Kazuhito Imanaka

Non-activated APJ suppresses the angiotensin II type 1 receptor, whereas apelin-activated APJ acts conversely

Apelin and its G-protein-coupled receptor APJ are potent regulators of the cardiovascular system. Recent studies have suggested that apelin–APJ reverses the function of angiotensin II (Ang II)–the Ang II type 1 receptor (AT1). However, the mechanism remains unclear because of the accumulating evidences that apelin–APJ may contribute to both cardioprotection and pathological progression. In human embryonic kidney 293 cells, we found that coexpression with APJ significantly suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) induced by Ang II–AT1, whereas apelin abolished this attenuation through activated APJ independently of its heterodimerization. Pretreatment with the Gi/o-specific inhibitor pertussis toxin (PTX) restituted the ERK1/2 phosphorylation level similar to that found with AT1 and APJ coexpression without apelin stimulation. In contrast, coexpression of the beta-2-adrenergic receptor or the pharmacologically non-activated Ang II type 2 receptor (AT2) pretreated with the AT2-specific antagonist, PD123319, did not affect ERK1/2 phosphorylation through AT1. Pretreatment with 30 nM of the AT1 blocker (ARB) TA-606A suppressed 50% of the AT1-mediated ERK1/2 phosphorylation, whereas 30 nM of TA-606A achieved 75% suppression when the non-activated APJ was coexpressed without ligand or PTX. However, 120 nM of TA-606A failed to reach the target phosphorylation when it was coexpressed with activated APJ with apelin. Based on these results, we demonstrated that non-activated APJ may suppress Ang II–AT1 signaling, whereas this ligand-independent function was diminished with apelin activation. These results may be relevant to the potential contribution of apelin–APJ to ARB treatment in the clinical realm.

Importance of luxury flow for critically ill patients receiving a left ventricular assist system

The presence of a significant organ dysfunction does not immediately exclude patients from consideration for treatment with a left ventricular assist system (LVAS). However, in treating morbid circulatory shock patients with multiple organ failure, it is important to know the preoperative and postoperative factor or factors related to the recovery of the damaged organ function. In this study, we retrospectively analyzed patients receiving a LVAS at our institution and tried to determine the important factors related to the survival of patients with multisystem failure. Twenty-seven patients who underwent LVAS placement at Saitama Medical School Hospital between 1993 and 2003 were included in this study. The preoperative risk factors analyzed were renal dysfunction, respiratory dysfunction, hepatic dysfunction, the existence of active infection, and the combination of all four factors. As a postoperative factor, the pump flow index (mean LVAS pump flow during the first 2 weeks after LVAS surgery divided by the body surface area) was analyzed. None of the analyzed preoperative factors could predict survival after LVAS surgery, but a pump flow index of less than 2.5 l/min/m2 had a significant relationship with death after LVAS surgery. Further analysis revealed that all the patients with a pump flow index of 3.0 l/min/m2 or more could overcome preoperative organ dysfunction. Congestive heart failure patients with multisystem failure need luxury pump flow for successful LVAS surgery; this factor could be especially important in device selection and postoperative management.

Successful bridge to resynchronization therapy with a left ventricular assist system in a patient with idiopathic dilated cardiomyopathy

Implantation of a left ventricular assist system (LVAS) in patients with idiopathic dilated cardiomyopathy (DCM) may improve cardiac function and allow explantation of the device. Generally, an ejection fraction of more than 40% is considered necessary for successful weaning from an LVAS, but less than 10% of DCM patients with an LVAS can achieve such a significant recovery of cardiac function. Cardiac resynchronization therapy, or atrial-synchronized biventricular pacing, has been found to treat congestive heart failure and ventricular dyssynchrony effectively. Here we report on a patient with an LVAS, in whom enough functional recovery could be obtained with resynchronization therapy for the device to be explanted successfully. A 32-year-old man was implanted with a Toyobo-NCVC paracorporeal LVAS to treat his intractable heart failure caused by idiopathic dilated cardiomyopathy. While on the LVAS for 8 months, his cardiac function recovered to some extent. The ejection fraction of his left ventricle (LVEF) improved from 9% to 41%. He chose explantation of the device rather than heart transplantation. Because he occasionally showed a wide QRS pattern on his ECG, epicardial biventricular pacing leads as well as a biventricular pacemaker were implanted on LVAS explantation surgery. An echocardiogram 2 weeks after explantation showed a marked difference in his LVEF by switching his biventricular pacing on and off (40% with biventricular pacing on and 29% with it off). Biventricular pacing may help recovery of cardiac function in selected LVAS patients and contribute to the increase in bridge to recovery cases.

Unilateral Absence of Pulmonary Artery and Ventricular Septal Defect in an Infant

A 2-month-old boy was diagnosed as having a rare combination of absence of left pulmonary artery and ventricular septal defect. He underwent intracardiac repair at the age of 8 months. Reconstruction of the left pulmonary artery was impossible because it could not be visualized through a median sternotomy. Although his early postoperative course was uneventful, he needed ipsilateral pneumonectomy 3 months later because of unremitting hemoptysis. Hilar left pulmonary artery, which used to exist, was not found even by histologic examination.

Fifteen-month circulatory support for sustained ventricular fibrillation by left ventricular assist device

1. Pennington DG, McBride LR, Peigh PS, Miller LW, Swartz MT. Eight years’ experience with bridging to cardiac transplantation. J Thorac Cardiovasc Surg. 1994;107:472-81. 2. Peterze B, Lonn U, Jansson K, Rutberg H, Casimir-Ahn H, Nylander E. Long-term follow-up of patients treated with an implantable left ventricular assist device as an extended bridge to heart transplantation. J Heart Lung Transplant. 2002;21:604-7. 3. Bank AJ, Mir SH, Nguyen DQ, Bolman RM 3rd, Shumway SJ, Miller LW, et al. Effects of left ventricular assist devices on outcomes in patients undergoing heart transplantation. Ann Thorac Surg. 2000;69: 1369-75. 4. Sun BC, Catanese KA, Spanier TB, Flannery MR, Gardocki MT, Marcus LS, et al. 100 long-term implantable left ventricular assist devices: the Columbia Presbyterian interim experience. Ann Thorac Surg. 1999;68:688-94. 5. Massad MG, McCarthy PM, Smedira NG, Cook DJ, Ratliff NB, Goormastic M, et al. Does successful bridging with the implantable left ventricular assist device affect cardiac transplantation outcome? J Thorac Cardiovasc Surg. 1996;112:1275-83.

Mitral regurgitation late after manouguian's anulus enlargement and aortic valve replacement

after RFCA therapy and led to a slow accumulation of hemopericardium. Although we were not able to determine the exact site of the chamber perforated, rupture of the right atrium would have been unlikely. The immediate accumulation of blood within the pericardium owing to the inability of atrial tissue to locally contract and contain extravasation would have acutely manifested itself as pericardial tamponade. The etiologic spectrum of constrictive pericarditis consists of postradiotherapy, postoperative, and postinfectious sequelae, as well as neoplasia, connective tissue disorders, and autoimmune disease. A persistent intrapericardial hematoma induces pericardial inflammation, leading to granulation tissue, adhesions, and finally constriction. Thus the possibility of an organized pericardial hematoma should not be overlooked in the differential diagnosis of constrictive pericarditis after RFCA therapy. Definitive diagnosis and therapy of constricting pericardial masses depends on operative removal as illustrated in this report.

Severe pulmonary stenosis and aortopulmonary fistula caused by a dissecting aneurysm in the ascending aorta

Discussion Surgical repair of aortic coarctation has expanded to include resection with end-to-end anastomosis, prosthetic patch aortoplasty, subclavian flap aortoplasty, and aortic resection with graft replacement. Because further aortic growth is not a problem in adult patients, graft replacement or bypass is often used and produces the best results. As the aortic wall in the portion of coarctation was thought to be fragile in our case because of the median necrosis, we used an open proxymal anastomosis technique to avoid possible aortic injury caused by crossclamping. The central cannulation technique is preferred for correction of postductal coarctation of the aorta to secure sufficient cerebral perfusion. In our case, this technique also had the advantage of preventing scattering of debris by the blood jet in an aortic aneurysm to cerebral blood flow. We prefer insertion of a venous cannula into the right atrium through the right femoral vein rather than insertion into the main pulmonary artery, as originally reported by Westaby and colleagues, because we have sometimes found that the wall of the main pulmonary artery is very fragile and thus susceptible to injury. We routinely insert a double-staged venous cannula through the right femoral vein in operations for descending aortic aneurysms and have experienced no technical problems. In conclusion, our “modified” central cannulation technique and open proxymal anastomosis technique seem to be safe. This is an appropriate approach for surgical correction, and we recommend it as the standard approach for the coarctation of the aorta in adults.

Effects of preoperative β-blocker use on clinical outcomes after coronary artery bypass grafting: A report from the Japanese cardiovascular surgery database

Background:The authors evaluated the effect of preoperative &bgr;-blocker use on early outcomes in patients undergoing coronary artery bypass grafting (CABG) in Japan. Methods:The authors analyzed 34,980 cases of isolated CABGs, performed between 2008 and 2011, at the 333 sites recorded in the Japanese Cardiovascular Surgical Database. In addition to the use of multivariate models, a one-to-one matched analysis, based on estimated propensity scores for patients with or without preoperative &bgr;-blocker use, was performed. Results:The study population (mean age, 68 yr) comprised 20% women, and &bgr;-blockers were used in 10,496 patients (30%), who were more likely to have risk factors and comorbidities than patients in whom &bgr;-blockers were not used. In the &bgr;-blocker and non-&bgr;-blocker groups, the crude in-hospital mortality rate was 1.7 versus 2.5%, whereas the composite complication rate was 9.7 versus 11.6%, respectively. However, after adjustment, preoperative &bgr;-blocker use was not a predictor of in-hospital mortality (odds ratio, 1.00; 95% CI, 0.82 to 1.21) or complications (odds ratio, 0.99; 95% CI, 0.91 to 1.08). When the outcomes of the two propensity-matched patient groups were compared, differences were not seen in the 30-day operative mortality (1.6 vs. 1.5%, respectively; P = 0.49) or postoperative complication (9.8 vs. 9.7%; P = 1.00) rates. The main findings were broadly consistent in a subgroup analysis of low-risk and high-risk groups. Conclusion:In this nationwide registry, the use of preoperative &bgr;-blockers did not affect short-term mortality or morbidity in patients undergoing CABG.

Left atrial appendage aneurysm causes severe mitral regurgitation and heart failure: Report of a successfully treated case

Left atrial appendage aneurysm (LAAA) is a rare cardiac anomaly. Its cause is believed to be a congenital dysplasia of the left atrial muscle. LAAA is different from acquired enlargement of the left atrium secondary to other cardiac diseases. In the second to third decades of life, some patients with LAAA experience palpitation, atrial tachyarrhythmia, progressive dyspnea, or atypical chest pain. LAAA usually appears as an isolated anomaly, and resultant mitral regurgitation (MR) has not been reported in the literature.

Successful treatment of ascending aortic graft infection after operation for acute aortic dissection with peripheral malperfusion

Mediastinitis with infection of an ascending aortic graft is hard to heal and is a highly fatal complication. We had a patient in whom mediastinitis with infection of such a graft as well as an ascending aorta-femoral artery bypass graft developed after the initial operation for type A aortic dissection accompanied by peripheral malperfusion. We treated it successfully by inserting a stent into the true lumen of the thoracoabdominal aorta and using a cryopreserved homograft to replace the infected ascending aortic fabric graft.