Clinical effects of long-term administration of pimobendan in patients with moderate congestive heart failure

Summary The long-term efficacy of the positive inotropic and vasodilator drug, pimobendan, was assessed in 21 patients suffering from symptomatic heart failure. Patients were randomized to 16 weeks of double-blind therapy with either 2.5 or 5.0mg/day of pimobendan (n = 10), or a matching placebo (n = 11). Patients were blinded on the study drug if their clinical status had not substantially worsened during the study. Of the placebo-treated patients, 5 patients were withdrawn from the study because of a deterioration of their heart failure, while none of the active treated group was withdrawn because of increased symptoms. Quality of life, assessed by the specific activity scale derived from the metabolic costs of individual physical activity, was 3.45 ± 0.90 (SD) mets in the baseline state and increased significantly after week 16, averaging 5.07 ± 1.40 and 4.67 ± 1.47 mets at weeks 16 and 24, respectively. In the placebo-treated group, the specific activity scale was 3.27 ± 1.21 mets at the baseline and remained unchanged throughout the study period. Patients treated with pimobendan were able to significantly increase their exercise duration. The accompanying increase in peak oxygen uptake was statistically insignificant, due to the limited number of patients enrolled in the study. These results suggest that in contrast to the recent pessimistic view of the long-term efficacy of cardiotonic drugs, pimobendan is beneficial in treating patients with congestive heart failure and may favorably modify their prognosis. Further largescale evaluation of this agent is warranted.     

Diagnosis of important fixed coronary stenosis in patients with variant angina by exercise tests after treatment with calcium antagonists

A 12 lead electrocardiogram was recorded during treadmill exercise in 57 patients with variant angina in whom coronary angiography was performed. Thirty six patients performed exercise tests with and without calcium antagonists, and 21 performed them only with calcium antagonists. In 55 patients calcium antagonists had prevented spontaneous attacks of variant angina for more than two days before the test. The other two patients were given a single dose of diltiazem (90 mg) two hours before the test. Exercise testing without calcium antagonists induced ST segment elevation with chest pain in nine patients, ST segment depression in 10 (nine with chest pain), and no important shift of the ST segment in 17. Five patients had severe coronary stenosis (greater than or equal to 75%) and all of them showed positive response. Thirty one patients had no important coronary stenosis and 14 of them showed positive response. The sensitivity of the exercise test in detecting a coronary stenosis greater than or equal to 75% was 100% without calcium antagonists but the specificity was low (55%). When the exercise test was done in patients taking calcium antagonists, only two (specificity 96%) of 48 patients without severe coronary stenosis showed positive response (elevation of ST segment in one and depression in another) whereas all nine patients with severe coronary stenosis had a positive response (depression of ST segment in six and elevation in three (sensitivity 100%). It is concluded that exercise testing with calcium antagonists may be a useful method for detecting severe coronary stenosis in patients with variant angina.     

Predictive factors for postoperative tachyarrhythmia after thoracoscopic esophagectomy and the usefulness of landiolol hydrochloride for its treatment

Background

Tachyarrhythmia after esophagectomy is a severe complication that should not be underestimated because of its negative impact. The aims of this study were to clarify the cause and impact of postoperative tachyarrhythmia after thoracoscopic esophagectomy. Additionally, we analyzed the usefulness of landiolol administration for postoperative tachyarrhythmia.

Methods

We evaluated the predictive factors for tachyarrhythmia onset after surgery and its clinical impact in 127 patients who underwent thoracoscopic esophagectomy with extended lymphadenectomy. Moreover, we analyzed the efficacy of landiolol for postoperative tachyarrhythmia.

Results

Tachyarrhythmia developed in 38 of the 127 patients. Multivariate analysis showed that advanced age, heart disease, and hyperlipidemia were associated with postoperative tachyarrhythmia. Hyponatremia, hypoalbuminemia, and leukocytosis on postoperative day 3 were significantly associated with tachyarrhythmia onset. The incidence of all complications and respiratory complications, including pneumonia, was significantly higher in patients with than in those without tachyarrhythmia. The mortality rate in the tachyarrhythmia group tended to be higher than that in the nontachyarrhythmia group. Landiolol as a treatment for tachyarrhythmia immediately decreased heart rate and safely reduced subsequent respiratory complications.

Conclusion

In elderly patients with cardiac disease or hyperlipidemia, surgeons should be alert for the occurrence of tachyarrhythmia after esophagectomy. Postoperative tachyarrhythmia is a marker of morbidities with particular emphasis on respiratory complications. However, it can be adequately managed by landiolol, resulting in fewer respiratory complications. Landiolol might be a safe and convenient agent for managing postoperative tachyarrhythmia after thoracoscopic esophagectomy, resulting in lower mortality and morbidity rates.     

A case of pancreatic schwannoma - The features in imaging studies compared with its pathological findings: Report of a case

Pancreatic schwannoma is a very rare tumor that tends to be confused with other pancreatic tumors preoperatively. We report a case of schwannoma of the pancreatic head. A 40-year-old woman was admitted to our hospital for treatment of a pancreatic tumor which was found by medical checkup. It was a well-defined solid tumor exhibiting heterogeneous enhancement with some necrotic foci on contrast-enhanced computed tomography (CT) and on magnetic resonance imaging (MRI). Angiography and CT during arteriography revealed the main feeding arteries of the tumor to be the posterior and anterior superior pancreaticoduodenal arteries. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed accumulation of FDG in the tumor with a maximum standardized uptake value of 3.6. We diagnosed a solid pseudopapillary neoplasm or a pancreatic neuroendocrine tumor preoperatively and performed pylorus-preserving pancreaticoduodenectomy. The tumor had well a well-defined capsule and was composed of a large solid portion containing spindle cells and a smaller hemorrhagic portion containing hypocellular stroma, and diagnosed as pancreatic schwannoma by immunohistochemistry. In this case, CT during arteriography was useful in determining the origin of the tumor. MRI reflected the pathological features of the tumor. The most important finding was that FDG-PET showed abnormal accumulation of FDG in the benign pancreatic schwannoma.     

A newly designed bioabsorbable substitute for the treatment of diaphragmatic defects

Purpose

Earlier studies have investigated the suitability of various materials and autologous grafts for the repair of diaphragmatic defects. Our group investigated the feasibility of using an artificial diaphragm (AD) to repair wide diaphragmatic defects.

Methods

Twelve pigs were laparotomized and, in each pig, a defect was fashioned by resecting a round 8-cm diameter hole in the left diaphragm. Next, the defect was repaired by implanting an AD. The animals were relaparotomized 8 or 24 weeks after implantation for gross, histological and radiological observation of the implanted sites.

Results

All recipient animals survived until killing for evaluation. Chest X-ray examinations showed no differences between the preoperative diaphragms and the grafted diaphragms at 8 and 24 weeks after implantation. At 8 weeks after implantation, the implanted sites exhibited fibrous adhesions to the liver and lungs without deformities or penetrations. Parts of the surface tissue at the graft sites had a varnished appearance similar to those of the native diaphragm. Histology performed at 8 weeks detected no trace of the ADs in the graft sites; however, numerous inflammatory cells and profuse fibrous connective tissue were observed. At 24 weeks after implantation, no differences were found in the thorax between the areas with the grafts and the unaffected areas. Histology of the graft sites in the thorax confirmed growth of mesothelial cells similar to that observed in the native diaphragm.

Conclusions

Artificial diaphragms can be a novel substitute for diaphragmatic repair.     

A Double-blind Clinical Evaluation of the Effect of Nizofenone (Y-9179) on Delayed Ischemic Neurological Deficits Following Aneurysmal Rupture

The effect of Nizofenone (Y-9179), a verebral protective agent, on delayed ischemic neurological deficits following subarachnoid hemorrhage (SAH) due to aneurysmal rupture was investigated by a cooperative double-blind clinical trial. Delayed ischemic neurological deficits following SAH are closely associated with the occurrence of vasospasm, and the effectiveness of any cerebral protective agent depends on sufficient coverage by the drug over the period around the onset of ischemic insult. Therefore, the study was designed so that the effect of Nizofenone could be analyzed in terms of these two factors.

In patients admitted within day 9 of SAH, drug administration was immediately initiated and continued for 5 days. When delayed ischemic neurological deficits occurred, angiography was carried out to confirm the presence of vasospasm, and then drug administration was extended for an additional 5 days. Ten of the 100 cases enlisted in the study were excluded prior to code-breaking because of the occurrence of severe complications not related to vasospasm.

Out of the 42 cases of the Nizofenone group and 48 of the placebo group, 25 and 29 developed vasospasm, respectively. Thus Nizofenone did not prevent vasospasm. Of the 25 cases of the Nizofenone group with vasospasm, 13 cases received sufficient drug coverage around the onset of vasospasm. The placebo group, the total Nizofenone group, and the Nizofenone group with sufficient drug coverage were stratified according to the occurrence of vasospasm. The disability status index one month after admission and the neurological functions, such as motor and speech functions, of each group were then compared. In patients who developed vasospasm, only the Nizofenone group with sufficient drug coverage had a significantly better outcome than the placebo group (p < 0.05). No particular side effect of Nizofenone was observed.

Thus, the results indicate that Nizofenone may be useful in the therapy of delayed ischemic neurological deficits following SAH, although the effect of the drug may be considerably influenced by the timing of its administration.     

Extracranial-intracranial bypass for internal carotid/middle cerebral atherosclerotic steno-occlusive diseases in conjunction with carotid endarterectomy for contralateral cervical carotid stenosis: clinical results and cognitive performance

Clinical results as well as cognitive performances after extracranial to intracranial (EC-IC) bypass in conjunction with contralateral carotid endarterectomy (CEA) are poorly understood. Data from 14 patients who underwent unilateral EC-IC bypass for atherosclerotic internal carotid artery (ICA)/middle cerebral artery (MCA) steno-occlusive disease in conjunction with CEA for contralateral cervical carotid stenosis were retrospectively reviewed. Postoperative results were evaluated by MRI imagings. Nine patients also underwent neuropsychological examinations (NPEs), including assessment by the Wechsler Adult Intelligence Scale-Third Edition and the Wechsler Memory Scale-Revised (WMS-R) before and about 6 months after bilateral surgeries. Postoperative MRI follow-up (median, 8 months; interquartile range, 7–8 months) confirmed successful bypass in all patients, with no additional ischemic lesions on T2WI when compared with preoperative imaging. Further, MRA showed patent bypass and contralateral smooth patency at CEA portion in all patients. In the group rate analysis, all five postoperative NPE scores (Verbal IQ, Performance IQ, WMS-memory, WMS-attention, and Average scores of all those four scores) were improved relative to preoperative NPE scores. Performance IQ and Average score improvements were statistically significant. Clinical results after EC-IC bypass in conjunction with contralateral CEA were feasible. Based on the group rate analysis, we conclude that successful unilateral EC-IC bypass and contralateral carotid endarterectomy does not adversely affect postoperative cognitive function.