Masahiro Higashi

Unblinded Pilot Study of Autologous Transplantation of Bone Marrow Mononuclear Cells in Patients With Thromboangiitis Obliterans

Background— The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans. Methods and Results— Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684±549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1±0.7 to 1.5±1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year. Conclusions— In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.

Rapid Evaluation Of Right And Left Ventricular Function And Mass Using Real-time True-fisp Cine Mr Imaging Without Breath-hold: Comparison With Segmented True-fisp Cine Mr Imaging With Breath-hold

PURPOSEnTo evaluate the accuracy of cardiac function measured with real-time true fast imaging with steady-state precession (True-FISP) cine without breath-hold compared with those measured from segmented True-FISP cine with breath-hold.nnnMETHODSnEighteen consecutive patients and six healthy volunteers were enrolled in the study group. Both real-time multislice True-FISP cine imaging without breath-hold and single-slice segmented True-FISP cine imaging with multiple breath-holds were performed in short-axis imaging sections to encompass the entire ventricles. Vertical long-axis cine imaging using real-time True-FISP cine sequence without breath-hold was performed to evaluate heart motion during respiration in 13 subjects. Ventricular volume and mass were evaluated by four observers independently with manual tracing.nnnRESULTSnReal-time True-FISP cine quality was sufficient for contour detection in all 24 subjects. Cardiodynamic measurements based on real-time True-FISP cine correlated well with those based on segmented True-FISP cine [left ventricular (LV) end-diastolic volume: r = 0.98; LV end-systolic volume: r = 0.98; LV ejection fraction: r = 0.91; LV mass: r = 0.96; right ventricular (RV) end-diastolic volume: r = 0.89; RV end-systolic volume: r = 0.94; RV ejection fraction: r = 0.79]. Intra- and interobserver variability were sufficiently small in real-time True-FISP cine without breath-hold. Heart motion during respiration along the long axis of the left ventricle (2.2 mm to 3.7 mm) was much less than the slice interval (10 mm), confirming that misregistration of slice position during respiration was low.nnnCONCLUSIONnReal-time True-FISP cine without breath-hold has high reproducibility and is applicable to patients with severe cardiac dysfunction and/or arrhythmias.

Characteristics in Phenotypic Manifestations of Genetically Proved Marfan Syndrome in a Japanese Population

Diagnosis of Marfan syndrome (MS) is made according to the Ghent nosology, which is based on data from European and American populations. The validity of applying the Ghent nosology to other than Western populations is an ongoing discussion because there may be racial differences in basic physical features. The validity of applying the Ghent nosology to patients other than Westerners suspected of having MS was examined. One hundred thirteen Japanese patients who were suspected of having MS and underwent genetic analysis were examined to see whether they fulfilled the Ghent nosology. Of 113 patients, MS was diagnosed in 58 patients/51 probands. Of these 51 probands, 46 (90%) showed mutations in the Fibrillin-1 gene(FBN1) and were enrolled in this study. The frequency of each manifestation of Ghent nosology in the Japanese population was compared with those reported in the FBN1 Universal Mutation Database that was mainly obtained from the Western population (n = 1,013 probands). Frequencies were lower in the Japanese population than the Western population of the manifestations of arm span to height ratio >1.05 (20% vs 55%; p <0.01), scoliosis (40% vs 53%; p <0.05), reduced extension at elbows (2% vs 16%; p <0.05), and joint hypermobility (46% vs 63%; p <0.05). In conclusion, we found a lower frequency of skeletal manifestations of MS in Japanese patients than reported in the database for Western patients with MS. It was possible that the diagnosis of MS according to the Ghent nosology for Japanese patients was underestimated, especially for skeletal involvements.

Impact of Elevated D-Dimer on Diagnosis of Acute Aortic Dissection With Isolated Neurological Symptoms in Ischemic Stroke

BACKGROUNDnPlasma D-dimer is known to be a useful clinical marker of thrombogenic status, and D-dimer is used as a diagnostic marker for acute aortic dissection (AAD). Little is known, however, regarding the clinical value of D-dimer for diagnosis of asymptomatic AAD in patients with ischemic stroke. We investigated whether D-dimer could be used for early diagnosis of AAD with isolated neurological symptoms in ischemic stroke patients.nnnMETHODS AND RESULTSnWe evaluated a total of 1,236 consecutive patients with symptomatic ischemic stroke without chest or back pain who underwent either head computed tomography or magnetic resonance imaging. D-dimer was measured within 24 h after onset. There were 9 patients with Stanford type A AAD and they had significantly higher D-dimer than the patients without AAD (mean, 46.47±54.48 μg/ml; range, 6.9-167.1 μg/ml vs. 2.33±3.58 μg/ml, 0.3-57.9 μg/ml, P<0.001). When a cut-off of 6.9 μg/ml was adopted for d-dimer on the basis of receiver operating characteristics analysis, the sensitivity and specificity for AAD were 100% and 94.8%, respectively, while the positive and negative predictive values were 14.7% and 100%, respectively.nnnCONCLUSIONSnD-dimer might be a useful marker for the early diagnosis of AAD with isolated neurological symptoms in ischemic stroke patients. Whole-body contrast-enhanced computed tomography should be performed in ischemic stroke patients who have high D-dimer.

Detectability of Ischemic Lesions on Diffusion-Weighted Imaging Is Biphasic after Transient Ischemic Attack

BACKGROUNDnExperimental studies of transient focal ischemia indicate biphasic detectability of lesions by diffusion-weighted imaging (DWI); poorly detectable phase exists at 1-12 hours after reperfusion. The present study aimed to clarify whether poorly detectable phase also exists in DWI of transient ischemic attack (TIA) patients.nnnMETHODSnA retrospective study was conducted in 144 consecutive TIA patients who underwent magnetic resonance imaging (MRI) within 2 weeks after carotid TIA. Patients were classified into 9 groups according to time from disappearance of TIA symptoms to DWI: intraischemic period, 0-1 hour, 1-12 hours, 12-24 hours, 1-2 days, 2-3 days, 3-7 days, 7-10 days, and 10-14 days after the end of TIA.nnnRESULTSnLesions were detected in 33 of 144 patients (22.9%). The frequency of positive lesions was 20% in the intraischemic period and 30.8% at 0-1 hour after the end of TIA; it markedly decreased to 8.7% at 1-12 hours after end of TIA. Thereafter, it increased to 21.7%, 30.8%, 36.4%, 37.0%, 38.5%, and 30% at 12-24 hours, 1-2 days, 2-3 days, 3-7 days, 7-10 days, and 10-14 days after the end of TIA, respectively. In 7 patients, MRI was repeated twice, at 1-12 hours and then at 5-13 days after the end of TIA. Lesions were never detected on the first MRI but were clearly demonstrated in 4 of 7 patients on the second MRI.nnnCONCLUSIONSnThe detectability of ischemic lesions may be biphasic after TIA as indicated by experimental studies.

Radiation-Dose-Lowering Effects of Landiolol Hydrochloride in Coronary Angiography Using Computed Tomography (DELIGHT) – A Prospective Multicenter Study –

BACKGROUNDnControlling and decreasing the heart rate (HR) of patients during coronary computed tomography angiography (CCTA) is necessary to reduce radiation exposure and improve image quality. This prospective multicenter study aimed to investigate whether HR control with landiolol hydrochloride is useful for reducing radiation exposure during CCTA.nnnMETHODSANDRESULTSnWe investigated 219 patients with suspected ischemic heart disease whose pretest HRs were 50-80 beats/min. We measured the HR before and after administration of landiolol hydrochloride and compared the estimated exposure inferred from the HR before administration of landiolol hydrochloride with the actual dose. After administration of landiolol hydrochloride, the mean HR (59.9±6.4 beats/min) at the time of CCTA was significantly lower than before administration (69.3±7.3 beats/min; P<0.001); 80% of the patients had controlled HRs at ≤65 beats/min. HR and blood pressure of all the patients recovered after the scan. The mean radiation dose in all patients was approximately 50% derived from the inferred dose before use of landiolol hydrochloride (4.5±3.2 vs. 9.0±3.7 mSv; P<0.001). There were no adverse events during this study.nnnCONCLUSIONSnThe use of landiolol hydrochloride during CCTA was safe and resulted in approximately 50% decrease in radiation exposure dose, suggesting the clinical usefulness of this drug. (Circ J 2016; 80: 1225-1231).

Bone-destroying candida infection following left ventricular assist device explant

Infections associated with left ventricular assist devices (LVADs) constitute an important clinical issue because they are difficult to completely eradicate without removal of the LVAD itself and can sometimes be fatal. We encountered a case of extracorporeal LVAD-related candida infection in a patient who was successfully weaned from LVAD support. Although the patient appeared to have recovered from the infection, the patient was readmitted to our institute due to a relapse of candida infection 9xa0months after LVAD removal. Although the patient did not demonstrate any systemic sign of infection on admission, computed tomography images clearly showed that the residual apical cuff of the LVAD inflow cannula, which was infected with Candida albicans during the initial admission, resulted in re-infection that involved the chest wall with destruction of the adjacent rib.

Pseudoaneurysm at the cannulation site of the ascending aorta arising 8 days postoperatively: report of a case

A postoperative pseudoaneurysm is a rare complication that is difficult to diagnose. Computed tomography (CT) revealed a pseudoaneurysm in the ascending aorta of a 68-year-old female 8xa0days after mitral valve replacement and tricuspid annuloplasty. The defect was simply repaired during emergency surgery without cardiopulmonary bypass (CPB). The early detection of a postoperative pseudoaneurysm is important to avoid a second operation complicated by adhesions. Enhanced CT was useful for early detection in this patient. Pseudoaneurysm of the ascending aorta at the cannulation site can occur soon after surgery, and early recognition might allow simpler surgery without CPB.

Tricaprin Rescues Myocardial Abnormality in a Mouse Model of Triglyceride Deposit Cardiomyovasculopathy

Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable cardiovascular disease for which a specific treatment is urgently required. In TGCV, adipose triglyceride lipase (ATGL) deficiency results in the abnormal intracellular metabolism of long-chain fatty acid (LCFA) which leads to TG deposition. Medium-chain triglycerides have been used as an important functional food for various human diseases. To address the potential activities of tricaprin, a medium-chain triglyceride, on cardiac dysfunctions of TGCV, we examined the effects of tricaprin diet on Atgl knock out (KO) mice, an animal model for TGCV. Cardiac imaging tests showed that the tricaprin diet reduced TG accumulation, resulting from improvement of LCFA metabolism, and improved left ventricular function in Atgl KO mice compared to that in mice fed the control diet. In conclusion, tricaprin improved myocardial abnormality in the TGCV model, thus, it may be useful for the treatment of patients with TGCV.

Surgical Indication for Chronic Aortic Dissection in Descending Thoracic and Thoracoabdominal Aorta

Background— To address the lack of information about the size of ruptures associated with chronic dissection in the descending and thoracoabdominal aorta, we evaluated the natural history of this pathology. Methods and Results— We analyzed data from 571 patients (mean age, 69.4±11.6 years) with unrepaired chronic aortic dissection in the descending or thoracoabdominal aorta with a maximal aortic diameter of ≥3.5 cm from 2007 to 2014. This was a cross-sectional study. Data on the timing of computed tomographic scan were as follows: for ruptured cases: at the time of rupture; for nonruptured cases: the initial aortic diameter. Patients with connective tissue disorders were excluded. The primary end point was evidence of aortic rupture on computed tomographic images. The median maximal diameter was 4.3 cm (limits, 3.5–9.0 cm) for all aortas and 5.6 cm (n=31; limits, 3.6–8.0 cm) for ruptured aortas. For aortic diameters of 4.0 to 4.4, 4.5 to 4.9, 5.0 to 5.4, 5.5 to 5.9, and 6.0 to 6.4 cm, the incidence of rupture was 0%, 3.3%, 15.3%, 18.8%, and 28.6%, respectively. The risk factors for rupture were absence of hypertension, chronic heart failure, chronic-phase dissection, and Yale index. Conclusions— The risk of aortic rupture increased with an aortic diameter of ≥5.0 cm in patients with chronic aortic dissection in the descending or thoracoabdominal aorta. We would recommend 5.0 cm as an acceptable size for elective resection of subacute or chronic aortic dissection in the descending or thoracoabdominal aorta.