Large Coronary Arteries Research Articles

Intravascular assessment of coronary arteries in patients with cyanotic congenital heart disease.

Patients with cyanotic congenital heart disease (CCHD) have been suggested to develop less atherosclerosis than the general population. This study aimed to evaluate the extent of coronary atherosclerosis in patients with CCHD using intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS). Fifteen patients with CCHD (women, 9; median age, 53 years) and 14 acyanotic controls (women, 6; median age, 53 years) were examined with IVUS-NIRS of the right coronary artery (RCA). The patients with CCHD presented with a larger RCA diameter than the controls (external elastic membrane diameter, 6.1 [4.8-6.7] vs. 4.7 [4.1-5.1] mm, respectively; p=0.01). No difference in area stenosis was found between the patients and the controls (15.8% [12.3-19.7] vs. 15.2% [9.5-18.8]; p=0.87). The presence of lipid by NIRS was noted in 43% of patients with CCHD and in 92% of the controls; however, no differences in total or max 4 mm lipid core burden index (LCBI) or in plasma lipid profile were found. Patients with CCHD presented with larger coronary arteries than acyanotic controls. No difference in the degree of area stenosis in the coronary arteries was found between the cyanotic and acyanotic patients; however, a lower proportion of patients with CCHD showed a positive LCBI.

TCTAP C-227 Endovascular Embolization of Large and Tortuous Coronary Artery Fistula

### Patient Initials or Identifier Number Ms. C, 05482480 ### Relevant Clinical History and Physical Exam A 60-year-old female with a history of hypertension. She suffered from palpitation with chest tightness and dyspnea for 3 months. A focused physical examination discovered regular heartbeat

FURIN Inhibition Reduces Vascular Remodeling and Atherosclerotic Lesion Progression in Mice.

Objective- Atherosclerotic coronary artery disease is the leading cause of death worldwide, and current treatment options are insufficient. Using systems-level network cluster analyses on a large coronary artery disease case-control cohort, we previously identified PCSK3 (proprotein convertase subtilisin/kexin family member 3; FURIN) as a member of several coronary artery disease-associated pathways. Thus, our objective is to determine the role of FURIN in atherosclerosis. Approach and Results- In vitro, FURIN inhibitor treatment resulted in reduced monocyte migration and reduced macrophage and vascular endothelial cell inflammatory and cytokine gene expression. In vivo, administration of an irreversible inhibitor of FURIN, α-1-PDX (α1-antitrypsin Portland), to hyperlipidemic Ldlr-/- mice resulted in lower atherosclerotic lesion area and a specific reduction in severe lesions. Significantly lower lesional macrophage and collagen area, as well as systemic inflammatory markers, were observed. MMP2 (matrix metallopeptidase 2), an effector of endothelial function and atherosclerotic lesion progression, and a FURIN substrate was significantly reduced in the aorta of inhibitor-treated mice. To determine FURIN's role in vascular endothelial function, we administered α-1-PDX to Apoe-/- mice harboring a wire injury in the common carotid artery. We observed significantly decreased carotid intimal thickness and lower plaque cellularity, smooth muscle cell, macrophage, and inflammatory marker content, suggesting protection against vascular remodeling. Overexpression of FURIN in this model resulted in a significant 67% increase in intimal plaque thickness, confirming that FURIN levels directly correlate with atherosclerosis. Conclusions- We show that systemic inhibition of FURIN in mice decreases vascular remodeling and atherosclerosis. FURIN-mediated modulation of MMP2 activity may contribute to the atheroprotection observed in these mice.

Drug Coated Balloon-Only Strategy in De Novo Lesions of Large Coronary Vessels.

Objectives We analyzed the efficacy of drug coated balloons (DCB) as a stand-alone-therapy in de novo lesions of large coronary arteries. DCBs seem to be an attractive alternative for the stent-free interventional treatment of de novo coronary artery disease (CAD). However, data regarding a DCB-only approach in de novo CAD are currently limited to vessels of small caliber. Methods By means of propensity score (PS) matching 234 individuals with de novo CAD were identified with similar demographic characteristics. This patient population was stratified in a 1:1 fashion according to a reference vessel diameter cut-off of 2.75 mm in small and large vessel disease. The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) at 9 months. Results Patients with small vessel disease had an average reference diameter of 2.45 ± 0.23 mm, while the large vessel group averaged 3.16 ± 0.27 mm. Regarding 9-month major adverse cardiac event (MACE), 5.7% of the patients with small and 6.1% of the patients with large vessels had MACE (p=0.903). Analysis of the individual MACE components revealed a TLR rate of 3.8% in small and 1.0% in large vessels (p=0.200). Of note, no thrombotic events in the DCB treated coronary segments occurred in either group during the 9-month follow-up. Conclusions Our data demonstrate for the first time that DCB-only PCI of de novo lesions in large coronary arteries (>2.75 mm) is safe and as effective. Interventional treatment for CAD without permanent or temporary scaffolding, demonstrated a similar efficacy for large and small vessels.

Effects of Aerobic Training on the Microcirculation: A Mini Reviewm

The microcirculation is composed of four different sections: arterioles, capillaries, sphincters and venules. The coronary arteries microcirculation consists the heart and large coronary arteries. The myocardium almost solely dependent on the ability of aerobic metabolism, therefore, oxygen demand must be balance by increasing coronary blood flow compared to rest, almost six-folds at maximal oxygen uptake. Increase in skeletal muscle oxygen demand is met by increasing oxygen delivery namely cardiac output, muscle’s oxygen extraction and microcirculation blood flow.

Short-term outcomes from drug-coated balloon for coronary de novo lesions in large vessels

BackgroundA drug-coated balloon (DCB) has been designed as a new device for the treatment of coronary artery disease. The data regarding DCB-treated lesions in large coronary artery are limited. The purpose of our study was to explore the effectiveness and safety of DCB in large coronary artery. MethodsWe prospectively analyzed all patients treated with DCB in de novo lesions consistent with inclusion criteria between May 2015 and April 2017. The observed outcomes included target lesion revascularization (TLR), myocardial infarction, cardiac death and non-cardiac death, and major adverse cardiac events (MACE). ResultsThere were 92 patients including 94 coronary de novo lesions treated in all. The most often utilized DCB diameters were 3.0 mm (41.5%) and 3.5 mm (39.4%). Two acute closures occurred in hospital. Six bailout drug-eluting stents were used in the percutaneous coronary interventions (6.4%). Quantitative coronary angiography measurement at follow-up showed late lumen loss was -0.02 ± 0.49 mm. The TLR rate and overall MACE rates were 4.3% and 4.3% during the follow-up period in the whole patient population, respectively. ConclusionsOur study showed that the “DCB only” strategy is safe and efficient in large vessel lesions of patients whose predilation achieved an acceptable result.

Rare Cause for a Continuous Murmur: Large Left Coronary Artery to Coronary Sinus Fistula.

Rare Cause for a Continuous Murmur: Large Left Coronary Artery to Coronary Sinus Fistula.

Genetic Susceptibility Loci for Cardiovascular Disease and Their Impact on Atherosclerotic Plaques.

Atherosclerosis is a chronic inflammatory disease in part caused by lipid uptake in the vascular wall, but the exact underlying mechanisms leading to acute myocardial infarction and stroke remain poorly understood. Large consortia identified genetic susceptibility loci that associate with large artery ischemic stroke and coronary artery disease. However, deciphering their underlying mechanisms are challenging. Histological studies identified destabilizing characteristics in human atherosclerotic plaques that associate with clinical outcome. To what extent established susceptibility loci for large artery ischemic stroke and coronary artery disease relate to plaque characteristics is thus far unknown but may point to novel mechanisms. We studied the associations of 61 established cardiovascular risk loci with 7 histological plaque characteristics assessed in 1443 carotid plaque specimens from the Athero-Express Biobank Study. We also assessed if the genotyped cardiovascular risk loci impact the tissue-specific gene expression in 2 independent biobanks, Biobank of Karolinska Endarterectomy and Stockholm Atherosclerosis Gene Expression. A total of 21 established risk variants (out of 61) nominally associated to a plaque characteristic. One variant (rs12539895, risk allele A) at 7q22 associated to a reduction of intraplaque fat, P=5.09×10-6 after correction for multiple testing. We further characterized this 7q22 Locus and show tissue-specific effects of rs12539895 on HBP1 expression in plaques and COG5 expression in whole blood and provide data from public resources showing an association with decreased LDL (low-density lipoprotein) and increase HDL (high-density lipoprotein) in the blood. Our study supports the view that cardiovascular susceptibility loci may exert their effect by influencing the atherosclerotic plaque characteristics.

Height, VKORC1 1173, and CYP2C9 Genotypes Determine Warfarin Dose for Pediatric Patients with Kawasaki Disease in Southwest China

Long-term oral warfarin is recommended in pediatric Kawasaki disease patients with large coronary artery aneurysms; however, heterogeneity is considerable. This study aimed to determine variables affecting warfarin dosage in Kawasaki disease. The enrolled individuals (194 children) were divided into four groups: (1) Cases with severe coronary artery lesions (CAL) of IV to V degrees or thrombogenesis treated with oral warfarin were assigned to Group A; (2) Group B, CAL of I degrees; (3) Group C, CAL of II and III degrees cases with small or medium-sized CAL not treated with warfarin; (4) Group D, normal children without Kawasaki disease. The relevant genotypes of CYP2C9, VKORC1 (1173, − 1639, and 3730), and CYP4F2 were assessed. There were no statistically significant differences in CYP2C9, VKORC1, and CYP4F2 mutation frequencies among the 4 groups. In the 44 Group A patients, demographic features, clinical characteristics, and genotypes were recorded, and their associations with warfarin dose variability were assessed. Multivariate linear regression analysis revealed that height, VKORC1 1173, and CYP2C9 accounted for 61.2%, 7.9%, and 4.3% of dosing variability, respectively. Conclusions: Patient height is the main factor determining warfarin dosage, while genotype effects on warfarin dosage vary among studies. New formula should be defined using data obtained from children in cases with demonstrated efficacy.

Persisting Angina after Successful Surgical Removal of a Large Coronary Artery Aneurysm Attached to the Proximal Portion of the Left Circumflex Artery: Role of Coronary Artery Spasm

Persisting Angina after Successful Surgical Removal of a Large Coronary Artery Aneurysm Attached to the Proximal Portion of the Left Circumflex Artery: Role of Coronary Artery Spasm

Value of Z score in evaluating coronary artery lesions in children with Kawasaki disease

Objective To explore the clinical value of Z score in assessing coronary artery lesions (CAL) of children with Kawasaki disease. Methods The clinical records of 102 children with Kawasaki disease from January 2012 to December 2016 in Gansu Provincial Hospital were retrospectively analyzed.The internal diameter of left main coronary artery (LMCA) and right coronary artery (RCA) was measured by echocardiography (ECHO), and the incidence of CAL was preliminarily judged.The Z scores of LMCA and RCA were calculated on the basis of the coronary artery diameter, the age of the children and the body surface area, and the incidence of CAL was judged again. Results A total of 22 cases(21.6%) of CAL were found in 102 cases by ECHO examination, of which 18 cases(17.6%) of LMCA lesions, and 22 cases(21.6%) of RCA lesions.A total of 33 cases(32.4%) of CAL were found by calculating the Z score of coronary artery, of which 29 cases(28.4%) of LMCA lesions and 33 cases(32.4%) of RCA lesions.There was significant difference between two methods for determining LMCA lesions (χ2=3.35, P 0.05). Z score of coronary artery was more accurate to detect the CAL in Kawasaki disease, especially LMCA lesions.A large coronary artery aneurysm was found in the patients with the largest Z score by selective coronary angiography. Conclusion The Z score can be more conductive to assess the CAL in children with Kawasaki disease, and the higher the Z score, the more serious the CAL is. Key words: Kawasaki disease; Coronary artery lesions; Z score; Echocardiography

Management of a large coronary artery aneurysm with graft-coated stent during the acute phase of myocardial infarction

Coronary aneurysms in adults are rare clinical entities. Herein, we presented a 54-year-old man who was admitted with an acute extensive anterior myocardial infarction. The emergency coronary angiography revealed an isolated large aneurysm at the proximal segment of the left anterior descending coronary artery. The patient was successfully treated with a graft-coated stent

Early life stress induces endothelial‐derived HDAC9 and ET‐1 expression

Exposure to adverse childhood experiences, also known as early life stress (ELS), is an independent risk factor for the development of cardiovascular disease (CVD) in adulthood. Endothelial dysfunction is a major contributor to the development of CVD and has been linked to childhood adversity induced CVD risk. We previously reported circulating ET‐1 levels are significantly elevated in young adults exposed to childhood adversity in humans. Endothelin‐1 (ET‐1) via the ETA receptor promotes endothelial dysfunction and vascular inflammation. However, the regulation of ET‐1 by ELS and the mechanistic link between elevated ET‐1 levels and ELS‐induced increase in CVD risk remains unknown. In a mouse model of ELS involving maternal separation and early weaning (MSEW), we previously reported that ELS induced elevated plasma ET‐1 as well as increased vascular histone deacetylase 9 (HDAC9) protein expression with no changes in expression of other HDAC isoforms. Moreover, MSEW mice develop endothelial dysfunction in adulthood that is attenuated by a pan‐inhibitor of Class I and class II HDAC proteins, trichostatin A (TSA). HDACs are a family of epigenetic enzymes that regulate transcription through deacetylation of histone and non‐histone proteins. In humans, previous studies have shown SNPs in the HDAC9 gene are prominent in large artery stroke and coronary artery disease and that upregulated HDAC9 expression is localized in endothelial cells of carotid atherosclerotic human tissue suggesting HDAC9 may play an important role in atherogenesis. Therefore, we hypothesized that vascular HDAC9 upregulation promotes endothelial dysfunction in MSEW mice via increased ET‐1. MSEW involves maternal separation 4 h/day (postnatal (PD) 2 to 5) and 8 h/day (PD6 to 16) and weaned at PD17. Normally reared litters weaned at PD21 were used as controls (CON). In adult male CON and MSEW mice, we determined aortic localization of HDAC9 and ET‐1. Immunohistolocalization showed aortic HDAC9 is upregulated specifically in the endothelial cells of MSEW mice (n=5/group). Confocal immunofluorescence imaging revealed aortic ET‐1 expression is also localized in the endothelium of both CON and MSEW mice. To examine the effects of endothelial HDAC9 on ET‐1 expression, we used mouse aortic endothelial cells (MAECs) transfected with control vector or HDAC9 plasmid incubated in the presence or absence of TSA. Cultured MAECs treated with TSA blunted ET‐1 expression (70% decrease from vehicle, p<0.05, n=3/group). Furthermore, HDAC9 over‐expression in cultured MAECs significantly increased ET‐1 expression (relative to control vector group, 1.0±0.08 vs 1.73±0.44 arbitrary units, p<0.05, n=3/group) and TSA reduced the HDAC9‐dependent ET‐1 expression (1.68 fold decrease from control vector vehicle group, p<0.05, n=3/group). Our findings indicate endothelial dysfunction previously observed in our MSEW mouse model may be mediated by HDAC9‐dependent elevated ET‐1 production. In conclusion, this study highlights the importance of ELS in the development of CVD and the implications of an epigenetic pathway as a potential mechanistic link.Support or Funding InformationNIH P01 HLP0169999; NIH K01 DK105038This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Valentín Fuster: From Platelets to Preschoolers, Always With Scientific Rigor.

Why did Sesame Street’s Cookie Monster cut his consumption of the sweet treat from daily to once a week? The credit (or blame, depending on your perspective) goes to Valentin Fuster, who was asked to consult on the Spanish version of the show and eventually became Dr Ruster, a muppet sharing health advice with its young and avid audience. “Our behavior as adults depends greatly on the environment we are in between ages 3 and 6, and Sesame Street wasn’t taking advantage of this to focus on prevention and heart health,” says Fuster. Fuster, a renowned physician scientist with a daunting schedule and a decades-long record of bench and translational science and clinical trials, sees no discontinuity between the work that made him famous and his recent focus on preschoolers. “I became convinced that the same scientific tools I used to understand disease could be used to understand and promote health and prevent disease,” Fuster says. Fuster received his undergraduate and medical degrees in his hometown, Barcelona, and did clinical training and completed his doctorate in pathology at the University of Edinburgh. While at the Mayo Clinic between 1971 and 1982, starting as a medical resident and ending as professor of medicine and cardiovascular diseases, he showed in a dog model that platelets were important in the occlusion of bypass grafts and that aspirin could prevent it. Then, in the first clinical trial of aspirin in cardiac disease,1 the team demonstrated that aspirin prevented the occlusion of bypass grafts, leading to clinical guidelines calling for its use. In 1982, Fuster was recruited to become head of cardiology at Mt. Sinai Hospital in New York. After 10 years there, he spent 3 years in Boston at Harvard Medical School and Massachusetts General Hospital, where he began work on using magnetic …

A patient-specific lumped-parameter model of coronary circulation

A new lumped-parameter model for coronary hemodynamics is developed. This model is developed for the whole coronary network based on CT scans of a patient-specific geometry including the right coronary tree, which is absent in many previous mathematical models. The model adopts the structured tree model boundary conditions similar to the work of Olufsen et al., thus avoiding the necessity of invasive perfusion measurements. In addition, we also incorporated the effects of the head loss at the two inlets of the large coronary arteries for the first time. The head loss could explain the phenomenon of a sudden increase of the resistance at the inlet of coronary vessel. The estimated blood pressure and flow rate results from the model agree well with the clinical measurements. The computed impedances also match the experimental perfusion measurement. The effects of coronary arterial stenosis are considered and the fractional flow reserve and relative flow in the coronary vessels for a stenotic vessel computed in this model show good agreement with published experimental data. It is believed that the approach could be readily translated to clinical practice to facilitate real time clinical diagnosis.

Connecting the Dots: VF Arrest Secondary to Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery Syndrome

A 16-year-old male water polo player with no significant past history, was admitted to the current institution in cardiogenic shock following an out-of-hospital ventricular fibrillation arrest whilst swimming. The patient had return of spontaneous circulation following timely defibrillation for monomorphic left ventricular (LV) tachycardia. Transthoracic echocardiography (TTE) demonstrated a severely dilated LV, with severe global systolic dysfunction and an estimated LV ejection fraction (LVEF) of 30%. Troponin I assay was 5,760 ng/L. Intravenous methylprednisolone was commenced empirically for presumed myocarditis. Endomyocardial biopsy demonstrated mild non-specific cardiomyopathic changes and an increased number of blood vessels suggestive of a vascular malformation. Left ventricular systolic function improved, with repeat TTE a week after admission showing an LVEF of 50%. Cardiac magnetic resonance imaging showed a dilated LV with increased wall thickness and vascularity, primarily septal, and evidence of an old distal anterior myocardial infarct with wall thinning and transmural late gadolinium enhancement. Coronary angiography showed a large-calibre, ectatic right coronary artery, with retrograde filling of a highly abnormal left-sided system that could not be engaged. Computed tomography coronary angiogram was subsequently performed, demonstrating an anomalous left main coronary artery arising from the main pulmonary artery. There was a large dominant right coronary artery with multiple collaterals. This was a rare case of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA syndrome), in which survival to adulthood was due to extensive collateralisation from the right coronary system. Silent myocardial ischaemia and infarct is not uncommon, as was seen in this patient. The patient underwent successful reimplantation of the left coronary artery to the aorta at a quaternary paediatric cardiothoracic referral centre.

A snare retrieval experience of coil migration in a large coronary artery fistula

A 45-year-old female patient was referred due to the abnormal myocardial perfusion scintigraphy showing ischemia in the inferior and lateral wall. Coronary arteries were normal, and a large fistula was detected from the proximal portion of the circumflex coronary artery (Cx) draining into the pulmonary artery. Percutaneous closure of the coronary artery fistula (CAF) was considered, and a 3 mm × 50 mm-Balt coil was planned to place the proximal portion of the fistulized artery. Unfortunately, during placement of the coil, it was opened early and migrated to the proximal segment of the Cx, the left anterior descending artery, and the distal part of the left main coronary artery. A snare was moved into the extra backup guiding catheter immediately. The migrated coil was retrieved with the snare successfully. Subsequently, 4 mm × 12 mm and 2 mm × 25 mm-Balt coils were placed in the mid portion of the fistulized artery until total occlusion was obtained. A CAF is described as a direct connection between one or more of the coronary arteries and a cardiac chamber or great vessel. The fistula may cause serious hemodynamic disturbances such as myocardial ischemia, high-flow heart failure, right ventricle volume overload, endocarditis, rupture, thrombosis, embolism, and arrhythmias. Percutaneous closure is the prior technique, in the absence of complex conditions such as multiple fistulas and large fistula branches and in cases where the fistula can be simply reached. There have been very rare data which contain complications about the percutaneous closure of CAFs.

Control of electrical turbulence by periodic excitation of cardiac tissue.

Electrical turbulence in cardiac tissue is associated with arrhythmias such as life-threatening ventricular fibrillation. Recent experimental studies have shown that a sequence of low-energy electrical far-field pulses is able to terminate fibrillation more gently than a single high-energy pulse which causes severe side effects. During this low-energy antifibrillation pacing (LEAP), only tissue near sufficiently large conduction heterogeneities, such as large coronary arteries, is activated. In order to optimize LEAP, we performed extensive simulations of cardiac tissue perforated by blood vessels, employing two alternative cellular models that exhibit electrical turbulence at a similar length scale. Moreover, the scale of blood vessels in our two-dimensional simulations was chosen such that the threshold for single pulse defibrillation matches experimental values. For each of the 100 initial conditions, we tested different electrical field strengths, pulse shapes, numbers of pulses, and periods between the pulses. LEAP is successful for both models, albeit with substantial differences. One model exhibits a spectrum of chaotic activity featuring a narrow peak around a dominant frequency. In this case, the optimal period between low-energy pulses matches this frequency and LEAP greatly reduces the required energy for successful defibrillation. For pulses with larger energies, the system is perturbed such that underdrive pacing becomes advantageous. The spectrum of the second model features a broader peak, resulting in a less pronounced optimal pacing period and a decreased energy reduction. In both cases, pacing with five or six pulses which are separated by the dominant period maximizes the energy reduction.

Comparison of drug eluting stent (DES) and bare metal stent (BMS) in large coronary arteries

Comparison of drug eluting stent (DES) and bare metal stent (BMS) in large coronary arteries

Anomalous left anterior descending artery arising from the pulmonary trunk: a rare cause of angina

A 60-year-old man with a medical history of hypertension and dyslipidaemia presented to our rapid access chest pain clinic with a 2-month history of chest pain on exertion. An exercise...