Megumi Koshikawa

Therapeutic angiogenesis by bone marrow implantation for critical hand ischemia in patients with peripheral arterial disease : a pilot study

ABSTRACT Objective: Implantation of bone marrow mononuclear cells (BM-MNCs), including endothelial progenitor cells, into ischemic lower limbs has been shown to improve symptoms in patients with peripheral arterial diseases (PAD). This study investigated whether BM-MNC implantation (BMI) is also effective for the ischemic hands of these patients. Methods: Seven PAD patients with hand ischemia were enrolled: six patients had thromboangiitis obliterans and one had collagen disease. All seven had symptoms involving either resting pain or non-healing ischemic ulcers of the hand. Approximately 600 mL of MNCs were separated from BM and concentrated to a final volume of 40–50 mL, which were injected into ischemic hands. Ischemic status was evaluated by measuring the digital/brachial pressure index (DBI), visual analog pain scale, and the healing of ulcers before and 6 months after BMI. Results: The mean number of implanted MNCs, CD34-positive cells, and CD34,133-positive cells was 3.67 ± 0.53 × 109, 4.94 ± 2.45 × 107, and 2.52 ± 1.57 × 107, respectively. Mean DBI in those patients was 0.15 ± 0.30 before BMI and significantly increased to 0.67 ± 0.19 at 6 months after BMI ( p = 0.004). All patients also showed improvement of pain scale and ischemic ulcers. There was no significant correlation between the number of implanted cells and improvement in the degree of DBI or the pain scale. Conclusion: Autologous BMI could be a promising and safe method of therapeutic angiogenesis for critical hand ischemia in PAD patients.

Changes in angiogenesis-related factors in serum following autologous bone marrow cell implantation for severe limb ischemia

Objective: Bone marrow mononuclear cell (BM-MNC) implantation (BMI) for critical severe limb ischemia especially for Buergers disease shows excellent clinical results but the mechanism of this treatment is still unknown. In this study, we investigated the changes in serum levels of angiogenesis-related factors after BMI treatment. Research design/methods: Twelve patients whose BMI treatments were clinically very effective was selected out of ninteen cases, nine patients had Buergers disease, two patients had arteriosclerosis obliterans and one had systemic sclerosis. Venous bood from femoral vein or brachial vein of the recipient limbs of these patients. Results: Adrenomedulin (AM), soluble vascular cell adhesion molecule-1 (sVCAM-1), and C-reactive protein (CRP) serum levels 24 h after BMI treatment were significantly increased compared with those before BMI treatment (p < 0.05). Vascular endothelial growth factor (VEGF) serum levels after BMI treatment significantly increased between 1 week and 3 months after BMI treatment (p < 0.05). Nitric oxide (NO) serum levels after BMI treatment increased significantly 2 weeks after BMI treatment (p < 0.05). There was no correlation between the numbers of implanted cells and serum levels of measured angiogenesis-related factors that were significantly increased after BMI treatment. Conclusion: It was concluded that the mechanism underlying BMI treatment consists of early and late phases. The early phase involves the direct action by implanted cells, and the late phase involves indirect paracrine action. In addition, it was considered that BMI treatment is effective when we implant a sufficient level of bone marrow (600 ml) to treat severe limb ischemia.

Rationale and design of assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (the ALPS-AMI) study

BACKGROUND Statins reduce the incidence of cardiovascular events in patients with acute myocardial infarction (AMI). Although all statins are equally effective in secondary prevention, there might be certain differences in the effects of lipophilic and hydrophilic statins. Therefore, our aim is to compare the effectiveness of lipophilic atorvastatin and hydrophilic pravastatin in secondary prevention after AMI. METHODS AND RESULTS This study is a prospective, randomized, open-label, multicenter study of 500 patients with AMI. Patients that have undergone successful percutaneous coronary intervention will be randomly allocated to receive either atorvastatin or pravastatin with the treatment goal of lowering their low-density lipoprotein-cholesterol level below 100 mg/dl for 2 years. The primary endpoint will be death due to any cause, nonfatal MI, nonfatal stroke, unstable angina, or congestive heart failure requiring hospital admission, or any type of coronary revascularization. CONCLUSION This is the first multicenter trial to compare the effects and safety of lipophilic and hydrophilic statin therapy in Japanese patients with AMI. It addresses an important issue and could influence the use of statin treatment in the secondary prevention of coronary artery disease.

Temporary inferior vena cava filter for deep vein thrombosis and acute pulmonary thromboembolism: effectiveness and indication

Although the temporary inferior vena cava filter (IVC-F) is being used increasingly for protection against pulmonary thromboembolism (PTE), indications for its use are not established. Our strategy for the prevention of PTE is: (1) contraindication or failure of anticoagulation: permanent IVC-F; (2) for patients with residual proximal deep vein thrombosis (a) who have permanent risk factor: permanent IVC-F; (b) who have transient risk factor: temporary IVC-F; (3) others: no IVC-F. Temporary IVC-F was also implanted in deep vein thrombosis (DVT) patients without PTE who were preoperation or had floating thrombus. We investigated the outcome of patients given a temporary IVC-F versus those given a permanent IVC-F to clarify the efficacy and our strategy for implantation of a temporary IVC-F. Subjects were 12 men and 38 women with acute PTE and/or floating DVT admitted to our hospital between April 1999 and April 2002. Patient age was 25–91 years (mean 63 years). Eighteen patients were given a permanent IVC-F (group A) and 32 patients were given a temporary IVC-F (group B) as primary treatment, according to our criteria. There were no major complications in either group. Mortality after implantation of the IVC-F was 35% (6/17) in group A and 16% (4/25) in group B, with no significant difference (P = 0.14). Pulmonary thromboembolism recurred in 18% (3/17) of group A patients but in no group B patients (P = 0.10). All recurrences resulted in death. The 14 patients in group B who were not given a permanent IVC-F after removal of the temporary IVC-F survived. The temporary IVC-F can be used safely in patients with venous thromboembolism and is efficacious in preventing recurrence of PTE. Prognosis after removal of the temporary IVC-F is excellent.

Elevated Osteopontin Levels in Patients With Peripheral Arterial Disease

This study was carried out to compare concentrations of osteopontin (OPN) and osteoprotegerin (OPG) in peripheral arterial disease (PAD). The study population consisted of 200 consecutive subjects in whom both OPN/OPG and ankle—brachial index were measured. It was found that OPN levels, but not OPG levels, were significantly more increased in patients with PAD than those without PAD. Serum OPN levels were significantly lower in subjects with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers than those without these agents. In this study, it has been demonstrated for the first time that serum OPN levels are related to PAD. Inhibition of renin— angiotensin system could decrease OPN levels and prevent the progression of PAD.

Association between estimated glomerular filtration rate and peripheral arterial disease

BACKGROUND Chronic kidney disease (CKD) is an evolving paradigm for the risk assessment of cardiovascular diseases. We hypothesized that an advanced stage of CKD may predict the presence of peripheral arterial disease (PAD). METHODS Screening for PAD by an ankle-brachial pressure index (ABI) ≤0.9 was conducted in a consecutive series of 583 subjects (mean age 68.1±12.9 years, 411 men). Levels of estimated glomerular filtration rate (eGFR) and factors associated with the presence of PAD were examined. RESULTS Sixty patients (10.3%) had PAD and 192 patients (32.9%) had eGFR <60mL/min/1.73m(2) among all subjects. In patients with an advanced stage of CKD (stage ≥3, equivalent to eGFR <60mL/min/1.73m(2)), high prevalence of PAD (17.2%) and lower ABI levels (1.04±0.18) were observed. Univariate analyses revealed that PAD was associated with an advanced stage of CKD [odds ratio (OR) 1.850, 95% confidence interval (CI) 1.322-2.588, p<0.001], as well as age, male gender, systolic blood pressure, and hemoglobin A1c. Multivariate logistic regression analyses revealed that PAD was independently predicted by the CKD stages (OR 1.498, 95% CI 1.011-2.220, p=0.044, adjusted for covariates). CONCLUSIONS An advanced stage of CKD is independently and significantly associated with the presence of PAD. Targeted screening with ABI measurement can be beneficial in patients with CKD.

Influence of circumferential pulmonary vein isolation for atrial fibrillation on ST elevation in patient with Brugada syndrome

We present a patient with Brugada syndrome and paroxysmal atrial fibrillation who underwent circumferential pulmonary vein isolation. His electrocardiogram showed normal sinus rhythm and first-degree AV block (P-R 280 ms) with coved-type ST elevation in V1-2 (+2.0 mm) before ablation. During ablation around the left pulmonary vein ostium, atrial fibrillation, progression of ST elevation (+4.5 mm), and T wave alternans occurred. After right pulmonary vein encirclement was complete, ST elevation improved to +1.0 mm. The following day, the ST segments remained lower than baseline levels.

Transient pseudorestrictive pattern of transmitral flow velocity curve in patients with paroxysmal atrial fibrillation.

Background: Early diastolic velocity of the mitral annulus and transmitral flow propagation velocity are reported as more reliable determinants of left ventricular diastolic function in patients with atrial fibrillation than are transmitral Doppler indices. This study aimed to test the hypothesis that transmitral flow curve shows pseudorestrictive pattern during rate‐controlled atrial fibrillation. Methods: Thirteen paroxysmal atrial fibrillation patients were monitored for three phases: before atrial fibrillation, during atrial fibrillation, and after the recovery of atrial fibrillation to sinus rhythm. Standard two‐dimensional, color flow, and tissue Doppler echocardiography were performed. We compared the indices of left ventricular diastolic function among the three phases. Results: The early diastolic velocity of transmitral flow increased significantly during atrial fibrillation (before, 0.76 ± 0.19 m/sec; during, 0.86 ± 0.20 m/sec; after recovery to sinus rhythm, 0.73 ± 0.16 m/sec; P < 0.01). The deceleration time of early transmitral diastolic wave decreased during atrial fibrillation (182.5 ± 39.6 ms; 149.1 ± 38.7 ms; 184.0 ± 44.5 ms, respectively, P < 0.01). The early diastolic velocity of the mitral annulus increased during atrial fibrillation (5.37 ± 1.31 cm/sec; 7.29 ± 1.25 cm/sec; 5.37 ± 1.32 cm/sec; respectively, P < 0.01). The transmitral propagation velocity did not change significantly during atrial fibrillation. Conclusion: Although conventional Doppler indices showed abnormal relaxation pattern, left ventricular diastolic function was preserved during rate‐controlled atrial fibrillation, as determined from early diastolic velocity of the mitral annulus and transmitral flow propagation velocity. (Echocardiography 2011;28:289‐297)

Dynamic left ventricular outflow tract obstruction due to anemia in a 71-year-old patient with sigmoid septum

Sigmoid septum, although frequently observed in the elderly, has no pathophysiological significance in general. A 71-year-old woman with sigmoid septum developed acute heart failure because of a significant left ventricular outflow tract obstruction associated with the aggravation of anemia. This report provides the evidence that a hypercontractile cardiac state induced by anemia can be critical, especially in patients with sigmoid septum. Assessment of the left ventricular outflow tract pressure gradient is important in heart failure patients with sigmoid septum and dynamic obstruction.

Catheter ablation of non-inducible atrial tachycardia after surgical repair of heart disease

We present a patient with non-inducible atrial tachycardia (AT) after atriotomy for surgical repair of heart disease who underwent ablation successfully. Using a 3-D mapping system, we presumed the atriotomy site on the lateral right atrial wall by searching for linear double potentials (DP) during sinus/paced rhythm from the coronary sinus, but it was evaluated incompletely. We could verify the edges of the atriotomy scar precisely by pacing from close to the linear DP lesion and the opposite site. After ablation between the presumed atriotomy scar and the inferior vena cava and cavotricuspid isthmus, no AT recurred without anti-arrhythmic drugs.