Balloon pulmonary angioplasty (BPA) has been reported to improve haemodynamics and functional capacity, with an acceptable risk, in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not candidates for pulmonary endarterectomy. However, right ventricular (RV) function, an important predictor in CTEPH, remains to be elucidated. We aimed to examine the impact of BPA on RV remodelling and dysfunction relative to haemodynamic improvements in patients with inoperable CTEPH.20 consecutive patients with inoperable CTEPH who underwent BPA with cardiovascular magnetic resonance before and after BPA were retrospectively studied.BPA led to significant amelioration of the mean pulmonary arterial pressure, cardiac index and pulmonary vascular resistance (PVR), without death or major complications. Furthermore, BPA significantly ameliorated right-sided heart failure symptoms and signs, and exercise capacity. Cardiovascular magnetic resonance revealed a marked improvement in RV end-diastolic and end-systolic volume index, with concomitant improvements in RV ejection fraction, mass and interventricular septal bowing after BPA. Changes in RV volumes strongly correlated with changes in cardiac index and PVR.BPA induced RV reverse remodelling and improved systolic dysfunction safely by ameliorating haemodynamics in patients with inoperable CTEPH. Evaluating RV function with cardiovascular magnetic resonance may be effective for noninvasively monitoring BPA efficacy. @ERSpublications BPA safely ameliorates haemodynamics, leading to right ventricular reverse remodelling in inoperable CTEPH

Hypertension in patients with chronic kidney disease (CKD) strongly associates with cardiovascular events. Among patients with CKD, reducing the accumulation of uremic toxins may protect against the development of hypertension and progression of renal damage, but there are no established therapies to accomplish this. Here, overexpression of human kidney-specific organic anion transporter SLCO4C1 in rat kidney reduced hypertension, cardiomegaly, and inflammation in the setting of renal failure. In addition, SLCO4C1 overexpression decreased plasma levels of the uremic toxins guanidino succinate, asymmetric dimethylarginine, and the newly identified trans-aconitate. We found that xenobiotic responsive element core motifs regulate SLCO4C1 transcription, and various statins, which act as inducers of nuclear aryl hydrocarbon receptors, upregulate SLCO4C1 transcription. Pravastatin, which is cardioprotective, increased the clearance of asymmetric dimethylarginine and trans-aconitate in renal failure. These data suggest that drugs that upregulate SLCO4C1 may have therapeutic potential for patients with CKD.

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ObjectiveTo determine safety and efficacy of cardiac rehabilitation (CR) initiated immediately following balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) who presented with continuing exercise intolerance and symptoms on effort even after a course of BPA; 2–8 sessions/patient.MethodsForty-one consecutive patients with inoperable CTEPH who underwent their final BPA with improved resting mean pulmonary arterial pressure of 24.7±5.5 mm Hg and who suffered remaining exercise intolerance were prospectively studied. Participants were divided into two groups just after the final BPA (6.8±2.3 days): patients with (CR group, n=17) or without (non-CR group, n=24) participation in a 12-week CR of 1-week inhospital training followed by an 11-week outpatient programme. Cardiopulmonary exercise testing, haemodynamics, and quality of life (QOL) were assessed before and after CR.ResultsNo significant between-group differences were found for any baseline characteristics. At week 12, peak oxygen uptake (VO2), per cent predicted peak VO2 (70.7±9.4% to 78.2±12.8%, p<0.01), peak workload, and oxygen pulse significantly improved in the CR group compared with the non-CR group, with a tendency towards improvement in mental health-related QOL. Quadriceps strength and heart failure (HF) symptoms (WHO functional class, 2.2–1.8, p=0.01) significantly improved within the CR group. During the CR, no patient experienced adverse events or deterioration of right-sided HF or haemodynamics as confirmed via catheterisation.ConclusionsThe combination of BPA and subsequent CR is a new treatment strategy for inoperable CTEPH to improve exercise capacity to near-normal levels and HF symptoms, with a good safety profile.

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ancer is a major risk factors for thrombotic pulmonary embolism (PE), [1][2][3][4] and thrombotic PE associated with cancer is known as Trousseau's syndrome. Cancer induces not only thrombotic PE but also tumor PE and tumor invasion into large veins. However, there is lack of epidemiological data from the general population to compare the incidence of thrombotic PE, tumor PE and tumor invasion to large veins according to the histopathology and the site of the cancer. Clinicians have given more attention to the prevention of venous thromboembolism (VTE) with chemotherapeutic and surgical treatment of cancer patients, but it is important to evaluate the risk of the development of VTE according to the histopathology and primary site of the cancer.The goal of this study was to investigate variations in the incidence of thrombotic PE, tumor PE and tumor invasion into large veins according to tumor histopathology and tumor site. MethodsA total of 65,181 cancer patients (66.0%) were identified from 98,736 postmortem examinations. [5][6][7] The incidence of PE, as well as the tumor site and the histopathology, was recorded for each case. PE was defined as critical (critical PE) when it was the primary cause of death or main diagnosis, and "total PE" was used to indicate the total number of thrombotic PEs, tumor PEs, bacterial PEs, mycotic PEs and other emboli (eg, fat, amniotic fluid etc). The type of emboli was determined by the pathologist performing the autopsy. Cases with 2 different types of emboli were counted twice. All cases were also reviewed for the presence of tumor invasion into a large vein. Within each PE group, the incidence of PE was compared between specific tumor types (adenocarcinoma, mucinous carcinoma, transi- Takeshi Nakano, MD*; Kunio Shirato, MDBackground The specific incidence of thrombotic pulmonary embolism (PE), tumor PE and tumor invasion into large veins according to tumor type and tumor site remains unclear. Methods and Results A total of 65,181 cancer patients were identified from 98,736 postmortem examinations. Thrombotic PE occurred in 2.32% of all cancer patients and comprised 88.6% of the total number of all PE events. The incidence of thrombotic PE was high in those with adenocarcinoma, leukemia and large cell carcinoma, and was low in those with hepatic cell carcinoma. The incidence of PE was high when tumor was present in hematogenous tissue, lungs, ovaries, pancreas and the biliary system, and was low when tumor was present in the liver. The incidence of tumor PE was high with large cell carcinoma, hepatic cell carcinoma and adenocarcinoma, and was also high when tumor was present in the lungs, ovaries, kidneys and liver. There was a significant correlation between the incidence of tumor PE and the incidence of tumor invasion into large veins. Conclusion The incidence of thrombotic PE, tumor PE and tumor invasion into large veins varies significantly according to tumor histopathology and tumor site. (Circ J 2006; 70: 744 -749)

Diastolic heart failure (DHF) is a major cardiovascular disorder with poor prognosis; however, its molecular mechanism still remains to be fully elucidated. We have previously demonstrated the important roles of Rho-kinase pathway in the molecular mechanisms of cardiovascular fibrosis/hypertrophy and oxidative stress, but not examined in the development of heart failure. Therefore, we examined in this study whether Rho-kinase pathway is also involved in the pathogenesis of DHF in Dahl salt-sensitive rats, an established animal model of DHF. They were maintained with or without fasudil, a Rho-kinase inhibitor (30 or 100 mg/kg/day, PO) for 10 weeks. Untreated DHF group exhibited overt heart failure associated with diastolic dysfunction but with preserved systolic function, characterized by increased myocardial stiffness, cardiomyocyte hypertrophy, and enhanced cardiac fibrosis and superoxide production. Fasudil treatment significantly ameliorated those DHF-related myocardial changes. Western blot analysis showed that cardiac Rho-kinase activity was significantly increased in the untreated DHF group and was dose-dependently inhibited by fasudil. Importantly, there was a significant correlation between the extent of myocardial stiffness and that of cardiac Rho-kinase activity. These results indicate that Rho-kinase pathway plays an important role in the pathogenesis of DHF and thus could be an important therapeutic target for the disorder.

Strong psychosocial stress is considered to be a precipitating factor in acute coronary events. To assess the hypothesis that the incidence of acute myocardial infarction (AMI) and its severity was remarkably heightened after the great earthquake, we retrospectively analyzed the clinical data of patients with AMI admitted to our hospital during a 3-week period between March 11 and March 31, 2011 (disaster group) as compared with AMI patients during the corresponding time period of 2010 (non-disaster group). The number of patients with AMI in the disaster group increased by about threefold (22 in the disaster group vs. seven in the non-disaster group). Compared with the previous years 2010 or 2009, the odds ratios [OR] for AMI during a 3-week period in 2011 were 4.40 (95 % confidence interval [CI]: 1.05-18.35), 5.66 (95 % CI: 1.42-22.59), respectively. Although the number of patients who underwent coronary revascularization was higher in the disaster group than in the non-disaster group (68.2 vs. 42.9 %, p = 0.0397), peak serum creatine kinase (CK)-MB level was significantly higher in the disaster group than in the non-disaster group (208.0 ± 159.0 vs. 149.3 ± 102.7 IU/l, p = 0.0431). In the disaster group, four patients died of cardiac causes, whereas no patient died in the non-disaster group (in-hospital mortality rate in the disaster vs. non-disaster group: 18.2 vs. 0 %, p = 0.0281). These results suggest that patients with AMI after the earthquake might be subject to strong psychosocial stress, and that psychological stress brought on by such disaster could trigger cardiac events and cardiac death.