Spontaneous Coronary Artery Dissection Resulting in Acute Myocardial Infarction With Cardiac Rupture.

Spontaneous coronary artery dissection occurs predominantly in women and is associated with fibromuscular dysplasia. We illustrate a rare case of sudden coronary death as a result of cardiac rupture from spontaneous coronary artery dissection in a 54-year-old man without fibromuscular dysplasia. Cardiac rupture has been previously reported in 6 cases, mostly in women.

Polygenic Risk Score Associates With Atherosclerotic Plaque Characteristics at Autopsy.

BACKGROUND: Polygenic risk scores (PRSs) for coronary artery disease (CAD) potentially improve cardiovascular risk prediction. However, their relationship with histopathologic features of CAD has never been examined systematically. METHODS: From 4327 subjects referred to CVPath by the State of Maryland Office Chief Medical Examiner for sudden death between 1994 and 2015, 2455 cases were randomly selected for genotyping. We generated PRS from 291 known CAD risk loci. Detailed histopathologic examination of the coronary arteries was performed in all subjects. The primary study outcome measurements were histopathologic plaque features determining severity of atherosclerosis, including %stenosis, calcification, thin-cap fibroatheromas, and thrombotic CAD. RESULTS: After exclusion of cases with insufficient DNA sample quality or with missing data, 954 cases (mean age, 48.8±14.7 years; 75.7% men) remained in the final study cohort. Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared with subjects in the lowest quintile, with greater %stenosis (80.3%±27.0% versus 50.4%±38.7%; adjusted P<0.001) and a higher frequency of calcification (69.6% versus 35.8%; adjusted P=0.004) and thin-cap fibroatheroma (26.7% versus 9.5%; adjusted P=0.007). Even after adjustment for traditional CAD risk factors, subjects within the highest PRS quintile had higher odds of severe atherosclerosis (ie, ≥75% stenosis; adjusted odds ratio, 3.77 [95% CI, 2.10-6.78]; P<0.001) and plaque rupture (adjusted odds ratio, 4.05 [95% CI, 2.26-7.24]; P<0.001). Moreover, subjects within the highest quintile had higher odds of CAD-associated cause of death, especially among those aged ≤50 years (adjusted odds ratio, 4.08 [95% CI, 2.01-8.30]; P<0.001). No statistically significant associations were observed with plaque erosion after adjusting for covariates. CONCLUSIONS: This is the first autopsy study investigating associations between PRS and atherosclerosis severity at the histopathologic level in subjects with sudden death. Our pathological analysis suggests PRS correlates with plaque burden and features of advanced atherosclerosis and may be useful as a method for CAD risk stratification, especially in younger subjects.

Polygenic Risk Score Associates with Atherosclerotic Plaque Characteristics at Autopsy.

Background: Polygenic risk scores (PRS) for coronary artery disease (CAD) potentially improve cardiovascular risk prediction. However, their relationship with histopathologic features of CAD has never been examined systematically. Methods: From 4,327 subjects referred to CVPath by the State of Maryland Office Chief Medical Examiner (OCME) for sudden death between 1994 and 2015, 2,455 cases were randomly selected for genotyping. We generated PRS from 291 known CAD risk loci. Detailed histopathologic examination of the coronary arteries was performed in all subjects. The primary study outcome measurements were histopathologic plaque features determining severity of atherosclerosis, including %stenosis, calcification, thin-cap fibroatheromas (TCFA), and thrombotic CAD. Results: After exclusion of cases with insufficient DNA sample quality or with missing data, 954 cases (mean age 48.8±14.7; 75.7% men) remained in the final study cohort. Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared to subjects in the lowest quintile, with greater %stenosis (80.3%±27.0% vs. 50.4%±38.7%; adjusted p<0.001) and a higher frequency of calcification (69.6% vs. 35.8%; adjusted p=0.004) and TCFAs (26.7% vs. 9.5%; adjusted p=0.007). Even after adjustment for traditional CAD risk factors subjects within the highest PRS quintile had higher odds of severe atherosclerosis (i.e., ≥75% stenosis; adjusted OR 3.77; 95%CI 2.10-6.78; p<0.001) and plaque rupture (adjusted OR 4.05; 95%CI 2.26-7.24; p<0.001). Moreover, subjects within the highest quintile had higher odds of CAD-associated cause of death, especially among those aged 50 years and younger (adjusted OR 4.08; 95%CI 2.01-8.30; p<0.001). No associations were observed with plaque erosion. Conclusions: This is the first autopsy study investigating associations between PRS and atherosclerosis severity at the histopathologic level in subjects with sudden death. Our pathological analysis suggests PRS correlates with plaque burden and features of advanced atherosclerosis and may be useful as a method for CAD risk stratification, especially in younger subjects. Highlights: In this autopsy study including 954 subjects within the CVPath Sudden Death Registry, high PRS correlated with plaque burden and atherosclerosis severity.The PRS showed differential associations with plaque rupture and plaque erosion, suggesting different etiologies to these two causes of thrombotic CAD.PRS may be useful for risk stratification, particularly in the young. Further examination of individual risk loci and their association with plaque morphology may help understand molecular mechanisms of atherosclerosis, potentially revealing new therapy targets of CAD. Graphic Abstract: A polygenic risk score, generated from 291 known CAD risk loci, was assessed in 954 subjects within the CVPath Sudden Death Registry. Histopathologic examination of the coronary arteries was performed in all subjects. Subjects in the highest PRS quintile exhibited more severe atherosclerosis as compared to subjects in the lowest quintile, with a greater plaque burden, more calcification, and a higher frequency of plaque rupture.

CD163+ macrophages restrain vascular calcification, promoting the development of high-risk plaque.

Vascular calcification (VC) is concomitant with atherosclerosis, yet it remains uncertain why rupture-prone high-risk plaques do not typically show extensive calcification. Intraplaque hemorrhage (IPH) deposits erythrocyte-derived cholesterol, enlarging the necrotic core and promoting high-risk plaque development. Pro-atherogenic CD163+ alternative macrophages engulf hemoglobin:haptoglobin (HH) complexes at IPH sites. However, their role in VC has never been examined to our knowledge. Here we show, in human arteries, the distribution of CD163+ macrophages correlated inversely with VC. In vitro experiments using vascular smooth muscle cells (VSMCs) cultured with HH-exposed human macrophage - M(Hb) - supernatant reduced calcification, while arteries from ApoE-/- CD163-/- mice showed greater VC. M(Hb) supernatant-exposed VSMCs showed activated NF-κB, while blocking NF-κB attenuated the anticalcific effect of M(Hb) on VSMCs. CD163+ macrophages altered VC through NF-κB-induced transcription of hyaluronan synthase (HAS), an enzyme that catalyzes the formation of the extracellular matrix glycosaminoglycan, hyaluronan, within VSMCs. M(Hb) supernatants enhanced HAS production in VSMCs, while knocking down HAS attenuated its anticalcific effect. NF-κB blockade in ApoE-/- mice reduced hyaluronan and increased VC. In human arteries, hyaluronan and HAS were increased in areas of CD163+ macrophage presence. Our findings highlight an important mechanism by which CD163+ macrophages inhibit VC through NF-κB-induced HAS augmentation and thus promote the high-risk plaque development.

Relationships between neighborhood disadvantage and cardiovascular findings at autopsy in subjects with sudden death.

BACKGROUND: Neighborhood disadvantage is associated with a higher risk of sudden cardiac death. However, autopsy findings have never been investigated in this context. Here, we sought to explore associations between neighborhood disadvantage and cardiovascular findings at autopsy in cases of sudden death in the State of Maryland. METHODS: State of Maryland investigation reports from 2,278 subjects within the CVPath Sudden Death Registry were screened for street addresses and 9-digit zip codes. Area deprivation index (ADI), used as metric for neighborhood disadvantage, was available for 1,464 subjects; 650 of whom self-identified as Black and 814 as White. The primary study outcome measurements were causes of death and gross and histopathologic findings of the heart. RESULTS: Subjects from most disadvantaged neighborhoods (i.e., ADI ≥ 8; n = 607) died at younger age compared with subjects from less disadvantaged neighborhoods (i.e., ADI ≤ 7; n = 857; 46.07 ± 14.10 vs 47.78 ± 13.86 years; P = 0.02) and were more likely Black or women. They were less likely to die from cardiac causes of death (61.8% vs 67.7%; P = 0.02) and had less severe atherosclerotic plaque features, including plaque burden, calcification, intraplaque hemorrhage, and thin-cap fibroatheromas. In addition, subjects from most disadvantaged neighborhoods had lower frequencies of plaque rupture (18.8% vs 25.1%, P = 0.004). However, these associations were omitted after adjustment for traditional risk factors and race. CONCLUSION: Neighborhood disadvantage did not associate with cause of death or coronary histopathology after adjustment for cardiovascular risk factors and race, implying that social determinants of health other than neighborhood disadvantage play a more prominent role in sudden cardiac death.

Generalized Arterial Calcification of Infancy (GACI): Optimizing Care with a Multidisciplinary Approach.

It is very unusual to see evidence of arterial calcification in infants and children, and when detected, genetic disorders of calcium metabolism should be suspected. Generalized arterial calcification of infancy (GACI) is a hereditary disease, which is characterized by severe arterial calcification of medium sized arteries, mostly involving the media with marked intimal proliferation and ectopic mineralization of the extravascular tissues. It is caused by inactivating variants in genes encoding either ENPP1, in a majority of cases (70-75%), or ABCC6, in a minority (9-10%). Despite similar histologic appearances between ENPP1 and ABCC6 deficiencies, including arterial calcification, organ calcification, and cardiovascular calcification, mortality is higher in subjects carrying the ENPP1 versus ABCC6 variants (40% vs 10%, respectively). Overall mortality in individuals with GACI is high (55%) before the age of 6 months, with 24.4% dying in utero or being stillborn. Rare cases show spontaneous regression with age, while others who survive into adulthood often manifest musculoskeletal complications (osteoarthritis and interosseous membrane ossification), enthesis mineralization, and cervical spine fusion. Despite recent advances in the understanding of the genetic mechanisms underlying this disease, there is still no ideal therapy for the resolution of vascular calcification in GACI. Although bisphosphonates with anti-calcification properties have been commonly used for the treatment of CAGI, their benefit is controversial, with favorable results reported at one year and questionable benefit with delayed initiation of treatment. Enzyme replacement therapy with administration of recombinant form of ENPP1 prevents calcification and mortality, improves hypertension and cardiac function, and prevents intimal proliferation and osteomalacia in mouse models of ENPP1 deficiency. Therefore, newer treatments targeting genes are on the horizon. In this article, we review up to date knowledge of the understanding of GACI, its clinical, pathologic, and etiologic understanding and treatment in support of more comprehensive care of GACI patients.

Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals.

Importance: Unexplained sudden cardiac death (SCD) describes SCD with no cause identified. Genetic testing helps to diagnose inherited cardiac diseases in unexplained SCD; however, the associations between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes and the risk of unexplained SCD in both White and African American adults living the United States has never been systematically examined. Objective: To investigate cases of unexplained SCD to determine the frequency of P/LP genetic variants of inherited CMs and arrhythmia syndromes. Design, Setting, and Participants: This genetic association study included 683 African American and White adults who died of unexplained SCD and were included in an autopsy registry. Overall, 413 individuals had DNA of acceptable quality for genetic sequencing. Data were collected from January 1995 to December 2015. A total of 30 CM genes and 38 arrhythmia genes were sequenced, and variants in these genes, curated as P/LP, were examined to study their frequency. Data analysis was performed from June 2018 to March 2021. Main Outcomes and Measures: The frequency of P/LP variants for CM or arrhythmia in individuals with unexplained SCD. Results: The median (interquartile range) age at death of the 413 included individuals was 41 (29-48) years, 259 (62.7%) were men, and 208 (50.4%) were African American adults. A total of 76 patients (18.4%) with unexplained SCD carried variants considered P/LP for CM and arrhythmia genes. In total, 52 patients (12.6%) had 49 P/LP variants for CM, 22 (5.3%) carried 23 P/LP variants for arrhythmia, and 2 (0.5%) had P/LP variants for both CM and arrhythmia. Overall, 41 P/LP variants for hypertrophic CM were found in 45 patients (10.9%), 9 P/LP variants for dilated CM were found in 11 patients (2.7%), and 10 P/LP variants for long QT syndrome were found in 11 patients (2.7%). No significant difference was found in clinical and heart characteristics between individuals with or without P/LP variants. African American and White patients were equally likely to harbor P/LP variants. Conclusions and Relevance: In this large genetic association study of community cases of unexplained SCD, nearly 20% of patients carried P/LP variants, suggesting that genetics may contribute to a significant number of cases of unexplained SCD. Our findings regarding both the association of unexplained SCD with CM genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.

APOL1 Genetic Variants Are Associated With Increased Risk of Coronary Atherosclerotic Plaque Rupture in the Black Population.

[Figure: see text].

Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study.

BACKGROUND: Cardiac injury is common in patients who are hospitalized with coronavirus disease 2019 (COVID-19) and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain uncertain. METHODS: We conducted a systematic pathological analysis of 40 hearts from hospitalized patients dying of COVID-19 in Bergamo, Italy, to determine the pathological mechanisms of cardiac injury. We divided the hearts according to presence or absence of acute myocyte necrosis and then determined the underlying mechanisms of cardiac injury. RESULTS: Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. Compared with subjects without necrosis, subjects with necrosis tended to be female, have chronic kidney disease, and have shorter symptom onset to admission. The incidence of severe coronary artery disease (ie, >75% cross-sectional narrowing) was not significantly different between those with and without necrosis. Three of 14 (21.4%) subjects with myocyte necrosis showed evidence of acute myocardial infarction, defined as ≥1 cm2 area of necrosis, whereas 11 of 14 (78.6%) showed evidence of focal (>20 necrotic myocytes with an area of ≥0.05 mm2 but <1 cm2) myocyte necrosis. Cardiac thrombi were present in 11 of 14 (78.6%) cases with necrosis, with 2 of 14 (14.2%) having epicardial coronary artery thrombi, whereas 9 of 14 (64.3%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries. We compared cardiac microthrombi from COVID-19-positive autopsy cases to intramyocardial thromboemboli from COVID-19 cases as well as to aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19-infected patients presenting with ST-segment-elevation myocardial infarction. Microthrombi had significantly greater fibrin and terminal complement C5b-9 immunostaining compared with intramyocardial thromboemboli from COVID-19-negative subjects and with aspirated thrombi. There were no significant differences between the constituents of thrombi aspirated from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction. CONCLUSIONS: The most common pathological cause of myocyte necrosis was microthrombi. Microthrombi were different in composition from intramyocardial thromboemboli from COVID-19-negative subjects and from coronary thrombi retrieved from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction. Tailored antithrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.

Pathology of stent implantation in internal mammary artery.

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 stent lesions (2 bare metal stents, 2 drug-eluting stents) involving IMA grafts. The mean age of our patients was 63 years and the duration of stent implantation in the IMA ranged from 5 days to 5 years. Stented arteries were dissected from hearts and embedded in plastic, segmented at 3 mm intervals, sectioned at 4-6 microns and stained with H&E and Movat pentachrome stains. Histological observations were performed. Majority of stents (3 of 4) were implanted in anastomosis between IMA and LAD while 1 stent was implanted in IMA body. One stent with duration of 5 days showed stent thrombosis while others were all patent with fully coverage by varying degrees of neointima. Foamy macrophage, lipid pool and calcification in neointima were observed in 1 stent with duration of 5 years but it was limited only to the distal LAD part within the stented segment. Overall, in this small pathologic series, the majorities of stents were implanted in IMA-to-LAD anastomosis site and demonstrated acceptable pathologic responses.

Quantitative measurement of lipid rich plaque by coronary computed tomography angiography: A correlation of histology in sudden cardiac death.

BACKGROUND AND AIMS: Recent advancements in coronary computed tomography angiography (CCTA) have allowed for the quantitative measurement of high-risk lipid rich plaque. Determination of the optimal threshold for Hounsfield units (HU) by CCTA for identifying lipid rich plaque remains unknown. We aimed to validate reliable cut-points of HU for quantitative assessment of lipid rich plaque. METHODS: 8 post-mortem sudden coronary death hearts were evaluated with CCTA and histologic analysis. Quantitative plaque analysis was performed in histopathology images and lipid rich plaque area was defined as intra-plaque necrotic core area. CCTA images were analyzed for quantitative plaque measurement. Low attenuation plaque (LAP) was defined as any pixel < 30, 45, 60, 75, and 90 HU cut-offs within a coronary plaque. The area of LAP was calculated in each cross-section. RESULTS: Among 105 cross-sections, 37 (35.2%) cross-sectional histology images contained lipid rich plaque. Although the highest specificity for identifying lipid rich plaque was shown with <30 HU cut-off (88.2%), sensitivity (e.g. 55.6% for <75 HU, 16.2% for <30 HU) and negative predictive value (e.g. 75.9% for <75 HU, 65.9% for <30 HU) tended to increase with higher HU cut-offs. For quantitative measurement, <75 HU showed the highest correlation coefficient (0.292, p = 0.003) and no significant differences were observed between lipid rich plaque area and LAP area between histology and CT analysis (Histology: 0.34 ±â€¯0.73 mm2, QCT: 0.37 ±â€¯0.71 mm2, p = 0.701). CONCLUSIONS: LAP area by CCTA using a <75 HU cut-off value demonstrated high sensitivity and quantitative agreement with lipid rich plaque area by histology analysis.

Pathological mechanisms of left main stent failure.

BACKGROUND: Despite the increasing use of left main (LM) percutaneous coronary intervention (LM-PCI), there have been no pathological studies devoted to understanding the causes of LM stent failure. We aimed to systematically determine the pathological mechanisms of LM stent failure. METHODS AND RESULTS: From the CVPath Stent registry, a total of 46 lesions were identified to have LM-PCI. Pathologic stent failure (PSF) was defined as stent thrombosis, restenosis and in-stent chronic total occlusion (CTO). Failed and patent LM stented lesions were pathologically assessed to determine predictors of PSF. Malapposition and uncovered struts were numerically greater in the LM ostium, body, and bifurcation while neointimal thickness was relatively greater in bifurcation and proximal circumflex. In this study cohort, half of the lesions (n = 23) showed PSF. Stent thrombosis (ST, n = 18) was the major mode of PSF followed by in-stent CTO (n = 4) and restenosis (n = 1). Failed lesions showed significantly greater prevalence of malapposition >20% of struts/section (65% vs. 13%, P < 0.01), stent struts crossing an ostial side branch >30% of the circumference (48% vs. 13%, P < 0.01) and uncovered struts >30% (57% vs. 18%, P = 0.03). In multivariate analysis, the prevalence of malapposition >20% was the strongest risk factor for PSF (Odds ratio 8.0, 95% confidence interval 1.8-45.4, P < 0.01) followed by struts crossing an ostial side branch >30% (Odds ratio 4.2, 95% confidence interval 0.8-24.7, P = 0.09). CONCLUSION: Our data demonstrate the main pathological predictors for LM stent failure are malapposition and struts crossing an ostial side branch and suggest that imaging-guided PCI may be important.

CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis.

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 cells, and a mouse model of advanced atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage function with respect to angiogenesis, vascular permeability, inflammation, and plaque progression. In human atherosclerotic lesions, CD163+ macrophages were associated with plaque progression, microvascularity, and a high level of HIF1α and VEGF-A expression. We observed irregular vascular endothelial cadherin in intraplaque microvessels surrounded by CD163+ macrophages. Within these cells, activation of HIF1α via inhibition of prolyl hydroxylases promoted VEGF-mediated increases in intraplaque angiogenesis, vascular permeability, and inflammatory cell recruitment. CD163+ macrophages increased intraplaque endothelial VCAM expression and plaque inflammation. Subjects with homozygous minor alleles of the SNP rs7136716 had elevated microvessel density, increased expression of CD163 in ruptured coronary plaques, and a higher risk of myocardial infarction and coronary heart disease in population cohorts. Thus, our findings highlight a nonlipid-driven mechanism by which alternative macrophages promote plaque angiogenesis, leakiness, inflammation, and progression via the CD163/HIF1α/VEGF-A pathway.

Vascular Permeability Assay in Human Coronary and Mouse Brachiocephalic Arteries.

Coronary artery disease remains an important cause of morbidity and mortality. Previous work, including ours, has focused on the role of intraplaque hemorrhage, particularly from immature microvessel angiogenesis, as an important contributor to plaque progression via increases in vascular permeability leading to further intraplaque hemorrhage, which increases red cell membrane-derived free cholesterol in plaque content and inflammatory cell recruitment. Evans Blue Dye (EBD) assay is widely used as a standard assay for vasculature permeability. However, the method has not been established in fresh human coronary artery autopsy samples to evaluate intraplaque microvessel permeability and angiogenesis. In this protocol, we describe a method to evaluate human coronary samples for microvascular permeability, including procedures to perfuse coronary arteries, collection of artery samples for histological analysis and immunostaining as well as the use of appropriate methodology to analyze the images. An optional procedure is also provided for the use of FITC-dextran in mouse model to evaluate vascular permeability. These Evans Blue Dye procedures may be useful in providing functional measure of the endothelium integrity and permeability in both human samples and animal models in various pathological conditions.

Pathology of self-expanding transcatheter aortic valves: Findings from the CoreValve US pivotal trials.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has recently become an alternative to surgical aortic valve replacement for patients with severe aortic stenosis. However, paravalvular leaks, possible leaflet thrombosis, and device durability following TAVR remain unresolved issues. METHODS AND RESULTS: We conducted the first systematic microscopic and macroscopic pathologic analysis of self-expanding CoreValve transcatheter aortic valves removed at autopsy or surgically from the U.S. pivotal trial of extreme- and high-risk patients. Implants were evaluated for histopathologic changes in the valve frame and leaflets. Thrombus/neointima on the leaflets was graded depending on the leaflet thickness and the extent of leaflet involvement. Inflammation, calcification, and structural integrity were also assessed. A total of 21 cases (median age 86.0 years [IQR, 79.0-91.0]), with median duration of implant duration of 17.0 days ranged from 0 to 503 days were evaluated. No valve frame fracture was observed and severe paravalvular gaps were uncommon. Inflammation and thrombus in the valve frame was minimal, but neointimal growth increased overtime. Symptomatic valve thrombosis was observed in one case (5%) and subclinical moderate leaflet thrombus was observed in four additional cases (19%). Inflammation of the leaflets was mild, while structural changes were minimal, and one case had infective endocarditis. Pannus or leaflet calcification were not observed. CONCLUSIONS: This first systematic macroscopic and microscopic pathologic analysis of self-expanding transcatheter aortic valves demonstrates favorable short-term pathologic findings. However, our finding of subclinical leaflet thrombus formation confirms prior observations and warrants further investigation.

Very Late Pathological Responses to Cobalt-Chromium Everolimus-Eluting, Stainless Steel Sirolimus-Eluting, and Cobalt-Chromium Bare Metal Stents in Humans.

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 this issue. We evaluated the very late (≥1 year) pathologic responses to durable polymer drug-eluting stents (cobalt-chromium [CoCr] everolimus-eluting stents [EESs] and stainless steel sirolimus-eluting stents [SS-SESs]) versus BMSs (CoCr-BMSs). METHODS AND RESULTS: From the CVPath stent registry, we studied a total of 119 lesions (40 CoCr-EESs, 44 SS-SESs, 35 CoCr-BMSs) from 92 autopsy cases with a duration ranging from 1 to 5 years. Sections of stented coronary segments were pathologically analyzed. Inflammation score and the percentage of struts with giant cells were lowest in CoCr-EESs (median inflammation score: 0.6; median percentage of struts with giant cells: 3.8%) followed by CoCr-BMSs (median inflammation score: 1.3 [P<0.01]; median percentage of struts with giant cells: 8.9% [P=0.02]) and SS-SESs (median inflammation score: 1.7 [P<0.01]; median percentage of struts with giant cells: 15.3% [P<0.01]). Polymer delamination was observed exclusively in SS-SESs and was associated with increased inflammatory and giant cell reactions. The prevalence of neoatherosclerosis with CoCr-EESs (50%) was significantly less than with SS-SESs (77%, P=0.02) but significantly greater than with CoCr-BMSs (20%, P<0.01). CONCLUSIONS: CoCr-EESs, SS-SESs, and BMSs each demonstrated distinct vascular responses. CoCr-EESs demonstrated the least inflammation, near-equivalent healing to BMSs, and lower neointimal formation. These results challenge the belief that BMSs have superior biocompatibility compared with some polymeric coated drug-eluting stents and may have implications for future stent design.

Cardiac CT assessment of tissue thickness at the ostium of the left atrial appendage predicts acute success of radiofrequency ablation.

BACKGROUND: Tissue thickness at the site of ablation is a determinant of lesion transmurality. We reported the feasibility, safety, and efficacy of longstanding persistent atrial fibrillation ablation, incorporating deliberate left atrial appendage (LAA) isolation and occlusion, and identified systematic differences in ostial LAA tissue thickness in a matched cohort of cadaveric specimens. METHODS: Preprocedural cardiac computed tomography (CCT) scans were acquired from 22 patients undergoing LAA isolation and subsequent occlusion. Using a novel CCT wall thickness algorithm, LAA ostial wall thickness was assessed in vivo, compared with measurements from the cadaveric specimens, and analyzed for differences between regions that demonstrated acute electrical reconnection and those that did not. RESULTS: Mean tissue thickness calculated for each LAA ostial quadrant was 2.1 (±0.6) mm (anterior quadrant), 1.9 (±0.4) mm (superior quadrant), 1.5 (±0.4) mm (posterior quadrant), and 1.8 (±0.7) mm (inferior quadrant). Tissue was significantly thicker in the anterior (P  =  0.004) and superior quadrants (P  =  0.014) than the posterior quadrant. Higher thickness measurements were recorded from quadrants demonstrated to be thicker from histology. Tissue was significantly thicker in regions that demonstrated acute electrical reconnection (1.9 (±0.6) mm) when compared with those that did not (1.6 (±0.5) mm) (P  =  0.008). CONCLUSIONS: CCT imaging may be used to detect differences in wall thickness at different atrial locations and success of LAA ablation may be affected by local tissue thickness. Atrial wall thickness may need to be considered as a metric to guide titration of radiofrequency energy for safe and successful ablation.