Masahito Sakuma

Accumulation of risk markers predicts the incidence of sudden death in patients with chronic heart failure

Sudden death is common in chronic heart failure (CHF). Risk stratification is the first step for primary prevention.

Risk factors of acute pulmonary thromboembolism in Japanese patients hospitalized for medical illness: results of a multicenter registry in the Japanese society of pulmonary embolism research

AbstractBackground: Although the prophylaxis of acute pulmonary thromboembolism (APTE) in hospitalized patients has been improving in Japan, there is no report concerning APTE of Japanese medical patients. Therefore, the present study was designed to investigate the characteristics of APTE in Japanese patients hospitalized for medical illness, through a retrospective study. Methods: In a total of 1,438 registry patients with pulmonary thromboembolism for recent 10 years, 1,027 patients with APTE were analyzed with respect to underlying diseases or predisposing factors, and clinical course. Results: A hundred thirty three patients hospitalized for medical illness developed APTE, among 433 in-hospital APTE patients. The prevalence of APTE in women was more than in men. The mean age of the patients at diagnosis was 61 ± 17 years. Main risk factors were a prolonged immobilization, stroke, cancer, indwelling central venous catheter. Fifty-four patients had 3 or more risk factors. In-hospital mortality rate was 23%. Conclusions: Japanese patients in this registry had almost the same findings as in western patients, except for some points that had the possibility of demonstrating a difference between westerners and Japanese in the development of APTE. Our results will be available for establishing the prevention of APTE in medical patients in Japan.

Arg506Gln mutation of the coagulation factor V gene not detected in Japanese pulmonary thromboembolism

SummaryThe incidence of pulmonary thromboembolism (PTE) is lower in Japanese than in Caucasians. The basis for the different incidence has not been clarified. A poor anticoagulant response to activated protein C based on a single point mutation of the factor V gene (Arg506Gln) was found to be a pathogenetic factor for venous thrombosis and PTE in North America and Europe. We investigated whether the Arg506Gln mutation of factor V is responsible for the occurrence of PTE among Japanese. We analyzed genomic DNA prepared from fresh peripheral blood of 25 patients with PTE of unknown etiology (12 of acute type and 13 of chronic type) and that of 110 controls without respiratory or circulatory disorders. To detect the Arg506Gln mutation, 267bp DNA fragments of the factor V gene including the Arg506Gln region were amplified by PCR, digested byMnlI and electrophoresed. After digestion of PCR products withMnlI, DNA fragments of 163bp length, but not DNA fragments of 200bp length, were identified in all samples, indicating the absence of the Arg506Gln mutation in the patients with PTE and control subjects. These results suggest that the Arg506Gln mutation is absent or very rare and not an important pathogenetic factor for PTE in Japanese.

HLA-DPB1 and NFKBIL1 may confer the susceptibility to chronic thromboembolic pulmonary hypertension in the absence of deep vein thrombosis.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by pulmonary hypertension caused by thromboembolism of the pulmonary artery. Etiology of CTEPH may be heterogeneous and is largely unknown, but genetic factors are considered to be involved in the etiology. It has been reported that deep vein thrombosis (DVT) and/or coagulation factor variants are predisposing factors to CTEPH. However, more than half of the CTEPH patients, especially the Japanese, do not have prior DVT or coagulation abnormality, suggesting that there should be other risk factors for CTEPH. Moreover, there are several reports on the association between CTEPH and human leukocyte antigen (HLA). To further clarify the HLA-linked gene(s) controlling the susceptibility to CTEPH, 160 patients (99 without DVT and 61 with DVT) and 380 healthy controls were analyzed for polymorphisms in 15 microsatellite markers and 5 genes in the HLA region. We found a strong association of HLA markers with the DVT-negative CTEPH, DPB1*0202 (odds ratio (OR)=5.07, 95% confidence interval (CI)=2.52–10.19, P=0.00000075, corrected P-value (Pc)=0.00014), IKBL-p*03 (OR=2.33, 95% CI=1.49–3.66, P=0.00017, Pc=0.033) and B*5201 (OR=2.47, 95% CI=1.56–3.90, P=0.000086, Pc=0.016), whereas no significant association was observed for the DVT-positive CTEPH. The comparison of clinical characteristics of patients stratified by the presence of susceptibility genes implied that the DPB1 gene controlled the severity of the vascular lesion, whereas the IKBL gene (NFKBIL1) was associated with a relatively mild phenotype.

Characteristics of the increase in plasma brain natriuretic peptide level in left ventricular systolic dysfunction, associated with muscular dystrophy in comparison with idiopathic dilated cardiomyopathy

To determine whether the plasma brain natriuretic peptide level increases differentially in muscular dystrophy and idiopathic dilated cardiomyopathy, we investigated the plasma brain natriuretic peptide level and echocardiographic parameters in patients with similarly low left ventricular ejection fraction. The plasma brain natriuretic peptide level was lower, and the left ventricular end-diastolic diameter was shorter in the patients with muscular dystrophy than in those with idiopathic dilated cardiomyopathy. The correlation between the plasma brain natriuretic peptide and left ventricular ejection fraction was shifted downward in the patients with muscular dystrophy compared with those with idiopathic dilated cardiomyopathy. Those between the brain natriuretic peptide and left ventricular end-diastolic diameter were superimposable, although the data from the muscular dystrophy patients were located at the shorter left ventricular end-diastolic diameter side. The plasma brain natriuretic peptide level may differentially increase in the two diseases with similar left ventricular systolic dysfunction. Differences in the left ventricular distension and in the physical activity might explain at least partially the different plasma brain natriuretic peptide levels.

Pulmonary embolism is an important cause of death in young adults.

BACKGROUND Population-based analysis shows that deaths from pulmonary embolism (PE) are increasing in the older age groups, but it is unclear to what degree PE contributes to death in different ages and gender. METHODS AND RESULTS Potential contribution factors for all PE and for critical PE (in which PE was the primary cause of death or the main diagnosis) were examined in 396,982 autopsy cases. For all PE, odds ratio (OR) in males was 0.61 (95% confidence interval (CI) 0.59-0.64, p<0.0001), compared with that in females. ORs were 1.10 (95% CI 1.05-1.14, p<0.0001) in 1991-1994 and 1.19 (95% CI 1.14-1.25, p<0.0001) in 1995-1998, compared with those in 1987-1990. ORs for ages 0-9 and 40+ were significantly low compared with that for ages 20-39. For critical PE, similar results were obtained. Pregnancy and/or delivery were found in 38.5% in cases of critical PE in females aged 20-39. CONCLUSION Compared with other age groups, PE contributed more to deaths in those aged 20-39 years. In recent years, deaths from PE have been slightly but significantly increasing. The incidence of clinically diagnosed critical PE also has been increasing.

Outcome of pulmonary embolectomy for acute pulmonary thromboembolism: analysis of 32 patients from a multicentre registry in Japan.

OBJECTIVE Massive pulmonary embolism is relatively rare but a potentially life-threatening condition. The purpose of this study was to analyse the outcome of pulmonary embolectomy in registered data from the Japanese Society of Pulmonary Embolism Research (JaSPER). METHODS From 1994 to 2006, 1661 cases of acute pulmonary embolism were registered in the JaSPER database. Retrospective analysis of 32 patients undergoing pulmonary embolectomy was conducted. The overall incidence of pulmonary embolectomy was 1.9% [95% confidence interval (CI): 1.8-3.2%]. The mean age of patients was 57 years and 66% were female. RESULTS Overall mortality of pulmonary embolectomy was 18.8% [95% CI: 5.2-25.6%]. Most of the patients had massive or submassive pulmonary thromboembolism, and three patients experienced cardiopulmonary arrest before embolectomy. Ten patients received preoperative percutaneous cardiopulmonary bypass, and mortality was 30% in this subgroup. CONCLUSIONS Pulmonary embolectomy is an effective therapeutic option for patients with massive or submassive pulmonary embolism. Prompt triage of patients with haemodynamic instability is important.

Left ventricular end-systolic stress-volume index ratio in aortic and mitral regurgitation with normal ejection fraction

To evaluate the left ventricular contractile state in regurgitant valvular disease with normal ejection fraction, we analyzed the end-systolic stress-volume index relationship (ESSVR) by means of cineangiography in 15 normal subjects, 11 patients with aortic regurgitation (AR), and 10 patients with mitral regurgitation (MR) whose ejection fraction (EF) was 60% or more. The end-systolic stress-volume index ratio in normal subjects was 5.57 +/- 0.60 kdyne/cm5/m2 (mean +/- standard deviation), and we defined the range including +/- 2 standard deviations of the ratio as the normal ESSVR range. Six patients with AR and five patients with MR placed inside the normal ESSVR range, termed AR IN and MR IN, but the remaining five patients with AR and MR placed to the right of the normal range, termed AR OUT and MR OUT. EF did not differ between patients with AR IN and AR OUT (69.4 +/- 5.4 verus 70.7 +/- 6.1%) and between MR IN and MR OUT (71.6 +/- 3.6 versus 71.1 +/- 7.9%). The EF of the subdivided groups with AR and MR also did not differ from that of normal subjects (70.7 +/- 7.3%). This finding showed that the left ventricular contractile state was depressed in patients with AR OUT and MR OUT despite a normal EF. In AR and MR the end-systolic stress and end-systolic volume index of OUT did not differ from those of IN, but the end-diastolic volume index of OUT was larger than that of IN (AR OUT 156.8 +/- 27.9 versus AR IN 110.8 +/- 24.1 ml/m2, MR OUT 160.5 +/- 44.7 versus MR IN 101.0 +/ 16.6 ml/m2; both p less than 0.05), and the regurgitant fraction of OUT was higher than that of IN (AR OUT 52.6 +/- 13.6 versus AR IN 29.7 +/- 13.3%, MR OUT 52.9 +/- 10.2 versus MR IN 30.2 +/- 11.4%; both p less than 0.05). In addition, there was a linear inverse correlation between the end-systolic stress-volume index ratio and the end-diastolic volume index in all subjects (r = -0.82, n = 36). In normal subjects there was a linear inverse correlation between end-systolic stress and the EF (r = -0.91, n = 15), but this relationship failed to separate patients with OUT from those with IN. Results of the present study suggest that some patients with AR and MR whose EF was normal had a depressed contractile state, and these patients had a large end-diastolic volume index and a high regurgitant fraction.(ABSTRACT TRUNCATED AT 400 WORDS)

Epidemiology of Pulmonary Embolism in Japan

The incidence of PE is low in Japan compared with Western countries, but it has been increasing in recent years. The reasons for the low incidence may be genetic predisposition, lifestyle, and diagnostic power. On the other hand, the recent increment in incidence may result from changes in lifestyle and improvement in the diagnostic power.

Incidence and Characteristics of Ventricular Fibrillation in Bystander-witnessed Out-of-hospital Cardiac Arrest with Cardiac Etiology in the City of Sendai, Japan

Ventricular fibrillation (VF) in out‐of‐hospital cardiac arrest (OHCA) is a main target for resuscitation.