Sensitivity Of Endomyocardial Biopsy Research Articles

Imaging diagnostics of cardiac sarcoidosis

Cardiac involvement is clinically apparent in approximately 5% of all patients with systemic sarcoidosis, whereas evidence of cardiac involvement by imaging studies can be found in approximately 20% of cases. Occasionally, isolated cardiac sarcoidosis is encountered and is the only sign of the disease. The most frequent cardiac manifestations of the multifocal granulomatous inflammation include atrioventricular (AV) blocks and other conduction disorders, ventricular arrhythmias, sudden cardiac death and left and right ventricular wall disorders. Accordingly, symptoms that should raise suspicion include palpitations, lightheadedness and syncope. The diagnostic approach to cardiac sarcoidosis is not straightforward. Typical echocardiographic findings include regional thinning and contraction abnormalities particularly in basal, septal and lateral locations. Infrequently, myocardial hypertrophy may be present; however, the sensitivity of echocardiography is low and cardiac sarcoidosis can be present even when an echocardiogram is unrevealing. Cardiac magnetic resonance imaging (MRI) frequently shows late gadolinium enhancement (LGE) in amultifocal pattern often involving the basal septum and lateral walls. The sensitivity and specificity of MRI for detecting cardiac sarcoidosis are high. Fluorodeoxyglucose positron emission tomography (FDG-PET) plays an important role in the diagnostic algorithm due to its ability to visualize focal inflammatory activity both in the myocardium and in extracardiac locations. This may help target the optimal location for biopsy in order to obtain histologic proof of sarcoidosis and can also be used to follow the response to anti-inflammatory treatment. Notably, the sensitivity of endomyocardial biopsy is poor due to the patchy nature of myocardial involvement. In clinical practice, either histologic evidence of noncaseating granulomas from the myocardium or evidence from extracardiac tissue in combination with typical cardiac imaging findings are required to establish the diagnosis.

Utility of updated diagnositc criteria to detect isolated cardiac sarcoidosis

Abstract Background Prior study reported around one-third of cardiac sarcoidosis (CS) are considered as isolated CS. Detection of CS is challenging due to the limited sensitivity of endomyocardial biopsy and applicability of guidelines, especially in patients without extra-cardiac involvement. Existing diagnostic criteria by Japanese Ministry of health and Welfare (JMHW) or Heart Rhythm Society (HRS) require the presence of extra-cardiac sarcoidosis for clinical diagnosis, isolated CS is not diagnosable in the absence of a positive histological finding. Recently, Japanese Society of Cardiology (JCS) updated diagnostic criteria for CS, which provides the pathway to diagnose isolated CS. Purpose We aimed to assess the reliability of the updated CS guideline in diagnosing CS compared to the prior guidelines. Methods We retrospectively identified 162 consecutive patients who underwent FDG-PET for suspected CS from 2012 through 2019. According to the updated JCS diagnostic criteria, patients were classified as histologic diagnosis of CS, clinical diagnosis of CS, or isolated CS (Figure A). We compared the association between diagnostic criteria and response with anti-inflammatory therapy. Results The JCS criteria classified 24 patients (15%) as having clinical CS, 4 (3%) as histological diagnosis of CS, and 21 (13%) as isolated CS. The JMHW criteria defined 22 patients (14%) as having CS (clinical 11%, histological 3%) and HRS criteria classified 11 patients (7%) as having CS (clinical 4%, histological 3%). Extra-cardiac involvement was detected in 36 patients (22%) with 8% of histological confirmation. Among the 126 patients without extra-cardiac involvement, prevalence of cardiac involvement was higher in isolated CS (P<0.05 for all). Compared with clinical diagnosis group, patients with isolated CS showed higher incident of regional wall motion abnormality (WMA) or left ventricular (LV) dysfunction (p=0.023). In the subgroup of 45 patients with serial FDG-PET evaluation, only updated CS criteria was associate with improvement in myocardial inflammation by FDG-PET (p<0.001). Conclusions Updated JCS diagnostic criteria detects CS patients with active myocardial inflammation which require anti-inflammatory therapy regardless of extra-cardiac involvement better than the prior guidelines. Diagnostic criteria for CS Funding Acknowledgement Type of funding source: None

The quest for diagnostic approaches of cardiac involvement in polymyositis and dermatomyositis.

Polymyositis (PM) and dermatomyositis (DM) are autoimmune diseases characterized by inflammation of skeletal muscle, primarily manifesting as chronic muscle weakness. Extramuscular organs can also be affected. Cardiac involvement is one of the visceral organ damages whose prevalence is underestimated and is a marker of poor prognosis leading to irreversible dysfunction or even death. Although early and accurate recognition of cardiac involvement remains a key barrier to improving survival in PM/ DM patients, considerable progress has been made, and an overview will be provided in this review. The new concept of multimodality imaging, which involves an integrated approach of echocardiography (Echo), cardiac magnetic resonance and sometimes positron emission tomography (PET), can facilitate diagnosis. The development of ultrasound technology, including strain analysis, stress Echo and contrast-enhanced Echo, helps disclose early cardiac dysfunction more sensitively than conventional Echo. Cardiac magnetic resonance unveils silent, acute or chronic myocarditis in PM/DM and is used to monitor treatment efficacy due to its excellent tissue characterization. PET can be useful thanks to the appearance of new tracers that can eliminate the effects of glucose uptake by normal cardiomyocytes. The sensitivity of endomyocardial biopsy may be increased by targeted sampling with the guidance of cardiac imaging. Troponin I is specific to cardiac injury, and investigations into antibodies against cardiac tissue are being carried out. Disease-specific mechanisms and therapies are also discussed to give more insights into cardiac involvement in PM and DM.

The Many Faces of Cardiac Sarcoidosis

Abstract Introduction Cardiac involvement by sarcoidosis, a disease characterized by nonnecrotizing granulomas of unknown etiology, is rare and affects up to 7% of sarcoidosis patients clinically, but with an autopsy prevalence of 15% to 90%. The clinical presentation, as well as macroscopic and microscopic findings in cardiac sarcoidosis patients, varies. Methods Retrospective clinical chart review and gross and microscopic examination of surgical specimen from two adult cardiac sarcoidosis patients with literature review were performed. Results Case 1: A 23-year-old woman with no past medical history presented with 2 months of heart failure symptoms following a viral gastrointestinal infection. Endomyocardial biopsy showed a dense chronic inflammatory infiltrate, without giant cells. Anterior mediastinal lymph node biopsy and left apical core showed effacement by nonnecrotizing granulomas with giant cells and multifocal calcification, supporting cardiac sarcoidosis. Twelve months later, she underwent cardiac transplantation. The explanted heart showed concentric ventricular scarring, which microscopically corresponded to myocardial fibrosis with scattered lymphocytic inflammation with no residual granulomas. Case 2: A 52-year-old man with a medical history significant for ischemic cardiomyopathy and cutaneous sarcoidosis with lung involvement presented with congestive heart failure. Endomyocardial biopsy and left apical core showed myocyte hypertrophy and scattered interstitial inflammation. Mediastinal lymph node showed nonnecrotizing granulomas, consistent with sarcoidosis. Eighteen months later, he underwent cardiac transplantation. The explanted heart showed biventricular dilatation with interstitial fibrosis. There was also mild diffuse inflammation and occasional granulomas with rare focal necrosis. Conclusion Though the gold standard for diagnosing cardiac sarcoidosis is demonstration of myocardial nonnecrotizing granulomas, the sensitivity of endomyocardial biopsy is low. This is due to sampling error and stage of disease. Chronic end-stage disease can lead to fibrous encasement of granulomas and end-stage heart failure, necessitating cardiac transplantation. Current guidelines employ a combination of clinical, radiologic, and histologic criteria for diagnosing cardiac sarcoidosis.

Rapid Recovery of Acute Giant Cell Myocarditis with Hypereosinophilia with Combined Immunosuppression and Benralizumab

Introduction Myocarditis is often an elusive diagnosis as the clinical presentation can be nonspecific and definitive diagnosis can be challenging due to the low sensitivity of endomyocardial biopsy. Additionally, treatment of myocarditis is controversial with no guidelines and limited data available regarding efficacy. Nevertheless, recent studies have demonstrated a treatment benefit with immunosuppression, particularly in giant cell myocarditis (GCM). This report highlights a unique case of histologically confirmed GCM in which the patient also had a significant peripheral hypereosinophilia, and examines the response of combined immunosuppression with rabbit anti-thymocyte globulin (RATG), corticosteroids, cyclosporine, and benralizumab–an interleukin-5 receptor antagonist–that resulted in rapid recovery. Case Report A 25 year old woman with a history of asthma for 3 years and a recent diagnosis of heart failure with reduced ejection fraction (40%) presented with acute chest pain and worsening left ventricular (LV) dysfunction with a reduction of her left ventricular ejection fraction (LVEF) to 25-30% within 2 weeks. Laboratory studies revealed a 40% peripheral eosinophilia. Further workup was negative for infection, eosinophilic granulomatosis with polyangiitis, or malignancy. A cardiac MRI showed late-gadolinium enhancement and an endomyocardial biopsy confirmed significant eosinophilic tissue infiltration, myocyte necrosis, and the presence of giant cells. She was treated with a combined immunosuppression regimen of RATG induction, corticosteroids, cyclosporine, and benralizumab. Despite this regimen, she had a recurrence of peripheral eosinophilia during the course of her hospitalization. Nevertheless, she had significant clinical improvement in symptomatology, functional status, and hemodynamics. Her peripheral eosinophilia resolved over the following days with increased corticosteroids and thereafter remained negligible. A repeat echocardiogram 3 weeks after initial initiation of immunosuppression demonstrated significant improvement in her LVEF to 53%, improvement of global strain, and reduction of left atrial dilatation. Discussion Emerging data suggests that treatment with immunosuppression can improve outcomes in patients with GCM. Indeed, this patient did have a marked improvement in LV function within 3 weeks of initiating treatment. Additionally, the use of benralizumab to treat her peripheral eosinophilia demonstrates potential implications for use in other hypereosinophilic syndromes. However, given that her serum eosinophila recurred despite being on a multi-drug immunosuppression regimen, including benralizumab, identifies potential focus areas of future research including further examination of the exact mechanism of action, the relevance of expanded use in other hypereosinophilic syndromes, and delineation of appropriate end points for measuring response.

Myocardial Immunocompetent Cells and Macrophage Phenotypes asHistopathological Surrogates for Diagnosis of Cardiac Sarcoidosis in Japanese.

BackgroundThe histological diagnosis of cardiac sarcoidosis (CS) is based on the presence of myocardial granulomas; however, the sensitivity of endomyocardial biopsy is relatively low. We investigated whether immunocompetent cells including dendritic cells (DC) and macrophages in nongranuloma sections of endomyocardial biopsy samples could be histopathological surrogates for CS diagnosis.Methods and ResultsThe numbers of DC and macrophages were investigated in 95 consecutive CS patients and 50 patients with nonischemic cardiomyopathy as controls. All patients underwent endomyocardial biopsy, and immunohistochemical staining was performed on all samples. We examined these immunocompetent cells in nongranuloma sections in CS patients diagnosed by the presence of myocardial granulomas (n=26) and in CS patients without myocardial granulomas diagnosed by the Japanese Ministry of Health Welfare 2007 criteria (n=65) or the Heart Rhythm Society 2014 criteria (n=26). In CS patients with and without myocardial granulomas, CD209+ DC and CD68+ macrophages were more frequently observed (P<0.01) and CD163+M2 macrophages were less frequently observed (P<0.01) in nongranuloma sections compared to controls. Furthermore, the combination of decreased CD163+M2/CD68+ macrophage ratio and increased number of CD209+ DC in nongranuloma sections of CS patients demonstrated high specificity (100%, 95% CI 92.7–100) for CS diagnosis with each diagnostic criteria and the presence of myocardial granulomas.ConclusionsIncreased number of DC and decreased M2 among all macrophages in nongranuloma sections of myocardium showed high specificity for CS diagnosis, suggesting DC and macrophage phenotypes as histopathological surrogates for the diagnosis of CS.

T2-Mapping CMR increases the diagnostic sensitivity for detection of myocardial inflammation in patients with possible myocarditis - a prospective endomyocardial biopsy-controlled study

Myocarditis has been reported in up to 20% of sudden cardiac death in young adults and is a frequent precursor of dilated cardiomyopathy. Unfortunately, the diagnostic tools for detection of myocarditis are still imperfect: Sensitivity of endomyocardial biopsy (EMB) is reduced largely due to the inherent sampling error. Cardiac magnetic resonance (CMR) offers the advantage of analysing the whole myocardium, but contrast-enhanced as well as T2weighted CMR exhibit inadequate sensitivity, especially during early stages of inflammation. Our hypothesis was that quantitative T2 relaxation mapping increases diagnostic sensitivity in CMR-based diagnosis of myocarditis. Methods We carried out a prospective observational study in patients with probable acute myocarditis characterized by clinical presentation, new global or regional wall abnormalities or arrhythmias or hsTNT-elevation. Of the 55 patients screened, two patients did not undergo CMR (1 pacemaker, 1 ECLS-support) and 16 patients refused EMB. The remaining 37 patients underwent EMB and CMR examination (1.5 T, Archieva, Philips) within 36h. Histological evaluation was performed by two independent pathologists (hematoxylin eosin staining, picrosirius red, IH CD68, CD45R0 and CD3) and by molecular analysis for viral replication/genome. CMR data were analysed blinded with respect to ventricular volumes and ejection fraction as well as T2, LGE and Strain Encoded (SENC)Imaging. A GRASE sequence (15 Echoes separated by 10ms, res: 2x2x10 mm2, 3 short axis slices) was used for localized T2 mapping. Age-matched volunteers (37) served as controls for ROC curve analysis in terms of quantitative T2-mapping. Results were compared by two-sided t-Test; p<0.05 was considered significant. Results

Routine Performance of Endomyocardial Biopsy Decreases the Incidence of Orthotopic Heart Transplant for Myocarditis

In critically ill children presenting with dilated cardiomyopathy (DCM), the presence of myocarditis predicts an improved chance of myocardial recovery. Noninvasive differentiation of myocarditis from other causes of DCM is difficult. However, sensitivity of endomyocardial biopsy has been questioned. We reviewed clinical, echocardiographic, catheterization, and pathology data from all children admitted to the intensive care unit with DCM undergoing orthotopic heart transplantation since the inception of our transplant program in 1987 and all patients with definitively diagnosed myocarditis presenting since 1996. Thirty-six patients with DCM underwent orthotopic heart transplantation. Cellular infiltrate was present in 3 of 36 (8.3%) explanted specimens. Pre-transplant biopsy was performed in 81%. No explanted heart demonstrated infiltrates after a negative biopsy. One biopsy was positive with negative explant histology after transplant 6 months later. No patient with biopsy-proven myocarditis died while listed for transplantation. Eleven additional patients with myocarditis did not undergo transplant. Ten have survived and experienced complete (n = 9) or near complete (n = 1) recovery of myocardial function. One patient died shortly after presentation from fulminant myocarditis. The 10 transplant-free survivors could not be easily distinguished from our transplant cohort by clinical features at presentation. The incidence of cellular infiltrate in explanted hearts was significantly lower than that previously reported. Potentially, our aggressive myocarditis diagnostic protocol was useful in therapeutic stratification as a cohort of myocarditis patients avoided transplant and experienced complete recovery of myocardial function despite being difficult to distinguish clinically from our DCM transplant cohort at presentation.

A 32‐year‐old woman with arthralgias and severe hypotension

A 32‐year‐old woman with arthralgias and severe hypotension

Cardiac sarcoidosis: diagnostic, prognostic, and therapeutic considerations.

Cardiac involvement in patients with sarcoidosis is an important consideration for those who are concerned with this strange disease. Sarcoidosis is not an acute malignant disease but may be noticed at the time of sudden, expected death as fatal myocardial sarcoidosis at autopsy. Even with modern advances in our ability to diagnose heart disease, cardiac sarcoidosis is still often overlooked because of its subclinical disease progression. In view of this, an extensive review of previously published literature and of our own case analyses has been carried out because of the authors' long-term experience with performing Konno's endomyocardial biopsy, which was originally developed in 1962 at the author's institution. However, the sensitivity of endomyocardial biopsy in detecting sarcoid granuloma is low (20-30%), and, instead, various kinds of nongranulomatous pathologies are often seen. During the course of our research it was found that there might exist a racial difference in cardiac sarcoidosis. Cardiac death was much more frequent in Japanese patients. The possibility that heart disease in sarcoidosis is caused by cor pulmonale due to advanced pulmonary fibrosis should be reevaluated because only a limited amount of background data is available. The author's review clarified the fact that cardiac sarcoidosis is caused by myocardial or pericardial involvement, resulting in various kinds of bradyarrhythmias or tachyarrhythmias and/or congestive heart failure. Electrocardiographic (ECG) and Holter monitor readings provide a simple and effective method for early detection of this disease. The incidence of ECG abnormalities in a total of 963 sarcoidosis patients was 22.1%, which was more frequent than that of the sex- and age-matched healthy control subjects (17.9%; p < 0.025). Echocardiography and radionuclide studies also provide useful clinical information. Careful follow-up and early corticosteroid administration followed by small maintenance doses may prevent the progression of the disease and improve prognosis. Owing to the progress in antiarrhythmic drugs and pacemaker implantation, the primary cause of death in cardiac sarcoidosis has changed from sudden death (1976 report) to congestive heart failure (1985 report).