Factors influencing glomerular filtration rate as estimated using preoperative creatinine and cystatin C levels.

OBJECTIVES: Estimated glomerular filtration rate (eGFR) using serum creatinine (Cr) is commonly used to evaluate renal function. However, it can be influenced by other factors, which can risk the overestimation of the true GFR. Impaired renal function prior to cardiovascular surgery reportedly increases mortality and the incidence of postoperative complications. Thus, overestimation of renal function may affect the assessment of postoperative complication risks. Therefore, we aimed to compare the eGFR calculated from serum Cr and cystatin C (Cys-C) levels to assess preoperative renal function and to investigate factors affecting renal function overestimation. MATERIALS AND METHODS: 88 patients admitted for cardiovascular surgery who had preoperative serum Cr and Cys-C measurements were included in the study. Correlations between factors associated with eGFR calculated from serum Cr (eGFRcre) and Cys-C (eGFRcys) and their ratio (eGFRcre/eGFRcys) were examined using multiple regression analysis. RESULTS: Multiple regression analysis revealed that eGFRcre/eGFRcys was significantly negatively correlated with the Short Physical Performance Battery score (SPPB). A clinically significant difference in renal function overestimation was defined as GFRcre/eGFRcys > 1.2, with a cutoff value of 9 points for the SPPB score. The chair stand test, a component of the SPPB, had the same discriminative power as the SPPB for identification of renal function overestimation. CONCLUSION: The SPPB can be used to identify likely GFR overestimation in patients. Additionally, the chair stand test may be used as an alternative to the SPPB for the identification of renal function overestimation when the SPPB is difficult to perform.

[Amiodarone-induced Ventricular Tachycardia after Coronary Artery Bypass Grafting;Report of a Case].

A 57-year-old man on maintenance hemodialysis was admitted to a hospital after suffering from cardiac arrest. He had collapsed soon after hemodialysis and was restored to sinus rhythm after receiving direct-current shocks. Further examination revealed old myocardial infarction with triple-vessel disease, and he was referred to our hospital for surgical treatment. Soon after performing coronary artery bypass grafting, we started the patient on intravenous amiodarone for frequent ventricular tachycardia. However, incessant ventricular tachycardia occurred frequently which necessitated several countershocks. Although ventricular tachycardia disappeared by replacing intravenous amiodarone with intravenous nifekalant, it reappeared when we initiated oral amiodarone instead of intravenous nifekalant. So therefore, we stopped using any anti-arrhythmic drug except bisoprolol fumarate, whereby ventricular tachycardia ceased once again. Amiodarone is known as relatively safe anti-arrhythmic drug that is often used after cardiovascular surgery. However, we should pay close attention to the possibility of amiodarone-induced arrhythmia.

Comparison of the Long-Term Outcomes of Mechanical and Bioprosthetic Aortic Valves　- A Propensity Score Analysis.

BACKGROUND: The aim of this study was to assess the long-term outcomes of aortic valve replacement (AVR) with either mechanical or bioprosthetic valves according to age at operation.Methods and Results:A total of 1,002 patients (527 mechanical valves and 475 bioprosthetic valves) undergoing first-time AVR were categorized according to age at operation: group Y, age <60 years; group M, age 60-69 years; and group O, age ≥70 years). Outcomes were compared on propensity score analysis (adjusted for 28 variables). Hazard ratio (HR) was calculated using the Cox regression model with adjustment for propensity score with bioprosthetic valve as a reference (HR=1). There were no significant differences in overall mortality between mechanical and bioprosthetic valves for all age groups. Valve-related mortality was significantly higher for mechanical valves in group O (HR, 2.53; P=0.02). Reoperation rate was significantly lower for mechanical valves in group Y (HR, 0.16; P<0.01) and group M (no events for mechanical valves). Although the rate of thromboembolic events was higher in mechanical valves in group Y (no events for tissue valves) and group M (HR, 9.05; P=0.03), there were no significant differences in bleeding events between all age groups. CONCLUSIONS: The type of prosthetic valve used in AVR does not significantly influence overall mortality.

Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia.

As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I-IIa study that analyzed 10 CLI patients following a 200-µg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI.

Twenty-year outcome of aortic valve replacement with St. Jude Medical mechanical valves in Japanese patients.

BACKGROUND: Bioprostheses have become increasingly popular for aortic valve replacement (AVR) in recent years, but mechanical valves are still the standard choice, especially for younger patients. The aim of this study was to assess the very long-term outcomes in Japanese patients who underwent AVR with St. Jude Medical (SJM) mechanical valves. METHODS AND RESULTS: From 1991 to 2001, a total of 816 patients underwent AVR with SJM mechanical valves in 5 hospitals. Of these, 801 patients (mean age, 58.3±11.7 years) were analyzed in this study. There were 24 in-hospital deaths (3.0%). Mean follow-up duration was 11.6±6.7 years and the 10-year follow-up rate was 84.1%. Freedom from valve-related death at 5, 10, 15, and 20 years was 96.2%, 92.7%, 88.8%, and 86.6%, respectively. The linearized ratio of major bleeding events and thromboembolic events was 1.1% per patient-year and 1.0% per patient-year, respectively. Freedom from reoperation for the aortic prosthesis was 98.0% and 94.8% at 10 and 20 years, respectively. CONCLUSIONS: The SJM mechanical valve provided excellent long-term freedom from valve-related death and reoperation in patients undergoing AVR. Therefore, this valve should be recommended to younger patients who wish to avoid reoperation.

A natural p300-specific histone acetyltransferase inhibitor, curcumin, in addition to angiotensin-converting enzyme inhibitor, exerts beneficial effects on left ventricular systolic function after myocardial infarction in rats.

BACKGROUND: A natural p300-specific histone acetyltransferase (HAT) inhibitor, curcumin, may have therapeutic potential for heart failure. However, it is unclear whether curcumin exhibits beneficial additive or synergistic effects on conventional therapy with angiotensin-converting enzyme inhibitors (ACEIs). METHODS AND RESULTS: Rats were subjected to a sham operation or left coronary artery ligation. One week later, 34 rats with a moderate sized myocardial infarction (MI) were randomly assigned to 4 groups: solvents as control (n = 8), enalapril (an ACEI, 10 mg·kg⁻¹·day⁻¹) alone (n=8), curcumin (50 mg·kg⁻¹·day⁻¹) alone (n = 9) and enalapril plus curcumin (n = 9). Daily oral treatment was repeated and continued for 6 weeks. Echocardiographic data were similar among the 4 groups before treatment. After treatment, left ventricular (LV) fractional shortening (FS) was significantly higher in the enalapril (29.0 ± 1.9%) and curcumin (30.8 ± 1.7%) groups than in the vehicle group (19.7 ± 1.6%). Notably, LVFS further increased in the enalapril/curcumin combination group (34.4 ± 1.8%). Histologically, cardiomyocyte diameter in the non-infarct area was smaller in the enalapril/curcumin combination group than in the enalapril group. Perivascular fibrosis was significantly reduced in the enalapril/curcumin group compared with the curcumin group. CONCLUSIONS: A natural non-toxic dietary compound, curcumin, combined with an ACEI exerts beneficial effects on post-MI LV systolic function in rats.

Basic fibroblast growth factor attenuates left-ventricular remodeling following surgical ventricular restoration in a rat ischemic cardiomyopathy model.

OBJECTIVE: Although surgical ventricular restoration for ischemic cardiomyopathy is expected as an alternative or bridge to heart transplantation, post-operative remodeling of left ventricle (LV) needs to be addressed. This study aimed to examine the effect of basic fibroblast growth factor (bFGF), which induces angiogenesis and tissue regeneration in ischemic myocardium, to prevent remodeling after surgical ventricular restoration (SVR) using a rat ischemic cardiomyopathy model. METHODS: Four weeks after coronary artery ligation, rats were divided into two groups: rats treated with SVR alone (SVR; n = 21), and rats treated with SVR and local sustained release of bFGF using gelatin hydrogel sheet (SVR + bFGF; n = 22). Cardiac function was assessed by serial echocardiography and cardiac catheterization. Cardiac tissue sections were histologically examined for vascular density and fibrosis. RESULTS: Higher systolic function and lower LV end-diastolic pressure (LVEDP) were observed in rats treated with SVR + bFGF (SVR vs SVR + bFGF; Ees: 0.22 ± 0.11 vs 0.33 ± 0.22 mmHg/µL, p = 0.0328; LVEDP: 12.7 ± 7.0 vs 8.5 ± 4.3 mmHg, p = 0.0230). LV area tended to be lower in rats treated with SVR + bFGF compared to rats treated with SVR alone (left-ventricular end-diastolic area: 0.66 ± 0.07 vs 0.62 ± 0.07 cm2, p = 0.071). Vascular density tended to be higher in rats treated with SVR + bFGF than those without bFGF (23.3 ± 8.1 vs 28.8 ± 9.5/mm2, p = 0.0509). CONCLUSIONS: BFGF induced angiogenesis and attenuated remodeling after SVR which secured the efficacy of SVR in a rat ischemic cardiomyopathy model.

Hemorrhage as a life-threatening complication after valve replacement in end-stage renal disease patients.

OBJECTIVE: Hemodialysis patients have an increased risk of hemorrhage compared to other patients. This study reports the frequencies of hemorrhage and its impact on the survival of hemodialysis patients after valve replacement. METHODS: A total of 77 consecutive dialysis patients who underwent prosthetic valve surgery from 1991 to 2011 were retrospectively reviewed. Their mean age was 65.8 ± 9.2 years. Forty-three patients (56%) were male. Fifty-nine patients (77%) had aortic valve replacement, and 23 patients (30%) had mitral valve replacement. Bioprosthetic valves were used in 17 patients (22%). RESULTS: There were seven in-hospital mortalities (9.1%). The overall estimated Kaplan-Meier survival after 3, 5 and 7 years was 66.6 ± 5.6, 51.1 ± 6.3 and 34.4 ± 6.8%, respectively. Seventeen (22%) bleeding events were observed (5.9% per patient-years) in the follow-up period. Six of the nine patients with cerebral hemorrhages and two of the six with gastrointestinal hemorrhages died. There were no differences in the frequencies of hemorrhage between the patients treated with bioprostheses and mechanical valves. CONCLUSIONS: This study found that 22% of dialysis patients had hemorrhagic events after valve replacement, and approximately half of them died. Particularly, cerebral hemorrhage was fatal and two thirds of the patients died. So we should meditate the methods to reduce hemorrhage. Therefore, new methods to reduce the risk of hemorrhage are urgently needed.

Bilateral internal thoracic artery grafting for peripheral arterial disease patients.

BACKGROUND: Peripheral arterial disease (PAD) is known to have a poor prognosis. Some reports have also described poor late results after coronary artery bypass grafting (CABG). However, there have been few reports about whether bilateral internal thoracic artery grafting improves the long-term survival of PAD patients after CABG. We performed this study to clarify whether or not this is the case. METHODS: One hundred and thirty-six PAD patients who underwent elective CABG with two or more grafts were enrolled in this study. Patients were divided into two groups, 71 patients in the bilateral internal thoracic artery (BITA) group and 65 patients in the single internal thoracic artery (SITA) group. The maximum follow-up period was 19 years, with a mean of 5.7 ± 4.4 years. RESULTS: We investigated the long-term results based on three factors; survival, freedom from cardiac death, and freedom from cardiac events. The 3-, 5- and 10-year survival rates in the BITA group were 83.0, 74.2, and 43.1%, respectively. And those in the SITA group were 79.4, 67.7, and 32.3%, respectively. There were no significant differences between the two groups (p = 0.5843). There were also no statistically significant differences between the two groups in terms of the freedom from cardiac death (p = 0.8589) or in the freedom from cardiac events (p = 0.9445). CONCLUSION: No long-term advantage was observed for CABG with BITA in comparison to SITA alone in patients with PAD.

Oral pretreatment with a green tea polyphenol for cardioprotection against ischemia-reperfusion injury in an isolated rat heart model.

OBJECTIVE: Ischemia-reperfusion injury is among the most serious problems in cardiac surgery. Epigallocatechin-3-gallate, a major polyphenolic component of green tea, is thought to be cardioprotective through its antioxidant activities. We investigated cardioprotective effects of oral epigallocatechin-3-gallate pretreatment against ischemia-reperfusion injury in isolated rat hearts and considered possible underlying mechanisms. METHODS: Rats were given epigallocatechin-3-gallate solution orally at 0.1, 1, or 10 mmol/L (n=12 per group) for 2 weeks; controls (n=12) received tap water alone for 2 weeks. Subsequently, Langendorff-perfused hearts were subjected to global ischemia for 30 minutes, followed by 60 minutes of reperfusion. RESULTS: Recoveries at 60 minutes after reperfusion of left ventricular developed pressure and maximum positive and minimum negative first derivatives of left ventricular pressure were significantly higher in 1-mmol/L group than in 0.1-mmol/L (P<.0001), 10-mmol/L (P<.05), and control (P<.0001) groups. Oxidative stress after reperfusion, as reflected by 8-hydroxy-2'-deoxyguanosine index, was lower in 1-mmol/L group than in control (P<.01) and 0.1-mmol/L (P<.05) groups. Western blot analysis after reperfusion showed p38 activation and active caspase-3 expression to be lower in 1-mmol/L group than in control group (P<.05). CONCLUSIONS: Oral pretreatment with epigallocatechin-3-gallate preserved cardiac function after ischemia-reperfusion, an effect that may involve its antioxidative, antiapoptotic properties, although a high dose did not lead to dramatic improvement in cardiac function. Oral epigallocatechin-3-gallate pretreatment may be a novel and simple cardioprotective method for preventing perioperative cardiac dysfunction in cardiac surgery.

Sustained release of vancomycin from a new biodegradable glue to prevent methicillin-resistant Staphylococcus aureus graft infection.

Prosthetic graft infection with methicillin-resistant Staphylococcus aureus (MRSA) is one of the most serious complications of cardiovascular surgery. Seeking to prevent graft infection, we evaluated the efficacy of a new biodegradable hydrogel glue (new-glue) composed of aldehyded dextran and epsilon-poly(L-lysine) which acts as a local sustained-release carrier of vancomycin. Rats (n=40) were implanted with 1-cm(2) Dacron grafts in the subcutaneous pockets. Groups (n=10 each) were as follows: no treatment (group A), topical vancomycin solution (group B), new-glue without vancomycin (group C) or new-glue containing 1 mg of vancomycin (group D). Twenty-four h after the implantation, 2.0x10(7) colony-forming units of MRSA was inoculated onto the graft surface. Seven days thereafter, the graft was sampled and cultured. The quantity of MRSA was significantly lower in group D than in the other groups (P<0.0001). About 95% of the total vancomycin was released from the new-glue over the 72 h experimental period, and the tissue concentration of vancomycin remained above the minimum inhibitory concentration for the MRSA strain throughout the experiment. This new vancomycin-containing glue effectively prevented prosthetic graft infection and thus may be a promising biodegradable drug vehicle.