Multicenter investigation of the incidence of inferior vena cava filter fracture.

PURPOSE: Inferior vena cava filter fracture (FF) may cause life-threatening complications, including cardiac tamponade, although the actual prevalence remains unclear. Therefore, we investigated the incidence of FF. MATERIALS AND METHODS: Data on fracture incidence with filter brands, filter positions [suprarenal (SR) vs. infrarenal (IR)], and follow-up durations were collected from the databases of eight hospitals. RESULTS: Of 532 patients, Günther Tulip (GT), Trap/OptEase (TE/OE), ALN and VenaTech (VT) were implanted in 345, 147, 38 and 2 patients, respectively. Of these, filter retrieval was attempted in 110 (21.7%) patients and was successful in 106 (96.4%). Of the remaining 426 patients, FFs were observed in two (0.7%) of 270 GT filters and 19 (14.1%) of 135 TE/OE filters. Fragment embolization occurred in one patient with a GT filter (50.0%) and three with a TE/OE filter (15.8%) with a total follow-up interval of 718.0 ± 1019.4 days. FF occurred more frequently in TE/OE than in GT filters (p < 0.001). Kaplan-Meier estimates showed significantly higher fracture-free rates for GT than TE/OE (p < 0.001) and IR-TE/OE than SR-TE/OE (p < 0.05). CONCLUSIONS: TE/OE filters are not suitable for permanent implantation due to the relatively early and high fracture rates.

The change in low-density lipoprotein cholesterol concentration is positively related to plasma docosahexaenoic acid but not eicosapentaenoic acid.

AIM: The Japan EPA Lipid Intervention Study (JELIS) reported a 19% reduction of the risk for coronary artery disease after long-term use of pure eicosapentaenoic acid (EPA) in Japanese patients with hypercholesterolemia. The variation in plasma fatty acid composition influenced the risk of coronary events. The aim of this study was to examine in JELIS participants the possible correlation of changes in plasma fatty acids with those of serum lipids. METHODS: The coefficient for the correlation between the absolute change in plasma fatty acid concentrations and the changes in serum lipids was calculated in 13,901 JELIS participants. RESULTS: Low-density lipoprotein (LDL) cholesterol exhibited a positive correlation with docosahexaenoic acid (DHA; r=0.117 in control group, r=0.155 in EPA group) and linoleic acid (r=0.139 in control group, r=0.177 in EPA group), but the correlation coefficients with EPA (r=0.097 in control group, r=-0.032 in EPA group) were less than 0.1. We distributed the patients into 9 groups according to tertiles of the change in EPA and DHA. The average absolute decrease of LDL cholesterol and L/H ratio in each group was significantly smaller (p<0.001) in the DHA-high tertile, but not in any EPA tertile. CONCLUSION: The changes in DHA, but not in EPA, showed a positive correlation with the changes in LDL-cholesterol.

Long-term safety and efficacy of ambrisentan in Japanese adults with pulmonary arterial hypertension.

OBJECTIVE: To investigate the safety and efficacy of long-term administration of ambrisentan in Japanese adults with pulmonary arterial hypertension (PAH). RESEARCH DESIGN AND METHODS: In this open-label extension of a preceding multicenter dose-escalation study, 21 Japanese patients with PAH received treatment with 5 or 10 mg of ambrisentan once daily and were comprehensively evaluated every 12 weeks. The primary endpoint was the safety of long-term ambrisentan administration, as defined by the incidence and severity of adverse events. The secondary (efficacy) endpoints were change in exercise capacity (as indicated by 6-minute walk distance), World Health Organization functional class, Borg dyspnea index, plasma brain natriuretic peptide level, cardiopulmonary hemodynamics, and time to clinical worsening of PAH. CLINICAL TRIAL REGISTRATION: NCT00554619. RESULTS: The mean total duration of treatment (i.e., including the preceding dose-escalation study) was approximately 139 weeks. There were fewer adverse events related to ambrisentan in this study than in the preceding study, and we identified no new safety signals that might preclude the long-term use of ambrisentan among Japanese adults with PAH. Improvements observed in efficacy endpoints in the preceding study were maintained in the present study. LIMITATIONS: This study did not include a control group and lacked the statistical power to reach definite conclusions regarding the efficacy of ambrisentan. CONCLUSION: Our results suggest that long-term administration of ambrisentan is well tolerated and efficacious for Japanese adults with PAH.

Relationship between coronary artery disease and non-HDL-C, and effect of highly purified EPA on the risk of coronary artery disease in hypercholesterolemic patients treated with statins: sub-analysis of the Japan EPA Lipid Intervention Study (JELIS).

AIM: The present study examined the importance of reducing non-high-density lipoprotein cholesterol (non-HDL-C) for the primary prevention of the occurrence of coronary artery disease (CAD) in the JELIS, and the effects of EPA. METHODS: The patients were distributed into 4 subgroups using the lipid management goal for LDL-C recommended by the Japan Atherosclerosis Society guideline (2007) and the goal for non-HDL-C defined as 30 mg/dL higher than LDL-C: A) achieved both goals; B) achieved the LDL-C but not non-HDL-C goal; C) achieved the non-HDL-C but not LDL-C goal; and D) did not attain either goal. The incidences of CAD in the 4 subgroups were compared, and the effects of eicosapentaenoic acid (EPA) on the risk of CAD in these subgroups were examined. RESULTS: In the non-EPA group, the incidence of CAD in patients who did not achieve the goals for LDL-C or non-HDL-C was higher than in patients who achieved those goals. Patients in subgroups B, C, and D were at higher risk for CAD than those in subgroup A (B, HR 2.31; C, HR 1.90; D, HR 2.47). EPA reduced the risk of CAD by 38% in subgroups B, C, and D (p= 0.007). CONCLUSION: We reconfirmed non-HDL-C as a predictor of the risk for CAD and a residual risk marker of CAD after LDL-C-lowering therapy. EPA was useful to reduce the occurrence of CAD in patients who did not achieve the goals for LDL-C and/or non-HDL-C.

A sodium channel blocker, pilsicainide, produces atrial post-repolarization refractoriness through the reduction of sodium channel availability.

Atrial fibrillation (AF) is the most common tachyarrhythmia. Shortening of atrial action potential duration (APD) and effective refractory period (ERP) is one of the crucial factors in the occurrence and maintenance of AF. ERP is usually shorter than APD, but ERP can be prolonged beyond action potential repolarization in some situations. It is termed as post-repolarization refractoriness (PRR) that is thought to be one of main anti-arrhythmic mechanisms of class I sodium channel blockers (SCBs). Most of anti-arrhythmic agents, including SCBs, have multi-channel blocking effects. It is unknown whether atrial PRR with SCBs is associated with the reduction of sodium channel availability. We therefore explored the relationship between the reduction of sodium channel availability with a pure SCB (pilsicainide or tetrodotoxin) and atrial PRR using the left atrial appendage from male guinea pigs (each group, n = 3~10). Employing a standard microelectrode technique, we evaluated APD measured at 90% repolarization (APD(90)) and the sodium channel availability, judged from the maximal rate of rise of action potential (Vmax). At a 500-msec basic cycle length (BCL), pilsicainide prolonged atrial ERP assessed by a single extra-stimulus in response to the decrement of the Vmax in a dose-dependent manner without affecting APD(90). Furthermore, pilsicainide increased the ERP and decreased the Vmax in a rate-dependent manner without APD(90) prolongation at a shorter BCL (200 msec). Importantly, tetrodotoxin reproduced the effects of pilsicainide on atrial ERP, APD(90), and Vmax. These results indicate that SCBs produce atrial PRR through the reduction of sodium channel availability.

Efficacy, safety, and pharmacokinetics of ambrisentan in Japanese adults with pulmonary arterial hypertension.

OBJECTIVE: To investigate the efficacy, safety, and pharmacokinetics of ambrisentan in Japanese adults with pulmonary arterial hypertension (PAH). RESEARCH DESIGN AND METHODS: In this open-label, uncontrolled, dose-escalation study, 25 Japanese patients with PAH were scheduled to receive 5 mg of ambrisentan once daily for the first 12 weeks, and 10 mg once daily for an additional 12 weeks. The primary endpoint was improvement in exercise capacity from baseline which was indicated by 6-minute walk distance; the secondary endpoints included World Health Organization functional class, Borg dyspnea index, plasma brain natriuretic peptide level, and cardiopulmonary hemodynamics. CLINICAL TRIAL REGISTRATION: NCT00540436. RESULTS: At week 24, improvements were noted in all endpoints, with no clinically significant elevation of serum aminotransferase level. Pharmacokinetics in these Japanese patients was similar to that of non-Japanese populations, suggesting that once-daily dosing is appropriate in Japanese patients. Ambrisentan was generally well tolerated. No new safety signals were identified. LIMITATION: This study lacked a control group and was insufficiently powered to reach definitive conclusions on the efficacy of ambrisentan. CONCLUSION: Ambrisentan is considered as safe and effective for Japanese adults with PAH.

Acceleration of Ca2+ waves in monocrotaline-induced right ventricular hypertrophy in the rat.

BACKGROUND: Triggered arrhythmias arise from delayed afterdepolarizations (DADs), with Ca(2+) waves playing an important role in their formation. In ventricular hypertrophy, however, it remains unclear how Ca(2+) waves change their propagation features and affect arrhythmogenesis. We addressed this important issue in a rat model of hypertrophy. METHODS AND RESULTS: Rats were given a subcutaneous injection of 60 mg/kg monocrotaline (MCT-rats) or solvent (Ctr-rats). After 4 weeks, MCT-rats showed high right ventricular (RV) pressure and RV hypertrophy. Trabeculae were dissected from 36 right ventricles. The force was measured using a silicon strain gauge and regional intracellular Ca(2+) ([Ca(2+)](i)) was determined using microinjected fura-2. Reproducible Ca(2+) waves were induced by stimulus trains (2 Hz, 7.5s). MCT-rats showed a higher diastolic [Ca(2+)](i) and faster and larger Ca(2+) waves (P<0.01). The velocity and amplitude of Ca(2+) waves were correlated with the diastolic [Ca(2+)](i) both in the Ctr- and MCT-rats. The velocity of Ca(2+) waves in the MCT-rats was larger at the given amplitude of Ca(2+) waves than that in the Ctr-rats (P < 0.01). The amplitude of DADs was correlated with the velocity and amplitude of Ca(2+) waves in the Ctr- and MCT-rats. CONCLUSIONS: The results suggest that an increase in diastolic [Ca(2+)](i) and an increase in Ca(2+) sensitivity of the sarcoplasmic reticulum Ca(2+) release channel accelerate Ca(2+) waves in ventricular hypertrophy, thereby causing arrhythmogenesis.

Relationships between plasma fatty acid composition and coronary artery disease.

AIM: The Japan EPA Lipid Intervention Study (JELIS) was the first prospective randomized clinical trial to demonstrate prevention of coronary events by pure eicosapentaenoic acid (EPA). The aim of this study was to examine the relationships between various plasma fatty acid concentrations and the risk of coronary events in JELIS participants. METHODS: In 15,534 participants, we calculated the hazard ratio for major coronary events (sudden cardiac death, fatal or nonfatal myocardial infarction, unstable angina pectoris, and angioplasty/stenting or coronary artery bypass grafting) relative to the on-treatment average level of plasma fatty acids with the Cox proportional hazard model. RESULTS: As a result of EPA intervention, the plasma EPA concentration increased, but the docosahexaenoic acid (DHA) concentration did not. The other fatty acids measured decreased slightly. The higher plasma level of EPA (hazard ratio=0.83, p=0.049, in all participants and hazard ratio=0.71, p=0.018, in the EPA intervention group), but not of DHA, was inversely associated with the risk of major coronary events. The associations between other fatty acids and the risk of major coronary events were not significant. In all JELIS participants, the risk of major coronary events was significantly decreased (20%) in the group with high (150 µg/mL or more) on-treatment plasma EPA concentration compared with that in the low (less than 87 µg/mL) group. CONCLUSION: The risk of coronary artery disease is influenced by variations in plasma fatty acid composition. Among n-3 polyunsaturated fatty acids, EPA and DHA exhibited differences in the correlation with the risk of major coronary events.

Hypertension promotes phosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 in rats: implication for the pathogenesis of hypertensive vascular disease.

Atherosclerosis is initiated by adhesion and infiltration of inflammatory leukocytes into the intima, where non-receptor protein tyrosine kinases, such as focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2), play important roles as intracellular messengers of mechanical and biochemical signals. In the present study, we examined whether FAK and PYK2 are up-regulated by elevated blood pressure or circulating humoral factors in hypertension. We used a rat model of abdominal aortic banding that allows separate evaluation of elevated blood pressure (upper body) and circulating humoral factors (lower body). We obtained the proximal and distal aortas of the banding site, 6 hours, 3 days, and 1 and 4 weeks after the banding procedure, for evaluation of phosphorylation of FAK and PYK2 by Western blotting. Arterial pressure was significantly elevated only in the upper body throughout the experimental period. The expression of FAK and the FAK phosphorylation were significantly increased at 1 and 4 weeks only in the proximal aorta. This was also the case for the expression of total PYK2 and the PYK2 phosphorylation. In contrast, there was no significant change in FAK or PYK2 phosphorylation in the distal aorta, whereas plasma levels of angiotensin II were systemically elevated. In sham-operated rats, no change in FAK or PYK2 phoshorylation was noted in the proximal and distal aortas. These results indicate that phosphorylation of FAK and PYK2 is upregulated by elevated blood pressure but not by humoral factors in the rat aorta, demonstrating novel aspects of atherogenesis in hypertension.

Preventive effects of eicosapentaenoic acid on coronary artery disease in patients with peripheral artery disease.

BACKGROUND: The JELIS trial examined the preventive effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD) in hypercholesterolemia. Previous investigators have reported that patients with peripheral artery disease (PAD) have a poor prognosis due to the potential risk for CAD. We conducted a subanalysis to examine whether the incidence of CAD was high in patients with PAD and whether EPA prevented the occurrence of CAD. METHODS AND RESULTS: Of 18,645 the Japan EPA lipid intervention study (JELIS) patients, 223 had PAD (control group; complicated (n=77), newly diagnosed (n=29), EPA group; complicated (n=96), newly diagnosed (n=21)). We analyzed the incidence of major coronary events (MCE) in the 2 groups. Cox proportional hazard ratio adjusted for baseline risk factor levels was used to test differences between the 2 groups. The incidence of MCE in the control group was significantly higher in patients complicated with PAD and in those newly diagnosed with PAD than in patients without PAD (complicated: hazard ratio 1.97, P=0.039; newly diagnosed: hazard ratio 2.88, P=0.030). As for patients with PAD, the EPA group had a significantly lower MCE hazard ratio than the control group (hazard ratio 0.44, 95% confidence interval 0.19-0.97, P=0.041). CONCLUSIONS: Subanalysis of the JELIS trial demonstrated that in patients with PAD the incidence of CAD was higher than in controls, and that EPA markedly reduced the occurrence of CAD in those patients.

Mortality from pulmonary heart disease in Japan, 1979-2006.

OBJECTIVE: In Japan, there have been no reports on the time-trends of mortality rates from pulmonary heart disease without pulmonary embolism (PHD). Our aim was to examine the annual changes of mortality in Japan. MATERIALS AND METHODS: Annual age-adjusted and age-specific PHD mortality for Japanese residents during 1979-2006 were calculated from "Vital statistics of Japan" and census data and population estimates for intercensal years. RESULTS: The number of age-adjusted deaths from PHD continued to decrease throughout the study period. The age-specific mortality from PHD increased throughout the life span except below 1 year old and decreased in recent years. Male mortality was greater at most ages. In Poisson regression analysis, the relative risk of death from PHD was increased in males and the aged except below 1 year-age, and decreased in recent years. The annual number of deaths from idiopathic pulmonary arterial hypertension/heritable pulmonary arterial hypertension (IPAH/HPAH) continued to increase throughout the study period. The number of annual new cases with IPAH/HPAH was estimated to be about 400 in a recent period of 10 years. CONCLUSION: The annual number of deaths from PHD decreased, and those from IPAH/HPAH increased significantly during 1979-2006 in Japan.

Trends in acute myocardial infarction incidence and mortality over 30 years in Japan: report from the MIYAGI-AMI Registry Study.

BACKGROUND: Worldwide, the rate of aging is highest in Japan, especially the female population. To explore the trends for acute myocardial infarction (AMI) in Japan, the MIYAGI-AMI Registry Study has been conducted for 30 years since 1979, whereby all AMI patients in the Miyagi prefecture are prospectively registered. METHODS AND RESULTS: In 1979-2008, 22,551 AMI patients (male/female 16,238/6,313) were registered from 43 hospitals. The age-adjusted incidence of AMI (/100,000persons/year) increased from 7.4 in 1979 to 27.0 in 2008 (P<0.001). Although control of coronary risk factors remained insufficient, the rates of ambulance use and primary percutaneous coronary intervention (PCI) have increased, and the overall in-hospital mortality (age-adjusted) has decreased from 20.0% in 1979 to 7.8% in 2008 (P<0.0001). However, the in-hospital mortality remains relatively higher in female than in male patients (12.2% vs 6.3% in 2008). Female patients were characterized by higher age and lower PCI rate. CONCLUSIONS: The MIYAGI-AMI Registry Study demonstrates the steady trend of an increasing incidence, but decreasing mortality, for AMI in Japan over the past 30 years, although the female population still remains at higher risk for in-hospital death, despite improvements in the use of ambulances and primary PCI. (Circ J 2010; 74: 93 - 100).

Effects of long-acting beraprost sodium (TRK-100STP) in Japanese patients with pulmonary arterial hypertension.

The long-acting beraprost preparation TRK-100STP is formulated to provide sustained release of an orally active prostacyclin derivative to maintain the optimal plasma concentration for a longer period of time compared with the currently used conventional beraprost sodium. In the present study, we evaluated the efficacy of this newly developed formulation for pulmonary arterial hypertension (PAH).An open-label, 12-week multicenter clinical trial was performed in 46 patients with PAH. They were initially treated with 120 microg of TRK-100STP divided into 60 microg twice daily, followed by a stepwise increase to 360 microg given as 180 microg twice daily. The 6-minute walking distance showed a significant increase by 33.4+/-66.0 m (95% confidence interval [CI], 13.4 to 53.5) from the baseline measurement. Mean pulmonary artery pressure, total pulmonary vascular resistance, and pulmonary vascular resistance decreased by -2.8+/-5.5 mmHg (95% CI, -4.6 to -1.0), by -0.92+/-2.63 mmHg*L(-1)*min (95% CI, -1.78 to -0.05), and by -0.89+/-2.81 mmHg*L(-1)*min (95% CI, -1.84 to 0.06), respectively, from the baseline measurements. A higher efficacy was observed in patients with a maximum tolerated dose of 360 microg daily than those of 240 microg daily or less.Treatment with TRK-100STP for a 12-week period improved the exercise capacity, mean pulmonary artery pressure, and total pulmonary vascular resistance. TRK-100STP was effective for Japanese patients with PAH.

Contribution of Na+/Ca2+ exchange current to the formation of delayed afterdepolarizations in intact rat ventricular muscle.

AIM: To evaluate the role of the Na+-Ca2+ exchange current in the induction of arrhythmias during Ca2+ waves, we investigated the relationship between Ca2+ waves and delayed afterdepolarizations (DADs) and further investigated the effect of KB-R7943, an Na+-Ca2+ exchange inhibitor, on such relationship in multicellular muscle. METHODS: Force, sarcomere length, membrane potential, and [Ca2+]i dynamics were measured in 32 ventricular trabeculae from rat hearts. After the induction of Ca2+ waves by trains of electrical stimuli (400, 500, or 600 ms intervals) for 7.5 seconds, 23 Ca2+ waves in the absence of KB-R7943 and cilnidipine ([Ca2+]o = 2.3 +/- 0.2 mmol/L), 11 Ca2+ waves in the presence of 10 micromol/L KB-R7943 ([Ca2+]o = 2.5 +/- 0.5 mmol/L), and 8 Ca2+ waves in the presence of 1 micromol/L cilnidipine ([Ca]o = 4.1 +/- 0.3 mmol/L) were measured at a sarcomere length of 2.1 microm (23.9 +/- 0.8 degrees C). RESULTS: The amplitude of DADs correlated with the velocity (r = 0.90) and the amplitude (r = 0.90) of Ca2+ waves. The amplitude of DADs was significantly decreased to approximately 40% of the initial value by 10 micromol/L KB-R7943. CONCLUSIONS: These results suggest that the velocity and the amplitude of Ca2+ waves determine the formation of DADs principally through the activation of the Na+-Ca2+ exchange current, thereby inducing triggered arrhythmias in multicellular ventricular muscle.

Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease.

BACKGROUND: Results from JELIS (Japan EPA Lipid Intervention Study) demonstrated the efficacy of pure eicosapentaenoic acid (EPA) in preventing coronary artery disease (CAD) in hypercholesterolemic patients under statin treatment. The present study examined in detail whether EPA is effective for the secondary prevention of CAD. METHODS AND RESULTS: Patients with established CAD and a total cholesterol level > or =250 mg/dl were observed with a mean follow-up of 4.6 years. They were randomly assigned to receive either 1,800 mg of EPA + statin (EPA group) or statin alone (control group). The incidence of major coronary events (MCE) were compared in the 2 groups. The incidence of MCE was significantly lower in the EPA group (8.7% vs 10.7%, adjusted hazard ratio =0.77, 95% confidence interval (CI) 0.63-0.96, P=0.017, number needed to treat (NNT) =49). Among 1,050 patients with prior myocardial infarction (MI), the incidence of MCE in the EPA group (15.0%) was significantly lower than that in the control group (20.1%, adjusted hazard ratio =0.73, 95%CI 0.54-0.98, P=0.033, NNT =19). CONCLUSIONS: EPA is effective for secondary prevention of CAD, especially in individuals with prior MI, and should be added to conventional treatment.

Suppressive effect of EPA on the incidence of coronary events in hypercholesterolemia with impaired glucose metabolism: Sub-analysis of the Japan EPA Lipid Intervention Study (JELIS).

BACKGROUND: JELIS was a large-scale clinical trial that investigated the effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD). In this paper, the data of patients registered in JELIS were analysed to compare the incidence of CAD between patients with impaired glucose metabolism (IGM) and normoglycemic (NG) patients. The effect of EPA on the incidence of CAD in patients with IGM was also assessed. METHODS: The 18,645 hypercholesterolemic patients registered in JELIS were divided into two groups. One group consisted of patients with IGM (n=4565), which included the patients who had diabetes mellitus and patients who had a fasting plasma glucose of 110mg/dL or higher, either at the time of registration or after 6 months. The other group consisted of NG patients (n=14,080). CAD incidence of the two groups over the average 4.6-year follow-up period was compared, and the effect of EPA was assessed. RESULTS: Compared to NG patients, IGM patients had a significantly higher CAD hazard ratio (1.71 in the non-EPA group and 1.63 in the EPA group). The treatment with EPA resulted in a 22% decrease in the CAD incidence (P=0.048) in IGM patients and an 18% decrease (P=0.062) in NG patients. CONCLUSIONS: It was found that the CAD risk in IGM patients is higher than in NG patients, and that highly purified EPA is very effective in decreasing the incidence of CAD among Japanese IGM patients, even though the intake of fish is high.

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.

Long-term epoprostenol therapy in pulmonary artery hypertension.

BACKGROUND: Sequential changes in the hemodynamic effect of chronic epoprostenol therapy raise the following questions. Does an increase in cardiac output (CO) precede lowering of the pulmonary artery pressure (PAP) over the time course of improvement? What are the characteristics of good responders to chronic epoprostenol treatment? METHODS AND RESULTS: Hemodynamics were evaluated by catheter examination. Most patients still alive after >1 year showed an increase in CO either with no change in mean PAP or accompanied by a decrease in mean PAP during increased dosing of epoprostenol. Immediately before cessation of the increase in epoprostenol dose in good responders, the ratio of total pulmonary resistance to total systemic resistance was low, and the pulmonary artery wedge pressure minus right atrial pressure was high compared with the newest data in poor responders. One year after fixing at the best dose of epoprostenol, the mean PAP further decreased. CONCLUSIONS: In good responders, pulmonary selectivity to epoprostenol is high, and the blood returning to the left-sided heart through the pulmonary circulation increases. Hemodynamics further improve, even after fixing at the best dose of epoprostenol. The present data did not show that an increase in CO precedes lowering of the PAP over the course of improvement.

Venous thromboembolism: deep vein thrombosis with pulmonary embolism, deep vein thrombosis alone, and pulmonary embolism alone.

BACKGROUND: There are few data on the differences between deep vein thrombosis (DVT) with pulmonary embolism (PE) (Group A) and without PE (Group B), and no recent data on the incidence of PE and DVT in Japan. METHODS AND RESULTS: The symptoms and findings of the lower extremities and risks for venous thromboembolism were compared between Groups A and B, and the numbers of new patients with PE and those with DVT in 2006 were calculated. DVT was found equally in left and right legs in Group A, but more frequently in left legs than in right legs in Group B. Proximal thrombus was more frequent in Group A than in Group B, and the number of cases of symptoms resulting from DVT was less in Group A than in Group B. Proximal DVT, DVT in the right leg, no symptoms, and younger age were related to the presence of PE. The calculated number of new patients with PE per year was 7,864 (3,492 cases in 1996), and that with DVT per year was 14,674. CONCLUSION: DVT in patients with PE and those without PE differed in the site and symptoms. The calculated number of new patients with PE per year doubled in 1 decade in Japan.

Percutaneous cardiopulmonary support for the treatment of acute pulmonary embolism: summarized review of the literature in Japan including our own experience.

BACKGROUND: Acute pulmonary embolism (APE) has high mortality. Some APEs with circulatory collapse or cardiopulmonary arrest have been treated by percutaneous cardiopulmonary support (PCPS) in Japan. But there have been no reports with a large number of series of APE treated with the use of PCPS. METHODS AND RESULTS: We collected all the reported cases with acute thrombotic pulmonary embolism treated with PCPS before surgical embolectomy or those without surgical embolectomy in Japan, and assessed the effectiveness of PCPS. PCPS was combined with surgical embolectomy in 35% (68 of 193), thrombolytic therapy in 62% (120/193), and catheter therapy in 24% (46/193). The survival rate treated with PCPS was 73% (80% in surgical embolectomy, 71% in thrombolytic therapy, and 76% in catheter therapy). Logistic regression analysis showed that the mortality rate was elevated in cases with cardiopulmonary arrest (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.52-7.67; p-value, 0.003) but not by surgical embolectomy (OR, 0.99; 95% CI, 0.39-2.53; p-value, 0.98), catheter therapy (OR, 0.71; 95% CI, 0.30-1.72; p-value, 0.45), and thrombolysis (OR, 1.60; 95% CI, 0.64-3.99; p-value, 0.31) as regards to the concomitant therapies with PCPS. CONCLUSION: PCPS might improve the survival rate in APE patients with circulatory collapse or cardiopulmonary arrest, but there was no differences in outcome among cases treated by surgical embolectomy, catheter therapy, and thrombolysis as the concomitant therapies.