Severe Coronary Heart Disease Research Articles

The Success Story of LDL Cholesterol Lowering.

We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence.

Association of N-acetyltransferase-2 polymorphism with an increased risk of coronary heart disease in a Chinese population.

We investigated the possible correlations between N-acetyltransferase-2 (NAT2) gene polymorphisms and the risk of coronary heart disease (CHD). CHD patients (113) and healthy controls (118) were enrolled from the First People's Hospital of Yuhang between January 2013 and June 2014. The patients were divided into mild CHD (N = 72) and severe CHD (N = 41) subgroups. DNA samples were extracted and the distributions of NAT2 polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Clinical characteristic indexes of severe CHD patients were also examined for relevant statistical analysis. WT, M1, M2, and M3 alleles were observed in both case and control groups. PCR-RFLP identified a wild-type homozygote, WT/WT; a mutant heterozygote, WT/Mx; and a mutant homozygote, Mx/Mx (x = 1, 2, and 3) variant of the NAT2 genotype. Mx/Mx differed significantly between case and control groups (P < 0.05); the frequencies of all four alleles did not differ significantly between case and control groups (P > 0.05). Slow acetylator genotype frequencies were notably higher in the case group than in the control group (P < 0.05). Individuals with the slow acetylator genotype were at 1.97-times higher risk of CHD and also displayed higher triglyceride and lower high-density lipoprotein cholesterol levels than those with the rapid acetylator genotype (P < 0.05). Therefore, the NAT2 polymorphism was believed to be associated with increased risk of CHD, with the NAT2 slow acetylator genotype serving as a risk factor for severe CHD in a Chinese population.

Is Needed Dobutamine Stress Echocardiography for the Detection of Coronary Artery Stenosis in Women?

REFER TO THE PAGE 135-143 By American Heart Association statistics updated at 2013, more than one in three female adults has some form of cardiovascular disease (CVD). Since 1984, the number of CVD deaths for females has exceeded those for males.1) Twenty-six percent of women age 45 and older who have an initial recognized myocardial infarction (MI) die within a year compared with 19% of men. In addition, 64% of women who died suddenly of coronary heart disease (CHD) had no previous symptoms.1) Compared with men, women have a 10-to-20-year lag in the initial presentation of CHD. Additionally, women do not always present with the characteristic pattern of chest pain. Other typical symptoms for women during their initial presentation include shortness of breath, diaphoresis, nausea, epigastric pain, and fatigue.2) Therefore, early diagnosis of CHD is very important to women to reduce the incidence of disease and prevent sudden cardiac death. However it is not easy. Electrocardiograms and exercise electrocardiograms are less sensitive to changes in women, making it more difficult for providers to diagnose CHD.3) What was worse, as seen on angiography, plaque in women tends to be distributed diffusely, rather than in clumps, causing women's angiographic studies to be misinterpreted as normal.4) We also should consider the risk factors that affect women specifically. For example, men tend to develop hypertension at younger ages than women; women's low-density lipoprotein cholesterol levels tend to be lower than men's at younger ages but exceed those of men in advanced age; and while triglyceride levels decline in men of middle and older age, they rise in women of comparable ages.5) Therefore, the addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying women at risk for cardiovascular events.6) The wide spread use of echocardiography has contributed to the early recognition of several distinct cardiac diseases in women as well as management of women-specific cardiac diseases.7) Dobutamine stress echocardiography (DSE) is being used for the diagnosis of CHD especially patients with chest pain who cannot exercise adequately. And this test showed sensitivity for detecting coronary artery disease of 78% and a specificity of 93%.8) DSE is especially useful in women with chest pain because as we commented above, electrocardiograms and exercise electrocardiograms are less sensitive to changes in women and this test has been relatively high sensitivity and specificity. In this issue, DSE and execise electrocardiography for the detection of CHD in women with chest discomfort was compared.9) About two hundred consecutive female patients who presented with chest pain in outpatient clinic, and who underwent treadmill exercise test (TET), DSE and coronary angiography were included for the study. The results showed that the sensitivity and specificity were higher with DSE (70.4, 94.6%) than TET (53.7, 73.6%) for detection of > 50% CHD. And DSE also showed greater diagnostic accuracy than TET by > 75% CHD criteria, and in subsets of patient with intermediate pretest probability. This manuscript is meaningful to compare TET and DSE in Korean women with chest pain. And as a result, demonstrated that DSE had a higher diagnostic value than TET in Korean female patients and as the disease severity of CHD worse, DSE had greater diagnostic accuracy than TET. However, the sensitivity of both tests to diagnose CHD in this study appeared lower than previously reported values.10),11) The reason may be lower prevalence of CHD, and much more patients with only single vessel disease in this study compared to previous study. One thing we should know is that, enrolled all patients came to outpatient clinic with vague chest pain, so the possibility of severe CHD was somewhat low. If they had more severe CHD such as unstable angina or MI, the test results might be different from those of this manuscript. Recently, multimodality imaging such as CT, MRI and strain analysis also showed very high sensitivity and specificity for detection of CHD. And the prevalence of women's CVD had been increased gradually. Therefore, much more studies regarding best diagnostic accurate modality in women's heart field, management and prognosis should be performed continuously.

Relationship of the anxiety-depressive disorder with coronary heart disease, comorbid with metabolic syndrome

Aim. It is expected that combination of anxiety and depressive disorders with components of the metabolic syndrome can summarize their effects that can significantly affect the prognosis of patients with coronary heart disease. Methods and results. In order to establish an interconnections of the anxiety and depressive disorders with components of the metabolic syndrome in patients with coronary artery disease and to assess their impact on the course of the disease 81 patients with a diagnosis of coronary heart disease: angina pectoris II-III functional class were examined. The 1 st group consisted of the 35 patients with isolated coronary heart disease, group 2 - 46 patients with coronary heart disease and metabolic syndrome. With the help of clinical and biochemical analysis, daily ECG monitoring, Seattle Angina Questionnaire, SF-36 questionnaire, the Hospital Anxiety and Depression Scale HADS we investigated the severity of anxiety and depression and life quality of the patients , depending on higher overall levels of anxiety and depression on the scale of HADS. Conclusion . It was found that for coronary heart disease concomitant with the metabolic syndrome is associated with higher overall levels of anxiety and depression on the scale of HADS, correlated with components of metabolic syndrome such as abdominal obesity, dyslipidemia and hyperglycemia. The presence of anxiety and depressive disorders in patients with metabolic syndrome, accompanied by more severe clinical course coronary heart disease according to Seattle questionnaire, reduced quality of life for patients, an imbalance of the autonomic nervous system in the direction of increased activity of the sympathetic part.

The effects of mechanical stimulation on controlling and maintaining marrow stromal cell differentiation into vascular smooth muscle cells.

For patients suffering from severe coronary heart disease (CHD), the development of a cell-based tissue engineered blood vessel (TEBV) has great potential to overcome current issues with synthetic graft materials. While marrow stromal cells (MSCs) are a promising source of vascular smooth muscle cells (VSMCs) for TEBV construction, they have been shown to differentiate into both the VSMC and osteoblast lineages under different rates of dynamic strain. Determining the permanence of strain-induced MSC differentiation into VSMCs is therefore a significant step toward successful TEBV development. In this study, initial experiments where a cyclic 10% strain was imposed on MSCs for 24 h at 0.1 Hz, 0.5 Hz, and 1 Hz determined that cells stretched at 1 Hz expressed significantly higher levels of VSMC-specific genetic and protein markers compared to samples stretched at 0.1 Hz. Conversely, samples stretched at 0.1 Hz expressed higher levels of osteoblast-specific genetic and protein markers compared to the samples stretched at 1 Hz. More importantly, sequential application of 24-48 h periods of 0.1 Hz and 1 Hz strain-induced genetic and protein marker expression levels similar to the VSMC profile seen with 1 Hz alone. This effect was observed regardless of whether the cells were first strained at 0.1 Hz followed by strain at 1 Hz, or vice versa. Our results suggest that the strain-induced VSMC phenotype is a more terminally differentiated state than the strain-induced osteoblast phenotype, and as result, VSMC obtained from strain-induced differentiation would have potential uses in TEBV construction.

Effects of glomerular filtration rate on the severity of coronary heart disease.

Chronic kidney disease (CKD) is considered to be one of the most common risk factors for cardiovascular diseases. Glomerular filtration rate (GFR) is the best method of testing level of kidney function and determining stage of kidney disease. The aim of this study was to examine the impact of renal function on severity of coronary heart disease (CHD). The present study included 918 patients undergoing elective coronary angiography. GFR was evaluated by simplified Modification of Diet in Renal Disease (MDRD) formula (mL/min/1.73 m2). The extent and severity of CHD were evaluated according to SYNTAX score. According to SYNTAX score, 416 patients had normal coronary arteries or nonsignificant CHD (control group), 267 had mild CHD (SYNTAX score: 1-22), 129 had moderate CHD (SYNTAX score: 23-32), and 106 had severe CHD (SYNTAX score: ≥33). Estimated GFR values (median [25th-75th percentiles]) were 99.00 (83.00-116.00) in the control group, 85.00 (73.00-101.00) in the mild CHD group, 87.00 (73.25-101.75) in the moderate CHD group, and 81.00 (65.00-101.00) in the severe CHD group. According to Spearman's rank correlation analysis, a negative correlation found between MDRD and SYNTAX score was statistically significant (p<0.001, r=-0.268). Renal function is an important predictor of presence and severity of angiographic CHD in patients without severe renal impairment. Negative correlation between MDRD and SYNTAX score was determined. This simple biochemical test can be used in determining risk of cardiovascular disease aside from other risk factors during routine clinical practice.

Ultrasound guided continuous paravertebral block in a patient with coronary heart disease and sleep apnea syndrome

The case of a 77-year-old patient with severe coronary heart disease who underwent radical mastectomy with axillary lymph node dissection by ultrasound-guided continuous paravertebral block (CPVB) is described in the present report. Radical mastectomy with axillary dissection is a surgical procedure that necessitates endotracheal intubation and is usually performed under general anesthesia, which carries heightened risk for patients with coronary heart disease (CHD) and sleep apnea syndrome (SAS). Ultrasound-guided CPVB is a simple and safe alternative technique that allows for the use of anesthesia and postoperative analgesia with minimal side effects.

Levels of acylation stimulating protein and the complement component 3 precursor are associated with the occurrence and development of coronary heart disease.

The aim of the present study was to investigate whether acylation stimulating protein (ASP) and complement component 3 (C3) are associated with the occurrence and development of coronary heart disease (CHD). The participants of the study were divided into three groups, including the healthy control (n=42), metabolic syndrome (MS, n=56) and CHD (n=62) groups. An enzyme-linked immunosorbent assay was used to measure the ASP concentrations, while an immunoturbidimetric assay was employed to determine the C3 concentrations. In addition, coronary angiography was performed to determine the severity of coronary artery disease in the CHD group. The CHD group was divided into three subgroups, according to the final Gensini score of coronary artery stenosis for each patient (mild, ≤20 points; moderate, 21–40 points; severe, >40 points). Western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were performed to analyze the protein and mRNA expression levels of C3 in the CHD subgroups and the healthy control group. The concentrations of ASP and C3 in the CHD group were found to be significantly higher compared with the control and MS groups. In addition, the levels of ASP and C3 in the mild and moderate CHD subgroups were significantly higher compared with the healthy controls or mild CHD patients. Furthermore, the protein expression levels of C3 in the moderate and severe CHD patients were found to be significantly higher compared with the healthy individuals and the mild CHD patients. The quantitative RT-PCR results revealed that the mRNA expression levels of C3 in the moderate and severe CHD patients were significantly higher compared with the healthy control group and the mild CHD patients. Furthermore, the mean levels of C3 transcripts in the severe CHD patients were found to be higher compared with the moderate CHD subgroup (P<0.05). Therefore, ASP and C3 were found to be associated with the occurrence and development of CHD; thus, may be used as novel indexes for CHD.

Spermatocytic variant of classic seminoma: a report of five cases and a brief review of the literature.

BackgroundSpermatocytic seminoma is a rare testicular malignancy, appearing in the adult population. It has a good prognosis and a low rate of metastatic potential.ObjectivesWe present five cases diagnosed and treated with radiotherapy at Rambam Health Care Campus in Haifa, Israel.MethodsBetween 1974 and 1996, five patients with stage I spermatocytic seminoma were referred post-orchiectomy to the Northern Israel Oncology Center. All five patients presented with the typical pathological features of the spermatocytic variant of classic seminoma, and all were staged clinically and radiologically.ResultsMean age at diagnosis was 44 years (range 30–58 years). Main symptoms included a palpable testicular mass and/or testicular enlargement. Mean duration of symptoms was 9 months (range 0.5–24 months). Three patients were irradiated to the para-aortic/ipsilateral iliacal lymph nodes (mean total dose 2,500 cGy), one patient with 4,000 cGy. One patient was irradiated to the bilateral iliacal lymph nodes (2,600 cGy). With a median follow-up of 15 years, four patients are alive with no evidence of disease or severe late side effects. One patient developed severe lymphedema and symptomatic peripheral vascular disease, stage IIA prostate carcinoma (hormonal and brachytherapy treatment) and a non-secretory hypophyseal adenoma (surgically removed); he died at the age of 75 due to severe peripheral vascular and coronary heart disease with no evidence of his first or second primaries.ConclusionsPrognosis is excellent and does not differ from classic seminoma. As in the accumulated experience in early-stage, low-risk classic seminoma, we suggest surveillance as the preferred policy.

Mitral annulus displacement measured by two-dimensional speckle tracking imaging to assess the left ventricular longitudinal systolic function in coronary heart disease.

To assess the clinical utility of measuring mitral annulus displacement (MAD) by two-dimensional speckle tracking for the rapid evaluation of left ventricular longitudinal systolic function in patients with coronary heart disease (CHD). Left ventricular longitudinal systolic function was evaluated by MAD using speckle tracking echocardiography in 30 healthy volunteers (controls) as well as in 30 patients with mild, 30 patients with moderate, and 30 patients with severe CHD. All participants had their apical four-chamber and two-chamber view echocardiographic images recorded. Left ventricular end-diastolic volume, left ventricular end-systolic volume, and left ventricular ejection fraction were calculated by the biplane Simpson method. MAD of interventricular septum (MADsep), left ventricular lateral wall (MADlat), and the middle point of the mitral annulus (MADmid) were measured offline with speckle-tracking echocardiography. MADmid% was defined as MADmid divided by left ventricular end-diastolic diameter. MADmid% was 16.9 ± 1.9, 11.8 ± 3.2, 11.8 ± 2.9, and 10.3 ± 3.6, respectively, in controls and in patients with mild, moderate, and severe CHD. All MAD indexes were lower in patients with moderate or severe CHD than in controls or patients with mild CHD. MAD is an early and rapid index for the assessment of left ventricular longitudinal systolic function in patients with different degrees of coronary artery disease.

Gallic acid and gallic acid-loaded coating involved in selective regulation of platelet, endothelial and smooth muscle cell fate

The drug-eluting stent (DES) is the most common means for the treatment of severe coronary heart disease in the clinic. However the DES has some drawbacks, these are long-term endothelial dysfunction, non selective cytotoxicity and late stent thrombosis. Hence, it is significantly important to find a drug or molecule with selective cytotoxicity for the DES. In this work, the effect of gradient concentration of gallic acid on endothelial and smooth muscle cells was investigated through alone-culture and co-culture methods. It was demonstrated that gallic acid promoted the growth of human umbilical vein endothelial cells (HUVECs) and suppressed the proliferation of human umbilical artery smooth muscle cells (HUASMCs) at the concentration of ∼5 μg ml−1. Then, gallic acid was mixed into poly(1,3-trimethylene carbonate) to prepare GA-loaded PTMC film via solvent evaporation. And material characteristics and biological evaluations are carried out by different means. These results showed that the GA-loaded PTMC film inhibited the adhesion and activation of platelets, indicating a good anticoagulant performance. Also, this film with a certain GA loading (∼1 wt%) provided significant enhancement for the adhesion and proliferation of HUVECs and inhibition of the growth of HUASMCs. These data suggested the large potential of GA for drug-eluting stent and other vascular devices.

Contrast-induced encephalopathy, a rare complication of coronary catheterization

Background: Contrast-Induced Encephalopathy (CIE) is a rare situation characterized by development of neurological signs after the administration of intravenous contrast. This condition has a wide spectrum of clinical presentation, ranging from focal cortical or sub-cortical neurological deficits, to confusional syndromes, seizures and coma. Findings in neuro-imaging may be present and may include localized cortical or sub-cortical enhancement, subarachnoid hyper-density or cerebral edema. Methods: clinical case report and review of the published cases. Results: The authors present the case of a 61 year old man with known ischemic heart disease that was admitted to our hospital with an acute coronary syndrome. Early invasive approach was decided and the patient underwent coronary catheterization that showed severe coronary heart disease without indication for surgical or percutaneous revascularization. After the procedure the patient referred occipital pain, followed by confusion, disorientation and agitation, without apparent focal neurological deficits, without neck stiffness. A cerebral CT scan was performed, showing a hyper-dense signal, approximately 100 Houndsfield Units (HU), assumed to be compatible with cerebellum hemorrhagic collection with associated subarachnoid hemorrhage. The patient remained in vigilance for 24 h with no further degradation of the neurological status. The cerebral CT scan was repeated the next day, this time with no abnormal findings. The patient subsequently recovered his fully normal neurological status within 48 h after the event. The diagnosis of CIE was then considered. Conclusions: CIE has a good prognosis, with spontaneous resolution in few days. It is to be considered as a differential diagnosis in patients with acute neurological changes who have undergone angiography. Characteristic high density signals, 80 to 160 HU (when blood usually shows by 40 to 60 HU), is a distinguishable feature of CIE that may provide correct interpretation of a clinical picture, in order to avoid unnecessary treatments and procedures, and their associated risks.

Coronary subclavian steal syndrome: an extracoronary cause of acute coronary syndrome

Significant atherosclerotic changes of the coronary arteries are the common cause of cardiac chest pain. We report the case of an 80-year-old woman suffering from unstable angina caused by extracoronary atherosclerosis. The patient had an extensive medical history with severe coronary heart disease and cardiac bypass surgery (LIMA to LAD, two venous bypass grafts). An urgent coronary angiography was performed. The angiogram displayed the already known three-vessel disease, the bypass grafts were in a good functional condition. Subsequently, a stenosis of the proximal segment of the left subclavian artery was detected. Measurement of the pullback pressure gradient confirmed the significance of the stenosis. We suspected a "steal phenomenon" concerning the bypass graft LIMA to LAD. An ad hoc PTA with consecutive stenting (self-expandable stent) enabled a successful revascularization of the left subclavian artery without any adverse effects to the vertebral arteries. Cardiac chest pain did not occur any more. Coronary Subclavian Steal Syndrome should be considered a rare but important differential diagnosis in acute coronary syndrome after bypass surgery.

Clinical Frailty Assessment and Formal Frailty Testing—Clinical Decision Making in Severe Coronary and Valvular Heart Disease

Background: Frailty denotes a multidimensional syndrome of loss of reserves (energy, physical ability, cognition, and health) that gives rise to vulnerability. Frailty is proposed as a parameter independent of age describing the patient's condition. Aim was to clinically and formally assess frailty in patients presenting with coronary artery disease or valvular heart disease with indication for surgery.

症例 右冠動脈起始部病変にステントを挿入し,救命し得たウェルナー症候群の1症例

症例 右冠動脈起始部病変にステントを挿入し,救命し得たウェルナー症候群の1症例

024: STEMI in Lorraine nord - Epidemiological, clinical and angiographic features, mortality trends since 1997

One in two patients starts coronary disease by myocardial infarction (MI). The early management within efficient network and emergency revascularization are key determinants of patient's outcomes. With the evidence-based medicine, our attitudes are influenced by international guidelines. Downstream, it is essential to evaluate our practices. Our work is a retrospective single-center comparative study of STEMI patients undergoing catheterization (KT) at Metz hospital cardiology department. We focused on epidemiological, clinical and angiographic features and mortality rate of patients consecutively supported on three 2-year periods since 1997. Of the 2075 patients hospitalized for MI during 2010-2011 (Period3), 762 underwent KT within 12 hours above 36% (24.5% in 1997-1998 (Period1), 44% in 2005-2006 (Period2)). There is an increase of PPCI with 85% in P3 (76%P1, P267%, >0.001). In the same time, we observe a decrease in rescue angioplasty post thrombolysis (14%P1, 24%P2, 3.7%P3, >0.001). The rate of patient in cardiogenic shock remains stable over the 3 periods (10%). Patients older than 75 years decrease (35.5%P1, 21.2%P2, 18.4%P3). The percentage of patients with multivessel disease increases again between P2 and P3 (31.4%P1, 35.5%P2, 40.4%P3). Direct stenting remains the strategy most frequently used (59.5%P3, 55.8%P2, 1%P1, >0.001). The mortality analysis of the entire population showed no significant difference in the 3 periods (7%). However, there was a decline in mortality in the subgroup of STEMI with cardiogenic shock (62%P1, 48%P2, 23%P3, >0.001). STEMI patients underwent KT in the first 12 hours in our center appear younger and carrying more severe coronary heart disease. Despite technical changes, in overall mortality has been stable since 1997 except in cardiogenic shock whose outcome continues to improve. Regular analysis of our patients and practices appears essential for the optimization of our supported.

P-wave dispersion by 12-lead electrocardiography in carotid artery stenting

Although carotid artery stenting (CAS) is an effective treatment for severe carotid stenosis, it has been associated with alterations in autonomic functions during or shortly after the procedure. And, autonomic functions influence P-wave durations. In this study, our aim was to investigate P-wave durations on 12-lead surface electrocardiography after CAS. Patients (19 male, 8 female) who are suitable for CAS, without a history of hypertension, diabetes mellitus, severe coronary artery or valvular heart disease, were enrolled in our study. 12-lead surface electrocardiography recordings were obtained at the beginning, immediately after and at the 24 h of the procedure. P-wave maximum, minimum and dispersion durations were analyzed by double-blinded observers. Results were statistically analysed using Friedman and Wilcoxon tests. The P maximum and P dispersion values were significantly increased immediately after the procedure and continued with high levels at 24-h recordings, respectively (128 ± 10/19 ± 7, 143 ± 14/37 ± 11, and 137 ± 11/30 ± 7 ms, p value <0.05). The P minimum value was significantly decreased immediately after the procedure (109 ± 11/105 ± 10 ms, p value <0.05). At 24-h recordings, a nonsignificant increase occured in P minimum values (106 ± 8 ms). P maximum and dispersion durations were significantly increased after the CAS and continued with high levels at 24-h recordings, which may be associated with the alterations in autonomic functions via augmented parasympathetic activity by vagally mediated stimulus. Overall, these findings suggest that decline in cardiovascular activity is prolonged at least 24 h after CAS.

High dose of human plasma‐derived FVIII‐VWF as first‐line therapy in patients affected by acquired haemophilia A and concomitant cardiovascular disease: four case reports and a literature review

Haemostatic control is the first priority in acquired haemophilia A (AHA) and recent consensus recommendations suggest using bypassing agents (BAs) (recombinant activated FVII (rFVIIa) and activated prothrombin complex concentrate) as first-line treatment of bleeds. FVIII concentrates, both plasma-derived and recombinant, may be used with low inhibitor titre, minor haemorrhagic episodes and when bypassing drugs are not available [1]. The use of BAs may be associated with thrombotic complications, especially in the elderly with cardiovascular comorbidity, and should be carried out cautiously, as a literature review reported that 7% of patients treated with rFVIIa experienced thrombotic events [2]. Efficacy of FVIII concentrates in AHA has been reported since the early 1990s. Yet the published reports are retrospective, include few patients and deal with heterogeneous populations (see Table 1). Two main protocols have been recorded in the literature [3,4], but FVIII is often used at a much lower dosage. For instance, the data provided by the EACH2 Registry [5] reporting that the efficacy of FVIII treatment is lower than using BAs would show median doses inferior to those recommended in the literature (initial mean dose 50 U kg , total mean dose for patient 20 000 U, period-treatment range 4–6 days). This letter reports on the experience of our Centre in the use of high-dose human plasma-derived FVIII-VWF (HP-FVIII-VWF) concentrates in four patients affected by AHA and concomitant cardiovascular disease treated with a standardized protocol and include a review of the literature on the usage of HP-FVIII in the treatment of AHA.

Improved Hepatocyte Engraftment after Portal Vein Occlusion in LDL Receptor-Deficient WHHL Rabbits and Lentiviral-Mediated Phenotypic Correction in Vitro

Innovative cell-based therapies are considered as alternatives to liver transplantation. Recent progress in lentivirus-mediated hepatocyte transduction has renewed interest in cell therapy for the treatment of inherited liver diseases. However, hepatocyte transplantation is still hampered by inefficient hepatocyte engraftment. We previously showed that partial portal vein embolization (PVE) improved hepatocyte engraftment in a nonhuman primate model. We developed here an ex vivo approach based on PVE and lentiviral-mediated transduction of hepatocytes from normal (New Zealand White, NZW) and Watanabe heritable hyperlipidemic (WHHL) rabbits: the large animal model of familial hypercholesterolemia type IIa (FH). FH is a life-threatening human inherited autosomal disease caused by a mutation in the low-density lipoprotein receptor (LDLR) gene, which leads to severe hypercholesterolemia and premature coronary heart disease. Rabbit hepatocytes were isolated from the resected left liver lobe, and the portal branches of the median lobes were embolized with Histoacryl® glue under radiologic guidance. NZW and WHHL hepatocytes were each labeled with Hoechst dye or transduced with lentivirus expressing GFP under the control of a liver-specific promoter (mTTR, a modified murine transthyretin promoter) and were then immediately transplanted back into donor animals. In our conditions, 65-70% of the NZW and WHHL hepatocytes were transduced. Liver repopulation after transplantation with the Hoechst-labeled hepatocytes was 3.5 ± 2%. It was 1.4 ± 0.6% after transplantation with either the transduced NZW hepatocytes or the transduced WHHL hepatocytes, which was close to that obtained with Hoechst-labeled cells, given the mean transduction efficacy. Transgene expression persisted for at least 8 weeks posttransplantation. Transduction of WHHL hepatocytes with an LDLR-encoding vector resulted in phenotypic correction in vitro as assessed by internalization of fluorescent LDL ligands. In conclusion, our results have applications for the treatment of inherited metabolic liver diseases, such as FH, by transplantation of lentivirally transduced hepatocytes.

PP-099 IS THERE ANY RELATION BETWEEN CIRCULATING ENDOTHELIAL-LEUKOCYTE ADHESION MOLECULE-1 AND EXTENT OF CORONARY ARTERY INVOLVEMENTS IN MEN WITH ANGINA PECTORIS?

Background-Selectins as a group of adhesion molecule arise from the surface of activated cell and involved for atherosclerotic plaque production. Objective-To evaluate the relationship between Circulating Endothelial-Leukocyte adhesion molecule -1 (E-selectin) and the extent of coronary artery involvement in male Patients with coronary heart disease (CHD). MethodsParticipants were 103 male patients with symptoms of CHD. Patients underwent coronary angiography and according to angiography results they were divided to 80 patients with severe CHD and 23 with mild coronary involvements according to angiographic score. The Circulating E-selectin level was compared in both groups by ELISA method. Anova and analysis of covariant (ANCOVA) were used for evaluating possible association of E-selectin level and severity of coronary artery involvement by adjusting age, history of diabetes mellitus, hypertension, and dyslipidemia. ResultsThe mean age of 103 male patients was 58.32±9.42 years. The E-selectin level was not significantly different in both groups with sever and minimal (CHD) (P=0.78). ANCOVA test could not show after significant association between E-selectin level and the extent of coronary artery involvement adjusting age (P=0.94) as well as history of diabetes mellitus, hypertension, and dyslepidemia respectively (P=0.43). ConclusionThe circulating E-selectin level have no association with the severity of CHD in male patients(Iranian Heart Journal 2011; 12 (4):37-42). Key Word : Adhesion molecule■ E-selectin■ CAD■ coronary angiography■ extent Received June. 16, 2011; Accepted for publication Feb. 10, 2012 1. Associated Professor of Cardiology, Cardiac Rehabilitation Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran. 2. Assistant Researcher, Cardiac Rehabilitation Research Center, Isfahan Cardiovascular research Institute, Isfahan University of Medical Sciences, Isfahan, Iran. 3. Cardiology Fellow, Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical sciences, Isfahan, Iran. 4. MS, MS, Biologist, Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical sciences, Isfahan, Iran. 5. Researcher, Cardiac Rehabilitation Research Center, Isfahan Cardiovascular Research Institute, Isfahan, Iran. 6. Professor of Cardiology, Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical sciences, Isfahan, Iran. Correspondence to: Masoumeh Sadeghi, MD. Head of CVD in Women Department Isfahan Cardiovascular Research Institute WHO Collaborating Center. (http://crc.mui.ac.ir) Isfahan University of Medical Sciences (http://mui.ac.ir) PO BOX: 81465-1148 Phone: +98 311 3359797 Fax: +98 311 3373435 Email: sadeghimasoumeh@gmail.com Ar ch iv of S ID