Renu Virmani

• George Washington University

Objectives: This study sought to describe the impact of statins on individual coronary atherosclerotic plaques. Background: Although statins reduce the risk of major adverse cardiovascular events, their long-term effects on coronary atherosclerosis remain unclear. Methods: We performed a prospective, multinational study consisting of a registr...

Aims: Durable-fluoropolymer coated everolimus-eluting stents (FP-EES) have shown lower rates of stent thrombosis (ST) versus bare-metal stents (BMS) and 1st-generation bioabsorbable-polymer (BP) DES. However, the specific role of the FP in thromboresistance has not been explored. Methods and results: A total of 57 stents were assessed in 3 separ...

The COBRA-PzF™ (CeloNova BioSciences, Inc., TX, USA) is a new type of coronary stent composed of a cobalt chromium metallic backbone surrounded by a nanothin layer of Polyzene-F (PzF) without any added drug. Evidence from basic studies supports antithrombotic and anti-inflammatory properties for the PzF surface coating. Preclinical studies support...

Table S1. Comparison of Founder Swine Blood Lipoproteins by Nuclear Magnetic Resonance Table S2. Comparison of Cardiac Function Figure S1. Ectopic PtPCSK9D374Y expression reduces hepatic expression of LDLR. A, Serum PCSK9 levels, *P<0.05 compared to Control using ANOVA followed by t tests. B, Western blot shows decreased LDLR detection in liver e...

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Background: Ossabaw pigs are unique miniature swine with genetic predisposition to develop metabolic syndrome and coronary atherosclerosis after extended periods receiving atherogenic diets. We have hypothesized that transgenic Ossabaw swine expressing chimpPCSK9(proprotein convertase subtilisin-like/kexin type 9) containing the D374Y gain of func...

Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a distinct alternative non-foam cell antiinflammatory macrophage phenotype that was previously considered atheroprotective. Here, we reveal an unexpected but important pathogenic role for these macrophages in atherosclerosis. Using human atherosclerotic samples, cultured cel...

Objectives: The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. Background: TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was...

Objectives: The purpose of this study was to evaluate the feasibility of imaging apoptosis in experimental ischemia-reperfusion model by technetium-99m (99mTc)-labeled Duramycin, and compare it to an established tracer,99mTc-labeled Annexin-V, which has a relative disadvantage of high radiation burden to nontarget organs. Background: During apop...

Objectives The study investigated whether a dose response exists between myocardial salvage and the depth of therapeutic hypothermia. Background Cardiac protection from mild hypothermia during acute myocardial infarction (AMI) has yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve myocardial salvage. Methods Swine (n...

Coronary artery calcification is concomitant with the development of advanced atherosclerosis. Coronary artery calcification pathologically begins as microcalcifications (0.5 to 15.0 μm) and grows into larger calcium fragments, which eventually result in sheet-like deposits (>3 mm). This evolution is observed to occur concurrently with the progress...

The internal mammary artery (IMA) is the most durable conduit for bypassing the left anterior descending (LAD) coronary artery in patients undergoing coronary artery bypass graft surgery (CABG). However, little is known about how the IMA reacts histologically to stent implantation. From CVPath stent registry (1048 lesions, 614 cases), we obtained 4...

Purpose: To compare the safety of Zilver PTX drug-eluting stents (DES) following drug-coated balloon (DCB) angioplasty or conventional balloon angioplasty (BA) in a healthy porcine iliofemoral artery model. Methods: DES implantation following DCB (DCB+DES) or BA (BA+DES) was assessed by angiography and histology in the nondiseased iliofemoral arter...

Table S1. Pathological Assessment in the Lesions Without Target Lesion Failure

Objectives: This study sought to investigate endothelial coverage and barrier protein expression following stent implantation. Background: Biodegradable polymer drug-eluting stents (BP-DES) have been purported to have biological advantages in vessel healing versus durable polymer DES (DP-DES), although clinical trial data suggest equipoise. Met...

Background The “very late” clinical outcomes for durable polymer drug‐eluting stents and bare metal stents (BMSs) have been shown to be dissimilar in clinical studies. Conceptually, the long‐term vascular compatibility of BMSs is still regarded to be superior to drug‐eluting stents; however, no pathologic study to date has specifically addressed th...

Background and aims: Lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzymatic inflammatory biomarker primarily bound to low-density lipoprotein cholesterol, is associated with an approximate twofold increased risk of cardiovascular disease and stroke. Despite indications that circulating Lp-PLA2 is sensitive to statins, it remains largely u...

Introduction: Polymers are an essential component of drug-eluting stents (DES) used to control drug release but remain the most controversial component of DES technology. There are two types of polymers employed in DES: durable polymer based DES (DP-DES) and biodegradable polymer DES (BP-DES). First-generation DES were exclusively composed of DP an...

Background: Tissue thickness at the site of ablation is a determinant of lesion transmurality. We reported the feasibility, safety and efficacy of long-standing persistent atrial fibrillation (PsAF) ablation, incorporating deliberate LAA isolation and occlusion and identified systematic differences in ostial LAA tissue thickness in a matched cohor...

The polymers poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and poly(n-butyl methacrylate) (PBMA) are employed in manufacturing the XIENCE family of coronary stents. PBMA serves as a primer and adheres to both the stent and the drug coating. PVDF-HFP is employed in the drug matrix layer to hold the drug everolimus on the stent and cont...

Cardiovascular diseases (CVDs) as reported by the World Health Organization (WHO) represent the foremost cause of death worldwide [1]. Recent estimates in 2012 indicate 17.5 million deaths from CVDs, corresponding to 31 % deaths worldwide. Of these, an estimated 7.4 million were attributed to coronary artery disease (CAD) and 6.7 million strokes, w...

Aims: To examine the effect of under-expansion on stent thrombogenicity with an in-vitro perfusion model. Method and results: Drug eluting stent (DES) samples were partially under-deployed in silicone tubes and perfused with porcine blood containing 10% Anticoagulant Citrate Dextrose solution for 4 minutes at a flow rate of 200ml/min. Thrombus f...

Introduction: Despite advances in drug-eluting stent (DES) technology, stent thrombosis (ST) remains the most feared complication with high morbidity and mortality. Area covered: Stent related factors certainly play a role in the pathophysiology of ST and more recent data suggest coating technologies have the potential to favorable modify this risk...

Background: A comparison in acute thrombogenicity between the Magmaris sirolimus-eluting bioabsorbable magnesium scaffold and the Absorb bioresorbable vascular scaffold has not been performed. This study assessed acute thrombogenicity of Magmaris compared with Absorb and the Orsiro hybrid drug-eluting stent in a porcine arteriovenous shunt model....

Dr. Mori has received honoraria from Abbott Vascular Japan, Goodman, and Terumo Corp. Dr. Virmani is President of CVPath Institute; is a speaker for Merck; has received honoraria from Abbott Vascular, Boston Scientific, Lutonix, Medtronic, and Terumo Corp.; and is a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. Dr. Narul...

Background: The Placement of AoRtic TraNscathetER Valves trials (PARTNER) showed favorable safety and efficacy versus medical or surgical therapy in inoperable, high, and intermediate surgical risk patients with severe aortic stenosis. However, the biological responses to transcatheter aortic valves have not been well characterized. Objectives:...

In the era of drug-eluting stents, large-scale randomized trials and all-comer registries have shown excellent clinical results. However, even the latest-generation drug-eluting stent has not managed to address all the limitations of permanent metallic coronary stents, such as the risks of target lesion revascularization, neoatherosclerosis, preclu...

Intraplaque hemorrhage (IPH) is a phenomenon observed in advanced atherosclerotic plaques. Paterson1 was the first to propose vasa vasorum as the source of IPH. Barger et al2 described an abundance of plaque microvessels found in diseased coronary arteries compared with healthy ones and proposed that plaque neovascularization plays an important rol...

Objectives: Anatomic placement of lesions may impact efficacy of radio-frequency (RF) catheter renal denervation (RDN). However, it is unclear if it is necessary to perform treatments post bifurcation with systems that may provide deeper penetration to achieve successful RDN. Methods: Sixteen domestic swine (n=16) were randomly assigned to 4 gro...

The pathophysiology and natural history of atherosclerotic carotid disease is predicated upon a more extensive knowledge of lesion progression gained in the studies conducted in the coronary arteries, and these will be reviewed. While the precise sequence of lesion progression leading to carotid plaque vulnerability and cerebrovascular events remai...

Background: Necrotic core (NC) is difficult to distinguish from fibrous plaque (FP) in traditional single-energy CT. Dual-energy CT can be used theoretically to differentiate tissues with material decomposition (MD) base pairs and atomic number (effective-Z [EZ]). We assessed the optimal mode among MD base pairs and EZ to distinguish NC from FP. Me...

Background: Dual-energy CT (DECT) may permit monochromatic energy (MCE) imaging for identifying necrotic core (NC) as a proxy of high-risk plaque. To date, the exact MCE reconstruction mode that optimizes NC visualization by DECT remains unclear. Methods: Coronary specimens from 18 post-mortem hearts with suspected sudden cardiac death underwent DE...

Background: Determination of the optimal threshold by coronary CT angiography (CCTA) to maximize diagnostic accuracy of atherosclerotic plaque characteristics analyses remains unknown. We aimed to validate reliable cut-points of Hounsfield units (HU) by CCTA for quantitative assessment of necrotic core (NC). Methods: In total, 34 cross-sections der...

Objectives: The aim of this study was to explore the pathology of in-stent chronic total occlusion (IS-CTO) in bare-metal (BMS) versus drug-eluting stents (DES). Background: Despite a relatively high prevalence of IS-CTO, little is known about the underlying etiology and histopathologic characteristics of the occlusion. Methods: From CVPath In...

The major diseases affecting the aorta are atherosclerosis, aortic aneurysms (AAs), and aortic dissections (ADs), all of which are important clinically. In this chapter, we address all aneurysms of the aorta irrespective of underlying etiology. Abdominal aortic aneurysms (AAAs) are by far the most common type of AA and the vast majority of these ar...

Primary cardiac tumors are rare and more than three-fourths are benign. In surgical series, the most common primary tumor of the heart is a myxoma accounting for over 70% of cases, with the second most common being primary sarcomas. The autopsy incidence of cardiac tumors is reported to be 0.001-0.3%. Metastatic tumors are by far the most common in...

Aims: Inflammation drives atherosclerosis complications and is a promising therapeutic target for plaque stabilization. At present, it is unknown whether local stenting approaches can stabilize plaque inflammation in vivo. Here, we investigate whether everolimus-eluting stents (EES) can locally suppress plaque inflammatory protease activity in viv...

Aims: Intraplaque haemorrhage is considered a major contributor to lesion progression. We assessed coronary lesions with intraplaque haemorrhage using intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS). Methods and results: We evaluated coronary arteries from autopsy hearts using 40MHz IVUS and NIRS and compared the imaging fi...

A 32-year-old female recently postpartum was admitted with chest pain and shortness of breath. She was diagnosed with acute inferior myocardial infarction and taken to catheterization laboratory in cardiogenic shock. The proximal right coronary artery was occluded, and an everolimus-eluting stent (Abbott Vascular, Santa Clara, CA) was implanted suc...

The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased d...

Aims: The blood pressure lowering effect of percutaneous renal denervation (RDN) is controversial. Success of RDN may be device-dependent. We sought to compare the efficacy of RDN by chemical neurolysis using alcohol (Peregrine System™ Infusion Catheter, Ablative Solutions, Inc. Menlo Park, CA, USA) to RDN by radiofrequency (RF) ablation with the...

Table S1. Proximal and/or Distal Values Based on 161 Patients Table S2. Proximal Values Based on 161 Patients Table S3. Distal Values Based on 161 Patients

Background Histopathological analyses of debris captured by a cerebral protection system during transcatheter aortic valve replacement have been reported, but the origin of the captured debris was not determined and risk factors were not defined. Methods and Results Embolic debris was analyzed from 322 filters used in a dual‐cerebral‐filter protec...

Objectives: The aim of this study was to identify histological features that correlate with terms commonly used to describe optical coherence tomographic (OCT) and optical frequency-domain imaging (OFDI) images of stented vessels, by means of a histopathological validation study using stented human coronary arteries. Background: OCT imaging and...

Aims Aims of this case-series were to assess the feasibility of cerebral protection devices in interventional left atrial appendage occlusion (iLAAO) procedures and to yield insight into the pathomorphological correlate of early, procedural cerebral embolization during iLAAO. Methods and Results Five consecutive patients underwent iLLO flanked b...

We thank Vroomen et al1 for their letter detailing the benefits of hybrid atrial fibrillation ablation, involving thoracoscopic epicardial ablation combined with endocardial catheter ablation followed by an epicardial left atrial appendage (LAA) clip procedure, performed in an experienced center.2 However, wider adoption of this approach as routin...

Thin-cap fibroatheromas (TCFAs) are considered precursors for plaque rupture and subsequent acute coronary events. We investigated intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) characteristics of lesions that were histopathologic TCFAs. IVUS, NIRS, and histopathology were performed in 271 atherosclerotic lesions from 107 fre...

Purpose: Different carrier excipients unique to individual drug-coated balloons (DCBs) may influence embolic safety characteristics in peripheral vascular territories through embolization of released particulates. A comparator study of IN.PACT Admiral vs Lutonix 035 balloons in healthy swine was therefore performed to assess which balloon produces...

Purpose: To optimize conventional coronary optical coherence tomography (OCT) images using the attenuation-compensated technique to improve identification of plaques and the external elastic lamina (EEL) contour. Method: The attenuation-compensated technique was optimized via manipulating contrast exponent C, and compression exponent N, to achie...

Atherosclerosis results from maladaptive inflammation driven primarily by macrophages, whose recruitment and proliferation drive plaque progression. In advanced plaques, macrophage death contributes centrally to the formation of plaque necrosis, which underlies the instability that promotes plaque rupture and myocardial infarction. Hence, targeting...

Background: Left atrial appendage (LAA) electric isolation is reported to improve persistent atrial fibrillation (AF) ablation outcomes. However, loss of LAA mechanical function may increase thromboembolic risk. Concomitant LAA electric isolation and occlusion as part of conventional AF ablation has never been tested in humans. We therefore evalua...

Inflammatory diseases of the aorta broadly include noninfectious and infectious aortitis, periaortitis, atherosclerosis, and inflammatory atherosclerotic aneurysms. Aortitis is uncommon but is increasingly recognized as an important cause of aortic aneurysms and dissections. Abdominal (AAA) and thoracic aortic aneurysms (TAA) have different patholo...

Background: Treatment options for patients with coronary artery disease at high risk for bleeding complications are limited. The aim of the current preclinical study was to evaluate neointimal coverage, endothelial recovery, inflammation and thrombogenicity in a novel thin-strut (71μm thickness) Cobalt Chromium (CoCr) stent modified with a nano-th...

Background: Coatings consisting of a polymer and drug are widely used in drug-eluting stents (DES) and are essential in providing programmable drug release kinetics. Among other factors, stent coating technologies can influence blood compatibility, affect acute and sub-acute healing, and potentially trigger a chronic inflammatory response. Object...

There is an increasing need for percutaneous revascularization procedures of coronary Chronic Total Occlusion (CTO), because many patients with severe coronary artery disease have limited options for revascularization. Although the success rate of percutaneous revascularization of CTOs was unsatisfactory from the 1990s to the 2000s, recent technolo...

Background The concept of innate immunity is well recognized within the spectrum of atherosclerosis, which is primarily dictated by macrophages. Although current insights to this process are largely based on murine models, there are fundamental differences in the atherosclerotic microenvironment and associated inflammatory response relative to huma...

Purpose of the study: Left atrial appendage (LAA) electrical isolation may improve the efficacy of persistent atrial fibrillation (AF) ablation. We have previously demonstrated substantial acute LAA reconnection rates in both canines and humans following electrical isolation. We sought to establish whether LAA ostial thickness variations could be e...

Objective Histological analyses of debris captured by a cerebral protection system (CPS) during transcatheter valve-in-valve (VIV) procedures have not been reported. Methods Fifteen consecutive patients with stenotic aortic (n=13) or mitral (n=2) surgical or transcatheter bioprostheses were treated with implantation of a transcatheter heart valve (...

Background Stress calculations in atherosclerotic coronary vulnerable plaques can aid in predicting coronary cap rupture. In vivo plaque geometry and composition of coronary arteries can merely be obtained via intravascular imaging. Only optical driven imaging techniques have sufficient resolution to visualize the fibrous cap, but due to limited pe...

Data S1. Methods and materials. Figure S1. Movat's pentachrome and immunohistochemistry for leptin and leptin receptor (LepR) in ascending thoracic aortic aneurysm samples from bicuspid aortic valve (BAV) and Marfan syndrome (MFS) patients: subintimal and medial region. A through C, BAV patient: Movat's pentachrome (A), diffuse elastic fiber fragm...

Background Ascending thoracic aortic aneurysm (ATAA) is driven by angiotensin II (AngII) and contributes to the development of left ventricular (LV) remodeling through aortoventricular coupling. We previously showed that locally available leptin augments AngII‐induced abdominal aortic aneurysms in apolipoprotein E–deficient mice. We hypothesized th...