Hiroko Yaoita

Comparison of febuxostat and allopurinol for hyperuricemia in cardiac surgery patients with chronic kidney disease (NU-FLASH trial for CKD)

BACKGROUND The NU-FLASH trial demonstrated that febuxostat was more effective for hyperuricemia than allopurinol. This time, we compared these medications in patients with chronic kidney disease (CKD) from the NU-FLASH trial. METHODS AND RESULTS In the NU-FLASH trial, 141 cardiac surgery patients with hyperuricemia were randomized to a febuxostat group or an allopurinol group. This study analyzed 109 patients with an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m(2), and also analyzed 87 patients with stage 3 CKD. The primary endpoint was the serum uric acid level. Secondary endpoints included serum creatinine, urinary albumin, cystatin-C, oxidized low-density lipoprotein, eicosapentaenoic acid/arachidonic acid ratio, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, and high-sensitivity C-reactive protein. Among patients with an eGFR≤60 mL/min/1.73 m(2), uric acid levels were significantly lower in the febuxostat group than the allopurinol group from 1 month of treatment onward. The serum creatinine, urinary albumin, cystatin-C, oxidized low-density lipoprotein, eicosapentaenoic acid/arachidonic acid ratio, and high-sensitivity C-reactive protein were also significantly lower in the febuxostat group. Similar results were obtained in the patients with stage 3 CKD. CONCLUSION In cardiac surgery patients with renal dysfunction, febuxostat reduced uric acid earlier than allopurinol, had a stronger renoprotective effect than allopurinol, and also had superior antioxidant and anti-inflammatory effects.

Safety and efficacy of landiolol hydrochloride for prevention of atrial fibrillation after cardiac surgery in patients with left ventricular dysfunction: Prevention of Atrial Fibrillation After Cardiac Surgery With Landiolol Hydrochloride for Left Ventricular Dysfunction (PLATON) trial.

OBJECTIVES We previously conducted a prospective study of landiolol hydrochloride (INN landiolol), an ultrashort-acting β-blocker, and reported that it could prevent atrial fibrillation after cardiac surgery. This trial was performed to investigate the safety and efficacy of landiolol hydrochloride in patients with left ventricular dysfunction undergoing cardiac surgery. METHODS Sixty patients with a preoperative left ventricular ejection fraction of less than 35% were randomly assigned to 2 groups before cardiac surgery and then received intravenous infusion with landiolol hydrochloride (landiolol group) or without landiolol (control group). The primary end point was occurrence of atrial fibrillation as much as 1 week postoperatively. The secondary end points were blood pressure, heart rate, intensive care unit and hospital stays, ventilation time, ejection fraction, biomarkers of ischemia, and brain natriuretic peptide. RESULTS Atrial fibrillation occurred in 3 patients (10%) in the landiolol group versus 12 (40%) in the control group, and its frequency was significantly lower in the landiolol group (P = .002). During the early postoperative period, levels of brain natriuretic peptide and ischemic biomarkers were significantly lower in the landiolol group than the control group. The landiolol group also had a significantly shorter hospital stay (P = .019). Intravenous infusion was not discontinued for hypotension or bradycardia in either group. CONCLUSIONS Low-dose infusion of landiolol hydrochloride prevented atrial fibrillation after cardiac surgery in patients with cardiac dysfunction and was safe, with no effect on blood pressure. This intravenous β-blocker seems useful for perioperative management of cardiac surgical patients with left ventricular dysfunction.

Carperitide and Atrial Fibrillation After Coronary Bypass Grafting The Nihon University Working Group Study of Low-Dose HANP Infusion Therapy During Cardiac Surgery Trial for Postoperative Atrial Fibrillation

Background —Occurrence of atrial fibrillation after cardiac surgery is associated with long-term mortality. We investigated whether infusion of human atrial natriuretic peptide (carperitide) could prevent postoperative atrial fibrillation (POAF). Methods and Results —A total of 668 patients who underwent isolated coronary artery bypass grafting were randomized to receive infusion of carperitide or physiological saline from the initiation of cardiopulmonary bypass. Patients were monitored continuously for one week after surgery to detect atrial fibrillation. The risk factors were investigated by Cox proportional hazard model. POAF occurred in 41/335 patients (12.2%) from the carperitide group versus 110/333 patients (32.7%) from the placebo group (p 150ng/ml, preoperative non-use of angiotensin receptor antagonists, preoperative use of calcium antagonists, postoperative non-use of beta blockers, postoperative non-use of aldosterone blockers, and non-use of carperitide. Conclusions —Perioperative carperitide infusion reduced the occurrence of postoperative atrial fibrillation. Accordingly, carperitide could be a useful option for preventing POAF. Clinical Trial Registration —http://www.umin.ac.jp; Unique Identifier: UMIN000003958Background—Occurrence of atrial fibrillation after cardiac surgery is associated with long-term mortality. We investigated whether infusion of human atrial natriuretic peptide (carperitide) could prevent postoperative atrial fibrillation. Methods and Results—A total of 668 patients who underwent isolated coronary artery bypass grafting were randomized to receive infusion of carperitide or physiological saline from the initiation of cardiopulmonary bypass. Patients were monitored continuously for 1 week after surgery to detect atrial fibrillation. The risk factors were investigated by Cox proportional hazard model. Postoperative atrial fibrillation occurred in 41 of 335 patients (12.2%) from the carperitide group versus 110 of 333 patients (32.7%) from the placebo group (P<0.0001). Postoperative levels of angiotensin-II, aldosterone, creatine kinase MB isoenzyme, human heart fatty acid–binding protein, and brain natriuretic peptide were all significantly lower in the carperitide group. The risk factors for postoperative atrial fibrillation by the Cox proportional hazard model were an age ≥70 years, emergency surgery, preoperative aldosterone level >150 ng/mL, preoperative nonuse of angiotensin receptor antagonists, preoperative use of calcium antagonists, postoperative nonuse of &bgr;-blockers, postoperative nonuse of aldosterone blockers, and nonuse of carperitide. Conclusions—Perioperative carperitide infusion reduced the occurrence of postoperative atrial fibrillation. Accordingly, carperitide could be a useful option for preventing postoperative atrial fibrillation. Clinical Trial Registration—URL: http://www.umin.ac.jp. Unique Identifier: UMIN000003958.

Carperitide and Atrial Fibrillation after Coronary Bypass Grafting: The NU-HIT Trial for POAF

Background —Occurrence of atrial fibrillation after cardiac surgery is associated with long-term mortality. We investigated whether infusion of human atrial natriuretic peptide (carperitide) could prevent postoperative atrial fibrillation (POAF). Methods and Results —A total of 668 patients who underwent isolated coronary artery bypass grafting were randomized to receive infusion of carperitide or physiological saline from the initiation of cardiopulmonary bypass. Patients were monitored continuously for one week after surgery to detect atrial fibrillation. The risk factors were investigated by Cox proportional hazard model. POAF occurred in 41/335 patients (12.2%) from the carperitide group versus 110/333 patients (32.7%) from the placebo group (p 150ng/ml, preoperative non-use of angiotensin receptor antagonists, preoperative use of calcium antagonists, postoperative non-use of beta blockers, postoperative non-use of aldosterone blockers, and non-use of carperitide. Conclusions —Perioperative carperitide infusion reduced the occurrence of postoperative atrial fibrillation. Accordingly, carperitide could be a useful option for preventing POAF. Clinical Trial Registration —http://www.umin.ac.jp; Unique Identifier: UMIN000003958Background—Occurrence of atrial fibrillation after cardiac surgery is associated with long-term mortality. We investigated whether infusion of human atrial natriuretic peptide (carperitide) could prevent postoperative atrial fibrillation. Methods and Results—A total of 668 patients who underwent isolated coronary artery bypass grafting were randomized to receive infusion of carperitide or physiological saline from the initiation of cardiopulmonary bypass. Patients were monitored continuously for 1 week after surgery to detect atrial fibrillation. The risk factors were investigated by Cox proportional hazard model. Postoperative atrial fibrillation occurred in 41 of 335 patients (12.2%) from the carperitide group versus 110 of 333 patients (32.7%) from the placebo group (P<0.0001). Postoperative levels of angiotensin-II, aldosterone, creatine kinase MB isoenzyme, human heart fatty acid–binding protein, and brain natriuretic peptide were all significantly lower in the carperitide group. The risk factors for postoperative atrial fibrillation by the Cox proportional hazard model were an age ≥70 years, emergency surgery, preoperative aldosterone level >150 ng/mL, preoperative nonuse of angiotensin receptor antagonists, preoperative use of calcium antagonists, postoperative nonuse of &bgr;-blockers, postoperative nonuse of aldosterone blockers, and nonuse of carperitide. Conclusions—Perioperative carperitide infusion reduced the occurrence of postoperative atrial fibrillation. Accordingly, carperitide could be a useful option for preventing postoperative atrial fibrillation. Clinical Trial Registration—URL: http://www.umin.ac.jp. Unique Identifier: UMIN000003958.

Changeover Trial of Azilsartan and Olmesartan Comparing Effects on the Renin-Angiotensin-Aldosterone System in Patients with Essential Hypertension after Cardiac Surgery (CHAOS Study).

BACKGROUND Angiotensin II receptor blockers (ARBs) have been widely used to treat hypertension and large-scale clinical studies have shown various benefits. In this study, we compared olmesartan with azilsartan, the newest ARB. METHODS The subjects were outpatients who were clinically stable after cardiac surgery. Sixty patients were randomized to receive either azilsartan or olmesartan for 1 year and were switched to the other drug for the following 1 year. The primary endpoints were the levels of plasma renin activity, angiotensin II, and aldosterone. RESULTS Home blood pressure exceeded 140/90 mmHg and additional antihypertensive medication was administered to 12 patients (20 episodes) in the azilsartan group versus 4 patients (4 episodes) in the olmesartan group, with the number being significantly higher in the azilsartan group. After 1 year of treatment, both angiotensin II and aldosterone levels were significantly lower in the olmesartan group than the azilsartan group. Left ventricular mass index was also significantly lower in the olmesartan group than the azilsartan group. CONCLUSION This study showed that olmesartan reduces angiotensin II and aldosterone levels more effectively than azilsartan. Accordingly, it may be effective in patients with increased renin-angiotensin-aldosterone system activity after cardiac surgery or patients with severe cardiac hypertrophy.

Early and Long-Term Outcomes in Japanese Patients Aged 80 Years or Older Undergoing Conventional Aortic Valve Replacement.

UNLABELLED In this study, we investigated the early and long-term results of conventional aortic valve replacement (AVR) in very old patients. METHODS Seventy-five patients with aortic stenosis underwent conventional AVR for patients aged 80 years.We examined early death and major adverse cardiovascular and cerebrovascular event (MACCE). RESULTS The operative mortality was 0% for isolated AVR and 19.2% for concomitant surgery. The postoperative survival rate and MACCE free-rate were no significant differences between the isolated AVR and the concomitant surgery. Univariate analysis confirmed that cardiac dysfunction, severe chronic kidney disease (CKD), hemodialysis, + coronary artery bypass grafting, and norepinephrine use were risk factor of early death. Univariate analysis confirmed that severe CKD, BNP >1000 pg/ml, aortic cross clamping time (ACCT) >180 min, and non-use carperitide and multivariate analysis confirmed that ACCT >180 min, and non-use carperitide were risk factor of MACCE. CONCLUSIONS This study showed that the results of conventional AVR in very old patients were not satisfactory. However, the results obtained with isolated AVR were favorable with no operative deaths. The present study demonstrated that preoperative cardiac function, preoperative renal function, and operative factors have an important impact on early mortality and MACCE.

Safety of The Direct Oral Anticoagulant Edoxaban for Atrial Fibrillation After Cardiac Surgery: Pilot Study

Direct oral anticoagulants have recently been recommended for non-valvular atrial fibrillation, but have rarely been studied in the field of cardiac surgery. We prospectively investigated the safety of edoxaban, a novel oral anticoagulant, for use in cardiac surgery patients with postoperative atrial fibrillation (POAF), which is the most common complication of cardiac surgery and can lead to stroke. The subjects were adult cardiac surgery patients with POAF who received oral edoxaban for 2 months in an open-label pilot study. The primary endpoint was cerebrovascular/bleeding events up to 2 months, while the secondary endpoints were hemoglobin, prothrombin time, and activated partial thromboplastin time. There were no cerebrovascular or bleeding events during edoxaban treatment and the test drug was not discontinued by any patient. There was no macroscopic hematuria and hemoglobin did not decrease, being significantly higher than the baseline level after 2 months. The prothrombin time was significantly prolonged from 1 week to 2 months and the activated partial thromboplastin time was significantly prolonged from 1 day to 2 months. Echocardiography detected pericardial effusion in 1 patient, but hemoglobin did not decrease and the effusion improved with diuretic therapy. In conclusion, despite the limited sample size of this pilot study, it was demonstrated that edoxaban does not induce bleeding in patients with POAF after cardiac surgery, suggesting that it is safe to perform a large-scale efficacy study of edoxaban as anticoagulant therapy for POAF.

Sleep disordered breathing in cardiac surgery patients: The NU-SLEEP trial

BACKGROUND Sleep disordered breathing (SDB) is associated with lifestyle-related diseases and its treatment influence the prognosis of cardiac disease, but little investigation of SDB has been conducted in cardiac surgery patients. METHODS AND RESULTS A prospective study was performed in 1005 patients undergoing cardiac surgery. The primary endpoint was the severity of SDB determined from the apnea/hypopnea index. The secondary endpoints were patient background factors, cardiovascular risk factors, ejection fraction, atrial and brain natriuretic peptides, oxidative stress and inflammatory markers, and postoperative atrial fibrillation. While 227 patients (22.6%) did not have SDB, there were 361 patients (35.9%) with mild SDB, 260 patients (25.9%) with moderate SDB, and 157 patients (15.6%) with severe SDB. Patients with severe SDB had a lower ejection fraction and higher levels of atrial and brain natriuretic peptides than the other groups. Postoperative atrial fibrillation occurred in 28 patients without SDB (13.6%), 43 patients with mild SDB (13.5%), 74 patients with moderate SDB (31.9%), and 73 patients with severe SDB (52.5%), being significantly more frequent in the severe group than the other groups. CONCLUSIONS SDB was frequent in cardiac surgery patients. Activation of the renin-angiotensin-aldosterone system, postoperative atrial fibrillation atrial, and cardiac dysfunction were associated with severe SDB. Markers of inflammation and oxidative stress also increased as SDB became more severe.

New Treatment for Infection of the NIPRO LVAD Cannula Site: Nihon University Crystal Violet Method

Driveline and cannula site infections are still a frequent adverse event in patients with a ventricular assist device (VAD), and it is important to treat and prevent them because the spread of local infection may cause sepsis in some cases. We report our experience with a patient in whom infection of the NIPRO LVAD cannula site after implantation of an extracorporeal VAD was controlled by treatment with crystal violet Solbase (Nihon University crystal violet method).

New Treatment for Percutaneous Sites in Patients with a Ventricular Assist Device: Nihon University Crystal Violet Method.

BACKGROUND Infection of the percutaneous site of a ventricular assist device (VAD) is a challenging complication. We report our experience with crystal violet Solbase (Nihon University crystal violet method) for prevention of driveline or cannula infections in VAD patients. PATIENTS AND METHODS The crystal violet method was used in 10 patients (prophylaxis in nine and treatment in one). Eight patients had an extracorporeal VAD (Nipro) and two had an implantable VAD (Heart Mate II). RESULTS The infection-free period was 4-623 days (mean: 144.2 ± 222.9 days). All eight patients with an extracorporeal VAD died, while the two patients with an implantable VAD (Heart Mate II) survived. Infection was improved in a patient with MRSA, and the results of bacteriological examination were always negative in the patients receiving prophylaxis. The two patients with an implantable VAD had no infection for 2 and 20 months after implantation. CONCLUSION These findings suggest that the Nihon University crystal violet method is effective for prevention and treatment of driveline or cannula infections in patients with a VAD.