Safety and efficacy of verinurad, a selective URAT1 inhibitor, for the treatment of patients with gout and/or asymptomatic hyperuricemia in the United States and Japan: Findings from two phase II trials.

Objective: Evaluate efficacy/safety of verinurad monotherapy in patients with gout (Japan/US) or asymptomatic hyperuricemia (Japan).Methods: Two randomized, placebo-controlled, phase II studies were conducted (NCT01927198/NCT02078219). Patients were randomized to once-daily doses of placebo or escalating doses of verinurad (study 1: 5-12.5 mg; study 2: 2.5-15 mg). Primary endpoint was percentage change from baseline in serum urate (sUA) at week 12 (study 1)/week 16 (study 2). Safety was also assessed.Results: Most patients in study 1 (n = 171) were white (74.9%); all patients were Japanese in study 2 (n = 204). Least squares means (±SE) estimate of percentage change in sUA levels from baseline in study 1 was 1.2 ± 2.9 for placebo, and -17.5 ± 2.8, -29.1 ± 2.8, -34.4 ± 2.9 for verinurad 5, 10, 12.5 mg, respectively. In study 2, results were -2.4 ± 2.5 and -31.7 ± 2.5, -51.7 ± 2.6,-55.8 ± 2.5, respectively. Difference from placebo was significant for each verinurad dose (p<.0001). The proportion of patients with treatment-emergent adverse events (TEAEs) was similar across all groups. Renal-related TEAEs were more common with verinurad than placebo.Conclusion: Verinurad monotherapy resulted in sustained reductions in sUA in Japanese/US patients but renal AEs occurred, so verinurad alone is not recommended for treatment of hyperuricemia or gout. The renal consequences of excessive uric acid excretion deserve study.

A case report of papillary fibroelastoma attached to chorda tendineae of mitral valve.

The case was a Japanese man of 62 years old. A bulbar mass attached to mitral valve anterior leaflet was discovered in an echocardiography within detailed examination of ischemic heart disease accidentally. We diagnosed him as ischemic heart disease and doubt of heart tumor. We thought about the danger of future embolism, surgical treatment was decided. We dissected the tumor together with one chorda tendineae of mitral valve, and a performed aorta - coronary bypass surgery. We diagnosed the tumor as papillary fibroelastoma by pathological diagnosis. Papillary fibroelastoma is extremely rare with 7-9% of benign tumor of heart primary. Most of the papillary fibroelastoma is incidentally discovered by echocardiography or autopsy. Or it is discovered for systemic embolism. The tumor is benign, but there is a problem to cause embolism. Therefore, when we discovered papillary fibroelastoma, surgical resection of the tumor is the first-line therapy. A problem on surgical therapy is the range of resection area. Papillary fibroelastoma is benign tumor, but the pathological characteristic is still unidentified. Further epidemiological and pathological studies are necessary to determine the extent of surgical excision in associated with characteristics of papillary fibroelastoma.

Aortic root reconstruction in two patients with chronic aortic dissection by aortic valve-sparing procedures using a new aortic root conduit with the sinuses of valsalva (De Paulis Valsalva graft).

The durability of the aortic valve after aortic root reconstruction by an aortic valve-sparing procedure is of particular concern because of the absence of the sinuses of Valsalva in the David type-I reimplantation method. Various improvements have been made to the David-I method. In particular, a new aortic root conduit with the sinuses of Valsalva was developed recently and is expected to improve the long-term follow-up results of the aortic valve-sparing procedures. We used a Valsalva graft in two patients with aortic root dilation accompanied by aortic regurgitation and obtained good short-term results.

Aortic root reconstruction by aortic valve-sparing operation (David type I reimplantation) in Marfan syndrome accompanied by annuloaortic ectasia and acute type-A aortic dissection.

To reconstruct the aortic root for aneurysm of the ascending aorta accompanied by aortic regurgitation, annuloaortic ectasia (AAE) and acute type-A dissection with root destruction, the Bentall operation using a prosthetic valve still is the standard procedure today. Valve-sparing procedures have actively been used for aortic root lesions, and have also been attempted in aortic root reconstruction for Marfan syndrome which may have abnormalities in the valve leaflets. We conducted a valve-sparing procedure in a female patient with Marfan syndrome who had AAE accompanied by type-A acute aortic dissection. The patient was a 37-year-old woman complaining of severe pain from the chest to the back. The limbs were long, and funnel breast was observed. Diastolic murmurs were heard. On chest computed tomography, a dissection cavity was present from the ascending aorta to the left common iliac artery, and the root dilated to 55 mm. Grade II aortic regurgitation was observed on ultrasound cardiography. Regarding her family history, her father had died suddenly at 54 years of age. She was diagnosed with type-A acute dissection concurrent with Marfan syndrome and AAE. The structure of the aortic valve was normal, and root reconstruction by a valve-sparing operation and total replacement of the aortic arch was conducted. On postoperative ultrasound cardiography, the aortic regurgitation was within the allowable range, and the shortterm postoperative results were good.

Recent surgical outcomes of acute type-A aortic dissection.

The aim of this study is to assess the early outcome of the surgical treatment of acute type-A aortic dissection using recent improvements in antegrade selective cerebral perfusion. This study included 38 patients who had undergone surgery for acute type-A aortic dissection from October 2003 through March 2006. The surgery results were evaluated in 2 groups: group A was composed of those who had undergone the surgery before the procedures of antegrade selective cerebral perfusion was changed in December 2004, and group B consisted of those who had the surgery after the change. Operations were performed with hypothermic cardiopulmonary bypass, antegrade selective cerebral perfusion during the arch repair, and open distal anastomosis. Times to awakening after the surgery were 27.6±26.2 hours in group A and 19.8±22.3 hours in group B (p= 0.5). Intubation times were 8.55±7.09 days in group A and 5.11±2.56 days in group B (p=0.06). Permanent neurologic dysfunction was observed in 3 patients in group A and 1 in group B (p=0.6). Transient neurologic dysfunction was observed in 4 patients each in groups A and B (p=1). Mortality rates were 21.1% in group A and 10.5% in group B (p=0.65). There were no significant differences in mortality or morbidity between the two groups, but the intubation time tended to be shorter in group B.

Surgical treatment of chronic atrial fibrillation: Report of 8 cases.

Since February 2003, we have conducted surgical treatment on 8 patients complicated with chronic atrial fibrillation during cardiac surgery. A radial procedure was conducted on 7 patients, and pulmonary vein isolation was conducted on 1 patient. Underlying diseases included mitral regurgitation (MR) in 5 patients, mitral stenosis (MS) in 1 patient, aortic stenosis (AS) + MS in 1 patient and chronic type A dissociation in 1 patient. Simultaneous procedures included mitral valve plasty (MVP) in 3 patients, mitral valve replacement (MVR) in 3 patients, aortic valve replacement (AVR) + MVR in 1 patient, and aortic root reconstruction by reimplantation procedure + total arch replacement in 1 patient. The operation time was 320 to 840 minutes and 458.1± 171.1 minutes on average. The cardiopulmonary bypass time was 204 to 404 minutes and 266.7 ± 62.7 minutes on average. The aortic cross-clamp time was 142 to 271 minutes and 171± 41.5 minutes on average. One patient died in hospital. Six patients returned to sinus rhythm, and 1 patient required pacemaker implantation. The follow-up period was 2 to 37 months and 13.6 ± 15 months on average. When cryoablation was changed to radiofrequency ablation to assist preparation of the block line, a tendency toward shortening of the aortic clamping time was observed.

Surgical outcome of stentless aortic valve replacement for calcified aortic stenosis.

We have conducted aortic valve replacement (AVR) using a stentless bioprosthesis (Medtronic Freestyle valve) on 10 patients with calcified aortic stenosis since March 2004. There were 64-84 years of age and 75 ± 5.5 years old on average, and included 4 males. Implantation was conducted by a modified subcoronary method in all the patients. The preoperative New York Heart Association class was class II in 80% of the patients. The preoperative left ventricular mass and the left ventricular mass index (LVMI) were 193.1-524.1 g and 144.1-299.5 g/m2 and, on average 328.4 ± 104.7 g and 217.3 ± 55.7 g/m2, respectively. The annulus dimension was 18-24 mm and, on average, 20.3 ± 1.7 mm. The size of implanted valve was 19-25 mm and, on average, 21 ± 2.2 mm. The maximum pressure gradient of the aortic valve remained at 14.2-46.5 mmHg, 25.2 ± 10.2 mmHg on average, 1 or 2 months after surgery, but the LVMI significantly improved to 153.2 ± 33.9 g/m2 (p = 0.018). The hospitalization period were 24.7 ± 16.9 days for all the patients and 19.3 ± 5.1 days for patients undergoing the AVR alone. These results show that LVMI is significantly reduced by using a stentless bioprosthesis in the early phase after surgery, and early discharge from hospital can be expected by concurrently using minimally invasive cardiac surgery.

A patient who underwent surgical treatment of an adult-type aneurysm in the nonpatent arterial duct.

Adult-type aneurysms in the arterial duct are rare, and their spontaneous prognosis is poor. We performed surgical treatment of an aneurysm in the arterial duct in a 62-year-old male. The patient had had hoarseness since November 2003, and was referred to our hospital in March 2004. Thoracic CT and aortography demonstrated a sacciform aneurysm in the aorta in the distal arch region on the lesser curvature side. The patient was diagnosed as having an adult-type aneurysm in the nonpatent arterial duct, and underwent surgical treatment in April 2004. Thoracotomy in the fourth left intercostal space was performed up to the thoracic aorta, and a sacciform aneurysm, measuring 35 mm x 32 mm, was detected in the arterial duct. The recurrent laryngeal nerve adhering to the front surface of the aneurysm was overextended. Under partial extracorporeal circulation, the aneurysm was excised, and replaced by an artificial blood vessel. The postoperative course was satisfactory, and the patient was discharged from the hospital 14 days after surgery. The surgical outcome was good, and the hoarseness was improved. Taking possible complications into consideration, surgical treatment can be recommended in the early stage.

Subepicardial aneurysm detected during diagnosis of acute cardiac failure.

A 55-year-old female developed dyspnea at night and visited our hospital. A diagnosis of acute cardiac failure was made and the patient was immediately admitted. A false ventricular aneurysm with blood flow was found in the lateral wall of the left ventricle. Past history of myocardial infarction was not clear. Repeated cardiac failure may have resulted from decreased cardiac output by increased blood flow in the aneurysm due to its expansion. After patch closure was performed, the symptoms improved.