Thoracic endovascular aortic repair for acute aortic dissection complicated by mesenteric malperfusion: an evaluation by computational fluid dynamics.

Computational fluid dynamics was performed to simulate haemodynamics of type B aortic dissection complicated by mesenteric malperfusion caused by dynamic obstruction in a 70-year-old man. Streamline analysis showed disappearance of antegrade flow in the false lumen of the descending aorta and attenuation of intermittent flap-induced disruption of visceral vessel perfusion after entry coverage. Quantitative analysis showed endovascular repair increased perfusion volume of the coeliac artery and superior mesenteric artery by 55.6% and 77.4%, respectively. Entry closure with thoracic endovascular prosthesis improved mesenteric malperfusion by attenuating the intermittent flap-induced perfusion disruption.

The effect of balloon-expandable stent and self-expanding stent on changes in mitral annular motion after aortic valve replacement in patients with aortic stenosis.

OBJECTIVES: The purpose of this study was to evaluate the effect of decalcification and existence of stent at the aortic annulus on mitral annular motion after surgery. METHODS: Patients receiving Inspiris (Edwards, CA, USA, n = 117), Intuity (Edwards, n = 36), Perceval (Corcym, London, UK, n = 36), Evolut (Medtronics, MN, USA, n = 81) and Sapien 3 (Edwards, n = 250) were included in the study. Mitral annular motion was evaluated by E', using tissue doppler imaging. RESULTS: After surgery, a significant increase in E' was observed in patients receiving Inspiris (Before: 4.2 ± 1.21 cm/s vs. Discharge: 5.0 ± 1.23 cm/s, p < 0.001). Mid-term echocardiogram performed at 11.8 ± 2.2 months after the surgery, showed a significant increase in E' in patients receiving Inspiris (Before: 4.2 ± 1.21 cm/s vs. Mid-term: 5.2 ± 1.20 cm/s, p < 0.001) and Perceval (Before: 3.9 ± 1.34 cm/s vs. Mid-term: 4.5 ± 1.24 cm/s, p = 0.008). Univariable analysis showed a higher increase in E' in patients with decalcified annulus compared to those without decalcified annulus (Decalcification: 0.15 ± 1.321 cm/s vs. No Decalcification: 0.66 ± 1.420 cm/s, p < 0.001). Multivariable analysis showed that balloon-expandable stent (ß = - 0.6960, p < 0.001) and self-expanding stent (r = - 0.3592, p = 0.042) were independent limiting factors for an increase in E' at discharge. However, balloon-expandable stent (ß = - 0.8382, p < 0.001), and not self-expanding stent (ß = - 0.3682, p = 0.089), was a remaining independent factor associated with E' at mid-term follow-up. CONCLUSIONS: Decalcification was associated with improvement in E' after surgery. Balloon-expandable stent was an independent limiting factor for improvement in E' up to 1 year after the surgery, while self-expanding stent was not a significant factor after 1 year.

Left ventricular remodeling and long-term outcomes of aortic stenosis patients receiving 19 mm Mosaic.

Mosaic valve shows higher pressure gradient after aortic valve replacement compared to other same size labeled prostheses in postoperative echocardiogram. The purpose of this study was to evaluate the mid-term echocardiogram findings and long-term clinical outcomes of patients receiving a 19 mm Mosaic. Forty-six aortic stenosis patients receiving 19 mm Mosaic and 112 patients receiving either 19 mm Magna or Inspiris, who underwent mid-term follow-up echocardiogram were included in the study. Mid-term hemodynamic measurements evaluated by trans-thoracic echocardiogram and long-term outcomes were compared. Patients receiving Mosaic were significantly older (Mosaic: 76 ± 5.1 years vs. Magna/Inspiris: 74 ± 5.5 years, p = 0.046) and had smaller body surface area (Mosaic: 1.40 ± 0.114m2 vs. Magna/Inspiris: 1.48 ± 0.143m2, p < 0.001). There were no significant differences in comorbidities and medications. Post-operative echocardiogram performed at 1 week after the surgery showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 38 ± 13.5 mmHg vs. Magna/Inspiris: 31 ± 10.7 mmHg, p = 0.002). Furthermore, mid-term echocardiogram follow-up performed at median duration of 53 ± 14.9 months after the surgery continuously showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 45 ± 15.6 mmHg vs. Magna/Inspiris: 32 ± 13.0 mmHg, p < 0.001). However, there were no significant difference in changes in left ventricular mass from baseline in both groups. Kaplan-Meyer curve also showed no difference in long-term mortality and major adverse cardiac and cerebrovascular event between the two groups. Although the pressure gradient across the valve evaluated by echocardiogram was higher in 19 mm Mosaic compared to 19 mm Magna/Inspiris, there were no significant differences in left ventricular remodeling and long-term outcomes between the two groups.

[Non-A Non-B Aortic Dissection Complicated with Right Aortic Arch Treated by Extended Thoracic Aortic Repair].

A 44-year old man with a history of Stanford type B acute aortic dissection was admitted for the treatment of acute aortic dissection. Computed tomography( CT) scan showed a descending entry-type non-A non-B aortic dissection with a maximum diameter of 65 mm occurring in a patient with Edwards typeⅢ right aortic arch whose left subclavian artery was obliterated. The patient was initially treated conservatively and underwent one-stage extended aortic repair from the ascending aorta to the descending thoracic aorta via median sternotomy 22 days after the symptom onset. Although the patient suffered from right empyema postoperatively, he was discharged from the hospital on postoperative day 64 after 4 weeks antibiotics therapy. The patient was also complicated by right recurrent nerve palsy, hoarseness improved over the 8 months after surgery.

[Left Ventricular Rupture after Mitral Valve Replacement].

Ventricular rupture after mitral valve surgery is rare but a serious complication associated with high mortality rate. Of the 2,338 patients who underwent mitral valve surgery, 8 patients (0.7%) suffered from left ventricular rupture in our institution. All developed left ventricular rupture after mitral valve replacement and 3 patients( 37.5%) died within 30 days. To prevent left ventricular rupture, preservation of the mitral loop, appropriate valve sizing, and perioperative hemodynamic management to unload ventricular pressure are needed. Surgical repair for left ventricular rupture should be performed under cardiac arrest. Combination of external approach and endoventricular repair is recommended but epicardial tissue sealing may be an only option for patients with friable ventricular muscles and undetermined location of ruptured site. Use of intraaortic balloon pumping (IABP), percutaneous cardiopulmonary support (PCPS) and Impella are also important technique to unload left ventricular pressure and to maintain systemic hemodynamics.

The effect of stent and decalcification on mitral annular motion after aortic valve replacement.

OBJECTIVE: The purpose of this study was to evaluate the changes in mitral annular motion after surgery in patients with aortic stenosis. METHODS: Patients receiving Edwards (Edwards) valves were included in the study. Echocardiographic findings were compared among the three treatments postoperatively, at discharge, and at 1 year after the surgery. Mitral annular motion was evaluated by e prime, using tissue doppler imaging. RESULTS: There were 111 patients receiving Inspiris, 30 patients receiving Intuity and 241 patients receiving Sapien 3. The patients receiving Sapien 3 were significantly older, (Inspiris: 71 ± 6.7 years vs. Intuity: 75 ± 5.2 years vs. Sapien 3: 84 ± 5.1 years, p < .001), and prevalence of hemodialysis were significantly higher in patients receiving Intuity (Inspiris: 11.7% vs. Intuity: 46.7% vs. Sapien 3: 0.0%, p < .001). There was a significant improvement in mean pressure gradient in all groups (Inspiris: 55 ± 21.2-13 ± 5.2 mmHg, p < .001; Intuity: 48 ± 17.6-12 ± 4.9 mmHg, p < .001, Sapien 3: 55 ± 16.6-14 ± 5.2 mmHg, p < .001). Decalcification was associated with increase in e prime after surgery (no decalcification: 0.10 ± 1.280 cm/s vs. decalcification: 0.68 ± 1.405 cm/s, p < .001) Further, existence of stent was associated with less increase in e prime after surgery (no stent: 0.83 ± 1.210 cm/s vs. stent: 0.10 ± 1.356; p < .001). Multivariate analysis showed that existence of stent but not decalcification of the aortic valve was independently associated with changes in e prime after surgery (ß: -.4679, 95% confidence interval: -0.93389 to -0.00200, p = .049). CONCLUSIONS: Although improvement in pressure gradient was achieved in all treatments, existence of stent inhibited mitral annular motion after surgery.

An increased prothrombin time-international normalized ratio in patients with acute type A aortic dissection: contributing factors and their influence on outcomes.

PURPOSE: We investigated factors contributing to coagulopathy in patients with acute type A aortic dissection (ATAAD) and coagulopathy's influence on patient outcomes. METHODS: We grouped 420 patients who underwent ATAAD repair-none under anticoagulation therapy or with liver disease-by the prothrombin time-international normalized ratio (PT-INR) at admission: < 1.2 (no coagulopathy, n = 371), 1.2-1.49 (mild coagulopathy, n = 33), or ≥ 1.5 (severe coagulopathy, n = 16). We then compared the clinical presentation, dissection morphology, and outcomes among the groups. We assessed the PT-INR in relation to the preoperative hemodynamics and searched for factors predictive of a PT-INR ≥ 1.2. RESULTS: The transfusion volume and operation time were increased among patients with coagulopathy (P < 0.05). The in-hospital mortality (15.2-37.5% vs. 5.1%, P < 0.001) and 5-year survival (61.1-74.4% vs. 87.6%) were relatively poor for these patients. The median PT-INR was 1.03 (0.97-1.1) for patients with stable hemodynamics (n = 318), 1.11 (1.02-1.21) for those in shock (blood pressure < 80 mmHg) not given cardiopulmonary resuscitation (CPR) (n = 81), and 1.1 (1.0-1.54) for those in shock given CPR (n = 21) (P < 0.001). A multivariable analysis identified shock (P < 0.001), a partially thrombosed false lumen (P = 0.006), and mesenteric malperfusion (P = 0.016) as predictive variables. CONCLUSIONS: Shock, a partially thrombosed false lumen, and mesenteric malperfusion appear to be predictive of dissection-related coagulopathy, which influences outcomes negatively.

Evaluation of oversizing in association with conduction disorder after implantation of a rapid deployment valve.

Rapid deployment valve has expanded surgical indication for high-risk patients with aortic stenosis despite its accommodated risk for conduction disorder (CD). The purpose of this study was to evaluate the degree of oversizing in association with postoperative CD. During June 2019 to September 2021, 25 patients underwent aortic valve replacement with Edwards INTUITY. Device size selection was evaluated intraoperatively using provided sizers. Oversizing was evaluated retrospectively by measuring the difference of the dimension of the annulus and left ventricular outflow tract (LVOT) compared to the dimensions of the device used by preoperative-computed tomography. Although there was no incidence of pacemaker implantation, seven patients (28.0%) experienced CD after surgery. There was no difference in device area and annulus area (CD: - 37 ± 22.7 mm2 vs. no CD: - 56 ± 63.6 mm2, p = 0.47), and device circumference and annulus circumference (CD: - 4.4 ± 2.77 mm vs. no CD: - 6.9 ± 5.60 mm, p = 0.26) in patients with and without CD. However, there was a significant difference in area of the device skirt and sub-annular area at the LVOT (CD: 114 ± 28.4 mm2 vs. no CD: - 8 ± 80.0 mm2, p < 0.001), and circumference of device skirt and the LVOT (CD: 3.9 ± 2.08 mm vs. no CD: - 4.6 ± 5.24 mm, p < 0.001) between the two groups. Receiver operating characteristic curve analysis showed that an area difference of 77.7 mm2 and circumference difference of 0.91 mm at LVOT were associated with postoperative CD with specificities of 0.83, 0.78 and sensitivity of 1.0, 1.0, respectively. Preoperative measurement of the LVOT may be useful in evaluating the risk of postoperative CD in patients receiving rapid deployment valve.

The effect of aortic arch replacement on pulse wave velocity after surgery.

OBJECTIVES: The purpose of this study was to investigate the changes in pulse wave velocity (PWV) after aortic arch repair and to evaluate possible perioperative factors associated with an increase in PWV. METHODS: Eighty-nine patients with preoperative and postoperative PWV measurements who underwent surgical treatment for true aortic arch aneurysm were included in the study. The patients were treated by prosthetic graft replacement with or without the frozen elephant trunk technique or by hybrid surgery with a stent graft. Changes in PWV and perioperative factors were evaluated. RESULTS: Fifty-one patients were treated by prosthetic graft replacement; 22 patients were treated with the frozen elephant trunk procedure; and 16 patients were treated by hybrid surgery. A significant increase in PWV was observed in patients undergoing surgical treatment for aortic arch aneurysm regardless of the types of operations performed (all treatments: before, 1797 ± 397.8 cm/s vs after, 2061 ± 600.4 cm/s, P < 0.001; graft replacement: before, 1769 ± 398.1 cm/s vs after, 1895 ± 459.0 cm/s, P = 0.004; frozen elephant trunk procedure: before, 1911 ± 461.9 cm/s vs after 2307 ± 826.9 cm/s, P = 0.005; hybrid surgery: before, 1732 ± 273.3 cm/s vs after, 2254 ± 484.6 cm/s, P < 0.001). Differences in PWV were largest in patients treated with hybrid surgery and lowest in those treated with graft replacement (P = 0.002). In univariate analysis, an increase in PWV was positively correlated with treatment length (r = 0.41; P < 0.001); the use of a postoperative beta blocker was associated with a smaller increase in postoperative PWV (with: 165.0 ± 371.92 cm/s vs without: 439.4 ± 530.38 cm/s, P = 0.005). Multivariate analysis suggested that treatment length (coefficient 3.31, 95% confidence interval 0.056-6.562, P = 0.046) and postoperative beta blocker (coefficient -220.08, 95% confidence interval -401.972 to -38.183, P = 0.018) were factors independently associated with changes in PWV. CONCLUSIONS: There was a significant increase in PWV after aortic arch repair. Treatment length and use of postoperative beta blockers were factors associated with changes in postoperative PWV. Minimizing the treatment length and using postoperative beta blockers may attenuate the effects of prostheses on postoperative PWV.

Treatment Site Does Not Affect Changes in Pulse Wave Velocity but Treatment Length and Device Selection Are Associated With Increased Pulse Wave Velocity After Thoracic Endovascular Aortic Repair.

Background: Endovascular treatment of aortic aneurysm is associated with an increase in pulse wave velocity (PWV) after surgery. However, the effect of different types of endovascular devices on PWV at different sites of the thoracic aorta remains unclear. Objectives: The purposes of this study were (1) to investigate the changes in PWV after endovascular treatment of thoracic aortic aneurysm; (2) to evaluate whether there is a difference in the changes in PWV at different treatment sites; and (3) to evaluate the effect of treatment length on changes in PWV. Methods: From July 2008 to July 2021, 276 patients underwent endovascular treatment of the true thoracic aortic aneurysm. Of these patients, 183 patients who underwent preoperative and postoperative PWV measurement within 1 year of surgery were included in the study. The treatment length index was calculated by treatment length divided by the height of the patients. Results: Five different types of endovascular devices were used (Najuta, Kawasumi Laboratories, Inc., Tokyo, Japan; TAG, W.L. Gore & Associates, Inc., AZ, USA; Relay, Bolton Medical, Inc., FL, USA; Talent/Valiant, Medtronic, MN, USA; and Zenith, Cook Medical, IN, USA). There was no significant change in PWV in patients receiving Najuta (Before: 2,040 ± 346.8 cm/s vs. After: 2,084 ± 390.5 cm/s, p = 0.14). However, a significant increase was observed in other devices: TAG (Before: 2,090 ± 485.9 cm/s vs. After: 2,300 ± 512.1 cm/s, p = 0.025), Relay (Before: 2,102 ± 465.3 cm/s vs. After: 2,206 ± 444.4 cm/s, p = 0.004), Valiant (Before: 1,696 ± 330.2 cm/s vs. After: 2,186 ± 378.7 cm/s, p < 0.001), and Zenith (Before: 2,084 ± 431.7 cm/s vs. After: 2,321 ± 500.6 cm/s, p < 0.001). There was a significant increase in PWV in patients treated from aortic arch (Before: 2,006 ± 333.7 cm/s vs. After: 2,132 ± 423.7 cm/s, p < 0.001) and patients treated from descending thoracic aorta (Before: 2,116 ± 460.9 cm/s vs. After: 2,292 ± 460.9 cm/s, p < 0.001). Multivariate analysis showed that treatment site was not an independent factor associated with changes in PWV. However, Najuta (Coef -219.43, 95% CI -322.684 to -116.176, p < 0.001) and treatment index (Coef 147.57, 95% CI 24.826 to 270.312, p = 0.019) were independent factors associated with changes in PWV. Conclusion: Najuta did not show a significant increase in PWV, while other commercially available devices showed a significant increase. The treatment site did not have a different effect on PWV. However, the treatment length was an independent factor associated with an increase in PWV.

[Redo Aortic Valve Replacement].

With increasing number of patients undergoing aortic valve replacement, many patients are at risk for redo aortic valve surgery. It has been reported that 56.2% of the patients receiving a bioprostheis and 7.4% of the patients receiving a mechanical valve need reoperation 20 years after the primary surgery. Although valve in valve transcatheter aortic valve implantation (TAVI) is a less invasive approach, redo aortic valve replacement is preferred for patients with prosthetic valve endocarditis, small aortic valve prosthesis and poor access for TAVI. Special care should be prepared for safe re-sternotomy, cardiopulmonary bypass management and strategy for cardioplegia. As reported from high volume centers, redo aortic valve replacement could be performed at a similar mortality rate as the primary surgery. New prostheses such as sutureless valve and rapid deployment valve could be useful, as well as minimally invasive cardiac surgery approach, which may prevent tissue injury. However, redo aortic valve replacement via re-sternotomy remains a gold standard. Techniques and strategy for redo aortic valve replacement are reviewed.

[Rapid Growing Thoracic Aortic Aneurysm in a Patient with Relapsing Polychondritis].

A 26-year-old man with relapsing polychondritis was admitted for the treatment of multiple thoracic aortic aneurysms in the ascending and descending aorta. Descending thoracic aortic aneurysm showed rapid expansion, therefore, the patient underwent an extended thoracic aortic repair from the ascending aorta to the descending aorta via anterolateral thoracotomy and partial sternotomy. Although postoperative course was uneventful, aortic root enlargement and severe aortic insufficiency progressed over the next two years. He and his family refused redo surgical intervention and the patient died of heart failure. Careful perioperative follow-up may be mandatory in a patient with relapsing polychondritis complicated by cardiovascular disease.

Modified central extracorporeal membrane oxygenation for distended left ventricle.

A 38-year-old man who was resuscitated from ventricular fibrillation was diagnosed with acute aortic dissection complicated by coronary malperfusion. He underwent total aortic arch replacement and coronary artery bypass grafting to the left anterior descending coronary artery. Due to low cardiac output syndrome from cardiac ischemia, central extracorporeal membrane oxygenator (ECMO) was established with aortic cannulation from the side branch of the implanted prosthetic graft and venous drainage from the femoral vein. Ventricular venting was added from the right upper pulmonary vein for the distended left ventricle. ECMO was weaned off on postoperative Day 4. The patient is back on his normal daily life for more than 1 year after the surgery.

Relationship between endothelial function and vascular stiffness on lower limit of cerebral autoregulation in patients undergoing cardiovascular surgery.

Hemodynamic management based on cerebral autoregulation range is a possible strategy for preserving major organ perfusion during cardiovascular surgery. The purpose of this study was to evaluate the relation of vascular properties with lower limit of cerebral autoregulation (LLA). LLA was monitored in 66 patients undergoing cardiovascular surgery using near-infrared spectroscopy. To determine the clinical importance of LLA monitoring, association of blood pressure excursions below LLA and acute kidney injury (AKI) was evaluated. Flow-mediated dilation (FMD) and pulse wave velocity (PWV) were measured for the evaluation of endothelial function and aortic stiffness. Variables associated with LLA were evaluated. Excluding patients on hemodialysis, there were 15 patients (25.9%) who developed AKI. Blood pressure excursions below LLA were higher in patients who developed AKI (4.55 mm Hg × hr vs. 1.23 mm Hg × hr, P = .017). In the univariate analysis, prevalence of ischemic heart disease (No IHD: 53 ± 13.0 mm Hg vs. IHD: 60.0 ± 13.6 mm Hg, P = .056) and FMD (r = -0.42, 95% CI -0.61 to -0.19, P < .001) were associated with LLA before cardiopulmonary bypass (CPB). During CPB, calcium channel blocker (No Ca blocker: 42 ± 10.6 mm Hg vs. Ca blocker: 49 ± 14.3 mm Hg, P = .033), diabetes (no DM: 44 ± 13.2 mm Hg vs. DM: 55 ± 10.0 mm Hg, P = .024), FMD (r = -0.32, 95% CI -0.55 to -0.05, P = .021), and PWV (r = 0.28, 95% CI 0.012 to 0.513, P = .041) were associated with LLA. Multivariate analysis showed that FMD was correlated with LLA before CPB (r = -2.19, 95% CI -3.621 to -0.755, P = .003), while PWV was correlated with LLA during CPB (r = 0.01, 95% CI 0.001-0.019, P = .023). Endothelial function and aortic stiffness may be important factors in determining LLA at different phases in cardiovascular surgery.

Personalized Blood Pressure Management During Cardiac Surgery With Cerebral Autoregulation Monitoring: A Randomized Trial.

The purpose of this study was to determine if setting mean arterial pressure (MAP) targets during cardiopulmonary bypass (CPB) based on individualized cerebral autoregulation data reduces the frequency of neurological complications compared with usual care. Patients (n = 460) ≥ 55 years old at risk for neurological complications were randomized to have MAP targets during CPB to be above the lower limit of transcranial Doppler determined cerebral autoregulation versus usual institutional practices. The primary outcome was the frequency of the composite endpoint of clinical stroke, or new brain magnetic resonance imaging-detected ischemic injury, or cognitive decline 4-6 weeks after surgery from baseline. Secondary outcomes were components of the primary composite outcome and clinically detected delirium. Complete outcome data were available from 194 patients (stroke assessments, n = 460; magnetic resonance imaging data, n = 164; cognitive data n = 336). There was no difference between groups in the frequency of the composite neurological end-point or its components (P = 0.752). Compared with the usual care there was a 45% reduction in the frequency of clinically detected delirium in the autoregulation group (8.2% vs 14.9%, risk ratio = 0.55, 95% confidence interval = 0.32, 0.93, P = 0.035) and improved performance on test of memory 4-6 weeks after surgery from baseline (P = 0.019). Basing MAP during CPB on cerebral autoregulation monitoring did not reduce the frequency of the primary neurological outcome in high-risk patients compared with usual care but it was associated with a reduction in the frequency of delirium and better performance on tests of memory 4-6 weeks after surgery.

Dissected thoracoabdominal aortic aneurysm repair with modified parallel endografting.

A 67-year-old woman with a prior history of aortic dissection was admitted for enlarging the thoracoabdominal aortic aneurysm (TAAA). She has received multiple treatments including Bentall procedure, hemiarch replacement, and subsequent endovascular procedures for the closure of re-entry. Preoperative computed tomography revealed previously implanted thoracic endograft from distal arch to superior mesenteric artery with dissected TAAA measuring up to 70 mm in diameter. Re-entry was observed at bilateral common iliac arteries. The patient was successfully treated by endovascular treatment using a fenestrated stent graft to obtain a landing zone for parallel endograft technique to the iliac arteries for the closure of re-entry.

Early superior mesenteric artery revascularization for acute type A aortic dissection with cardiac tamponade and mesenteric malperfusion.

We report herein the successful treatment of a case of acute type A aortic dissection complicated by cardiac tamponade and mesenteric malperfusion. The patient was a 60-year-old man with back and abdominal pain and in shock, who was transported to our hospital 2 h after symptom onset. Computed tomography revealed DeBakey type I dissection with massive hemopericardium and obstruction of both the celiac artery and superior mesenteric artery. After emergency pericardiotomy and removal of the hematoma, superior mesenteric artery-external iliac artery bypass was constructed with a vein graft, and this restored mesenteric perfusion. Open distal hemiarch replacement was then performed. The postoperative course was uneventful. Superior mesenteric artery revascularization achieved immediately after release of the cardiac tamponade prevented further mesenteric ischemia and paved the way for the aortic repair.

Endothelial-Specific Overexpression of Histone Deacetylase 2 Protects Mice against Endothelial Dysfunction and Atherosclerosis.

BACKGROUND/AIMS: We recently described a novel regulatory role for histone deacetylase 2 (HDAC2) in protecting endothelial cells from oxidized low-density lipoprotein (OxLDL)-induced injury. In this study, we examined the effects of endothelial-specific HDAC2 overexpression on endothelial-dependent vasorelaxation and atherogenesis in vivo. METHODS: Endothelial-specific HDAC2-overexpressing transgenic mice (HDAC2-Tg) were generated under control of the Tie2 promoter. An atherosclerosis model was produced by injecting HDAC2-Tg and wild-type (WT) mice with adeno-associated virus encoding a PCSK9 gain-of-function mutant under control of a liver-specific promoter and feeding them a high-fat diet for 12 weeks. Aortic stiffness in vivo was determined by measuring pulse wave velocity. Wire myography was used to measure endothelium dependent (acetylcholine) and independent (sodium nitroprusside) relaxation in isolated mice aortas. Atherosclerotic plaque burden in aortas was determined by Oil Red O staining and protein expression was determined by western blotting. RESULTS: At baseline, HDAC2-Tg mice had normal mean arterial blood pressure (MAP) and body weight, but pulse wave velocity (PWV), an inverse measure of vascular health and stiffness, was decreased, suggesting that their vessels were more compliant. Moreover, basal nitric oxide production was enhanced in the vessels of HDAC2-Tg mice as compared to that in WT controls, although no significant differences in acetylcholine (endothelial component)- or sodium nitroprusside (non-endothelial component)-mediated relaxation were observed. However, after exposure to OxLDL, aortas from HDAC2-Tg mice exhibited greater acetylcholine-induced relaxation than did those from WT mice. Thus, endothelial-specific vasodilator production was enhanced despite oxidative injury. Atherosclerosis induction in WT mice led to a significant increase in PWV, but in HDAC2-Tg mice, PWV and MAP remained unchanged. Further, aortic rings from HDAC2-Tg exhibited better endothelial-dependent vascular relaxation than did those from WT mice, but not when treated with nitric oxide synthase inhibitor L-NAME. Finally, plaque burden, determined by Oil red O staining, was significantly increased in WT, but not HDAC2-Tg mice, subjected to the atherogenic model. Deletion of endothelial HDAC2 led to impaired endothelial cell-dependent vascular relaxation and increased PWV, compared with those in littermate controls. CONCLUSION: HDAC2 protects against endothelial dysfunction and atherogenesis induced by oxidized lipids. Hence, overexpression or activation of HDAC2 represents a novel therapy for endothelial dysfunction and atherosclerosis. HDAC2-Tg mice provide an opportunity to determine the role of endothelial HDAC2 in vascular endothelial homeostasis.

[Bioprosthetic Mitral Valve Thrombosis in Patient with Antiphospholipid Antibody Syndrome;Report of a Case].

A 66-year-old woman with primary antiphospholipid antibody syndrome (APS) was admitted due to severe dyspnea. Eight months prior to admission, she underwent bioprosthetic mitral valve replacement for mitral valve stenosis and regurgitation. Transthoracic echocardiogram showed thickening bioprosthetic valve leaflets and severe valve stenosis. Emergency reoperation for artificial valve failure was performed. The explanted bioprosthetic valve showed massive thrombus formation. After the operation, she started strict anticoagulant and antiplatelet therapies and was discharged without recurrence of valve thrombosis.

Effect of Transcatheter Aortic Valve Implantation on the Immune Response Associated With Surgical Aortic Valve Replacement.

The immune response after transcatheter aortic valve implantation (TAVI) in comparison to that after surgical aortic valve replacement (SAVR) remains to be fully elucidated. In a 2-part study, we assessed laboratory data obtained before, immediately after, and 24 and 48 hours after SAVR (128 patients; age ≥80 [mean 82] years) or transfemoral TAVI (102 patients; age ≥80 [mean 86] years) performed for aortic stenosis. In-hospital mortalities were similar (3% vs 0%), but leukocyte counts and aspartate aminotransferase and creatine kinas concentrations were decreased immediately and 24 hours after surgery (all, p <0.001). We performed cytokine profiling in a SAVR group (11 patients; mean age, 77 years) and transfemoral TAVI group (12 patients; mean age, 84 years). By measuring normalized concentrations of 71 cytokines at 3 time points, we found a significant difference (defined as fold change >1.7 and p <0.05 [by Mann-Whitney U-test]) in 23 cytokines. The differentially expressed cytokines fell into 3 hierarchical clusters: cluster A (high increase after SAVR and suppressed increase after TAVI only immediately after surgery [CCL2, CCL4, and 2 others]), cluster B (high increase after SAVR and suppressed increase after TAVI at 2 time points [IL-1Ra, IL-6, IL-8, IL-10, and 5 others]), and cluster C (various patterns [TRAIL, CCL11, and 8 others]). Gene enrichment analysis identified multiple pathways associated with the inflammatory responses in SAVR and altered responses in TAVI, including cellular responses to tumor necrosis factor (p = 0.0035) and interleukin-1 (p = 0.0062). In conclusion, a robust inflammatory response follows SAVR, and a comparatively attenuated response follows TAVI.