15 research outputs found

    Diagnosing myocarditis in endomyocardial biopsies: survey of current practice.

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    Dallas criteria (DC) and European Society of Cardiology criteria (ESCC) have provided valuable frameworks for the histologic diagnosis and classification of myocarditis in endomyocardial biopsy (EMB) specimens. However, the adaptation and the usage of these criteria are variable and depend on local practice settings and regions/countries. Moreover, several ancillary tests that are not included in the current criteria, such as immunohistochemistry (IHC) or viral polymerase chain reaction (PCR), have proven useful for the diagnosis of myocarditis. As a joint effort from the Association for European Cardiovascular Pathology (AECVP) and the Society for Cardiovascular Pathology (SCVP), we conducted an online survey to understand the current practice of diagnosing myocarditis. A total of 100 pathologists from 23 countries responded to the survey with the majority practicing in North America (45%) and Europe (45%). Most of the pathologists reported to examine less than 200 native heart biopsies per year (85%), and to routinely receive 3-5 fragments of tissue per case (90%). The number of hematoxylin-eosin-stained levels for each case varies from 1 to more than 9 levels, with 20% of pathologists routinely asking for more than 9 levels per case. Among the 100 pathologists, 52 reported to use the DC alone, 12 the ESCC alone, 28 both DC and ESCC and 8 reported to use neither the DC nor the ESCC. Overall, 80 pathologists reported to use the DC and 40 the ESCC. Use of DC alone is more common among North American pathologists compared to European ones (80% vs 32.6%) while use of ESCC alone is more common in Europe (20.9% vs 2.5%). IHC is utilized in either every case or selected cases by 79% of participants, and viral PCR is performed by 35% of participants. Variable terminologies are used in reporting, including both histological and clinical terms. The diagnosis of myocarditis is rendered even in the absence of myocyte injury (e.g., in cases of borderline or inactive/chronic myocarditis) by 46% respondents. The majority of the participants think it is time to update the current criteria (83%). The survey data demonstrated that pathologists who render a myocarditis diagnosis practice with variable tissue preparation methods, use of ancillary studies, guideline usage, and reporting. This result highlights the clinically unmet need to update and standardize the current diagnostic criteria for myocarditis on EMB. Additional studies are warranted to establish standard of practice

    An enhancer polymorphism at the cardiomyocyte intercalated disc protein NOS1AP locus is a major regulator of the QT interval.

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    QT interval variation is assumed to arise from variation in repolarization as evidenced from rare Na- and K-channel mutations in Mendelian QT prolongation syndromes. However, in the general population, common noncoding variants at a chromosome 1q locus are the most common genetic regulators of QT interval variation. In this study, we use multiple human genetic, molecular genetic, and cellular assays to identify a functional variant underlying trait association: a noncoding polymorphism (rs7539120) that maps within an enhancer of NOS1AP and affects cardiac function by increasing NOS1AP transcript expression. We further localized NOS1AP to cardiomyocyte intercalated discs (IDs) and demonstrate that overexpression of NOS1AP in cardiomyocytes leads to altered cellular electrophysiology. We advance the hypothesis that NOS1AP affects cardiac electrical conductance and coupling and thereby regulates the QT interval through propagation defects. As further evidence of an important role for propagation variation affecting QT interval in humans, we show that common polymorphisms mapping near a specific set of 170 genes encoding ID proteins are significantly enriched for association with the QT interval, as compared to genome-wide markers. These results suggest that focused studies of proteins within the cardiomyocyte ID are likely to provide insights into QT prolongation and its associated disorders
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