.

OBJECTIVE: Reoperative median sternotomy entails a risk of damaging the heart or great vessels. If the severity of retrosternal adhesion is accurately assessed before sternal re-entry, resternotomy-related complications can be prevented. The purpose of this investigation was to evaluate whether the severity of retrosternal adhesions can be accurately predicted by tagged cine magnetic resonance imaging. METHODS: Thirteen patients who were scheduled to undergo cardiac reoperation were investigated by electrocardiography-gated tagged cine magnetic resonance imaging before sternal re-entry. With the imaging data, the severity of retrosternal adhesion was scored visually on the basis of abnormality in regional myocardial motion and discordance in the tagged signals of the sternum and the myocardium. Also, with the aid of a finite element model, strain at the surface of the right ventricle was calculated on the basis of displacement of the tags on the heart over the cardiac cycle. For comparison, the adhesion severity was scored visually at the time of redo surgery by surgeons who were blinded to the preoperative assessment. RESULTS: The preoperative adhesion severity score, as determined visually by tagged cine magnetic resonance imaging, was correlated with the intraoperative severity score (correlation coefficient: r = 0.76, P < .01). Mean strain at the surface of the heart, as calculated preoperatively by finite element model analysis, was inversely correlated with the intraoperative adhesion severity score (r = -0.78, P < .01). CONCLUSION: Tagged cine magnetic resonance imaging with a finite element model can provide an accurate quantitative assessment of retrosternal adhesions before redo cardiac surgery.

A counterpulsation technique for use during complicated aortic surgery with residual thoracoabdominal aortic aneurysm.

Mechanical circulatory support can be difficult for patients with thoracoabdominal aortic disease. We herein describe a counterpulsation technique using an intra-graft balloon pump that can be safely used in the setting of thoracoabdominal aortic aneurysm remaining immediately after aortic root and arch replacement coupled with coronary artery bypass grafting.