Alternative therapeutic strategy for existing aortic aneurysms using mesenchymal stem cell-derived exosomes.

BACKGROUND: Several studies demonstrated the therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-exs) based on their anti-inflammatory properties. The objective was to determine the therapeutic effects of MSC-exs on aortic aneurysms (AAs) caused by atherosclerosis. RESEARCH DESIGN AND METHODS: Apolipoprotein E knockout mice with AAs induced by angiotensin II were injected with MSC-exs or saline as a control. The change in the diameter of the aorta was measured. The expression of AA-related proteins and the histology of the aortic wall were investigated at 1 week after treatment. MicroRNA and protein profiles of MSC-exs were examined. RESULTS: MSC-exs significantly attenuated AA progression (2.04 ± 0.20 mm in the saline group and 1.34 ± 0.13 mm in the MSC-ex group, P = 0.004). In the MSC-ex group, the expression of IL-1ß, TNF-α and MCP-1 decreased, and expression of IGF-1 and TIMP-2 increased. MSC-ex induced the M2 phenotype in macrophages and suppressed the destruction of the elastic lamellae in the aortic wall. MSC-exs contained high levels of 10 microRNAs that inhibit AA formation and 13 proteins that inhibit inflammation and promote extracellular matrix synthesis. CONCLUSIONS: MSC-ex might be a novel alternative therapeutic tool for treatment of existing AAs.

Comparison of Impella 5.0 and extracorporeal left ventricular assist device in patients with cardiogenic shock.

INTRODUCTION: Choice of mechanical circulatory support to stabilize hemodynamics until cardiac recovery or next treatment is a strategic cornerstone for improving outcomes in patients with severe cardiogenic shock. We aimed to clarify the difference in treatment course and outcomes with the use of Impella 5.0 and an extracorporeal left ventricular assist device (eLVAD) in patients with cardiogenic shock refractory to medical therapy or other mechanical circulatory support. METHODS: We performed a retrospective medical record review of consecutive patients who were implanted with Impella 5.0 or eLVAD as a bridge to decision at our medical center. RESULTS: A total of 26 patients (median age 40 years, 16 males) were analyzed. Of seven patients managed with Impella 5.0, the Impella 5.0 was removed successfully in two patients and five patients underwent surgery for durable LVAD implantation. Of 19 patients managed with eLVAD, the eLVAD was successfully removed in 3 patients, 9 patients required durable LVAD, and 7 patients died during eLVAD management. The period between Impella 5.0 or eLVAD implantation to durable LVAD surgery was significantly shorter with Impella 5.0 (58 vs 235 days, p = 0.001). Cardiopulmonary bypass time was significantly shorter and a significantly smaller amount of red blood cell transfusion was required with Impella 5.0 (149 vs 192 min, p = 0.042; 7.0 vs 15.0 units, p = 0.019). There were four massive stroke events with eLVAD, but no massive stroke event with Impella 5.0. CONCLUSION: Impella 5.0 facilitates smoother management as a bridge to decision and reduces surgical invasiveness during durable LVAD implantation.

Long term efficacy and fate of a right ventricular outflow tract replacement using an elastomeric cardiac patch consisting of caprolactone and D,L-lactide copolymers.

For decades, researchers have investigated the ideal material for clinical use in the cardiovascular field. Several substitute materials are used clinically, but each has drawbacks. Recently we developed biodegradable and elastic poly(ε-caprolactone-co-D,L-lactide) (P(CL-DLLA)) copolymers by adjusting the CL/DLLA composition, and evaluated the long-term efficacy and outcomes of these copolymers when used for right ventricular outflow tract (RVOT) replacement. This P(CL-DLLA) material was processed into a circular patch and used to replace a surgical defect in the RVOT of adult rats. Control rats were implanted with expanded polytetrafluoroethylene (ePTFE). Histologic evaluation was performed at 8, 24, and 48 weeks post-surgery. All animals survived the surgery with no aneurysm formation or thrombus. In all periods, ePTFE demonstrated fibrous tissue. In contrast, at 8 weeks P(CL-DLLA) showed infiltration of macrophages and fibroblast-like cells into the remaining material. At 24 weeks, P(CL-DLLA) was absorbed completely, and muscle-like tissue was present with positive staining for α-sarcomeric actinin and cardiac troponin T (cTnT). At 48 weeks, the cTnT-positive area had increased. The biodegradable and elastic P(CL-DLLA) induced cardiac regeneration throughout the 48-week study period. Future application of this material as a cardiovascular scaffold seems promising. STATEMENT OF SIGNIFICANCE: Biomaterials for reconstruction of tissue deficiencies in cardiovascular surgery require having suitable mechanical properties for cardiac tissue and biodegradation resulting in native tissue growth. Several biodegradable polymers such as poly-ε-caprolactone (PCL) and polylactic acid (PLA) have excellent biocompatibility and already been widely used clinically. In general, PCL and PLA are quite mechanically rigid. Meanwhile, significant elasticity is required in the high-pressure environment of the heart while the material is being replaced by new tissue. The present study provides a novel four-armed crosslinked poly(ε-caprolactone-co-D,L-lactide) (i.e., P(CL-DLLA)) material for cardiac patch, which was demonstrated properties including tissue-compatible, super-elastic nature, that made it suitable for long-term, in vivo RVOT repair. This super-elastic biomaterial could be useful for reconstruction of various muscular tissues deficiencies.

Hypofibrinogenemia can be estimated by the predictive formula in aortic surgery.

OBJECTIVE: Aortic surgery often causes massive bleeding due to hypofibrinogenemia. Predicting hypofibrinogenemia is useful for developing a hemostasis strategy, including preparing for blood transfusion. We made a formula for predicting the serum fibrinogen level (SFL) at the termination of cardiopulmonary bypass (CPB) in aortic surgery and examined its validity. METHODS: We performed a retrospective observational study that consisted of 267 patients (group A) who underwent aortic surgery from July 2013 to December 2016 and made a formula for predicting the SFL at the termination of CPB in group A by a multiple linear regression analysis. The validity of this formula was then examined in another 60 patients (group B) who underwent aortic surgery from January 2017 to December 2017. RESULTS: We developed the following predictive formula: SFL at the termination of CPB (mg/dL) = 14.7 + 0.44 × preoperative SFL (mg/dL) + (- 0.14) × CPB time (min) + 0.64 × preoperative body weight (kg) + (- 17.3) × lateral thoracotomy (Yes/No, Yes: 1, No: 0). In group B, the predictive formula proved to be statistically valid in group B (R2 = 0.531, p < 0.001). CONCLUSION: The SFL at the termination of CPB in aortic surgery can be predicted by the preoperative SFL, body weight, CPB time and surgical approach. The predictive formula is useful for developing a hemostasis strategy, including preparing for blood transfusion.

Associations between hemodynamic parameters at rest and exercise capacity in patients with implantable left ventricular assist devices.

BACKGROUND: Hemodynamic parameters at rest are known to correlate poorly with peak oxygen uptake (VO2) in heart failure. However, we hypothesized that hemodynamic parameters at rest could predict exercise capacity in patients with left ventricular assist device (LVAD), because LVAD pump rotational speed does not respond during exercise. Therefore, we investigated the relationships between hemodynamic parameters at rest (measured with right heart catheterization) and exercise capacity (measured with cardiopulmonary exercise testing) in patients with implantable LVAD. METHODS: We performed a retrospective medical record review of patients who received implantable LVAD at our institution from November 2013 to December 2017. RESULTS: A total of 20 patients were enrolled in this study (15 males; mean age, 45.8 years; median duration of LVAD support, 356 days). The mean peak VO2 and cardiac index (CI) were 13.5 mL/kg/min and 2.6 L/min/m2, respectively. CI and hemoglobin level were significantly associated with peak VO2 (CI: r = 0.632, p = 0.003; hemoglobin: r = 0.520, p = 0.019). In addition, pulmonary capillary wedge pressure, right atrial pressure, and right ventricular stroke work index were also significantly associated with peak VO2. In multiple linear regression analysis, CI and hemoglobin level remained independent predictors of peak VO2 (CI: ß = 0.559, p = 0.006; hemoglobin: ß = 0.414, p = 0.049). CONCLUSIONS: CI at rest and hemoglobin level are associated with poor exercise capacity in patients with LVAD.

Association between splenic volume and pulsatility index in patients with left ventricular assist devices.

The spleen serves as a blood volume reservoir for systemic volume regulation in heart failure (HF) patients. Changes are seen in spleen size in advanced HF patients after left ventricular assist device (LVAD) implantation. The pulsatility index (PI) is an indicator of native heart contractility with hemodynamic changes in patients using LVAD. We hypothesized that the splenic volume was associated with the PI, reflecting the hemodynamics in advanced HF patients with LVADs. Herein, we investigated the relationship between splenic volume and PI in these patients. Forty-four patients with advanced HF underwent implantation of HeartMate II® (Abbott, Chicago, IL, USA) as a bridge to heart transplantation at the Nagoya University Hospital between October 2013 and June 2019. The data of 27 patients (21 men, median age 46 years) were analyzed retrospectively. All patients underwent blood tests, echocardiography, right heart catheterization, and computed tomography (CT). Spleen size was measured via CT volumetry; the splenic volume (median: 190 mL) correlated with right arterial pressure (r = 0.431, p = 0.025) and pulmonary capillary wedge pressure (r = 0.384, p = 0.048). On multivariate linear regression analysis, the heart rate (ß = -0.452, p = 0.003), pump power (ß = -0.325, p = 0.023), and splenic volume (ß = 0.299, p = 0.038) were independent determinants of PI. The splenic volume was associated with PI, reflecting the cardiac preload in advanced HF patients with LVADs. Thus, spleen measurement using CT may help estimate the systemic volume status and understand the hemodynamic conditions in LVAD patients.

Surgery for Anomalous Papillary Muscle Directly Into the Anterior Mitral Leaflet.

BACKGROUND: The anomalous insertion of papillary muscle directly into the anterior mitral leaflet is a rare congenital anomaly concomitant with hypertrophic cardiomyopathy. We herein report our surgical technique, which is designed to relieve left ventricular obstruction and preserve the mitral valve and subvalvular apparatus. METHODS: Among 38 patients who underwent septal myectomy from 2007 to 2020, 4 had an anomalous mitral subvalvular apparatus with papillary muscle with direct insertion into the anterior mitral leaflets. In all cases, mitral valve repair was accomplished with excision and reconstruction of all anomalous papillary muscles, concomitant with septal myectomy. In another 34 patients, 20 cases needed mitral valve repair with regard to systolic anterior motion by hypertrophic cardiomyopathy. The comparison study was conducted between the anomalous papillary muscle group (group A) and the others (group B). RESULTS: There was no early or late death in group A, and there were 3 early deaths and 2 late deaths in group B. The mean peak gradient in the left ventricle was significantly decreased in both groups. Mitral valve regurgitation grade was also significantly decreased from 3 to 0.5 without valve replacement in group A, and from 2 to 0.6 in group B. Six patients needed mitral valve replacement because of the thickness of anterior mitral leaflet in group B. CONCLUSIONS: Hypertrophic obstructive cardiomyopathy associated with the anomalous insertion of papillary muscle can be successfully treated without mitral valve replacement. Excision and reconstruction with the anomalous papillary muscle seems to be a feasible operation to reduce mitral regurgitation and relieve outflow tract obstruction.

Sutures on the Anterior Mitral Leaflet to Prevent Systolic Anterior Motion.

Mitral valve systolic anterior motion and associated regurgitation remain a challenging problem in mitral valve plasty. A simple procedure to correct intraoperative systolic anterior motion using sutures applied between the tip of the anterior leaflet and the posterior annulus is presented. This technique reduces the movement of the anterior leaflet toward the septum while maintaining sufficient valve orifice area.

Predictors of residual mitral regurgitation after left ventricular assist device implantation.

Patients with advanced heart failure often have functional mitral regurgitation. Left ventricular assist device implantation improves functional mitral regurgitation through left ventricular unloading. However, residual mitral regurgitation after left ventricular assist device implantation leads to adverse outcomes, and whether patients need concomitant mitral valve surgery is not fully elucidated. Therefore, this study aimed to elucidate the predictors of residual mitral regurgitation and to describe the temporal changes in residual mitral regurgitation. We retrospectively enrolled 15 patients with implantable continuous-flow left ventricular assist device, who had significant mitral regurgitation on echocardiography before left ventricular assist device implantation. Three patients had residual mitral regurgitation (mitral regurgitation color jet area/left atrial area >0.2) 1 month after left ventricular assist device implantation. We investigated factors associated with residual mitral regurgitation and compared patients with or without residual mitral regurgitation. On univariate analysis, mitral valve tethering area and mitral regurgitation vena contracta before left ventricular assist device implantation were significantly associated with residual mitral regurgitation (odds ratio, 1.03; p = 0.036 and odds ratio, 10.45; p = 0.0087). One month after left ventricular assist device implantation, the mean pulmonary capillary wedge pressure and pulmonary artery pressure were higher in patients with residual mitral regurgitation (pulmonary capillary wedge pressure: 11.3 ± 3.5 vs 6.4 ± 3.4 mmHg, p = 0.029 and pulmonary artery pressure: 21.3 ± 4.0 vs 15.9 ± 3.3 mmHg, p = 0.023). However, the mitral regurgitation grading and hemodynamics were not significantly different 6 months after left ventricular assist device implantation. The hospitalization-free survival was not significantly different between the two groups. Mitral valve tethering area and mitral regurgitation vena contracta were predictors of residual mitral regurgitation. Residual mitral regurgitation improved until 6 months after left ventricular assist device implantation and might not affect the prognosis.

Impella 5.0 for Cardiogenic Shock After Thrombectomy in a Patient With Intraventricular Thrombosis.

A 43-year-old man was admitted to a referring hospital for cardiogenic shock caused by dilated cardiomyopathy. Intra-aortic balloon pump and percutaneous venoarterial extracorporeal membrane oxygenation (VA-ECMO) were started initially; however, a thrombus was detected in the left ventricle. After transfer to our institution, we performed thrombectomy through minithoracotomy. Subsequently, an Impella 5.0 device was inserted via the left subclavian artery. His cardiac function gradually improved, and both VA-ECMO and the Impella 5.0 could be weaned off. He was discharged without any thromboembolic event. Impella insertion with thrombectomy was possible, minimally invasive, and effective for a patient with intraventricular thrombosis associated with VA-ECMO.

Aortic insufficiency associated with Impella that required surgical intervention upon implantation of the durable left ventricular assist device.

The Impella is an axial-flow percutaneous ventricular assist device for cardiogenic shock. In this report, we describe two patients who developed aortic insufficiency (AI) associated with Impella and required surgical intervention upon implantation of the durable left ventricular assist device (LVAD). Both patients presented with cardiogenic shock and underwent insertion of Impella 5.0 as a bridge to decision. The cardiac function in these patients did not improve and obtaining approval for heart transplantation required time. They were managed with Impella for 91 and 98 days, respectively. In both cases, moderate AI that was not present before Impella insertion was observed when the Impella was removed. Therefore, we performed aortic valve closure to control the AI during durable LVAD implantation. In patients with durable LVAD implantation, AI may occur and progress after the operation in several cases. Aortic valve surgery is often performed to prevent deterioration of AI, especially in patients with AI before the surgery. Hence, AI is an important complication following Impella device implantation as a bridge to decision. Careful observation of AI is essential when the Impella is removed as the evaluation of AI by echocardiogram during Impella management is cumbersome because of device-generated artifacts.

Pathological changes of the myocardium in reworsening of anthracycline-induced cardiomyopathy after explant of a left ventricular assist device.

We herein report the long-term changes in cardiac function and pathological findings after successful explantation of a left ventricular assist device in a 42-year-old patient with anthracycline-induced cardiomyopathy with reworsening heart failure. Endomyocardial biopsy samples revealed that the cardiomyocyte diameter decreased and collagen volume fraction increased just after left ventricular assist device explantation. The collagen volume fraction decreased after 6 months, despite preserved systolic function. At 5 years after left ventricular assist device explantation, the systolic function markedly decreased and cardiomyocyte diameter increased. Pathological changes of the myocardium may enable the identification of cardiac dysfunction prior to echocardiographic changes in patients with reworsening heart failure after left ventricular assist device explantation.

The incidence and risk factors of hypofibrinogenemia in cardiovascular surgery.

OBJECTIVE: Cardiovascular surgery often causes massive bleeding due to coagulopathy, with hypofibrinogenemia being a major causative factor. We assessed the intraoperative incidence of hypofibrinogenemia and explored predictors of hypofibrinogenemia. METHODS: The intraoperative serum fibrinogen level (SFL) was routinely measured in 872 consecutive patients [mean age: 66.9 ± 13.3 years; 598 men (68.6%)] undergoing cardiovascular surgery from July 2013 to November 2016 at Nagoya University Hospital. There were 275 aortic surgeries, 200 cases of coronary artery bypass grafting (CABG), 334 valvular surgeries and 63 other surgeries. We estimated hypofibrinogenemia incidence (intraoperative lowest SFL ≤ 150 mg/dL) and identified its predictors by a logistic regression analysis. RESULTS: The average intraoperative lowest SFL of all cases, aortic surgery, CABG and valvular surgery was 185 ± 71, 156 ± 65, 198 ± 69 and 198 ± 68 mg/dL, respectively. Aortic surgery had a significantly lower intraoperative lowest SFL than CABG (p < 0.001) and valvular surgery (p < 0.001). The incidence of hypofibrinogenemia was 32.8%, 50.2%, 26.5% and 22.8% in all cases, aortic surgery, CABG and valvular surgery, respectively. The predictors of hypofibrinogenemia were the preoperative SFL, re-do surgery and perfusion time. A receiver operating characteristics curve analysis showed that the best preoperative SFL cutoff value for predicting hypofibrinogenemia was 308.5 mg/dL. Assuming preoperative SFL 300 mg/dL as the cutoff, the odds ratio for hypofibrinogenemia was 7.22 (95% confidence interval 5.26-9.92, p < 0.001). CONCLUSIONS: The incidence of hypofibrinogenemia in aortic surgery was high. The preoperative SFL, re-do surgery and perfusion time were identified as predictors for hypofibrinogenemia. Intraoperative measurement of SFL is important for detecting hypofibrinogenemia and applying appropriate and prompt transfusion treatment.

Spinal cord injury following aortic arch replacement.

PURPOSE: Postoperative spinal cord injury is a devastating complication after aortic arch replacement. The purpose of this study was to determine the predictors of this complication. METHODS: A group of 254 consecutive patients undergoing aortic arch replacement via median sternotomy, with (n = 78) or without (n = 176) extended replacement of the upper descending aorta, were included in a risk analysis. The frozen elephant trunk technique was used in 46 patients. The patients' atherothrombotic lesions (extensive intimal thickening of > 4 mm) were identified from computed tomography images. RESULTS: Complete paraplegia (n = 7) and incomplete paraparesis (n = 4) occurred immediately after the operation (permanent spinal cord injury rate, 1.97%; transient spinal cord injury rate, 2.36%). A multivariable logistic regression analysis identified the use of the frozen elephant trunk technique (odds ratio 36.3), previous repair of thoracoabdominal aorta or descending aorta (odds ratio 29.4), proximal atherothrombotic aorta (odds ratio 9.6), chronic obstructive lung disease (odds ratio 7.1) and old age (odds ratio 1.1) as predictors of spinal cord injury (p < 0.0001, area under curve 0.93). CONCLUSIONS: Spinal cord injury occurs with a non-negligible incidence following aortic arch replacement. The full objective assessment of the morphology of the whole aorta and the recognition of the risk factors are mandatory.

Neurologic Deficit After Aortic Arch Replacement: The Influence of the Aortic Atherosclerosis.

BACKGROUND: Postoperative neurologic deficits are associated with severe morbidity in aortic arch replacement. METHODS: A group of 198 consecutive patients undergoing isolated total aortic arch replacement with the use of antegrade cerebral perfusion were analyzed for the risk factors for predicting neurologic deficit. With the use of computed tomography, atherothrombotic lesions (defined as extensive intimal thickening exceeding 4 mm) were identified in the proximal aorta (the ascending aorta or aortic arch) in 26.2% of cases and in the distal aorta in 34.9% of cases. RESULTS: Permanent neurologic deficits occurred in 11.1% (including non-disabling stroke confirmed by imaging) and transient neurologic deficits in 8.1% of patients. A univariate analysis identified proximal atherothrombotic aorta (p = 0.0057), distal atherothrombotic aorta (p = 0.032), and retrograde systemic perfusion from the femoral artery in the presence of distal atherothrombotic aorta (p = 0.0022) as risk factors for neurologic deficits. A multivariate logistic regression analysis identified atherothrombotic proximal aorta (odds ratio 2.4, p = 0.033) as the independent risk factor. The presence of carotid stenosis did not affect the rate of neurologic deficit. Intracranial hemorrhagic lesions were found in 23% of permanent neurologic deficit cases. CONCLUSIONS: Atherothrombotic lesions found by objectively graded computed tomography were predictors of neurologic deficit. Retrograde perfusion in the presence of a distal atherothrombotic lesion should be avoided whenever possible. Strategies based on the full assessment of the whole aortic morphologic characteristics appear to be mandatory. Anticoagulation therapy should be performed carefully to avoid intracranial hemorrhagic changes.

Hemodynamics of cardiac tamponade during extracorporeal membrane oxygenation support in a patient with fulminant myocarditis.

Fulminant myocarditis (FM) causes rapid onset severe heart failure requiring inotropes or mechanical circulatory support. Myocarditis is sometimes associated with pericardial effusion, however, how this effusion affects the hemodynamics in patients with FM under venoarterial extracorporeal membrane oxygenation (VA-ECMO) management has not been fully reported. We show a case of FM presenting with cardiac tamponade during VA-ECMO management. A 64-year-old female diagnosed as having FM showed a rapid hemodynamic collapse and that led to the application of VA-ECMO. Although her left ventricular ejection fraction did not improve despite proper hemodynamics management for several days, a pericardial effusion accumulated gradually. Apparent elevation of right atrial pressure and reduction of blood pressure were not observed, however, we performed pericardiocentesis because we were not able to wean off VA-ECMO. After the drainage of pericardial effusion, the blood pressure and cardiac output elevated as did the left ventricular ejection fraction. We successfully removed VA-ECMO and the patient was discharged without any complications. This is a case report in which a cardiac tamponade under VA-ECMO did not show typical signs and pericardiocentesis contributed to withdrawal of a VA-ECMO system. .

Promising method for management of venoarterial extracorporeal membrane oxygenation: A case of severe heart failure successfully stabilized by "high-flow/vasodilation method".

We report the case of a 58-year-old man with dilated cardiomyopathy who was hospitalized because of worsening heart failure. As his symptoms were refractory even with the administration of inotropes, he was given peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) upon transfer to our hospital. On admission, serum creatinine was 2.62 mg/dL and total bilirubin 10.8 mg/dL. The cannulas inserted were 16-Fr for infusion and 21-Fr for drainage. When the blood flow was increased to 2.14 L/min/m2 to improve organ dysfunction, the aortic valve became continuously close with the mean arterial pressure of 85 mmHg. Therefore, we administrated vasodilators to decrease mean arterial pressure, or left ventricular afterload, which achieved opening aortic valve continuously. After the cannula sizes were scaled up to 18Fr for infusion and 24Fr for drainage to gain further blood flow, the aortic valve opened continuously and mean pulmonary pressure decreased. Our strategy to maintain adequate flow rate of VA-ECMO using vasodilator, "high-flow/vasodilation method", achieved hemodynamic stability. Additionally, the concentration of serum creatinine and total bilirubin gradually decreased to within the normal range, although the patient succumbed 58 days after transfer to our hospital. .

Strategy of Cardiovascular Surgery for Patients With Dementia as Evaluated by Mini-Mental State Examination.

BACKGROUND: The strategy for cardiovascular surgery in dementia patients is controversial, so we aimed to investigate whether preoperative dementia and its severity might affect the outcomes of cardiovascular surgery by evaluating with the Mini-Mental State Examination (MMSE). Methods and Results: The study group comprised 490 patients undergoing cardiovascular surgery. Their preoperative cognitive status was evaluated using the MMSE, and analysis was performed to compare the patients with MMSE score <24 (dementia group, n=51) or MMSE score 24-30 (non-dementia group, n=439). Furthermore, the effect of the severity of dementia was analyzed with a cut-off MMSE score of 19/20. Risk factors for surgical outcomes were explored using multivariate logistic regression analysis. Hospital mortality was 11.8% in the dementia group and 2.1% in the non-dementia group (P=0.002). Regarding the postoperative morbidities, the incidence of cerebrovascular disorder (P=0.001), pneumonia (P=0.039), delirium (P=0.004), and infection (P=0.006) was more frequent in dementia group. Among the patients with MMSE <20, hospital mortality was as high as 25%, and the rate of delirium was 58%. Multivariate logistic regression analysis revealed that MMSE score <24 (P=0.003), lower serum albumin (P=0.023) and aortic surgery (P=0.036) were independent risk factors for hospital death. CONCLUSIONS: Preoperative dementia affects the outcomes of cardiovascular surgery with regard to hospital death and delirium. The surgical indication for patients with MMSE <20 might be difficult, but surgery with an appropriate strategy should be considered for patients with MMSE <24.

The oral administration of clarithromycin prevents the progression and rupture of aortic aneurysm.

OBJECTIVE: The pathogenesis of aortic aneurysm (AA) is associated with chronic inflammation in the aortic wall with increased levels of matrix metalloproteinases (MMPs). Clarithromycin (CAM) has been reported to suppresses MMP activity. In this study, we investigated whether CAM could prevent the formation and rupture of AA. METHODS: Male apolipoprotein E-deficient mice (28-30 weeks of age) were infused with angiotensin II for 28 days. CAM (100 mg/kg/d) or saline (as a control) was administered orally to the mice every day (CAM group, n = 13; control group, n = 13). After the administration period, the aortic diameter, elastin content, macrophage infiltration, MMP levels, and levels of inflammatory cytokines, including nuclear factor κB (NF-κB), were measured. RESULTS: The aortic diameter was significantly suppressed in the CAM group (P < .001). No rupture death was observed in the CAM group in contrast to five deaths (38%) in the control group (P < .01). CAM significantly suppressed the degradation of aortic elastin (56.3% vs 16.5%; P < .001) and decreased the infiltration of inflammatory macrophages (0.05 vs 0.16; P < .01). Compared with the controls, the enzymatic activity of MMP-2 and MMP-9 was significantly reduced in the CAM group (MMP-2, 0.15 vs 0.56 [P < .01]; MMP-9, 0.12 vs 0.60 [P < .01]), and the levels of interleukin 1ß (346.6 vs 1066.0; P < .05), interleukin 6 (128.4 vs 346.2; P < .05), and phosphorylation of NF-κB were also decreased (0.3 vs 2.0; P < .01). CONCLUSIONS: CAM suppressed the progression and rupture of AA through the suppression of inflammatory macrophage infiltration, a reduction in MMP-2 and MMP-9 activity, and the inhibition of elastin degradation associated with the suppression of NF-κB phosphorylation.