Shunji Osaka

Influence of Continuous Infusion of Low-Dose Human Atrial Natriuretic Peptide on Renal Function During Cardiac Surgery A Randomized Controlled Study

OBJECTIVES The purpose of this study was to determine the effect of human atrial natriuretic peptide (hANP) in patients who underwent coronary artery bypass grafting (CABG) on renal function. BACKGROUND Acute renal failure after cardiac surgery is associated with high morbidity and mortality. METHODS A total of 504 patients who underwent CABG were divided into 2 groups: 1 group received hANP at 0.02 microg/kg/min from the start of cardiopulmonary bypass (hANP group), and 1 group did not receive hANP (placebo group). Various parameters were measured before and after surgery. RESULTS There was no difference in mortality between the 2 groups, but post-operative complications were less frequent in the hANP group (p = 0.0208). In the hANP group, serum creatinine (Cr) was significantly lower and urinary Cr and Cr clearance were significantly higher from post-operative day 1 to week 1. The maximum post-operative Cr level and percent increase of Cr were significantly lower in the hANP group (p < 0.0001). Patients with Cr exceeding 2.0 mg/dl included 1 in the hANP group and 8 in the placebo group, showing a significant difference (p = 0.0374). Four patients in the placebo group and none in the hANP group required hemodialysis, but the difference was not statistically significant. CONCLUSIONS Continuous infusion of low-dose hANP from the start of cardiopulmonary bypass effectively maintained post-operative renal function. Infusion of hANP prevents early post-operative acute renal failure and helps to achieve safer cardiac surgery. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000001440).

Should emergency surgical intervention be performed for an octogenarian with type A acute aortic dissection

OBJECTIVE The number of octogenarians undergoing emergency surgery is increasing and may negate the impact of the beneficial advances. The aim of this study was to review octogenarians with type A acute aortic dissection and assess the prognosis. METHODS Fifty-eight patients with acute aortic dissection, whose average age was 83.2 years, were divided into 2 groups: Group I comprised 30 patients who underwent emergency surgery, and group II comprised 28 patients who were treated conservatively. We compared the 2 groups in terms of mortality and morbidity. RESULTS In group I, postoperative hospital mortality was 13.3% (4 patients). In group II, 17 patients (60.7%) died in the hospital. In group I, although emergency aortic replacement was successfully completed, 5 patients became bedridden after surgery and 2 patients died of pneumonia or stroke in the early stages of institutional care. Thirteen patients in group I died of malignancies, abdominal aortic rupture, traffic accident, heart failure, or late-stage senility in later phase. There was no difference in actuarial survivals at 5 years, which were 48.5% in group I and 35.4% in group II. CONCLUSION Emergency surgery for octogenarians with acute aortic dissection showed acceptable mortality. However, families had to take responsibility for patients who experienced unconsciousness, had dementia, or became bedridden. It is important to have consensus between the family and surgeons about emergency surgical treatment for octogenarians.

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.

Giant Thrombus Formation Immediately After Mitral Valvuloplasty.

Patients with atrial fibrillation (AF) are at risk of cardioembolism.(1,2)) Atrial thrombus formation associated with AF typically occurs in the left atrial appendage (LAA);(3)) therefore, transesophageal echocardiography (TEE) is important for detection of such a thrombus and measurement of LAA flow velocity.(4,5)) LAA closure is routinely performed during mitral valve surgery in patients with AF to prevent cardiogenic stroke.(6)) We report the case of a 65-year-old woman with severe mitral regurgitation (MR) and AF in whom a giant thrombus formed almost immediately after mitral and tricuspid valvuloplasty and concurrent LAA resection. No atrial thrombus or spontaneous echo contrast (SEC) was detected by TEE before the surgery. However, a giant intramural thrombus was detected in the left atrium 7 days after surgery. It was thought that the atrial dysfunction as well as the change in morphology of the left atrium resulting from the severe MR complicated by AF and congestive heart failure produced a thrombotic substrate. This case suggests that careful surveillance for thrombus formation and careful maintenance of anticoagulation therapy are needed throughout the perioperative period even if no SEC or thrombus is detected before surgery.

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.

Experimental investigation of "hANP shot" using human atrial natriuretic peptide for myocardial protection in cardiac surgery.

BACKGROUND We investigated myocardial protection by human atrial natriuretic peptide (hANP) during cardiac surgery without cardioplegia and determined whether suppression of myocardial ischemic reperfusion injury by hANP allows intraoperative aortic cross-clamp time to be prolonged. METHODS AND RESULTS Thirty-two pigs were placed on cardiopulmonary bypass. Experimental pigs were divided into 4 groups: 15 min clamping; hANP 15 min clamping; 30 min clamping; and hANP 30 min clamping. In both hANP groups, a 100 μg dose of hANP was administered after clamping. Left ventricular function, premature ventricular contractions (PVCs), histopathological studies, 8-isoprostane, myocardial Ca(2+), and ATP concentrations were determined. Comparison of the myocardial contractile force indicator E(max), in the 30 min groups, showed a significantly higher recovery rate in the hANP than in the control group. PVC numbers were significantly lower in the hANP than in the control groups for both arrest durations. On microscopic examination, hANP reduced ischemic reperfusion injury in the 30 min groups. The myocardial ATP level was significantly higher in the hANP 30 min than in the control 30 min group. Increases in 8-isoprostane and myocardial Ca(2+) concentrations were significantly inhibited in both hANP groups. CONCLUSIONS This study demonstrated that hANP ameliorates ischemic reperfusion injury, improves postoperative myocardial contractility, and reduces reperfusion arrhythmias. We suggest that hANP allows aortic cross-clamping to be prolonged and thereby exerts a direct myocardial protective effect against cardiac arrest during cardiac surgery.