Rafael Wolff

Relationship between initial treatment strategy and quality of life in patients with coronary chronic total occlusions

AIMS Our objective was to evaluate the relationship between coronary chronic total occlusion (CTO) treatment strategy and quality of life improvements. METHODS AND RESULTS This multicentre prospective cohort study enrolled consecutive CTO patients undergoing a non-urgent coronary angiogram who completed the Seattle Angina Questionnaire (SAQ) and EQ-5D at baseline and at one year. Strategies were: i) medical therapy, ii) PCI to non-CTO, iii) PCI to CTO, and iv) CABG. Multivariable regression models compared quality of life changes over time among strategies, accounting for repeat measures per patient. In our cohort of 387 patients, 154 underwent medical therapy, 83 had PCI to the non-CTO artery, 104 underwent CABG, and 46 underwent PCI to the CTO. Medically treated patients had no improvement on any SAQ domains. Patients with revascularisation of the CTO territory with either PCI or CABG had significant improvements in the physical limitation (PCI to CTO 60.5-76.4; CABG 61.6-80.1; p<0.001), angina frequency (PCI to CTO 79.0-92.7; CABG 82.1-97.9; p<0.001), and disease perception (PCI to CTO 50.5-75.0; CABG 50.2-80.0; p<0.001) domains. In non-CTO PCI patients, improvement was restricted to the angina frequency (82.8-93.3; p<0.001), and disease perception (53.8-71.4; p<0.001) domains. CONCLUSIONS CTO territory revascularisation was associated with quality of life improvements.

Perlecan Heparan Sulfate Proteoglycan Is a Critical Determinant of Angiogenesis in Response to Mouse Hind-Limb Ischemia

BACKGROUND Perlecan is a heparan sulfate proteoglycan (HSPG) constituent of the extracellular matrix with roles in cell growth, differentiation, and angiogenesis. The role of the HS side chains in regulating in vivo angiogenesis after hind-limb ischemia is unknown. METHODS Heparan sulfate (HS)-deficient perlecan (Hspg2(Δ3/Δ3)) mice (n = 35), containing normal perlecan core protein but deficient in HS side chains, and wild-type (n = 33) littermates underwent surgical induction of hind-limb ischemia. Laser Doppler perfusion imaging (LDPI) and contrast-enhanced ultrasonography (CEU) provided serial assessment of hind-limb perfusion. Harvested muscles underwent immunostaining for endothelial cell density (CD31), real-time reverse transcription polymerase chain reaction RT-PCR for vascular endothelial growth factor (VEGF) mRNA expression and western blot analysis for VEGF and fibroblast growth factor (FGF)2 protein expression at days 2 and 28. RESULTS Serial LDPI showed significantly greater perfusion recovery in ischemic limbs of wild-type compared with Hspg2(Δ3/Δ3) mice. CEU showed that normalized microvascular perfusion was increased in wild-type compared with Hspg2(Δ3/Δ3) mice at day 28 (0.67 ± 0.12 vs 0.26 ± 0.08; P = 0.001). CD31-positive cell counts were significantly higher in wild-type compared with Hspg2(Δ3/Δ3) mice on day 28 (122 ± 30 cells vs 84 ± 34 cells per high-power field [HPF]; P < 0.05). Endogenous VEGF mRNA expression (P < 0.05) and VEGF protein expression (P < 0.002) were significantly decreased in the ischemic limbs of Hspg2(Δ3/Δ3) mice compared with wild-type mice at day 2 and day 28, respectively. FGF2 protein expression showed no significant differences. CONCLUSIONS These results suggest that the HS side chains in perlecan are important mediators of the angiogenic response to ischemia through a mechanism that involves upregulation of VEGF expression.

A novel lead attenuator to reduce operator exposure to scattered radiation in transradial coronary procedures.

Introduction The harmful effects of radiation were soon recognised after the discovery of x-rays by Wilhelm Roentgen in 18951. Increased incidences of skin cancer and leukemia confirmed the carcinogenic potential of x-rays in the early twentieth century2. Interventional cardiologists experience frequent radiation exposure through fluoroscopy. Interventional cardiology procedures performed via the radial approach are associated with longer fluoroscopy times and greater cumulative scatter radiation to the operator and staff 3. This approach is gaining popularity and exceeds 90% of cases in dedicated centres4. The cumulative risk associated with a lifetime of exposure could become significant5,6. The lower torso (from the umbilicus and down) acts as a source of scatter radiation to the operator and is not routinely shielded. We developed a uniquely designed, non-disposable lead attenuating material that could shield this region and significantly reduce the radiation scatter exposure to an operator in the catheterisation laboratory.

Evolution of right ventricular function post‐acute ST elevation myocardial infarction

To characterize the evolution of right ventricular (RV) function post‐myocardial infarction (MI), to describe the culprit vessel involved with RV injury and to assess the concordance between RV injury on magnetic resonance imaging (MRI) and RV infarct on electrocardiogram (EKG).

Gender differences in the prevalence and treatment of coronary chronic total occlusions

Gender differences exist in the presentation and outcomes of patients with coronary artery disease (CAD). Our study objective was to compare gender differences in prevalence, co‐morbidities, and revascularization treatment in CAD patients with chronic total occlusions (CTOs).

Heparan sulfate side chains have a critical role in the inhibitory effects of perlecan on vascular smooth muscle cell response to arterial injury

Perlecan is a proteoglycan composed of a 470-kDa core protein linked to three heparan sulfate (HS) glycosaminoglycan chains. The intact proteoglycan inhibits the smooth muscle cell (SMC) response to vascular injury. Hspg2(Δ3/Δ3) (MΔ3/Δ3) mice produce a mutant perlecan lacking the HS side chains. The objective of this study was to determine differences between these two types of perlecan in modifying SMC activities to the arterial injury response, in order to define the specific role of the HS side chains. In vitro proliferative and migratory activities were compared in SMC isolated from MΔ3/Δ3 and wild-type mice. Proliferation of MΔ3/Δ3 SMC was 1.5× greater than in wild type (P < 0.001), increased by addition of growth factors, and showed a 42% greater migratory response than wild-type cells to PDGF-BB (P < 0.001). In MΔ3/Δ3 SMC adhesion to fibronectin, and collagen types I and IV was significantly greater than wild type. Addition of DRL-12582, an inducer of perlecan expression, decreased proliferation and migratory response to PDGF-BB stimulation in wild-type SMC compared with MΔ3/Δ3. In an in vivo carotid artery wire injury model, the medial thickness, medial area/lumen ratio, and macrophage infiltration were significantly increased in the MΔ3/Δ3 mice, indicating a prominent role of the HS side chain in limiting vascular injury response. Mutant perlecan that lacks HS side chains had a marked reduction in the inhibition of in vitro SMC function and the in vivo arterial response to injury, indicating the critical role of HS side chains in perlecan function in the vessel wall.

MitraClip for Papillary Muscle Rupture in Patient With Cardiogenic Shock

We report the successful use of the MitraClip device (Abbott Vascular, Santa Clara, CA) in a 68-year-old man with posterolateral ST-elevation myocardial infarction complicated by papillary muscle rupture and cardiogenic shock.

The effect of distal coronary embolization on infarct size in a porcine acute myocardial infarction model

Background Reperfusion no-reflow (R-NR), characterized by TIMI 0/1 flow grade, is a phenomenon that occurs in up to 20% of percutaneous coronary intervention cases for acute myocardial infarction (AMI). R-NR involves reduced myocardial tissue perfusion in the presence of a reperfused and patent epicardial coronary artery. This phenomenon is associated with worse patient outcome and increased mortality. Potential contributing factors of R-NR include the initial ischemic insult, injury as a result of reperfusion, and possibly distal coronary embolization (DCE) of thrombotic material. The objective of this study was to develop a novel large animal model to investigate the effects of DCE in the setting of ischemia-reperfusion using microthrombi derived from autologous porcine blood. Methods 3.0 T CMR was performed on 25-30kg female Yorkshire pigs to determine baseline values of cardiac function, as well as the myocardial perfusion territory at risk using direct intracoronary injection of dilute GadoliniumDTPA. Pigs were then subjected to balloon occlusion mediated myocardial ischemia distal to the second diagonal branch of the left anterior descending coronary artery (LAD) for 60 minutes. Following reperfusion, intracoronary injection of sterile saline (n=4) or microthrombi particles to simulate DCE (n=7) was performed. Epicardial coronary blood flow was assessed at each stage using x-ray angiography. At 72 hours following ischemia-reperfusion, CMR was used to assess changes in cardiac function, extent of edema/hemorrhage using T2/T2* relaxation times, evaluate infarct size, and to determine the presence/absence of microvascular obstruction (MVO). Myocardial tissue samples were subsequently collected for biochemical and histological analysis.