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Giant cell arteritis (GCA) is the most common systemic vasculitis in adults in Europe and North America, typically involving the extra-cranial branches of the carotid arteries and the thoracic aorta. Despite advances in noninvasive imaging, temporal artery biopsy (TAB) remains the gold standard for establishing a GCA diagnosis. The processing of TAB depends largely on individual institutional protocol, and the interpretation and reporting practices vary among pathologists. To address this lack of uniformity, the Society for Cardiovascular Pathology formed a committee tasked with establishing consensus guidelines for the processing, interpretation, and reporting of TAB specimens, based on the existing literature. This consensus statement includes a discussion of the differential diagnoses including other forms of arteritis and noninflammatory changes of the temporal artery.
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The two histopathology benchmarks used to diagnose myocarditis are the Dallas Criteria, developed in 1984 and the European Society of Cardiology criteria, developed in 2013, which added immunohistochemistry for the detection of CD3+ T cells (lymphocytes) and CD68+ macrophages. Despite their near universal acceptance, the extent to which pathologists use these criteria or their own criteria to consistently render the diagnosis of myocarditis on endomyocardial biopsy (EMB) is unknown. We digitally scanned slides from 100 heart biopsies, including a trichrome stain and immunostaining, that were chosen as representative of myocarditis, non-myocarditis, and borderline myocarditis, as diagnosed per one institution's use of the Dallas Criteria. Eight blinded international cardiovascular experts were asked to render diagnoses and offer a confidence score on each case. No clinical histories were shared. There was full initial agreement across all experts on 37 cases (16 myocarditis and 21 non-myocarditis) and moderate consensus on 35 cases. After individual inquiries and group discussion, consensus was reached on 90 cases. Diagnostic confidence was highest among the myocarditis diagnoses, lowest for borderline cases, and significantly different between the three diagnostic categories (myocarditis, borderline myocarditis, non-myocarditis; P-value=8.49 × 10-57; ANOVA). Diagnosing myocarditis, particularly in cases with limited inflammation and injury, remains a challenge even for experts in the field. Intermediate cases, termed "borderline" in the Dallas Criteria, represent those for which consensus is particularly hard to achieve. To increase consistency for the histopathologic diagnosis of myocarditis, we will need more specifically defined criteria, more granular descriptions of positive and negative features, clarity on how to incorporate immunohistochemistry findings, and improved nomenclature.
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Sudden cardiac death is, by definition, an unexpected, untimely death caused by a cardiac condition in a person with known or unknown heart disease. This major international public health problem accounts for approximately 15-20% of all deaths. Typically more common in older adults with acquired heart disease, SCD also can occur in the young where the cause is more likely to be a genetically transmitted process. As these inherited disease processes can affect multiple family members, it is critical that these deaths are appropriately and thoroughly investigated. Across the United States, SCD cases in those less than 40 years of age will often fall under medical examiner/coroner jurisdiction resulting in scene investigation, review of available medical records and a complete autopsy including toxicological and histological studies. To date, there have not been consistent or uniform guidelines for cardiac examination in these cases. In addition, many medical examiner/coroner offices are understaffed and/or underfunded, both of which may hamper specialized examinations or studies (e.g., molecular testing). Use of such guidelines by pathologists in cases of SCD in decedents aged 1-39 years of age could result in life-saving medical intervention for other family members. These recommendations also may provide support for underfunded offices to argue for the significance of this specialized testing. As cardiac examinations in the setting of SCD in the young fall under ME/C jurisdiction, this consensus paper has been developed with members of the Society of Cardiovascular Pathology working with cardiovascular pathology-trained, practicing forensic pathologists.
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Cardiopatias , Patologistas , Humanos , Idoso , Adulto , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/patologia , Cardiopatias/complicações , Autopsia/métodos , CoraçãoRESUMO
Mechanical complications after acute myocardial infarction are well-described yet catastrophic complications of acute coronary syndromes. Uniquely, we describe a rare case of left ventricular free wall rupture at the site of a septic myocardial abscess after an anterior wall myocardial infarction. (Level of Difficulty: Advanced.).
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Giant cell arteritis (GCA) is a systemic vasculitis of medium and large sized blood vessels. The incidence is greater in women as compared to men (3:1) and most often occurs in the elderly. The most common symptoms are unilateral headaches, visual disturbances and scalp tenderness. If untreated, GCA may result in irreversible blindness. Prompt treatment is necessary to prevent progression of the disease, but accurate diagnosis is vital to prevent unwarranted side effects of the therapy. Temporal artery biopsy (TAB) remains the gold standard for diagnosis. TAB is an invasive procedure that can require up to 40 minutes to perform but is important for pathological confirmation. Variation amongst centers and practitioners exists in the type of biopsies performed. In 2013, a survey of over 1000 specialists showed that 37% recommended unilateral biopsy alone, 29% recommended initial unilateral biopsy with biopsy of the contralateral side if the first side is negative, 18% recommended bilateral biopsy in all cases, and 16% stated that their preference depended upon the degree of suspicion. Studies have shown that bilateral TAB can enhance diagnostic accuracy by 3 to 12.7%. Furthermore, temporal arteritis can involve the artery in a discontinuous fashion and there is no standardization of the number of sections or levels that should be examined in a segment of temporal artery. This study aims to shed light on the benefits of a bilateral temporal artery biopsy as well as to determine the optimum level for block sectioning for the diagnosis of temporal arteritis.
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Arterite de Células Gigantes , Idoso , Biópsia/métodos , Feminino , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/patologia , Humanos , Incidência , Masculino , Estudos Retrospectivos , Artérias Temporais/patologiaRESUMO
Background and Purpose: Unstable carotid plaques are a common cause of ischemic strokes. Identifying markers that reflect/contribute to plaque instability has become a prominent focus in cardiovascular research. The adipokines, resistin and chemerin, and ChemR23 (chemerin receptor), may play a role in carotid atherosclerosis, making them potential candidates to assess plaque instability. However, the expression and interrelationship of resistin and chemerin (and ChemR23) protein and mRNA within the carotid atherosclerotic plaque remains elusive. Thus, we investigated herein, the association between plaque mRNA and protein expression of resistin and chemerin (and ChemR23) and carotid plaque instability in humans, and whether sex differences exist in the relationship between these adipokines and plaque instability. Methods: Human carotid plaques were processed for immunohistochemical/mRNA analysis of resistin, chemerin, and ChemR23. Plaque instability was assessed by gold-standard histological classifications. A semi-quantitative scoring system was used to determine the intensity of adipokine expression on macrophages/foam cells, as well as the percentage of inflammatory cells stained positive. Plaque adipokine protein expression was also digitally quantified and mRNA expression was assessed by qRT-PCR. Results: Resistin and chemerin mRNA expression was 80% and 32% lower, respectively, in unstable versus stable plaques (P<0.05), while no difference in ChemR23 mRNA expression was observed. In contrast, greater resistin staining intensity and percentage of cells stained positive were detected in unstable versus stable plaques (P<0.01). Similarly, chemerin and ChemR23 staining intensity and percentage of cells stained were positively associated with plaque instability (P<0.05). No strong sex-specific relationship was observed between adipokines and plaque instability. Conclusions: This study examined the relationship between resistin, chemerin, and ChemR23, and carotid plaque instability, with a specific analysis at the plaque level. We reported a positive association between plaque instability and protein levels of resistin, chemerin, and ChemR23 but a negative association with resistin and chemerin mRNA expression. This suggests these adipokines exert proinflammatory roles in the process of carotid atherosclerosis and may be regulated via a negative feedback regulatory mechanism.
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Estenose das Carótidas/sangue , Quimiocinas/sangue , Placa Aterosclerótica/sangue , Receptores de Quimiocinas/sangue , Resistina/sangue , Caracteres Sexuais , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estenose das Carótidas/diagnóstico por imagem , Quimiocinas/biossíntese , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Estudos Prospectivos , Receptores de Quimiocinas/biossíntese , Resistina/biossínteseAssuntos
Cardiomiopatias , Miocardite , Sarcoidose , Células Gigantes , Humanos , Sarcoidose/diagnósticoRESUMO
We report a case of a 75-year-old female post orthotopic heart transplantation, who presented to the emergency department with a six-week history of shortness of breath, hand tremor and ultimately delirium. She had lobular breast carcinoma more than 5 years prior to her heart transplant, treated by lumpectomy followed by anthracycline based chemotherapy. The reason for her heart transplant was heart failure that was suspected to be from anthracycline cardiomyopathy, however, her explanted heart actually showed cardiac sarcoidosis. She was placed on long-term immunosuppression with tacrolimus, mycophenolate mofetil and prednisone. Two years after her heart transplant, she underwent bilateral mastectomies for recurrent breast cancer. Her neurological workup, including brain imaging (CT, MRI, LP and EEG) did not show any structural abnormalities, ischemia, mass or neurosarcoidosis as cause for delirium. Tacrolimus was held due to renal dysfunction and hemolytic anemia, and then she developed signs of right heart failure so an endomyocardial biopsy was carried out for suspected allograft rejection. The biopsy did not show any evidence of cellular or antibody medicated rejection; however, it demonstrated infiltration by bland appearing cells with signet ring morphology cells many of which showed intracytoplasmic mucin. The cells were strongly positive with cytokeratins AE1/3, CK7 and mammaglobin. The morphology and immunoprofile were consistent with metastatic lobular breast carcinoma and this was thought to be the cause of her clinical presentation with delirium, hemolytic anemia and renal dysfunction as a paraneoplastic syndrome.
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Carcinoma Lobular/secundário , Insuficiência Cardíaca/cirurgia , Neoplasias Cardíacas/secundário , Transplante de Coração , Miocárdio/patologia , Idoso , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Biópsia , Carcinoma Lobular/complicações , Carcinoma Lobular/terapia , Cardiomiopatias/induzido quimicamente , Cardiotoxicidade , Quimioterapia Adjuvante , Feminino , Insuficiência Cardíaca/etiologia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/terapia , Transplante de Coração/efeitos adversos , Humanos , Síndromes Paraneoplásicas/etiologia , Valor Preditivo dos Testes , Fatores de Risco , Sarcoidose/complicaçõesRESUMO
We present two patients who underwent cardiac surgery followed by post-operative low cardiac output, diastolic dysfunction and resistance to inotropic support. Despite aggressive medical management, both patients died. At autopsy, the hearts were enlarged and showed previously undiagnosed myocardial and vascular amyloidosis. Occult cardiac amyloidosis is an uncommon, often occult, contributor to post-operative complications post cardiac surgery. Pre-operative or intraoperative myocardial biopsy may be useful in patients with unexplained diastolic dysfunction. Brief Summary: We present two patients who underwent cardiac surgery followed by low cardiac output, diastolic dysfunction and resistance to inotropic support. Cardiac dysfunction was due to occult amyloidosis. Pre-operative or intra-operative myocardial biopsy may be useful in patients with unexplained diastolic dysfunction. With recent therapy advances, classification and possible treatment of amyloid are possible.
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Amiloidose/complicações , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiomiopatias/complicações , Amiloidose/patologia , Animais , Cardiomiopatias/patologia , Humanos , Masculino , Camundongos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Atherosclerosis and its thrombotic complications are major causes of morbidity and mortality worldwide. Plaque stability assessment is considered to be important for both clinical and fundamental applications. The current gold standard method to investigate plaque stability is performed by histological assessment of plaque features using semi-quantitative classifications. However, these assessments can be limited by subjectivity and variability. Thus, the aim was to develop a new digital image analysis method to measure quantitatively individual plaque features that is more precise than existing semi-quantitative methods. METHODS: A quantitative method was developed using Image Pro Primer software. Carotid plaque specimens were obtained from patients who underwent carotid endarterectomy and categorised according to stability (definitely stable, probably stable, probably unstable, definitely unstable) based on the gold standard semi-quantitative method that assesses 10 histological plaque features. Using the new quantitative method, plaque features (n = 15) from each stability grade were then analysed by two independent raters. For the semi-quantitative analysis, quadratic weighted Cohen's kappa was used to test intra- and inter-rater reliability, while for the quantitative analysis, intraclass correlation coefficients (ICCs) were assessed. RESULTS: Intra-rater reliability demonstrated almost perfect agreement between both methods (Cohen's kappa range 0.831-0.969, ICC range 0.848-1.000). However, inter-rater reliability demonstrated mainly fair to moderate agreement (Cohen's kappa range 0.341-0.778) for the semi-quantitative analysis, while the digital image analysis method performed most optimally regarding reproducibility, yielding high ICCs close to 1 (ICC range 0.816-0.999). Using quantitative measurements, a statistically significant proportion of the individual plaque features (p < .05) were re-classified from one grade to another (shift by one) under the semi-quantitative classification. CONCLUSION: A new quantitative digital image analysis was developed for the accurate assessment of histological plaque features, which demonstrated higher precision than the gold standard semi-quantitative methods, as measured by between and within rater analysis. Moreover, quantitative image analysis of histological plaque features provided more detailed insight into plaque morphology and composition.
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Artérias Carótidas , Estenose das Carótidas/diagnóstico , Interpretação de Imagem Assistida por Computador/métodos , Placa Aterosclerótica , Idoso , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Correlação de Dados , Precisão da Medição Dimensional , Endarterectomia das Carótidas/métodos , Feminino , Humanos , Imuno-Histoquímica , Masculino , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Reprodutibilidade dos Testes , Manejo de Espécimes/métodosRESUMO
Lysosomal storage disorders (LSD) comprise a group of diseases caused by a deficiency of lysosomal enzymes, membrane transporters or other proteins involved in lysosomal biology. Lysosomal storage disorders result from an accumulation of specific substrates, due to the inability to break them down. The diseases are classified according to the type of material that is accumulated; for example, lipid storage disorders, mucopolysaccharidoses and glycoproteinoses. Cardiac disease is particularly important in lysosomal glycogen storage diseases (Pompe and Danon disease), mucopolysaccharidoses and in glycosphingolipidoses (Anderson-Fabry disease). Various disease manifestations may be observed including hypertrophic and dilated cardiomyopathy, coronary artery disease and valvular diseases. Endomyocardial biopsies can play an important role in the diagnosis of these diseases. Microscopic features along with ancillary tests like special stains and ultrastructural studies help in the diagnosis of these disorders. Diagnosis is further confirmed based upon enzymatic and molecular genetic analysis. Emerging evidence suggests that Enzyme replacement therapy (ERT) substantially improves many of the features of the disease, including some aspects of cardiac involvement. The identification of these disorders is important due to the availability of ERT, the need for family screening, as well as appropriate patient management and counseling.
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Cardiopatias/patologia , Doenças por Armazenamento dos Lisossomos/patologia , Miocárdio/patologia , Biópsia , Terapia de Reposição de Enzimas , Predisposição Genética para Doença , Cardiopatias/tratamento farmacológico , Cardiopatias/enzimologia , Cardiopatias/genética , Humanos , Doenças por Armazenamento dos Lisossomos/tratamento farmacológico , Doenças por Armazenamento dos Lisossomos/enzimologia , Doenças por Armazenamento dos Lisossomos/genética , Miocárdio/ultraestrutura , Fenótipo , Fatores de Risco , Resultado do TratamentoRESUMO
Glutaredoxin 2 (GRX2), a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC) to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies.
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Metabolismo Energético , Glutarredoxinas/metabolismo , Cardiopatias/metabolismo , Dinâmica Mitocondrial , Acetilcisteína/uso terapêutico , Animais , Cardiomegalia/genética , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/prevenção & controle , Células Cultivadas , Glutarredoxinas/genética , Cardiopatias/genética , Cardiopatias/patologia , Cardiopatias/prevenção & controle , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Oxirredução , Estresse Oxidativo , Fatores de ProteçãoRESUMO
BACKGROUND: Idiopathic aortitis became recognized relatively recently, and the body of knowledge concerning this condition is scarce. We aimed to determine the frequency of idiopathic aortitis in aortic specimens, the clinical, laboratory and radiologic characteristics at diagnosis and during follow-up, and the approach to investigation, treatment and monitoring taken by the treating physicians. METHODS: We identified cases of aortitis diagnosed on pathological specimens of the aorta between Jan. 1, 2003, and July 31, 2013, at The Ottawa Hospital by reviewing the hospital's pathology database. Charts of identified patients were reviewed, and data on patient demographic characteristics, clinical features, laboratory and imaging tests, treatment and outcomes were analyzed. RESULTS: A total of 684 aortic specimens were analyzed during the study period; 47 cases of aortitis were identified, 32 of which were idiopathic. Twenty-one patients (66%) had complete imaging of branch vessels at baseline, 16 (76%) of whom had additional aortic or branch vessel lesions. Twelve patients (38%) received corticosteroids postoperatively. Over a mean follow-up period of 47.5 months, among the 12 patients (38%) who had complete imaging of branch vessels at least once, new aortic or branch lesions were diagnosed in 5 (42%); 3/32 patients (9%) required additional vascular surgery; and a new systemic condition was diagnosed in 2/32 (6%). INTERPRETATION: Idiopathic aortitis is commonly discovered incidentally on examination of the pathological specimen following ascending aortic aneurysm repair. No guidelines exist for the investigation, treatment and follow-up of this condition, resulting in great variability of practice. Good-quality prospective studies are needed to address the many unanswered clinical questions regarding idiopathic aortitis and to allow formulation of more definitive recommendations.
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We report a 45-year-old man with rapidly progressive cardiac amyloidosis, who required heart transplantation within 2 years of symptomatic onset. Hematologic testing and initial tissue biopsy results confirmed amyloid infiltration but were inconclusive for the amyloidogenic protein source. Mass spectroscopy and transthyretin (TTR) sequencing were required to reach a diagnosis of TTR amyloidosis resulting from a Glu89Lys mutation. Although a predominantly neuropathic phenotype has previously been described with this mutation, the present kinship documents a primarily cardiac presentation. This case report highlights the diagnostic challenge of TTR amyloidosis and the marked variability of the genotype-phenotype correlation.
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Amiloidose/genética , Cardiomiopatias/genética , DNA/genética , Mutação , Pré-Albumina/genética , Amiloidose/diagnóstico , Biópsia , Cardiomiopatias/diagnóstico , Análise Mutacional de DNA , Ecocardiografia , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , FenótipoRESUMO
BACKGROUND AND PURPOSE: Adiponectin, the most abundantly secreted anti-inflammatory adipokine, protects against all stages of atherosclerotic plaque formation by acting on its receptors, AdipoR1 (adiponectin receptor 1) and AdipoR2 (adiponectin receptor 2). Through binding of AdipoR1, adiponectin leads to the activation of the AMPK (adenosine monophosphate-activated protein kinase) pathway, whereas stimulation of PPAR-α (peroxisome proliferator-activated receptor-α) is attributed to the binding of AdipoR2. However, the role of adiponectin and its receptors in plaque instability remains to be characterized. Thus, we aimed to investigate whether the adiponectin-AdipoR pathway is associated with carotid atherosclerotic plaque instability. METHODS: The instability of plaque specimens obtained from patients who underwent a carotid endarterectomy (n=143) was assessed using gold standard histological classifications. RESULTS: Using immunohistochemistry, we showed that adiponectin and AdipoR1/AdipoR2 are expressed in human carotid plaques and that their expression was localized most abundantly in areas of macrophage and foam cell accumulation. Unstable plaques expressed more adiponectin protein (Western blot, P<0.05) and less AdipoR2 mRNA (2.11-fold decrease, P<0.05) than stable plaques, whereas AdipoR1 expression remained similar between stable and unstable plaques. Beyond AdipoR1/AdipoR2 expression, a graded decrease in PPAR-α protein levels was observed in relation to carotid plaque instability (P<0.001), whereas AMPK phosphorylation was increased (P<0.05). Our in vitro model of plaque instability, involving the induction of foam cells from human THP-1 (Tamm-Horsfall protein 1) macrophages treated with acetylated low-density lipoprotein, supported our in vivo conclusions. CONCLUSIONS: An overall abundance of adiponectin with a decrease in AdipoR2 expression and activity was observed in unstable plaques, suggesting that reduced signaling through the AdipoR2 pathway, and not through AdipoR1, may contribute to plaque instability.
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Adiponectina/metabolismo , Doenças das Artérias Carótidas/metabolismo , Placa Aterosclerótica/metabolismo , Receptores de Adiponectina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doenças das Artérias Carótidas/cirurgia , Endarterectomia das Carótidas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/cirurgiaRESUMO
The Nkx2.5 gene encodes a transcription factor that plays a critical role in heart development. In humans, heterozygous mutations in NKX2.5 result in congenital heart defects (CHDs). However, the molecular mechanisms by which these mutations cause the disease remain unknown. NKX2.5-R142C is a mutation that was reported to be associated with atrial septal defect (ASD) and atrioventricular (AV) block in 13-patients from one family. The R142C mutation is located within both the DNA-binding domain and the nuclear localization sequence of NKX2.5 protein. The pathogenesis of CHDs in humans with R142C point mutation is not well understood. To examine the functional deficit associated with this mutation in vivo, we generated and characterized a knock-in mouse that harbours the human mutation R142C. Systematic structural and functional examination of the embryonic, newborn, and adult mice revealed that the homozygous embryos Nkx2.5R141C/R141C are developmentally arrested around E10.5 with delayed heart morphogenesis and downregulation of Nkx2.5 target genes, Anf, Mlc2v, Actc1 and Cx40. Histological examination of Nkx2.5R141C/+ newborn hearts showed that 36% displayed ASD, with at least 80% 0f adult heterozygotes displaying a septal defect. Moreover, heterozygous Nkx2.5R141C/+ newborn mice have downregulation of ion channel genes with 11/12 adult mice manifesting a prolonged PR interval that is indicative of 1st degree AV block. Collectively, the present study demonstrates that mice with the R141C point mutation in the Nkx2.5 allele phenocopies humans with the NKX2.5 R142C point mutation.
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Estudos de Associação Genética , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/fisiopatologia , Proteína Homeobox Nkx-2.5/genética , Mutação , Animais , Modelos Animais de Doenças , Ecocardiografia , Feminino , Expressão Gênica , Marcação de Genes , Vetores Genéticos/genética , Genótipo , Cardiopatias Congênitas/diagnóstico , Humanos , Masculino , Camundongos , Camundongos Transgênicos , FenótipoRESUMO
Stroke is associated with vulnerable carotid artery plaques showing specific histopathologic features, namely a lipid-rich necrotic core, intraplaque hemorrhage, ulceration, and thin fibrous cap. While ultrasound and computed tomography (CT) can identify carotid plaques and determine the extent of stenosis, magnetic resonance imaging (MRI) provides further information regarding plaque composition and morphology. In this feasibility study, three patients with symptomatic, moderately stenosed plaques were imaged with CT angiography (CTA) and MRI (3T and 1.5T) without a dedicated receiver coil. The patients subsequently underwent carotid endarterectomy with en-bloc excision of the plaque. The CT and MR images were analyzed independently by three neuroradiologists to identify vulnerable plaque features. The images were correlated with the histopathology to confirm the findings. All three patients had one or more vulnerable plaque features on histopathology. MRI allowed for better characterization of these features when compared to CTA. The pre- and post-contrast T1-weighted (T1W) images were most helpful for identifying the lipid-rich necrotic core and thin fibrous cap, while the time of flight-magnetic resonance angiography (TOF-MRA) and contrast-enhanced (CE)-MRA were excellent for detecting plaque hemorrhage and ulceration, respectively. The 3T images showed superior spatial and contrast resolution compared to the 1.5T images for all sequences. By providing direct correlation between imaging and histopathology, this study demonstrates that 3T MRI without a dedicated surface coil is an excellent tool for assessing plaque vulnerability. In smaller hospitals or those with limited resources, it is reasonable to consider conventional MRI for patient risk stratification. Further studies are needed to determine how MRI and plaque vulnerability can be incorporated into routine clinical practice.
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Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Idoso , Doenças das Artérias Carótidas/complicações , Estenose das Carótidas/complicações , Humanos , Imageamento Tridimensional , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The rupture of unstable carotid atherosclerotic plaques is one of the main causes of cerebrovascular ischemic events. There is need for circulating markers that can predict plaque instability and risk of stroke. Proinflammatory chemerin, leptin, and resistin, along with anti-inflammatory adiponectin, are adipokines with direct influence on vascular function. We investigated the association of circulating adipokines with carotid plaque instability and cerebrovascular symptomatology. APPROACH AND RESULTS: Neurologically symptomatic and asymptomatic patients (n=165) scheduled for carotid endarterectomy were recruited. Fasting blood samples were collected preoperatively; adiponectin and leptin levels were determined by radioimmunoassay; and chemerin and resistin levels were measured by enzyme-linked immunosorbent assays. The instability of plaque specimens was assessed using gold-standard histological classifications. Chemerin was significantly associated with plaque instability. The fully adjusted model, accounting for age, sex, body mass index, high-sensitivity C-reactive protein, type 2 diabetes mellitus, and circulating adiponectin, leptin, and resistin, yielded an odds ratio of 0.991 (95% confidence interval 0.985-0.998) for plaque instability per unit increase in chemerin. High leptin levels were significantly associated with presence of specific features of plaque instability. In subjects with type 2 diabetes mellitus, resistin levels were significantly elevated in symptomatic when compared with asymptomatic subjects (P=0.001) and increased the risk of cerebrovascular symptomatology (adjusted odds ratio 1.264, 95% confidence interval 1.004-1.594). CONCLUSIONS: Low chemerin and high resistin levels were associated with carotid disease severity, suggesting that these adipokines may act as potential markers for plaque instability and stroke risk. Future studies are needed to assess causation between circulating adipokines and plaque instability.