Shinji Wakui

Thoracic and cardiovascular surgery in Japan during 2014

The Japanese Association for Thoracic Surgery has conducted annual surveys of thoracic surgery throughout Japan since 1986 to determine the statistics regarding the number of procedures according to operative category. Here, we have summarized the results from our annual survey of thoracic surgery performed during 2014.

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).

Results of low-dose human atrial natriuretic peptide infusion in nondialysis patients with chronic kidney disease undergoing coronary artery bypass grafting: the NU-HIT (Nihon University working group study of low-dose HANP Infusion Therapy during cardiac surgery) trial for CKD.

OBJECTIVES The purpose of this comparative study is to prove the efficacy of the human atrial natriuretic peptide (hANP) in patients with chronic kidney disease (CKD) undergoing coronary artery bypass graft surgery (CABG). BACKGROUND CKD is an important risk factor for cardiac surgery. METHODS This was a randomized controlled study of 303 patients with CKD who underwent CABG, and were divided into a group who received carperitide infusion and another group without carperitide. The primary endpoints were: 1) the post-operative dialysis-free rate; and 2) serum creatinine (sCr) and estimated glomerular filtration rate. The secondary endpoints were: 1) the early post-operative outcome; 2) outcome at 1 year post-operatively; 3) the maximum sCr, the rate of increase of sCr, and an increase of sCr by ≥ 0.3 mg/dl compared with the pre-operative value; and 4) ANP and cyclic-guanosine monophosphate levels. RESULTS The post-operative sCr was significantly lower in the hANP group not only in the post-operative acute stage but also in the first year. The maximum Cr and Cr increase rate were significantly lower in the hANP group (p = 0.00665, p < 0.0001). There was no difference in mortality rate in the first year post-operatively, and fewer cardiac events and patients going on dialysis were found in the hANP group (p < 0.0001 and p = 0.0014, respectively). CONCLUSIONS In the post-operative acute stage, carperitide showed cardiorenal protective effects that prevented post-operative cardiac events and initiation of dialysis. Thus, perioperative infusion of low-dose carperitide may have a significant role in management of patients with renal dysfunction undergoing on-pump CABG. (Effectiveness of hANP for Cardiac Surgery in Patients With Moderate to Severe Preoperative Renal Dysfunction Without Dialysis [NU-HIT for CRF]; UMIN000001462).

Continuous Low-Dose Infusion of Human Atrial Natriuretic Peptide in Patients With Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting: The NU-HIT (Nihon University working group study of low-dose Human ANP Infusion Therapy during cardiac surgery) for Left Ventricular Dysfunction

OBJECTIVES Continuous low-dose infusion of human atrial natriuretic peptide (hANP) in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) inhibits the renin-angiotensin-aldosterone system and compensates for the adverse effects of CPB. BACKGROUND We examined the influence of hANP infusion on cardiac and renal function in patients with left ventricular dysfunction undergoing coronary artery bypass grafting (CABG). METHODS The subjects were 133 patients who underwent CABG and had a pre-operative ejection fraction < or =35%. They were randomized to receive 0.02 microg/kg/min of hANP from the initiation of CPB (hANP group) or placebo (saline) infusion. RESULTS Early post-operative mortality did not show a significant difference between the 2 groups, but perioperative complications were significantly less frequent in the hANP group (p = 0.015). Long-term all-cause mortality showed no difference, but the cardiac death-free rate at 5 or 8 years post-operatively was 98.5% in the hANP group and 85.5% in the placebo group (p = 0.0285). Post-operative ejection fraction was significantly larger and the post-operative brain natriuretic peptide level was significantly lower in the hANP group. Serum creatinine was significantly lower in the hANP group than the placebo group at 1 month, 6 months, and 1 year post-operatively, whereas the estimated glomerular filtration rate was significantly higher in the hANP group at these times. CONCLUSIONS In patients with left ventricular dysfunction undergoing CABG, hANP showed renal- and cardio-protective effects and reduced post-operative complications. It also improved the long-term prognosis. We suggest that hANP should be considered as part of perioperative management of patients with cardiac dysfunction undergoing cardiac surgery. (NU-HIT trial for LVD; UMIN000001652).

Results of low-dose carperitide infusion in high-risk patients undergoing coronary artery bypass grafting.

BACKGROUND This study investigated the efficacy of human atrial natriuretic peptide (hANP, carperitide) for high-risk patients undergoing coronary artery bypass grafting (CABG). METHODS This was a randomized controlled trial of 367 high-risk patients (European System for Cardiac Operative Risk Evaluation above 6) undergoing CABG. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints were (1) postoperative death, (2) MACCE + hemodialysis, and (3) serum creatinine and brain natriuretic peptide (BNP) levels. Logistic regression analysis was conducted to identify preoperative and perioperative factors related to early death and MACCE. RESULTS There was no significant difference of survival between the hANP and placebo groups (p = 0.1651), but the MACCE-free rate was significantly higher in the hANP group than in the placebo group (p < 0.0001). No patient from the hANP group started hemodialysis after operation, but 7 patients did in the placebo group, and the dialysis rate was significantly lower in the hANP group (p = 0.0147). Serum creatinine and BNP were also significantly lower in the hANP group at 1 year postoperatively. MACCE were strongly associated with age 75 years or older, chronic kidney disease, hemodialysis, left ventricular dysfunction, and nonuse of carperitide. CONCLUSIONS In the early postoperative period, carperitide has a cardiorenal protective effect that prevents postoperative MACCE and hemodialysis. Perioperative low-dose carperitide infusion may be useful in high-risk patients undergoing on-pump CABG.

First clinical application of the DuraHeart centrifugal ventricular assist device for a Japanese patient.

The DuraHeart ventricular assist device (VAD) is a third-generation implantable centrifugal pump with a magnetically levitated impeller. Since February 2007, the device has been clinically applied with excellent results as a bridge to heart transplantation in Europe. As of this writing, however, the device has yet to be approved by the Ministry of Health, Labour and Welfare for clinical use in Japan. We herein report the first clinical application of this device for a Japanese patient. A 31-year-old man with dilated cardiomyopathy was transferred to the Heart and Diabetes Center NRW (HDZ-NRW) in Bad Oeynhausen, Germany, where he was to await heart transplantation. The transfer was safely completed under management with low-dose dopamine. His condition gradually deteriorated at HDZ-NRW, and the DuraHeart left ventricular assist device was implanted for the left ventricle at 7 weeks after admission. Shortly thereafter, however, on POD 7, a Thoratec VAD had to be inserted on the right side due to refractory right heart failure. The right ventricular assist device could be explanted after a 3-month assist, and the patient is now waiting for heart transplantation at home in Germany.

Efficacy of continuous low-dose human atrial natriuretic peptide given from the beginning of cardiopulmonary bypass for thoracic aortic surgery.

PurposeCardiac surgery performed under cardiopulmonary bypass (CPB) causes abnormalities of the renin-angiotensin-aldosterone system, resulting in decreased urine output and an accumulation of water in the third space. We studied the efficacy of continuous low-dose human atrial natriuretic peptide (hANP) in patients undergoing thoracic aortic surgery.MethodsWe divided 40 patients undergoing thoracic aortic surgery into two groups: the hANP group, which received 0.02 μg/kg per minute of hANP and the non-hANP group, which did not. The hemodynamics, urine output, intensive care unit (ICU) and hospital stay, bleeding volume, homologous blood transfusion volume, furosemide dose, corrected KCl volume, and postoperative respiratory, hepatic, and renal function were compared in the two groups.ResultsThe urine output during CPB and from CPB weaning to return to ICU was significantly better in the hANP group. The bleeding volume, homologous blood transfusion volume, furosemide dose, and corrected KCl volume were all significantly less in the hANP group.ConclusionsThese findings support the consensus that hANP exerts its diuretic effects to their full potential when administered continuously at low doses during thoracic aortic surgery. We found it to be effective for postoperative hemostasis and for preventing ischemic reperfusion injury.

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.

Optimal treatment strategy for type A acute aortic dissection with intramural hematoma

OBJECTIVE The management strategy for type A acute aortic dissection (AAD) with intramural hematoma (IMH) remains controversial. The aim of this study was to compare the outcomes of emergency surgery and medical treatment for patients with acute type A IMH. METHODS One hundred seventy-one patients with acute type A IMH, whose average age was 69.4 years (range, 39-90 years) were divided into 3 groups: groups I and II consisted of 74 and 33 patients undergoing emergency surgery for complicated and uncomplicated type A IMH, respectively, and group III comprised 66 patients who were treated conservatively. We compared the 3 groups in terms of mortality and morbidity. RESULTS In group I, postoperative hospital mortality was 5.4% (4 patients). In group II, all patients survived without any complications after surgery. On the other hand, in group III, 5 patients underwent emergency surgery within 7 days after onset owing to newly developed cardiac tamponade and 17 (25.8%) patients died in the hospital, which was a significantly higher rate than those in groups I and II. Furthermore, although the group III patients survived, 5 patients required mechanical ventilation owing to heart failure or pneumonia, and 4 patients had a stroke during the hospital stay. There was no difference in actuarial survivals at 10 years, which were 64.2% in group I, 64.9% in group II, and 68.7% in group III. CONCLUSIONS Emergency surgery for patients with type A IMH showed favorable mortality rates because most of the patients were in hemodynamically stable condition preoperatively. On the other hand, several patients died suddenly during medical care. Emergency surgical treatment may provide a better outcome than medical treatment at the time of onset, even for patients with type A IMH.

Experimental investigation of direct myocardial protective effect of atrial natriuretic peptide in cardiac surgery.

OBJECTIVE Human atrial natriuretic peptide has recently become known not only as a heart failure drug but also for myocardial protection. We investigated its direct myocardial protective effect on ischemia-reperfusion injury in cardiac surgery. METHODS Male pigs (35-45 kg) undergoing surgery with cardiopulmonary bypass, with 60-minute reperfusion after 30-minute cardioplegia, were grouped by timing of atrial natriuretic peptide administration: group C (n = 8), no atrial natriuretic peptide (cardioplegia only); group H1 (n = 8); 100-mug atrial natriuretic peptide administration after aortic crossclamping; group H2 (n = 8), administration before aortic declamping; and group H1 + H2 (n = 8), administration both after crossclamping and before declamping. Blood and myocardial cyclic guanosine monophosphate, calcium, and residual adenosine triphosphate levels were determined. Histologic investigation was conducted by electron and optical microscopy. RESULTS Atrial natriuretic peptide increased blood and myocardial cyclic guanosine monophosphate levels (P < .0001, P < .0001, P < .007 H1 + H2 vs C; P < .0014, P < .0007, P < .003 H1 vs C), decreased myocardial calcium (P < .0038 H1 + H2 vs C), and increased myocardial residual adenosine triphosphate. Electron microscopy revealed ischemic changes in mitochondria and nuclei in group C but not in treatment groups. CONCLUSIONS Ischemia-reperfusion injury was inhibited with equal effectiveness by atrial natriuretic peptide both during ischemia and immediately before reperfusion, acting directly on myocardium through cyclic guanosine monophosphate. Atrial natriuretic peptide may be useful as a supportive measure for patients with long aortic crossclamping time or difficulties in weaning from cardiopulmonary bypass.