Reassessing the Carotid Artery Plaque "Rim Sign" on CTA: A New Analysis with Histopathologic Confirmation.

BACKGROUND AND PURPOSE: The CTA "rim sign" has been proposed as an imaging marker of intraplaque hemorrhage in carotid plaques. This study sought to investigate such findings using histopathologic confirmation. MATERIALS AND METHODS: Included patients had CTA neck imaging <1 year before carotid endarterectomy. On imaging, luminal stenosis and the presence of adventitial (<2-mm peripheral) and "bulky" (≥2-mm) calcifications, total plaque thickness, soft-tissue plaque thickness, calcification thickness, and the presence of ulcerations were assessed. The rim sign was defined as the presence of adventitial calcifications with internal soft-tissue plaque of ≥2 mm in maximum thickness. Carotid endarterectomy specimens were assessed for both the presence and the proportional makeup of lipid material, intraplaque hemorrhage, and calcification. RESULTS: Sixty-seven patients were included. Twenty-three (34.3%) were women; the average age was 70.4 years. Thirty-eight (57.7%) plaques had a rim sign on imaging, with strong interobserver agreement (κ = 0.85). A lipid core was present in 64 (95.5%) plaques (average, 22.2% proportion of plaque composition); intraplaque hemorrhage was present in 52 (77.6%), making up, on average, 13.7% of the plaque composition. The rim sign was not associated with the presence of intraplaque hemorrhage (P = .11); however, it was associated with a greater proportion of intraplaque hemorrhage in a plaque (P = .049). The sensitivity and specificity of the rim sign for intraplaque hemorrhage were 61.5% and 60.0%, respectively. CONCLUSIONS: The rim sign is not associated with the presence of intraplaque hemorrhage on histology. However, it is associated with a higher proportion of hemorrhage within a plaque and therefore may be a biomarker of more severe intraplaque hemorrhage, if present.

Why Not Dipyridamole: a Review of Current Guidelines and Re-evaluation of Utility in the Modern Era.

Dipyridamole is an old anti-platelet and coronary vasodilator agent that inhibits platelet phosphodiesterase and increases interstitial adenosine levels. Its use in coronary artery disease (CAD) has fallen out of practice in the modern era with the advent of new anti-platelet agents, and most modern guidelines on the management of CAD either neglect to comment on its utility or outright recommend against it. The majority of the studies used in these guidelines are outdated and took place in an era when high doses of aspirin were used and statins were not widely utilized. There is growing evidence in rat models of dipyridamole's synergy with statins through adenosine modulation resulting in significant myocardial protection against ischemia-reperfusion injury and limitation of infract size. The data in human studies are limited but show a similar potential synergy between dipyridamole and statins. It would thus be prudent to reconsider the recommendations against the use of dipyridamole in CAD and to re-evaluate its possible role and potential benefits through well-designed randomized trials combining it with statins, low-dose aspirin, and/or other anti-platelet agents.

A Metabolic Intravascular Platform to Study FDG Uptake in Vascular Injury.

PURPOSE: Metabolic alterations underlie many pathophysiological conditions, and their understanding is critical for the development of novel therapies. Although the assessment of metabolic changes in vivo has been historically challenging, recent developments in molecular imaging have allowed us to study novel metabolic research concepts directly in the living subject, bringing us closer to patients. However, in many instances, there is need for sensors that are in close proximity to the organ under investigation, for example to study vascular metabolism. METHODS: In this study, we developed and validated a metabolic detection platform directly in the living subject under an inflammatory condition. The signal collected by a scintillating fiber is amplified using a photomultiplier tube and decodified by an in-house tunable analysis platform. For in vivo testing, we based our experiments on the metabolic characteristics of macrophages, cells closely linked to inflammation and avid for glucose and its analog 18F-fluorodeoxyglucose (18F-FDG). The sensor was validated in New Zealand rabbits, in which inflammation was induced by either a) high cholesterol (HC) diet for 16 weeks or b) vascular balloon endothelial denudation followed by HC diet. RESULTS: There was no difference in weight, hemodynamics, blood pressure, or heart rate between the groups. Vascular inflammation was detected by the metabolic sensor (Inflammation: 0.60 ± 0.03 AU vs. control: 0.48 ± 0.03 AU, p = 0.01), even though no significant inflammation/atherosclerosis was detected by intravascular ultrasound, underscoring the high sensitivity of the system. These findings were confirmed by the presence of macrophages on ex vivo aortic tissue staining. CONCLUSION: In this study, we validated a tunable very sensitive metabolic sensor platform that can be used for the detection of vascular metabolism, such as inflammation. This sensor can be used not only for the detection of macrophage activity but, with alternative probes, it could allow the detection of other pathophysiological processes.

Urinary mitochondrial DNA copy number identifies renal mitochondrial injury in renovascular hypertensive patients undergoing renal revascularization: A Pilot Study.

AIMS: Patients with renovascular hypertension (RVH) exhibit elevated urinary mtDNA copy numbers, considered to constitute surrogate markers of renal mitochondrial injury. The modest success of percutaneous transluminal renal angioplasty (PTRA) in restoring renal function in RVH has been postulated to be partly attributable to acute reperfusion injury. We hypothesized that mitoprotection during revascularization would ameliorate PTRA-induced renal mitochondrial injury, reflected in elevated urinary mtDNA copy numbers and improve blood pressure and functional outcomes 3 months later. METHODS: We prospectively measured urinary copy number of the mtDNA genes COX3 and ND1 using qPCR in RVH patients before and 24 hrs after PTRA, performed during IV infusion of vehicle (n = 8) or the mitoprotective drug elamipretide (ELAM, 0.05 mg/kg/h, n = 6). Five healthy volunteers (HV) served as controls. Urinary mtDNA levels were also assessed in RVH and normal pigs (n = 7 each), in which renal mitochondrial structure and density were studied ex-vivo. RESULTS: Baseline urinary mtDNA levels were elevated in all RVH patients vs HV and directly correlated with serum creatinine levels. An increase in urinary mtDNA 24 hours after PTRA was blunted in PTRA+ELAM vs PTRA+Placebo. Furthermore, 3-months after PTRA, systolic blood pressure decreased and estimated glomerular filtration rate increased only in ELAM-treated subjects. In RVH pigs, mitochondrial damage was observed using electron microscopy in tubular cells and elevated urinary mtDNA levels correlated inversely with renal mitochondrial density. CONCLUSIONS: PTRA leads to an acute rise in urinary mtDNA, reflecting renal mitochondrial injury that in turn inhibits renal recovery. Mitoprotection might minimize PTRA-associated mitochondrial injury and improve renal outcomes after revascularization.

Micro-RNAS Regulate Metabolic Syndrome-induced Senescence in Porcine Adipose Tissue-derived Mesenchymal Stem Cells through the P16/MAPK Pathway.

Mesenchymal stem cells (MSCs) constitute an important repair system, but may be impaired by exposure to cardiovascular risk factors. Consequently, adipose tissue-derived MSCs from pigs with the metabolic syndrome (MetS) show decreased vitality. A growing number of microRNAs (miRNAs) are recognized as key modulators of senescence, but their role in regulating senescence in MSC in MetS is unclear. We tested the hypothesis that MetS upregulates in MSC expression of miRNAs that can serve as post-transcriptional regulators of senescence-associated (SA) genes. MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet ( n = 6 each). Next-generation miRNA sequencing (miRNA-seq) was performed to identify miRNAs up-or down-regulated in MetS-MSCs compared with Lean-MSCs. Functional pathways of SA genes targeted by miRNAs were analyzed using gene ontology. MSC senescence was evaluated by p16 and p21 immunoreactivity, H2AX protein expression, and SA-ß-Galactosidase activity. In addition, gene expression of p16, p21, MAPK3 (ERK1) and MAPK14, and MSC migration were studied after inhibition of SA-miR-27b. Senescence biomarkers were significantly elevated in MetS-MSCs. We found seven upregulated miRNAs, including miR-27b, and three downregulated miRNAs in MetS-MSCs, which regulate 35 SA genes, particularly MAPK signaling. Inhibition of miR-27b in cultured MSCs downregulated p16 and MARP3 genes, and increased MSC migration. MetS modulates MSC expression of SA-miRNAs that may regulate their senescence, and the p16 pathway seems to play an important role in MetS-induced MSC senescence.

Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in Older Adults with Coronary Artery Disease: Results of a Pilot Study.

Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased. Adipose tissue expression of mRNAs (arbitrary units) for MCP-1 (3585 vs 2020, p=0.06), PPAR-γ (1257 vs 1166), PAI-1 (823 vs 338, p=0.08) increased, whereas interleukin-8 (163 vs 312), TNF-α (75 vs 94) and p16 (129 vs 169) decreased. Cellular senescence-associated beta galactosidase activity (2.2% vs 3.6%, p=0.18) tended to decrease. We observed some correlation between some senescence markers and physical performance but no improvement in frailty with rapamycin was noted. (NCT01649960).

Fotogrametría del perfil facial en ortodoncia / Photogrammetry of facial profile in orthodontics

Se incorporaron dos sencillos elementos en las fotografías del perfil facial en ortodoncia. La aplicación de un sello, automático, de tinta común con una escala preestablecida de aplicación fácil, ágil y reproducible, directamente sobre la piel del paciente, para otorgar mayorprecisión en la comparación de imágenes en el tiempo; como así también, la utilización de un plano de referencia denominado plano lefraconformado por dos puntos que unen ojo y oído, permitiendo evaluar los cambios producidos en el rostro por medio de la superposición fotográfica. Al finalizar el presente trabajo se concluyo que la utilización del sello y la superposición sobre el plano lefra permiten asimilar eltamaño de las fotografías y a su vez dar una zona referencial estable, facilitando la comparación entre el pre y post tratamiento.

Two simple elements were incorporated in the photographs of facial profile in orthodontics. The application of a seal, automatic, common ink on a prescribed scale of easy, fast and reproducible application, directly on the skin of the patient profile, which gives more accurate comparison of images in time; as well as the use of a reference plane called lefra plane, which consists of two points linking eye and ear, allowing to evaluate the changes in the face by means of photographic superimposition. Upon completion of this work, was concluded that the use of the seal and the overlay on the lefra plane allow to assimilate the size of the photographs and in turn provide a stable reference area to facilitate the comparison between pre and post treatment.

Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis.

PURPOSE: Diets rich in plant-derived polyphenols such as olive oil (OO) and/or catechins such as epigallocatechin 3-gallate (EGCG) have been shown to reduce the incidence of cardiovascular diseases, potentially by improving endothelial function, an important surrogate for atherosclerosis. The possible augmentation of endothelial function with the combined efforts of OO and EGCG is intriguing, yet unknown. METHODS: Eighty-two patients with early atherosclerosis (presence of endothelial dysfunction) were enrolled in this double-blind, randomized trial with 52 completing the study. The aim of the study was to compare the effect of a daily intake of 30 ml simple OO, with 30 ml of EGCG-supplemented OO, on endothelial function as well as on inflammation and oxidative stress after a period of 4 months. Endothelial function was assessed noninvasively via peripheral arterial tonometry (Endo-PAT®). RESULTS: After 4 months, when OO and EGCG-supplemented OO groups were combined, OO significantly improved endothelial function (RHI, 1.59 ± 0.25-1.75 ± 0.45; p < 0.05). However, there were no significant differences in results between the two olive oil groups. Interestingly, with OO supplementation there was a significant reduction in inflammatory parameters: sICAM (196 to 183 ng/mL, p = < 0.001); white blood cells (WBCs) (6.0 × 109/L-5.8 × 109/L, p < 0.05); monocytes (0.48 × 109/L to 0.44 × 109/L, p = 0.05); lymphocytes (1.85 × 109/L to 1.6 × 109/L, p = 0.01); and platelets (242-229 × 109/L, p = 0.047). CONCLUSIONS: Improvement in endothelial dysfunction in patients with early atherosclerosis in association with significant reduction in leukocytes may suggest an important role of early cellular inflammatory mediators on endothelial function. The current study supports one potential mechanism for the role of olive oil, independent of EGCG, modestly supplemented to a healthy cardiovascular diet.

Circulating humanin levels are associated with preserved coronary endothelial function.

Humanin is a small endogenous antiapoptotic peptide, originally identified as protective against Alzheimer's disease, but subsequently also found on human endothelium as well as carotid artery plaques. Endothelial dysfunction is a precursor to the development of atherosclerotic plaques, which are characterized by a highly proinflammatory, reactive oxygen species, and apoptotic milieu. Previous animal studies demonstrated that humanin administration may improve endothelial function. Thus the aim of this study was to test the hypothesis that patients with coronary endothelial dysfunction have reduced systemic levels of humanin. Forty patients undergoing coronary angiography and endothelial function testing were included and subsequently divided into two groups based on coronary blood flow (CBF) response to intracoronary acetylcholine (normal ≥ 50% increase from baseline, n = 20 each). Aortic plasma samples were obtained at the time of catheterization for the analysis of humanin levels and traditional biomarkers of atherosclerosis including C-reactive protein, Lp-Pla(2), and homocysteine. Baseline characteristics were similar in both groups. Patients with coronary endothelial dysfunction (change in CBF = -33 ± 25%) had significantly lower humanin levels (1.3 ± 1.1 vs. 2.2 ± 1.5 ng/ml, P = 0.03) compared with those with normal coronary endothelial function (change in CBF = 194 ± 157%). There was a significant and positive correlation between improved CBF and humanin levels (P = 0.0091) not seen with changes in coronary flow reserve (P = 0.76). C-reactive protein, Lp-Pla(2), and homocysteine were not associated with humanin levels. Thus we observed that preserved human coronary endothelial function is uniquely associated with higher systemic humanin levels, introducing a potential diagnostic and/or therapeutic target for patients with coronary endothelial function.

Role of oxidative stress in hypoxia preconditioning of cells transplanted to the myocardium: a molecular imaging study.

AIM: Cell-based therapies are a potential therapeutic alternative for the treatment of coronary artery disease (CAD). However, transplanted cells undergo significant death in the living subject. Hypoxic preconditioning (HPC) is a potential intervention to increase transplanted cell survival. However, the biological mechanisms of this benefit remain unclear. We hypothesize that the beneficial effect of HPC on stem cell survival is in part due to preservation of oxidant status, an effect that will be monitored using state-of-the-art molecular imaging. METHODS: H9c2 rat cardiomyoblasts expressing the construct CMV-firefly luciferase (h9c2-fluc), with and without HPC, were exposed to hypoxia, and oxidative stress and cell survival were measured. Subsequently, H9c2-fluc cells, with and without HPC, were injected into the myocardium of rats and cell survival was monitored daily with Bioluminescence (BLI) using a CCD camera. RESULTS: Compared to controls, cells exposed to hypoxia had increased amount of reactive oxygen species (ROS, control: 14.1±0.9 vs. hypoxia: 19.5 ± 2.0 RFU/µg protein, P=0.02) and decreased cell survival (control: 0.29 ± 0.005 vs. hypoxia: 0.24 ± 0.005 OD, P<0.001). HPC treatment decreased the amount of hypoxia-induced ROS (HPC: 11.5 ± 0.7RFU/µg protein, P=0.002 vs. hypoxia and P=0.11 vs. control), associated with improved survival (HPC: 0.27 ± 0.004OD/µg protein, P=0.002 vs. hypoxia and P=0.005 vs. control). Most importantly, compared to un-conditioned cells, HPC-cells had increased cell survival after transplantation to the myocardium (C: 34.7 ± 6.7% vs. HPC: 83.4 ± 17.5% at day 5 compared to day 1, P=0.01). CONCLUSION: The beneficial effect of HPC is in part due to preservation of oxidant status. Molecular imaging can assess changes in cell survival in the living subject and has the potential to be applied clinically.

Surveillance and identification of influenza A viruses in wild aquatic birds in the Crimea, Ukraine (2006-2008).

The ecology of avian influenza (AI) viruses in wild aquatic birds of Asia is poorly understood, especially for the H5N1 high pathogenicity AI (HPAI) viruses. From March 2006 through November 2008, 20 AI viruses were isolated in the Crimea region of Ukraine with an overall frequency of virus recovery of 3.3%. All the viruses were isolated from three species of dabbling ducks: mallard (Anas platyrhynchos), wigeon (Anas penelope), and garganey (Anas querquedula), making the frequency of virus recovery for dabbling ducks 6.3%. The viruses were predominantly isolated during the fall sampling period. All viruses were genetically and antigenically characterized. No H5N1 HPAI viruses were isolated, but other HA and NA subtypes were identified including H3N1 (2), H3N6 (3), H3N8 (4), H4N6 (6), H5N2 (3), H7N8 (1), and H10N6 (1) subtypes. All isolates were of low pathogenicity, as determined by the intravenous pathogenicity index of 0.00. For H5N2 and H7N8 isolates, the HA gene was sequenced and the phylogenetic analysis revealed possible ecologic connections of the Crimea region with AI viruses from Siberia and Europe. No influenza A isolates were recovered from other Anseriformes (diving ducks [two species of pochards] and graylag geese), Columbiformes (collared doves), Gruiformes (coot), and Galliformes (gray partridges).

Segmental coronary endothelial dysfunction in patients with minimal atherosclerosis is associated with necrotic core plaques.

BACKGROUND/OBJECTIVE: Endothelial dysfunction and atherosclerosis are systemic disorders, but are often characterised by segmental involvement and complications. A potential mechanism for local involvement early in the disease process may be related to plaque composition. This study was designed to test the hypothesis that in patients with minimal coronary atherosclerosis, coronary artery segments with abnormal endothelial function have specific plaque characteristics. METHODS: Intravascular ultrasound (IVUS) images were obtained from 30 patients who underwent coronary endothelial function assessment. Spectral analysis of the IVUS radiofrequency data was used for assessment of plaque composition. IVUS findings of the coronary sections were compared according to the corresponding endothelial response to acetylcholine. RESULTS: Sections with a decrease epicardial coronary arterial diameter in response to acetylcholine had smaller baseline lumen (7.5 (2.4) mm(2) vs 8.8 (3.3) mm(2), p = 0.006) but larger plaque burden (37.1% (9.4%) vs 31% (7%), p = 0.003) than sections with normal endothelial response. Sections with endothelial dysfunction had larger necrotic core plaques: 0.13 (0.03-0.33) mm(2) vs 0.0 (0.0-0.07), p<0.001 and more dense calcium: 0.03 (IQR 0.0-0.13) mm(2) vs 0.0 (0.0-0.10) mm(2), p<0.01), than those with normal endothelial response. Only necrotic core area was associated with endothelial dysfunction (p<0.001) after adjusting for other measures. CONCLUSIONS: This study suggests that local coronary endothelial dysfunction in patients with minimal coronary atherosclerosis is associated with plaque characteristics that are typical of vulnerable plaques.

Stress hormone and circulating biomarker profile of apical ballooning syndrome (Takotsubo cardiomyopathy): insights into the clinical significance of B-type natriuretic peptide and troponin levels.

OBJECTIVE: To evaluate the stress neurohumoral and cardiac biomarker profile of patients with apical ballooning syndrome (ABS). METHODS: Plasma-free metanephrines, B-type natriuretic peptide (BNP), high sensitivity C-reactive protein (hsCRP) and troponin T, as well as 24-hour urine catecholamines, metanephrines and free cortisol were measured in 19 ABS and 10 ST-elevation myocardial infarction (STEMI) patients. RESULTS: An antecedent stressful event was identified in 15 ABS patients. There were no differences in plasma normetanephrine (median 0.64 (IQ range 0.43-0.97) nmol/l vs 0.53 (0.32-0.77) nmol/l, p = 0.44), metanephrine (0.10 (0.10-0.22) nmol/l vs 0.16 (0.10-0.38) nmol/l, p = 0.29), or cortisol levels (16.0 (7.3-44.0) microg/dl vs 13.0 (10.5-23.5) microg/dl, p = 0.95) between ABS and STEMI patients. The 24-hour urine metanephrines, catecholamines and cortisol levels were normal in the majority of ABS patients. Troponin T levels were lower (0.62 (0.18-0.84) ng/ml vs 3.80 (2.04-6.57) ng/ml, p<0.001), but BNP levels were higher in ABS compared with STEMI (944 (650-2022) pg/ml vs 206 (140-669) pg/ml, p = 0.009). HsCRP was similarly elevated in the two groups (11.0 (5.1-110.8) mg/l and 24.3 (8.1-88.6) mg/l, p = 0.78). CONCLUSIONS: Catecholamine and cortisol levels were not elevated in our cohort of ABS, suggesting that routine measurement of these stress hormones is unlikely to be of diagnostic value in practice. In contrast to STEMI, ABS is characterised by a greater elevation in BNP and less myonecrosis.

Low-dose nesiritide in human anterior myocardial infarction suppresses aldosterone and preserves ventricular function and structure: a proof of concept study.

BACKGROUND: B-type natriuretic peptide (BNP, nesiritide) has anti-fibrotic, anti-hypertrophic, anti-inflammatory, vasodilating, lusitropic and aldosterone-inhibiting properties but conventional doses of BNP cause hypotension, limiting its use in heart failure. OBJECTIVE: To determine whether infusion of low-dose BNP within 24 h of successful reperfusion for anterior acute myocardial infarction (AMI) would prevent adverse left ventricular (LV) remodelling and suppress aldosterone. METHODS: A translational proof-of-concept study was carried out to determine tolerability and biological activity of intravenous BNP at 0.003 and 0.006 microg/kg/min, without bolus started within 24 h of successful reperfusion for anterior AMI. 24 patients with first anterior wall ST elevation AMI and successful revascularisation were randomly assigned to receive 0.003 (n = 12) or 0.006 (n = 12) microg/kg/min of IV BNP for 72 h in addition to standard care during hospitalisation for anterior AMI. RESULTS: Baseline characteristics, drugs and peak cardiac biomarkers for myocardial damage were similar between both groups. Infusion of BNP at 0.006 microg/kg/min resulted in greater biological activity than infusion at 0.003 microg/kg/min as measured by higher mean (SEM) plasma cGMP levels (8.6 (1) vs 5.5 (1) pmol/ml, p<0.05) and suppression of plasma aldosterone (8.0 (2) to 4.6 (1) ng/dl, p<0.05), which was not seen in the 0.003 microg/kg/min group. LV ejection fraction (LVEF) improved significantly from baseline to 1 month (40 (4)% to 54 (5)%, p<0.05) in the 0.006 group but not in the 0.003 group. Infusion of BNP at 0.006 microg/kg/min was associated with a decrease of LV end-systolic volume index (61 (9) to 43 (8) ml/m(2), p<0.05) at 1 month, which was not seen in the 0.003 group. No drug-related serious adverse events occurred in either group. CONCLUSIONS: 72 h infusion of low BNP at the time of anterior AMI is well tolerated and biologically active. Patients treated with low-dose BNP had improved LVEF and smaller LV end-systolic volume at 1 month.

Immediate improvement in coronary flow reserve after alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: To examine whether percutaneous alcohol septal ablation affects coronary flow reserve (CFR) in patients with hypertrophic cardiomyopathy (HCM). METHODS: CFR was measured immediately before and after septal ablation in patients with symptomatic obstructive HCM. CFR was also obtained in normal subjects (NL) for comparison. RESULTS: Patients with HCM (n = 11), compared with NL (n = 22), had a lower mean (SD) baseline CFR (1.96 (0.5) vs 3.0 (0.7), p<0.001), a lower coronary resistance (1.04 (0.45) vs 3.0 (2.6), p = 0.002), a higher coronary diastolic/systolic velocity ratio (DSVR; 5.1 (3.0) vs 1.8 (0.5), p = 0.04) and a lower hyperaemic coronary flow per left ventricular (LV) mass (0.73 (0.4) vs 1.1 (0.6) ml/min/g, p = 0.007). Septal ablation in the HCM group (n = 7) reduced the outflow tract gradient but not the left atrial or LV diastolic pressures. Ablation resulted in immediate normalisation of CFR (to 3.1 (1), p = 0.01) and DSVR (to 1.9 (0.8), p = 0.09) and an increase in coronary resistance (to 1.91 (0.6), p = 0.02). This was probably related to an improvement in the systolic coronary flow. CONCLUSIONS: This study demonstrates that successful septal ablation in patients with symptomatic HCM results in immediate improvement in CFR, which is reduced in HCM partly because of the increased systolic contraction load.

Predictors of slow flow during primary percutaneous coronary intervention: an intravascular ultrasound-virtual histology study.

OBJECTIVES: Slow flow phenomenon is a serious complication of percutaneous coronary intervention (PCI) and is associated with a poor prognosis. We sought to evaluate the characteristics of lesions predisposing to the slow/no-reflow phenomenon during primary PCI in patients with acute myocardial infarction. METHODS: The study subjects consisted of 57 consecutive patients (mean age 58.5 (SD 14.5) years, 45 males) who underwent primary PCI for acute myocardial infarction and intravascular ultrasound-virtual histology (IVUS-VH) examination. Slow flow was defined as

A double-blind, randomized study evaluating losartan potassium monotherapy or in combination with hydrochlorothiazide versus placebo in obese patients with hypertension.

OBJECTIVES: The objective of this study was to evaluate the effects of losartan +/- hydrochlorothiazide (HCTZ) versus placebo in obese patients with systolic and diastolic hypertension. RESEARCH DESIGN AND METHODS: Randomized patients (n = 261) were non-diabetic with systolic blood pressure (SBP) > or = 140 and < or = 180 mmHg and diastolic BP (DBP) > or = 95 and < or = 115 mmHg, body mass index > 30 kg/m(2), and waist circumference > 40 (males)/> 35 (females) inches. Patients were randomized to placebo or a forced titration of losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/HCTZ 12.5 mg, and losartan 100 mg/HCTZ 25 mg. Primary efficacy measurements were change from baseline in SBP and DBP at 12 weeks. Secondary measurements were change from baseline in BPs at 8 and 16 weeks, percent responders at 12 and 16 weeks, and safety/tolerability. Post-hoc analyses were BP at 4 weeks and achievement of controlled BP (SBP < 140 and/or DBP < 90 mmHg) at 12 and 16 weeks. RESULTS: Losartan 50 mg reduced BP from 151.6/99.2 mmHg at baseline to 140.1/89.8 mmHg at week 4 (post hoc), 139.5/89.6 mmHg with losartan 100 mg at week 8 (secondary), 134.3/85.9 mmHg with losartan 100 mg/HCTZ 12.5 mg at week 12 (primary), and 132.1/84.9 mmHg with losartan 100 mg/HCTZ 50 mg at week 16 (secondary) (all p < 0.05). Rates of clinical adverse experiences were similar between treatment groups. A limitation of these analyses is the relatively rapid rate of study drug titration, which may not have allowed for the evaluation of the full treatment effect at each titration step. CONCLUSIONS: We conclude that losartan alone or in combination with HCTZ was generally well tolerated and effective in the treatment of elevated systolic and diastolic BP in obese patients with hypertension.

The importance of reendothelialization after arterial injury.

Atherosclerosis is still the principal cause of morbidity and mortality in Western countries and although a significant progress has been made in the understanding of its pathophysiology, the determinants of atherosclerotic plaque instability are still poorly understood. The endothelium plays a pivotal role for the development, progression, and complication of atherosclerosis. Endothelial dysfunction is widely recognized as one of the early alteration in the vessel wall preceding the development of the plaque. However, considering the plethora of vascular functions which are regulated by endothelium, it plays a pivotal role throughout the atherosclerotic process and indeed the loss of endothelial cells, leading to plaque denudation, is one of the main causes of plaque complication. It is therefore conceivable that the maintenance of the endothelial layer physical continuity and function is crucial for the prevention of atherosclerosis. In the presence of cardiovascular risk factors, endothelial cells are continuously injured and repaired by the proliferation of resident cells and circulating endothelial progenitor cells. Indeed the number of circulating endothelial progenitor cells has been identified as an predictor of cardiovascular events. The increase in bone marrow release of endogenous progenitor cells or the enhancement of their homing in arterial denuded sites or in intravascular stent surface, are currently pursued to reduce atherosclerosis development/complication and intrastent restenosis, respectively. However, some challenges may arise from procedures enhancing endothelialization, including unwanted angiogenesis which may favor neoplasia progression and paradoxically atherosclerotic plaque expansion and complication.

In vivo veritas: thrombosis mechanisms in animal models.

Experimental models have enhanced our understanding of atherothrombosis pathophysiology and have played a major role in the search for adequate therapeutic interventions. Various animal models have been developed to simulate thrombosis and to study in vivo parameters related to hemodynamics and rheology that lead to thrombogenesis. Although no model completely mimics the human condition, much can be learned from existing models about specific biologic processes in disease causation and therapeutic intervention. In general, large animals such as pigs and monkeys have been better suited to study atherosclerosis and arterial and venous thrombosis than smaller species such as rats, rabbits, and dogs. On the other hand, mouse models of arterial and venous thrombosis have attracted increasing interest over the past two decades, owing to direct availability of a growing number of genetically modified mice, improved technical feasibility, standardization of new models of local thrombosis, and low maintenance costs. To simulate rupture of an atherosclerotic plaque, models of arterial thrombosis often involve vascular injury, which can be achieved by several means. There is no animal model that is sufficiently tall, that can mimic the ability of humans to walk upright, and that possesses the calf muscle pump that plays an important role in human venous hemodynamics. A number of spontaneous or genetically engineered animals with overexpression or deletion of various elements in the coagulation, platelet, and fibrinolysis pathways are now available. These animal models can replicate important aspects of thrombosis in humans, and provide a valuable resource in the development of novel concepts of disease mechanisms in human patients.

Vascular wall elasticity measurement by magnetic resonance imaging.

The goal of this current study was to determine whether an MRI-based elastography (MRE) method can visualize and assess propagating mechanical waves within fluid-filled vessels and to investigate the feasibility of measuring the elastic properties of vessel walls and quantitatively assessing stenotic lesions by using MRE. The ability to measure the Young's modulus-wall thickness product was tested using a thin-walled latex vessel model. Also tested in vessel models was the ability to quantitate the degree of stenosis by measuring transmitted and reflected mechanical waves. This method was then applied to ex vivo porcine models and in vivo human arteries to further test its feasibility. The results provide preliminary evidence that MRE can be used to quantitatively assess the stiffness of blood vessels, and provide a non-morphologic method to measure stenosis. With further development, it is possible that the method can be implemented in vivo.