natriuretic-peptide--brain and Sarcoidosis

This study evaluated the prognosis and prognostic factors of patients with cardiac sarcoidosis (CS), an underdiagnosed disease.. Patients from a retrospective multicentre registry, diagnosed with CS between 2001 and 2017 based on the 2016 Japanese Circulation Society or 2014 Heart Rhythm Society criteria, were included. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, and documented fatal ventricular arrhythmia events (FVAE), each constituting exploratory endpoints. Among 512 registered patients, 148 combined events (56 heart failure hospitalizations, 99 documented FVAE, and 49 all-cause deaths) were observed during a median follow-up of 1042 (interquartile range: 518-1917) days. The 10-year estimated event rates for the primary endpoint, all-cause death, heart failure hospitalizations, and FVAE were 48.1, 18.0, 21.1, and 31.9%, respectively. On multivariable Cox regression, a history of ventricular tachycardia (VT) or fibrillation [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.59-4.00, P < 0.001], log-transformed brain natriuretic peptide (BNP) levels (HR 1.28, 95% CI 1.07-1.53, P = 0.008), left ventricular ejection fraction (LVEF) (HR 0.94 per 5% increase, 95% CI 0.88-1.00, P = 0.046), and post-diagnosis radiofrequency ablation for VT (HR 2.65, 95% CI 1.02-6.86, P = 0.045) independently predicted the primary endpoint.. Although mortality is relatively low in CS, adverse events are common, mainly due to FVAE. Patients with low LVEF, with high BNP levels, with VT/fibrillation history, and requiring ablation to treat VT are at high risk.

Topics: Atrial Fibrillation; Heart Failure; Humans; Japan; Natriuretic Peptide, Brain; Registries; Risk Assessment; Sarcoidosis; Stroke Volume; Tachycardia, Ventricular; Ventricular Function, Left

Topics: Aged; Biomarkers; Female; Heart Failure; Humans; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Sarcoidosis; Stroke Volume; Ventricular Function, Left

Topics: Atrioventricular Block; Biopsy; Cardiomyopathies; Diagnosis, Differential; Disease Progression; Echocardiography; Fluorodeoxyglucose F18; Giant Cells; Granuloma; Heart Block; Heart Failure; Heart Transplantation; Humans; Lymph Nodes; Magnetic Resonance Imaging; Male; Middle Aged; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sarcoidosis; Stroke Volume; Troponin I

Cardiac sarcoidosis (CS) is a potentially life-threatening condition. Early detection of CS is therefore important. The aim of this study was to eludicate the usefulness of different investigations in a subgroup of patients with sarcoidosis regarded as having an increased risk for cardiac involvement.. 42 sarcoidosis patients, who had an abnormal resting electrocardiogram (ECG) and/or symptoms indicating possible cardiac involvement (i.e. palpitations, pre-syncope or syncope), were included in the study. They were identified in a consecutive manner among patients followed-up at outpatient clinics for respiratory disorders. Holter monitoring, exercise test, transthoracic echocardiogram (TTE), cardiovascular magnetic resonance (CMR) and analysis of N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in serum were performed. Note, that the role of FDG-PET was not investigated in this study.. In the group with a pathologic ECG 11/25 (44%) were ultimately diagnosed with CS (all with pathologic CMR). However, in the group with only symptoms but a normal ECG just 1/17 got the diagnosis CS (p<0.05). This patient had a pathologic Holter monitoring. The risk for CS was increased if serum NT-pro-BNP was elevated (i.e. NT-pro-BNP>125 ng/L), sensitivity 78% (p<0.05), specificity 67%. By adding a pathologic ECG to an elevated NT-pro-BNP increased specificity to 93% and sensitivity remained at 78%.. Our findings indicate that CMR should be performed at an early stage in sarcoidosis patients with an abnormal resting ECG. Holter monitoring and elevated levels of NT-pro-BNP may enhance the diagnostic accuracy whereas exercise testing and TTE in this study had less impact on the identification of CS.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Diagnostic Techniques, Cardiovascular; Early Diagnosis; Echocardiography; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Reproducibility of Results; Sarcoidosis; Sweden

Our aim is to clarify the factors for early diagnosis of cardiac sarcoidosis (CS) in patients with complete atrioventricular block (CAVB) and its impact on cardiac function after corticosteroid therapy.A total of 15 CS patients with CAVB who underwent corticosteroid therapy were retrospectively analyzed. Patients were divided into two groups according to the time from the first CAVB onset to the diagnosis of CS. Clinical characteristics and outcomes were compared between the early diagnosis group (within 1 year; group E, n = 10) and the late diagnosis group (over 1 year; group L, n = 5).The history of extracardiac sarcoidosis (60 versus 0%, P = 0.0440) and abnormal findings on echocardiography (70 versus 0%, P = 0.0256) at the CAVB onset were significantly more frequent in group E than in group L. The change of left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) levels was significantly better in group E than in group L (0.8 ± 2.8 versus -32.4 ± 3.9%, P < 0.0001; -11.1 ± 16.0 versus 161.8 ± 35.8 pg/mL, P = 0.0013, respectively). After corticosteroid therapy, the LVEF and BNP levels were also significantly better in group E than in group L (53.3 ± 10.7 versus 37.0 ± 9.3%, P = 0.0128; 63.0 ± 46.4 versus 458.8 ± 352.0 pg/mL, P = 0.0027).The diagnosis may be delayed in CS patients with CAVB without history of extracardiac sarcoidosis. Abnormal findings on echocardiography contributed to the early diagnosis of CS. Therefore, the diagnosis of CS may be missed or delayed in patients without them. Time delay from the CAVB onset to the CS diagnosis may exacerbate the cardiac function.

Topics: Adult; Atrioventricular Block; Cardiomyopathies; Diagnostic Errors; Early Diagnosis; Echocardiography; Electrocardiography; Female; Glucocorticoids; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Sarcoidosis; Stroke Volume; Ventricular Function, Left

Sarcoidosis is a systemic granulomatous disease including heart (cardiac sarcoidosis, CS). It has recently been reported that isolated CS, which presenting primarily cardiac symptoms without clinical evidence of sarcoid involvement in other organs. Diagnostic and prognostic biomarkers of CS, especially in isolated CS, have not yet been established.We studied plasma levels of angiotensin-converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R), B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) in consecutive 172 patients with diagnosed sarcoidosis. We compared these markers between non-cardiac sarcoidosis (non-CS, n = 123, 71.5%) and CS patients (n = 49, 28.5%), including non-isolated CS (n = 30, 17.4%) and isolated CS (n = 19, 11.1%). ROC analysis revealed that BNP identified CS with AUC of 0.85 (P < 0.01) in sarcoidosis patients. In addition, ACE and sIL-2R levels were significantly higher in non-isolated CS than in isolated CS (P < 0.05). Furthermore, in the Cox proportional hazard analysis, cTnI, but not ACE, IL2R or BNP, was a predictor of fatal arrhythmia in sarcoidosis patients (HR 2.418, P = 0.003).Higher ACE and sIL2-R are associated with systemic lesions, whereas BNP is a useful marker for detecting cardiac involvement in sarcoidosis patients. cTnI is a predictor of fatal arrhythmia in CS patients. A multiple biomarker approach supports comprehensive management of sarcoidosis.

Topics: Adult; Aged; Arrhythmias, Cardiac; Biomarkers; Echocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Receptors, Interleukin-2; Retrospective Studies; Sarcoidosis; Stroke Volume; Troponin I; Ventricular Function, Left

We investigated whether urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, is a prognosticator of cardiovascular-related death in patients with cardiac sarcoidosis (CS).. In this prospective study, 30 consecutive patients were divided into the active CS (n=20) and non-active CS (n=10) groups, based on abnormal isotope accumulation in the heart on (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) imaging. Nineteen patients in the active CS group underwent corticosteroid therapy. Before corticosteroid therapy initiation, U-8-OHdG, brain natriuretic peptide (BNP), other biomarkers, and indices of cardiac function were measured. Patients were followed-up for a median of 48months. The primary endpoint was the incidence of cardiovascular-related death. During the follow-up period, in the corticosteroid-treated active CS group, 7 of 19 patients experienced cardiovascular-related death. By contrast, in the non-active CS group, 1 of 10 patients died from cardiovascular-related causes. Univariate and multivariate analyses showed that U-8-OHdG and BNP were independent predictors for cardiovascular-related death. The cut-off values for predicting cardiovascular death in corticosteroid-treated patients with active CS were 19.1ng/mg·Cr and 209pg/mL for U-8-OHdG and BNP, respectively. Patients with a U-8-OHdG concentration ≥19.1ng/mg·Cr or a BNP concentration ≥209pg/mL had a significantly higher cardiovascular-related death risk, but U-8-OHdG had better predictive value compared with BNP.. These findings suggested that U-8-OHdG was a powerful predictor of cardiovascular-related death in patients with CS, suggesting that active CS patients with elevated U-8-OHdG levels might be resistant to corticosteroid therapy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adrenal Cortex Hormones; Adult; Aged; Biomarkers; Cardiomyopathies; Deoxyguanosine; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Sarcoidosis; Survival Analysis; Treatment Outcome

Since early intervention using corticosteroids improves prognosis in some patients with cardiac sarcoidosis, early and accurate diagnosis of this clinical condition is important. However, it is still not easy to evaluate the activity of cardiac sarcoidosis in clinical practice. The aim of this study was to determine whether high-sensitive cardiac troponin T (hscTnT) is useful as an additional parameter to standard assessment in patients with cardiac sarcoidosis. Twelve patients who were diagnosed as having cardiac sarcoidosis at our institution were retrospectively studied. Evaluation of patients included clinical examinations, electrocardiography, echocardiography, 67-gallium-citrate (Ga) scintigraphy, 18F-fluoro2-deoxyglucose positron emission tomography (18F-FDG PET) and laboratory data including hs-cTnT, angiotensin-converting enzyme (ACE), lysozyme and B-type natriuretic peptide (BNP). The activity of cardiac sarcoidosis was judged mainly by using 18F-FDG PET. Localized uptake of 18F-FDG, which was considered to be active cardiac sarcoidosis, was seen in 8 patients. Based on the findings of 18F-FDG PET, hs-cTnT was considered to be a reliable parameter: sensitivity and specificity were 87.5% and 75.0%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 87.5% and 75.0%, respectively. On the other hand, these values in lysozyme and BNP markers were not as high as those in hs-cTnT. Although an ACE marker and Ga-67 scintigraphy showed specificity and PPV of 100%, both sensitivity and NPV were less than 50%. Furthermore, hs-cTnT levels decreased after steroid therapy in some patients. Hs-cTnT seems to be a useful marker for evaluating the activity of cardiac sarcoidosis.

Topics: Aged; Biomarkers; Cardiomyopathies; Echocardiography; Electrocardiography; Female; Fluorodeoxyglucose F18; Glucocorticoids; Humans; Male; Middle Aged; Muramidase; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Positron-Emission Tomography; Predictive Value of Tests; Retrospective Studies; Sarcoidosis; Sensitivity and Specificity; Stroke Volume; Troponin T; Ventricular Function, Left

A 65-year-old woman presenting with cardiac sarcoidosis underwent serial measurement of her serum high-sensitivity cardiac troponin I (Hs-cTnI) and N-terminal proB-type natriuretic peptide (NT-proBNP) concentrations. She was treated with 1,000 mg/day methylprednisolone for 2 days, which was subsequently replaced by 30 mg/day prednisolone, and decreased to 20 mg/day at the time of discharge, 2 months later. Her echocardiogram showed improvements in the left ventricular systolic and diastolic function, along with a decrease in the concentration of Hs-cTnI and NT-proBNP. This is the first report suggesting that Hs-cTnI might be a reliable means of assessing the effects of treatment of cardiac sarcoidosis.

Topics: Aged; Cardiomyopathies; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Sarcoidosis; Troponin I

Cardiac involvement and pulmonary hypertension (PH) are life-threatening complications in sarcoidosis.. This study aimed to investigate the utility of plasma NT-proBNP in the assessment of these conditions in sarcoidosis patients.. A prospective, observational study was performed on 150 consecutive Japanese sarcoidosis patients. Doppler echocardiography was performed in all subjects, and those who were successfully evaluated for PH status were included in the analysis. Cardiac sarcoidosis was diagnosed based on Japanese guidelines, and PH was defined as estimated systolic pulmonary artery pressure (sPAP) > or = 35 mmHg. The diagnostic accuracy of NT-proBNP according to the presence of cardiac sarcoidosis and PH was assessed based on receiver-operator characteristic (ROC) curves.. 130 subjects were successfully evaluated for PH status. Of these, 29 met the diagnostic criteria of cardiac sarcoidosis, and 21 were diagnosed with PH. Plasma NT-proBNP levels were significantly higher in patients with cardiac sarcoidosis (p < 0.0001). Stepwise regression analysis showed that presence of cardiac sarcoidosis, decreased ejection fraction and increased sPAP were all independently associated with higher plasma NT-proBNP levels. Plasma NT-proBNP showed good accuracy in identifying patients with cardiac sarcoidosis (area under the ROC curve; AURC = 0.913). However, even when patients with cardiac sarcoidosis were excluded, plasma NT-proBNP levels could not be used reliably to identify patients with PH (AURC = 0.681).. In patients with sarcoidosis, plasma NT-proBNP levels are a useful biomarker to identify cardiac involvement, but not to identify PH.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Cardiomyopathies; Chi-Square Distribution; Echocardiography, Doppler; Female; Humans; Hypertension, Pulmonary; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Artery; Regression Analysis; ROC Curve; Sarcoidosis; Stroke Volume; Up-Regulation

The objective of our study was to use MRI to analyze the topographic localization of myocardial lesions and their relationship to plasma brain natriuretic peptide (BNP) levels and several cardiac function parameters in patients with cardiac sarcoidosis.. Delayed contrast-enhanced MRI was performed in 40 patients with sarcoidosis (11 cardiac, 29 extracardiac cases). Using a 29-segment model of the left ventricle (LV), the extent of myocardial hyperenhancement was visually scored (0 = no hyperenhancement, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 = 76-100% hyperenhancement) and was compared with plasma BNP level and several parameters of cardiac function.. Ten of the 11 patients with cardiac sarcoidosis showed myocardial hyperenhancement, whereas none of the 29 patients without cardiac sarcoidosis did. In patients with cardiac sarcoidosis, hyperenhancement was significantly more extensive in basal short axis slices than in apical short axis slices (p < 0.0005). Myocardial hyperenhancement was significantly more frequent in subepicardial layers than in subendocardial layers. The global extent of myocardial hyperenhancement was significantly correlated with plasma BNP levels and the LV end-diastolic volume index and was negatively correlated with the LV ejection fraction.. In patients with cardiac sarcoidosis, myocardial lesions detected on delayed contrast-enhanced MRI were predominantly localized in the basal and subepicardial myocardium. The extent of myocardial lesions may be related to LV dysfunction and plasma BNP level in patients with cardiac sarcoidosis.

Topics: Cardiomyopathies; Female; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Reproducibility of Results; Sarcoidosis; Sensitivity and Specificity; Ventricular Dysfunction, Left

We sought to examine whether the plasma brain natriuretic peptide (BNP) levels are elevated in the cardiac sarcoidosis patients even with a preserved ejection fraction. The data from the patients with either pulmonary sarcoidosis without any evidence of cardiac involvement (n = 13) or cardiac sarcoidosis (n = 8) with a preserved ejection fraction (>55%) on echocardiography were analyzed. The median plasma BNP levels were significantly higher in the patients with cardiac sarcoidosis than in those with pulmonary sarcoidosis (101.5 +/- 65.1 vs. 15.6 +/- 10.5 pg/ml, p < 0.001), although there was no significant difference in left ventricular ejection fraction between the two populations. The plasma BNP level is thus considered to be a useful non-invasive biomarker for identifying a possible cardiac involvement in the sarcoidosis patients with a preserved ejection fraction.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Sarcoidosis; Sarcoidosis, Pulmonary; Stroke Volume

In patients with cardiac sarcoidosis, ventricular arrhythmias and/or conduction disturbances are frequently observed and sometimes fatal. However, few reports on disease activity and arrhythmic events in cardiac sarcoidosis are available.. The purpose of this study was to investigate the relationship between disease activity and arrhythmic events in cardiac sarcoidosis and the effect of corticosteroid therapy.. The study population consisted of 15 cardiac sarcoidosis patients with new-onset symptomatic arrhythmia, including eight patients admitted once for complete atrioventricular block (CAVB), five patients admitted once for sustained ventricular tachycardia (VT), and two patients admitted twice for two arrhythmic events (one for CAVB and the other for sustained VT). Disease activity was evaluated by gallium-67 citrate (Ga) scintigraphy. All patients with positive Ga uptake were treated with corticosteroids, and arrhythmic events were evaluated by repeat Holter recordings.. Positive uptake of Ga was observed in 8 (80%) of the 10 CAVB events and in 1 (14%) of the 7 sustained VT events (80% vs 14%, P = .02). Corticosteroids abolished myocardial Ga uptake in all nine patients with positive Ga uptake. After corticosteroid therapy was started, AV conduction improved in 5 of 9 CAVB patients (including 8 patients with new-onset CAVB and one patient with history of CAVB). However, ventricular arrhythmias were not improved after corticosteroid therapy.. In cardiac sarcoidosis patients, CAVB develops mainly during the active phase of the disease. Early treatment with corticosteroids might improve AV conduction disturbance. However, sustained VT is not closely linked with disease activity and frequently develops in the advanced stage of disease.

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Atrioventricular Node; Biopsy; Cardiomyopathies; Citrates; Disease Progression; Drug Administration Schedule; Electrocardiography; Electrocardiography, Ambulatory; Endocardium; Female; Gallium; Heart Block; Hemodynamics; Humans; In Vitro Techniques; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Radionuclide Imaging; Sarcoidosis; Tachycardia, Ventricular

It is not known whether cardiac markers and cyclic variations of integrated backscatter can be used to detect cardiac sarcoidosis.. We studied 62 patients with sarcoidosis affecting the lung, eyes, skin, or heart (27 patients with cardiac involvement and 35 patients without). The cyclic variation of integrated backscatter and wall thickening was evaluated in the left ventricular anterior septum and posterior wall. Plasma A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) concentrations and serum cardiac troponin T were also determined.. Plasma natriuretic peptide concentrations were higher in the cardiac involvement group (ANP: 15.5 [interquartile range (IQR) 2.5-34.0] vs. 12.0 [10.0-16.5] pg/ml, P=0.25; BNP: 28.6 [5.9-141] vs. 10.1 [4.8-15.4] pg/ml, P=0.049). However, cardiac troponin T concentration was <0.01 ng/ml in all patients. Receiver-operator characteristic (ROC) analysis showed that both ANP and BNP could identify patients with high-degree atrioventricular block, ventricular tachyarrhythmias, or symptomatic heart failure (the areas under the ROC curve were 0.94 and 0.97, respectively). The cardiac involvement group could be distinguished from the noninvolvement group by combining cutoff values for the magnitude of integrated backscatter cyclic variation (5.5 dB) and wall thickening (30%), albeit only for the posterior wall.. Both ANP and BNP are useful markers for identifying patients with sarcoidosis and cardiac complication(s). Moreover, evaluation of integrated backscatter cyclic variation combined with wall thickening may be of help in detecting cardiac involvement in the posterior wall.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Echocardiography; Female; Follow-Up Studies; Gated Blood-Pool Imaging; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; ROC Curve; Sarcoidosis; Severity of Illness Index; Troponin T