Hiroshi Ohira

18F-Fluoro-2-deoxyglucose positron emission tomography in cardiac sarcoidosis

Cardiac sarcoidosis (CS) is a rare and potentially life-threatening disease that causes conduction disturbance, systolic dysfunction, and most notably sudden cardiac death. Accurate diagnosis of CS is thus mandatory; however, a reliable approach that enables diagnosis of CS with high sensitivity and specificity has yet to be established. Recent studies have demonstrated the promising potential of 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) in the diagnosis and assessment of CS. Indeed, 18F-FDG PET provides a wide variety of advantages over previous imaging modalities; however, there are pitfalls and limitations that should be recognized. In this review article, (1) the rationale for 18F-FDG PET application in CS, (2) suitable pretest preparations, and (3) evaluation protocols for the 18F-FDG PET images obtained will be addressed. In particular, sufficient suppression of physiological 18F-FDG uptake in the heart is essential for accurate assessment of CS. Also, (4) recent studies addressing the diagnostic role of 18F-FDG PET and (5) the clinically important differences between 18F-FDG PET and other imaging technologies will be reviewed. For example, active sarcoid lesions and their response to steroid treatment will be better detected by 18F-FDG PET, whereas fibrotic lesions might be shown more clearly by magnetic resonance imaging or other nuclear myocardial perfusion imaging. In the last decade, 18F-FDG PET has substantially enhanced detection of CS; however, CS would be better evaluated by a combination of multiple modalities. In the future, advances in 18F-FDG PET and other emerging imaging modalities are expected to enable better management of patients with sarcoidosis.

Electrophysiologic effects of ischemic preconditioning on QT dispersion during coronary angioplasty

OBJECTIVES The aim of this study was to examine the effect of ischemic preconditioning on the manner of ventricular repolarization by assessing the change in QT dispersion during coronary angioplasty. BACKGROUND QT interval dispersion reflects regional variations in ventricular repolarization and cardiac electrical instability. Previous studies have suggested that increased QT dispersion is associated with an increased incidence of malignant ventricular arrhythmias, whereas brief episodes of myocardial ischemia can render the heart more resistant to subsequent ischemic episodes, a phenomenon called ischemic preconditioning. METHODS To assess the effects of ischemic preconditioning on myocardial repolarization by examining the change in QT dispersion during coronary angioplasty, we studied 47 consecutive patients (39 men and 8 women; mean age 57 +/- 16 years). QT dispersion was measured after each balloon inflation during coronary angioplasty. Statistical analysis was performed by using repeated measurement of analysis of variance. RESULTS There were significant differences in QT dispersion as the number of balloon inflations increased (mean +/- SD 52 +/- 14, 42 +/- 11, 36 +/- 9, 31 +/- 10 and 29 +/- 11 ms, respectively [p < 0.01], for the first, second, third, fourth and fifth balloon inflations). The magnitude of decrease in QT dispersion was significant in the first and second balloon inflations, then became insignificant with later inflations. CONCLUSIONS These data indicate that the gradual decrease in QT dispersion provoked by coronary artery occlusion and reperfusion during coronary angioplasty may be associated with electrophysiologic effects of ischemic preconditioning on myocardium in the human heart.

Radiofrequency Catheter Ablation for AV Nodal Reentrant Tachycardia Associated with Persistent Left Superior Vena Cava

Slow A V nodal pathway ablation using RF is highly effective for patients with refractory A V nodal reentrant tachycardia (AVNRT). We report three catheter ablation cases using RF current in patients associated with persistent left superior vena cava (PLSVC). Three patients with drug refractory AVNHT of common variety were involved in this study. An electrode catheter introduced through the left subclavian vein inserted directly into the coronary sinus, a typical anatomical finding of PLSVC. The ablation procedure was initially performed at the posteroinferior region of Kochs triangle. A slow pathway potential could not be found from that area; nonsustained junctional tachycardia (NSJT) did not occur during the delivery of RF current; there was failure to eliminate slow AV nodal pathway conduction. The catheter then was moved into the bed of the proximal portion of the markedly enlarged coronary sinus. A slow AV nodal pathway potential was recorded through the ablation catheter, and the delivery of RF current caused NSJT in two patients. Complete elimination of slow AV nodal pathway conduction was accomplished in these two patients by this method. No adverse effects were provoked by this procedure. Catheter ablation of the slow A V nodal pathway guided by a slow pathway potential and the appearance of NSJT was feasible and safe in the area of the coronary sinus ostium in patients associated with PLSVC.

Associations among the plasma amino acid profile, obesity, and glucose metabolism in Japanese adults with normal glucose tolerance

BackgroundAmino acids (AAs) are emerging as a new class of effective molecules in the etiology of obesity and diabetes mellitus. However, most investigations have focused on subjects with obesity and/or impaired glucose regulation; the possible involvement of AAs in the initial phase of glucose dysregulation remains poorly understood. Furthermore, little attention has been given to possible associations between the pattern/degree of fat deposition and the plasma AA profile. Our objective was therefore to determine the relationships between plasma AA concentrations and the type/degree of obesity and glucose regulation in Japanese adults with normal glucose tolerance.MethodsEighty-three subjects with normal glucose tolerance were classified as obese or nonobese and as visceral obesity or nonvisceral obesity. Correlations between the plasma levels of 23 AAs and somatometric measurements, visceral fat area (VFA), subcutaneous fat area (SFA), and 75-g oral glucose tolerance test results were analyzed.ResultsObesity or visceral obesity was associated with higher levels of branched-chain AAs (isoleucine, leucine, and valine), lysine, tryptophan, cystine, and glutamate but lower levels of asparagine, citrulline, glutamine, glycine, and serine (p < 0.04). Age- and gender-adjusted analyses indicated that VFA was positively correlated with tryptophan and glutamate levels, whereas VFA and SFA were negatively correlated with citrulline, glutamine, and glycine levels (p < 0.05). The fasting and 2-h plasma glucose levels or the homeostasis model assessment of insulin resistance were positively correlated with valine, glutamate, and tyrosine levels but negatively correlated with citrulline, glutamine, and glycine levels. The homeostasis model assessment for the β-cell function index was positively correlated with leucine, tryptophan, valine, and glutamate levels but negatively correlated with citrulline, glutamine, glycine, and serine levels (p < 0.05).ConclusionsThe present study identified specific associations between 10 AAs and the type/degree of obesity, and indices of glucose/insulin regulation, in Japanese adults with preserved glucose metabolism. With the growing concern about the increasing prevalence of obesity and diabetes, the possible roles of these AAs as early markers and/or precursors warrant further investigation.

The short-term role of corticosteroid therapy for pulmonary arterial hypertension associated with connective tissue diseases: report of five cases and a literature review.

Pulmonary arterial hypertension (PAH) is a life-threatening complication in connective tissue diseases (CTD). It remains controversial whether immunosuppressive therapy is useful for PAH associated with CTD (PAH-CTD). The Dana Point algorithm does not refer such treatments in patients with PAH-CTD due to the lack of evidence. However, some case reports have shown the potential efficacy of immunosuppression for PAH-CTD. Here we report five cases of PAH-CTD treated with corticosteroids and discuss the current management of PAH-CTD with immunosuppressive agents. Our cases consisted of three active systemic lupus erythematosus (SLE), a quiescent SLE and an active polymyositis. WHO functional classes at baseline were class III in three cases and class II in two. Median follow-up period was 44 (28–92) weeks. PAH was diagnosed by right heart catheterization in all cases (median pulmonary arterial pressure was 45 (29–49) mmHg). All patients received 1 mg/kg of prednisolone (PSL) for 2–4 weeks, followed by appropriate dose reduction. Methylprednisolone pulse therapy was performed in patients resistant to the high dosage of PSL. Four patients received vasodilators in combination. The therapy as above improved WHO functional class 4 weeks after the initiation of PSL in all the patients. Two patients required dose increase or additional administration of vasodilators due to the dose reduction of PSL. Corticosteroid therapy may be effective for PAH-CTD at least in the short term, even in low general activity of CTD or moderate PAH. Our experience suggests that corticosteroid therapy, by itself or in conjunction with standard vasodilators, is effective for PAH-CTD patients.

Radiofrequency thermal balloon coronary angioplasty: A new device for successful percutaneous transluminal coronary angioplasty

OBJECTIVES The purpose of this study was to evaluate the effects of thermal balloon percutaneous transluminal coronary angioplasty using radiofrequency energy in the treatment of patients with failed coronary angioplasty and complex lesions. In addition, we evaluated restenosis after radiofrequency thermal balloon applications. BACKGROUND The efficacy of coronary angioplasty is limited by the relatively low success rate in complex lesions and the high frequency of restenosis. Few reports have studied the combined effects of pressure and laser thermal energy. This study describes a new device for coronary angioplasty using radiofrequency thermal energy. METHODS Thirty-two patients with failed conventional coronary angioplasty or complex lesions were treated with radiofrequency thermal balloon coronary angioplasty. Radiofrequency energy was delivered up to 11 times in exposures ranging from 30 to 60 s in duration. This combined effect allowed the vascular wall to be heated to temperatures ranging from 60 to 70 degrees C. Follow-up coronary angiography was performed, on average, 6 months after the procedure. RESULTS Successful radiofrequency coronary angioplasty was achieved in 28 (82%) of 34 lesions. There was one abrupt coronary artery occlusion (3%) and no death, perforation or dissection. Angiographic restenosis occurred in 14 (56%) of 25 lesions. CONCLUSIONS In patients with failed coronary angioplasty and difficult complex lesions, radiofrequency coronary angioplasty could potentially improve angioplasty success rates and may have important implications for bailout cases with abrupt occlusion. However, restenosis remains a significant problem.

Radiofrequency ablation of tachyarrhythmias in patients with Ebstein's anomaly

We performed radiofrequency catheter ablation in five patients associated with Ebsteins anomaly to cure their refractory tachyarrhythmias. The presenting arrhythmias were four cases of orthodromic circus movement tachycardia using accessory pathways as a requisite limb, including one case of a Mahaim fiber and one of atrial flutter of common variety. All accessory pathways, including the Mahaim fiber, were ablated by RF energy delivered through the catheter placed at the AV annulus rather than the displaced anatomical AV groove. Interestingly, the antegrade or retrograde conduction interval over these accessory pathways was relatively longer than that of usual accessory pathways, and the accessory pathway potential was fractionated in some cases. The location of the atrioventricular node was displaced from the usual position to the postero-inferior area of Kochs triangle in one case. The configuration of the flutter wave was larger than usual in height as well as in width. All tachyarrhythmias were cured by RF catheter ablation. In the case of RF catheter ablation for patients with Ebsteins anomaly, close attention is indispensable in order to accomplish it safely and successfully, because of the anatomical and functional differences peculiar to Ebsteins anomaly.

Outcome of prolonged balloon inflation for the management of coronary perforation.

BACKGROUND Coronary perforation (CP) is a rare, sometimes lethal complication of percutaneous coronary intervention (PCI). OBJECTIVES The purpose of this study was to review the cases of CP and to investigate the management after CP. METHODS A total of 3469 PCIs were performed in our institution from April 1999 to April 2008. All CP cases were identified from our computerized database. RESULTS Thirty patients were identified as having CP (0.86%). According to the Ellis classification, we determined the grade of perforation as type I in 17 cases (56%), type II in 2 cases (7%), and type III in 11 cases (37%). Most CPs were caused by wires (53%), while balloons, stents, and atherectomy devices were responsible for 7%, 37%, and 3%, respectively. Wire caused only 1 case of type III CP (6%), while stent caused 9 type III CPs (82%, p<0.01). Four patients (36%) with type III CP required urgent coronary artery bypass graft surgery (CABG), while no patient with type I/II CP required it (p<0.01). Prolonged balloon inflations were effective for 8 cases out of 11 stent CPs, however, the ballooning duration was significantly longer than that in wire and balloon CP (44±37min vs. 21±13min, p<0.05). CONCLUSIONS Stent CP often causes type III CP and one third of type III CP required urgent CABG. Although stent CP required longer balloon inflations for the management, prolonged balloon inflation might be useful for the management even in the stent CP.

Inter- and Intra- observer agreement of FDG-PET/CT image interpretation in patients referred for assessment of Cardiac Sarcoidosis

Recent studies have reported the usefulness of 18F-FDG PET in aiding with the diagnosis and management of patients with cardiac sarcoidosis (CS). However, image interpretation of 18F-FDG PET for CS is sometimes challenging. We sought to investigate the inter- and intraobserver agreement and explore factors that led to important discrepancies between readers. Methods: We studied consecutive patients with no significant coronary artery disease who were referred for assessment of CS. Two experienced readers masked to clinical information, imaging reports, independently reviewed 18F-FDG PET/CT images. 18F-FDG PET/CT images were interpreted according to a predefined standard operating procedure, with cardiac 18F-FDG uptake patterns categorized into 5 patterns: none, focal, focal on diffuse, diffuse, and isolated lateral wall or basal uptake. Overall image assessment was classified as either consistent with active CS or not. Results: One hundred scans were included from 71 patients. Of these, 46 underwent 18F-FDG PET/CT with a no-restriction diet (no-restriction group), and 54 underwent 18F-FDG PET/CT with a low-carbohydrate, high-fat and protein-permitted diet (low-carb group). There was agreement of the interpretation category in 74 of 100 scans. The κ-value of agreement among all 5 categories was 0.64, indicating moderate agreement. For overall clinical interpretation, there was agreement in 93 of 100 scans (κ = 0.85). When scans were divided into the preparation groups, there was a trend toward higher agreement in the low-carb group versus the no-restriction group (80% vs. 67%, P = 0.08). Regarding the overall clinical interpretation, there was also a trend toward greater agreement in the low-carb group versus the no-restriction group (96% vs. 89%, P = 0.08). Conclusion: The interobserver agreement of cardiac 18F-FDG uptake image patterns was moderate. However, agreement was better regarding overall interpretation of CS. Detailed prescan dietary preparation seemed to improve interobserver agreement.

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of 131I-huA33 with Concurrent Capecitabine

huA33 is a humanized antibody that targets the A33 antigen, which is highly expressed in intestinal epithelium and more than 95% of human colon cancers but not other normal tissues. Previous studies have shown huA33 can target and be retained in a metastatic tumor for 6 wk but eliminated from normal colonocytes within days. This phase I study used radiolabeled huA33 in combination with capecitabine to target chemoradiation to metastatic colorectal cancer. The primary objective was safety and tolerability of the combination of capecitabine and 131I-huA33. Pharmacokinetics, biodistribution, immunogenicity, and tumor response were also assessed. Methods: Eligibility included measurable metastatic colorectal cancer, adequate hematologic and biochemical function, and informed consent. An outpatient scout 131I-huA33 dose was followed by a single-therapy infusion 1 wk later, when capecitabine was commenced. Dose escalation occurred over 5 dose levels. Patients were evaluated weekly, with tumor response assessment at the end of the 12-wk trial. Tumor targeting was assessed using a γ camera and SPECT imaging. Results: Nineteen eligible patients were enrolled. The most frequently observed toxicity included myelosuppression, gastrointestinal symptoms, and asymptomatic hyperbilirubinemia. Biodistribution analysis demonstrated excellent tumor targeting of the known tumor sites, expected transient bowel uptake, but no other normal tissue uptake. 131I-huA33 demonstrated a mean terminal half-life and serum clearance suited to radioimmunotherapy (T1/2β, 100.24 ± 20.92 h, and clearance, 36.72 ± 8.01 mL/h). The mean total tumor dose was 13.8 ± 7.6 Gy (range, 5.1–26.9 Gy). One patient had a partial response, and 10 patients had stable disease. Conclusion: 131I-huA33 achieves specific targeting of radiotherapy to colorectal cancer metastases and can be safely combined with chemotherapy, providing an opportunity to deliver chemoradiation specifically to metastatic disease in colorectal cancer patients.