Ryouzou Nagai

Circulating malondialdehyde modified LDL is a biochemical risk marker for coronary artery disease

Oxidatively modified low density lipoprotein (OxLDL) plays an important role in the development of atherosclerosis as its uptake by macrophages and smooth muscle cells leads to formation of foam cells which is a critical step in the evolution of the pathological state.1,2 Circulating OxLDL concentrations may therefore reflect the state of pathological atherosclerosis, and be a possible biochemical risk marker for coronary artery disease (CAD). Numerous efforts have been directed at detecting OxLDL concentrations in the circulation for this reason, but technical difficulties have hampered detection of minute amounts of OxLDL. To overcome these limitations, we focused on circulating malondialdehyde modified LDL (MDA-LDL), a chemical modification thought to reflect naturally occurring oxidation of LDL,3,4 and developed a sensitive immunoassay of circulating MDA-LDL concentrations. The diagnostic performance of MDA-LDL in CAD was compared against known lipid markers. This comparison revealed, for the first time, that MDA-LDL is superior, thus suggesting that MDA-LDL may be a promising tool for the biochemical detection of CAD. Consenting patients with CAD defined as having greater than 75% stenosis in one or more arteries on coronary angiography were enrolled, as were normal control subjects which included patients with normal coronary angiograms, and subjects who were admitted for regular health examinations and had: (1) no history of CAD; (2) normal renal function; (3) normal ECG and chest x ray. Blood was drawn under fasting conditions and centrifuged within four hours. Stabilising reagent containing sucrose and EDTA was added and samples were stored at −20°C until the time of …

Improved Survival in Patients with Continuous-Flow Ventricular Assist Device for Bridge to Heart Transplantation

BACKGROUND Contemporary continuous-flow ventricular assist devices (CFVADs) have greatly improved patient survival for indications of bridge to transplantation (BTT) and destination therapy. In Japan, CFVAD is limited for BTT use. The waiting period for heart transplantation (HT) is long owing to donor shortage. We examined the results of CFVAD for BTT indication. METHODS Eighty-nine VAD treatments were performed among subjects whose preimplantation condition was profile 1 (n = 49) or profile 2 or 3 (n = 40). The device was the paracorporeal pulsatile Nipro VAD (n = 67) or CFVAD (n = 22). All CFVAD patients were profile 2 or 3. RESULTS The median assist period was 529 days (Nipro VAD, 530; CFVAD, 528). Twenty-six patients were on the device for >2 years. Actuarial survival was 81.6%, 69.5%, and 61.1% at 1, 3, and 5 years. Survival in profile 1 was significantly worse than in profile 2 or 3. Survival of CFVAD patients was superior to that of paracorporeal VAD. Six-month mortality rate of 20% in cases before 2009 (n = 60) was dramatically improved to 3% among those after 2010 (n = 29). All patients with CFVAD were alive and discharged home. 26 patients were transplanted, 7 had been weaned from VAD and 27 were on a device. The rate of events requiring hospital admission was 0.98 per patient-year in CFVAD patients. CONCLUSIONS Contemporary CFVADs have enabled advanced heart failure patients to await HT safely with an improved quality of life. The advent of CFVAD has also shifted their preimplantation condition to a less sick status. CFVADs were the safest, most reliable circulatory support devices for long-term waiting periods for the BTT indications.

Plasma brain natriuretic peptide is associated with hepatic veno-occlusive disease and early mortality after allogeneic hematopoietic stem cell transplantation

Fluid retention is characteristic of veno-occlusive disease (VOD). We hypothesized that plasma brain natriuretic peptide (BNP), a neurohormone secreted in response to volume expansion, may be associated with VOD after hematopoietic stem cell transplantation (HSCT). BNP was measured before and weekly after HSCT in 46 recipients. Sixteen patients developed VOD. BNP concentrations were similar before and on day 0 in patients with and without VOD, but were significantly higher on day 7 and later in those with VOD. Patients with VOD had significantly higher peak BNP concentrations before engraftment than those without VOD (median, 634.4 versus 80.9 pg ml−1; P=0.01). Multivariate analysis showed that VOD was independently associated with BNP elevation (odds ratio, 50.1; 95% CI: 5.2–478.4; P<0.01). Landmark analysis at day 7 showed that patients with peak BNP concentration of ⩾180 pg ml−1 had significantly worse 100-day survival than patients with peak BNP <180 pg ml−1 (54 versus 91%; P<0.01). In multivariate analysis, BNP elevation before day 7 significantly predicted 100-day survival (hazard ratio 5.3; 95% CI: 1.1–24.3; P=0.03). These findings suggest that plasma BNP may serve as a diagnostic and prognostic marker of VOD.

Complete aspiration of thrombi from an occluded coronary artery

A 43 year-old male heavy smoker with no specific medical history was brought to our hospital with sudden chest pain. An ECG revealed ST segment elevation in precordial leads. An echocardiogram detected severe hypokinesis in the anterior wall of the left ventricle. After …

THU0248 Efficacy of imatinib mesylate on scleroderma associated pulmonary arterial hypertension

Background Scleroderma is an autoimmune disorder mainly characterized by progressive dermal and vascular fibrosis. It has been reported that abnormal signaling through the platelet derived growth factor (PDGF) and transforming growth factor beta (TGF-β) plays a constitutive role in the pathogenesis of the scleroderma and pulmonary arterial hypertension (PAH) including activation of fibrosis or vasculature remodeling1). Imatinib mesylate as a tyrosine kinase inhibitor of the PDGF receptor and c-Abl, can inhibit signaling pathway involved in both PDGF and TGF-β. Efficacy of imatinib has been shown to be more pronounced in patients with greater hemodynamic impairment, and imatinib has been shown to be effective in patients who remain symptomatic despite optimized treatment with established PAH drugs, although imatinib has not been approved for the use in PAH2). However, it remains to be elucidated whether the efficacy of imatinib differs according to underlying etiologies of PAH. Objectives To assess the therapeutic effect of imatinib in scleroderma associated PAH (SSc-PAH) comparing with idiopathic/heritable PAH (I/HPAH) Methods Eight patients with PAH (5 SSc-PAH and 3 I/HPAH) in WHO functional class III receiving at least 2 PAH agents were treated with imatinib (100-400 mg daily) for 6 months. Right heart catheterization (RHC) and pulmonary function testing (PFT) were performed at baseline and 3 or 6 months after starting imatinib treatment. Results Seven patients underwent RHC and PFT at 6 months; 1 IPAH patient underwent RHC and PFT at 3 months and died from an exacerbation of right heart failure within 6 months. Diffusing capacity of lung for carbon monoxide (DLCO) was measured in all except 1 SSc-PAH patient whose vital capacity of lung was too small for the measurement of DLCO. There were no differences in the maintenance dose of imatinib between SSc-PAH patients and I/HPAH patients (180.0±130.4 mg/day versus 166.7±57.7 mg/day). Baseline pulmonary vascular resistance (PVR) and DLCO were lower in SSc-PAH patients than in I/HPAH patients, although the differences were insignificant (920.4±429.1 dyne s cm-5 versus 1417.3±664.2 dyne s cm-5, 30.1±6.0% versus 66.7±28.0%). Hemodynamic assessments revealed that improvements in PVR and pulmonary arterial pressure were greater in patients with SSc-PAH than in those with I/HPAH; differences were significant for PVR only (-28.0±21.5% versus 1.8±7.0%, P=0.04, -13.0±12.1% versus -0.1±4.8%, P=0.09 respectively). There were no significant differences in the improvement of DLCO between SSc-PAH patients and I/HPAH patients (8.3±6.6% versus 5.9±2.4%), however DLCO of overall patients significantly increased by 7.3 mmHg (N=7, P<0.01) as shown previously3). Conclusions The data presented here suggests that patients with SSc-PAH may benefit more from treatment than those with I/HPAH. Further large trials are needed to assess the efficacy of imatinib in patients with SSc-PAH compared with other etiologies of the disease. References Hatton N, Frech T, Smith B, et al. Int J Clin Pract Suppel. 2011; 172: 35-43. Ghofrani HA, Morrell NW, Hoeper MM, et al. Am J Respir Crit Care Med. 2010; 182: 1171-7. Hatano M, Yao A, Shiga T, et al. Int Heart J. 2010; 51: 272-6. Disclosure of Interest None Declared

FRI0266 Hemodynamic complications in systemic sclerosis patients with various stages of pulmonary arterial hypertension

Background Prognosis of pulmonary arterial hypertension (PH) in systemic sclerosis (SSc) patients is poor. PH is a pathophysiological state defined by an increase in mean pulmonary arterial pressure (mPAP) ≥25 mmHg as assessed by right heart catheterization (RHC) and borderline-PH is defined by mPAP ≥21 mmHg. A rise in mPAP is a late marker of the pulmonary arteries remodeling processes, and the pre-clinical phase of SSc (mPAP <21 mmHg) is largely unknown. Objectives To examine the hemodynamic characteristics in SSc with various stages from normal pulmonary pressure to PH stages. Methods Eighty-eight consecutive patients with SSc (80 women and 8 men, 72 limited cutaneous SSc and 16 diffuse cutaneous SSc; mean age 62±11 yr) were assessed by RHC in a single center from May 2005 to December 2011. They were classified into four groups by mPAP (Table): (1) normal pressure (NP) group; mPAP <15mmHg, (2) pre-PH group; 15≤ mPAP <20mmHg, (3) borderline-PH group; 21≤ mPAP <25 mmHg, (4) PH group; mPAP ≥25mmHg. Results Age was not different among 4 groups. The differences in the plasama levels of brain natriuretic peptide (BNP), peak VO2, and % vital capacity/% diffusing capacity for carbon monoxide (%VC/%DLCO) changed in parallel with PH stage. In only PH group, heart rate (HR) was significantly increased. Even in NP group, pulmonary vascular resistance (PVR) was already increased, which might imply that pulmonary arteries in SSc were impaired in the very early stage. In pre-PH group, while PVR slightly increased, cardiac index (CI) markedly decreased below normal limit. Decreases in stroke volume index (StVI) became significant in not only PH but also borderline-PH and pre-PH groups. Conclusions According to our results, pulmonary arterial remodeling progresses faster than expected from mPAP in SSc patients, and earlier pharmacological intervention may be beneficial. Disclosure of Interest None Declared