1172The increased serum level of troponin T after immunosuppression therapy reflects sustained myocardial FDG accumulation in cardiac sarcoidosis

Abstract Background and purpose Fluorine-18-flurodeoxyglucose positron emission computed tomography (18FDG-PET CT) is the sole but time-consuming and expensive examination assessing active inflammatory myocardium noninvasively in patients with cardiac sarcoidosis (CS). Though immunosuppression is used to treat CS, little is known about the cardiac biomarkers for determining therapeutic effect to immunosuppression therapy other than 18FDG-PET. Methods From Aug 2016, we prospectively enrolled 50 sarcoidosis patients with positively accumulated of FDG in the heart. The initial dose of prednisolone was 30mg/day, wherefrom the dose was tapered down 5mg/month until 6 months. After 6 months, follow-up 18FDG-PET was performed. Using 18FDG-PET images, we calculated total lesion glycolysis (TLG; SUVmeam x metabolic volume) and compared it to various cardiac markers. Non-responder was defined as TLG reduction rate <70% after immunosuppression therapy. Results In 50 CS patients, 41 patients had serial 18FDG-PET before and 6 months after immunosuppression therapy. 18FDG-PET images were acquired following 7 day's carbohydrate limitation and after at least 18-h fasting (mean free fatty acid level right before 18FDG-PET acquisition was 1.03 mEq/L). The mean age and plasma brain natriuretic peptide (BNP) level were 61.9 years old, 184 pg/mL at baseline, respectively. Because of immunosuppression therapy, TLG was significantly reduced from 195.3 (38.6–339.6) to 1.1 (0.01–7.37), p<0.001). Six (14.6%) patients were classified as NR group and the level of TnT at post therapy was significantly higher in NR group than responder-group (R-group) (0.021 (0.012–0.027) ng/ml vs 0.0095 (0.006–0.013) ng/ml, p=0.039) (Figure), while there were no significant differences between NR-group and R-group in the levels of ACE, sIL-2R, BNP, Dd, EF. Figure 1 Conclusions 1) By immunosuppression therapy using prednisolone for CS, about 85% patients showed significant reduction of increased myocardial FDG accumulation. 2) The sustained high level of serum TnT at post 6 months therapy indicates persistent inflammation of sarcoidosis in the heart, which could be an expedient marker for determining therapeutic effect.

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The efficacy of methotrexate for intolerance to prednisolone therapy in cardiac sarcoidosis

European Heart Journal ◽

10.1093/ehjci/ehaa946.2131 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

R Morimoto ◽

T Kuwayama ◽

H Ooishi ◽

S Kazama ◽

Y Kimura ◽

...

Keyword(s):

Cardiac Sarcoidosis ◽

Alternative Therapy ◽

Reduction Rate ◽

Free Fatty Acid Level ◽

Poor Responder ◽

Public Institution ◽

High Rate ◽

Funding Source ◽

18Fdg Pet ◽

Significant Difference

Abstract Background and purpose Fluorine-18-flurodeoxyglucose positron emission tomography (18FDG-PET) is a useful examination assessing active inflammatory myocardium noninvasively in patients with cardiac sarcoidosis (CS). Though immunosuppression like prednisolone (PSL) and Methotrexate (MTX) as alternative therapy is used to suppress the inflammation, little is known about the rate of response and efficacy of MTX for intolerance to PSL therapy. Methods From Aug 2016, we prospectively enrolled CS with positively accumulated of FDG in the heart. The initial dose of PSL was 30mg/day, wherefrom the dose was tapered down 5mg/month until 6 months. After 6 months, follow-up 18FDG-PET was performed. Using 18FDG-PET images, we calculated total lesion glycolysis (TLG; SUVmeam x metabolic volume) and calculated the reduction rate of TLG. In order to estimate the response rate to PSL therapy, responder group (R-group) was defined as TLG reduction rate ≥70% and poor-responder group (PR-group) was defined as TLG reduction rate <70% after PSL therapy. After prescribed PSL, subjects with PR-group randomized to PSL (maximum dose 30mg daily and tapered down 5mg/month until 6 months) or to MTX (6mg weekly). Results In 64 CS patients, 55 patients had serial 18FDG-PET before and 6 months after PSL therapy. 18FDG-PET images were acquired following 7 day's carbohydrate limitation and after at least 18-h fasting (mean free fatty acid level right before 18FDG-PET acquisition was 1.05 mEq/L). The mean age was 63.4 years old and 42 (76.4%) patients were female. Because of 6 months PSL therapy, even though there were no significant difference in BNP (from 59.9 (26.2–137.6) to 60.4 (18.5–122.0) (P=0.593), LV-Dd (from 50.9 (44.5–59.5) to 49.7 (45.5–61.3) (P=0.666) and LV-EF (from 49.5 (34.4–62.5) to 49.9 (38.0–62.0) (P=0.792) at pre and post therapy, respectively, TLG were detected significant reduction from 216.4 (74.2–411.6) to 0.8 (0.0–8.2), (p<0.001). In response to PSL therapy, 47 (85.5%) CS patients were classified to R-group and 8 (14.5%) were classified to PR-group. Furthermore, when performed block randomization and divide 8 PR-group patients into MTX (n=3) and re-increased PSL (n=5) for more 6 months, MTX group is prone to high rate of TLG reduction than re-increased PSL-group (89.4% vs 59.9%) and one patient belonged to re-increased PSL group showed that the further elevation of TLG level at additional 6-months PSL therapy (349⇒483) (Figure). Conclusions 1) By immunosuppression therapy using PSL for CS, about 86% patients showed significant reduction of myocardial FDG accumulation. 2) When detected intolerance for PSL therapy, MTX might be effective for reduction of inflammation of sarcoidosis in the heart, which might be effective as an alternate therapy in CS. The TLG level after randomization Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Grant-in-aid for scientific research

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Cardiac transthyretin amyloidosis 99mTc-DPD SPECT correlates with strain echocardiography and biomarkers

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05144-8 ◽

2020 ◽

Author(s):

Viktor Löfbacka ◽

Jan Axelsson ◽

Björn Pilebro ◽

Ole B. Suhr ◽

Per Lindqvist ◽

...

Keyword(s):

Single Photon ◽

Troponin T ◽

Photon Emission ◽

Cardiac Biomarkers ◽

Emission Computed Tomography ◽

Transthyretin Amyloidosis ◽

Cardiac Amyloid ◽

Amyloid Load ◽

Photon Emission Computed Tomography ◽

Strain Echocardiography

Abstract Purpose Hereditary transthyretin-amyloid amyloidosis (ATTRv) is an underdiagnosed condition commonly manifesting as congestive heart failure. Recently, scintigraphy utilizing DPD as a tracer was shown to identify ATTRv and wild-type ATTR cardiomyopathy. The aim of this study was to determine the value of quantified scintigraphy utilizing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) single-photon emission computed tomography (SPECT)/CT, and to correlate its uptake with well-established cardiac functional parameters. Methods Forty-eight patients with genetically verified ATTRv type-A fibril composition, positive 99mTc-DPD SPECT/CT, were retrospectively analyzed. Manual mapping of volumes of interest (VOIs) on DPD SPECT/CT examinations was used to quantify heart uptake. DPD mean and maximum uptake together with a calculated DPD-based amyloid burden (DPDload) was correlated with echocardiographic strain values and cardiac biomarkers. Results Statistically significant correlations were seen in VOIs between DPD uptakes and the corresponding echocardiographic strain values. Furthermore, DPDload had a strong correlation with echocardiographic strain parameters and also correlated with biomarkers troponin T and logarithmic NT-ProBNP. Conclusions In patients with ATTRv cardiomyopathy, DPD SPECT/CT measures the amyloid distribution and provides information on cardiac amyloid load. DPD amyloid load correlates with functional cardiac parameters.

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Cardiac biomarkers for cardiovascular risk prediction among women and men from the general population

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.240 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

F Zhu ◽

B Arshi ◽

E Aribas ◽

MA Ikram ◽

MK Ikram ◽

...

Keyword(s):

Risk Factors ◽

Coronary Heart Disease ◽

Heart Disease ◽

Cardiovascular Risk ◽

Predictive Value ◽

Troponin T ◽

Cardiac Biomarkers ◽

C Statistic ◽

Cardiovascular Risk Prediction ◽

Traditional Risk Factors

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); Purpose To evaluate the sex-specific predictive value of two cardiac biomarkers; N-terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT), alongside traditional cardiovascular risk factors, for 10-year cardiovascular risk prediction in general population. Methods A total of 5430 participants (mean age 68.1 years; 59.9% women) free of cardiovascular disease (CVD), with blood sample measurements between 1997 and 2001 were included. We developed a ‘base’ model using cardiovascular risk factors used in the Pooled Cohort Equation (includes age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and then extended the ‘base’ model with NT-proBNP or hs-cTnT. These models were developed for coronary heart disease (CHD), stroke, and heart failure (HF) and also for composite CVD outcomes. To evaluate biomarkers’ added predictive value, c-statistic, and net reclassification improvement index (NRI) for events and non-events were calculated. NRI was calculated using cutoffs of 5%, 7.5% and 20% to categorize participants as low, borderline, intermediate, or high risk. Results Adding NT-proBNP to the ‘base’ model significantly improved c-statistic for all outcomes (increases ranged between 0.012-0.047), with the largest improvement in HF [0.026 (95% CI, 0.013, 0.040) for women and 0.047 (95% CI, 0.026, 0.069) for men]. Adding hs-TnT to ‘base’ model increased the c-statistic for CHD in women by 0.040 (95% CI, 0.013, 0.067) and for HF in men by 0.032 (95% CI, 0.005, 0.059). Improvments in reclassification by both biomarkers were mostly limited to modest improvemetns in reclassification of non-events [largest non-event NRI for global CVD in women (NT-proBNP: 11.8%; hs-cTnT: 10.5%) and for HF in men (NT-proBNP: 9.6%; hs-cTnT: 8.4%)]. Conclusion NT-proBNP improved model performance for prediction of all cardiovascular outcomes, in particular for HF, beyond traditional risk factors for both women and men. Hs-cTnT showed modest added predictive value beyond traditional risk factors for CHD among women and for HF among men. Imropovements in reclassification by both biomarkers were modest and not clinically relevant. Improvements of 10-year risk predictions Events Adding NT-proBNP Adding troponin T Delta c-statistic* Event NRI, % Non-event NRI, % Delta c-statistic* Event NRI, % Non-event NRI, % WomenASCVD Global CVD 0.012 (0.004, 0.020) 0.018 (0.010, 0.026) -1.7 (-5.0, 1.5)-0.8 (-3.8, 2.2) 5.4 (3.5, 7.2)11.8 (9.6, 14.1) 0.028 (0.009, 0.048)0.025 (0.009, 0.040) -0.4 (-7.1, 6.2)2.9 (-2.4, 8.3) 6.9 (3.9, 9.9)10.5 (7.3, 13.8) MenASCVD Global CVD 0.016 (0.005, 0.027)0.023 (0.012, 0.033) 0.7 (-2.3, 3.7)-0.3 (-3.0, 2.4) 5.2 (3.2, 7.2)7.2 (4.9, 9.4) 0.007 (-0.002, 0.016)0.011 (0.000, 0.021) -1.1 (-5.0, 2.7)-1.6 (-6.0, 2.8) 4.0 (1.2, 6.9)6.4 (3.1, 9.7) ASCVD comprises coronary heart disease and stroke; Global CVD comprises coronary heart disease, stroke and heart failure.

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Cardiac Biomarkers Following Marathon Running: Is Running Time a Factor for Biomarker Change?

International Journal of Sports Physiology and Performance ◽

10.1123/ijspp.2020-0352 ◽

2020 ◽

pp. 1-8

Author(s):

Natthapon Traiperm ◽

Rungchai Chaunchaiyakul ◽

Martin Burtscher ◽

Hannes Gatterer

Keyword(s):

Cardiac Troponin ◽

Troponin T ◽

Transient Increase ◽

Cardiac Biomarkers ◽

Quadratic Model ◽

Curvilinear Relationship ◽

Marathon Running ◽

Cardiac Troponin T ◽

Running Time ◽

Marathon Race

Purpose: Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T levels show a transient increase after marathon running. The aim of this study was to investigate whether running duration influences the patterns of changes in cardiac biomarkers. Methods: Twenty participants with fast and slow finishing times were included in the study. Blood samples were taken before the marathon race, immediately after, and 24 hours after the race. Samples were analyzed for NT-proBNP and cardiac troponin T concentration. Furthermore, a complete blood cell count was performed. Results: After the marathon race, the fast and slow runners showed similar changes of NT-proBNP and cardiac troponin T (ie, a transient increase). Curve estimation regression analysis showed a curvilinear relationship (quadratic model) between running times and NT-proBNP increments immediately after the race, with less of an increase in the very fast and the very slow runners (r2 = .359, P = .023). NT-proBNP increments immediately after the race were correlated to the decline 24 hours after the marathon (r = −.612, P = .004). Conclusions: This study indicates that NT-proBNP release immediately after marathon running varies in a curvilinear fashion with running time. It is speculated that low NT-proBNP release is associated with training adaptation in most elite runners and the relatively low cardiac stress in the slowest (but experienced) runners. The combination of less adaptation and relatively large cardiac wall and metabolic stress may explain the highest NT-proBNP values in runners with average running times. In addition, NT-proBNP decrements 24 hours after the race depend primarily on the values reached after the marathon and not on running time.

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Hereditary transthyretin amyloidosis: predictors of conduction disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.2111 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A.F Dias De Frias ◽

P Rodrigues ◽

M Trepa ◽

M Fontes-Oliveira ◽

R Costa ◽

...

Keyword(s):

Troponin T ◽

Pacemaker Implantation ◽

Outcome Data ◽

Left Ventricular ◽

Cardiac Biomarkers ◽

P Value ◽

Neurologic Manifestations ◽

Ventricular Pacing ◽

Transthyretin Amyloidosis ◽

Formal Indication

Abstract Introduction Pacemakers are frequently needed due to a high prevalence of conduction disease in mutated ATTR amyloidosis (mATTR). We aimed to identify the variables associated with the need of pacemaker implantation in this population. Methods We retrospectively studied 255 patients with suspicion of heart involvement of mATTR observed at our cardiology clinic during the last year. Clinical and outcome data were retrieved by chart review. We have defined the need for pacemaker implantation as: 1) the formal guidelines indications or 2) Ventricular pacing >10% in patients who had prophylactic pacemaker implantation prior to liver transplantation (LT). This way, we have defined 3 different groups: group 1: patients with no evidence of conduction disease; group 2: patients with conduction disease, but no formal indication for pacemaker implantation; and group 3: patients with formal indication for pacemaker implantation or ventricular pacing >10% in patients who had prophylactic pacemaker implantation prior to hepatic transplantation. Results We included 255 patients (50±14 years, 53% male, 52.5% treated with tafamidis and 27% had prior LT, and 10% with atrial fibrillation), 43.3% with no evidence of conduction disease, 32.3% with conduction disease, but no formal indication for pacemaker implantation and 24.4% with formal indication for pacemaker implantation. Patients with formal indication for pacemaker implantation were older, with longer duration of neurologic manifestations, with higher concentration of both Troponin T and NT-proBNP and with higher number of organs affected. In multivariate analysis, longer duration of neurologic manifestations (OR 1.090 – 95% IC: 1.036–1.145, p-value 0.001), Left ventricular (LV) maximal wall thickness (OR 1.230 – 95% CI: 1.070–1.414, p-value 0.004), neurologic staging (OR 3.420 – 95% CI: 1.443–8.104, p-value 0.005) and higher number of organs affected (OR 1.719 – 95% CI: 1.218–2.424, p-value 0.002) all showed to be independent predictors of the need for pacemaker implantation, in contrast to LV ejection fraction and serum concentration of Troponin T and NT-proBNP. We've also found a statistical significant association between conduction disease and ophthalmic manifestations. Conclusions Our findings suggest that the need for pacemaker implantation in patients with mATTR is closer linked to the duration, severity and affected number of organs than to cardiac biomarkers or echocardiographic findings. Funding Acknowledgement Type of funding source: None

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Abstract P048: Segment-Specific Pulse Wave Velocity and Subclinical Cardiac Overload and Damage in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽

10.1161/circ.137.suppl_1.p048 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Shuiqing Liu ◽

Esther Kim ◽

Aozhou Wu ◽

Michelle L Meyer ◽

Susan Cheng ◽

...

Keyword(s):

Older Adults ◽

Arterial Stiffness ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Cardiac Disease ◽

Pulse Wave ◽

Troponin T ◽

High Sensitivity ◽

Clinical History ◽

Cardiac Biomarkers

Background: Pulse wave velocity (PWV) independently predicts cardiovascular disease. However, few studies simultaneously explored the associations of segment-specific PWV measures with markers of both cardiac overload (natriuretic peptide [NT-proBNP]) and damage (high-sensitivity cardiac troponin T [hs-cTnT]) among adults without cardiac disease. Methods: We examined 2,845 whites and blacks (67-90 years) without clinical history of cardiac disease during ARIC visit 5 (2011-13). The association of PWV quartiles (cf [carotid-femoral], hc [heart-carotid], hf [heart-femoral], ha [heart-ankle], ba [brachial-ankle], and fa [femoral-ankle]) with log-transformed NT-proBNP and hs-cTnT was evaluated using linear and logistic regression models to adjust for potential confounders. Results: Most PWV measures demonstrated J- or U-shaped associations with NTpro-BNP and hs-cTnT [Figure]. The highest vs. the second lowest quartile of central PWV measures (cfPWV, hfPWV, and hcPWV) was associated with higher levels of NT-proBNP independently of demographic characteristics. The associations were weaker for hs-cTnT. These associations were attenuated after further adjustment, but hcPWV and NT-proBNP remained borderline significant (p=0.069). haPWV, baPWV, and faPWV including peripheral elements had less evident positive associations after adjusting for traditional risk. Conclusion: The positive associations between PWV and cardiac biomarkers were stronger for central vs. peripheral arterial stiffness and for NT-proBNP vs. hs-cTnT among older adults without prevalent cardiac disease. Our findings indicate the relative importance of central arterial stiffness behind subclinical cardiac overload.

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Abstract 2832: Which Cardiac Marker is Most Useful to Predict Final Infarct Size and Cardiac Function Following Primary Percutaneous Coronary Intervention For Acute Myocardial Infarction?

Circulation ◽

10.1161/circ.116.suppl_16.ii_630-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Stanley Chia ◽

O. Christopher Raffel ◽

Faisal Merchant ◽

Frans J Wackers ◽

Fred Senatore ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Infarct Size ◽

Troponin I ◽

Troponin T ◽

Coronary Intervention ◽

Left Ventricular ◽

Cardiac Biomarkers ◽

Primary Pci ◽

Percutaneous Coronary

Background: Assessment of cardiac biomarker release has been traditionally used to estimate the size of myocardial damage after acute myocardial infarction (AMI). However, the significance of cardiac biomarkers in the setting of primary percutaneous coronary intervention (PCI) has not been systematically studied in a large patient cohort. We evaluated the usefulness of serial and single time-point measures of various cardiac biomarkers (creatine kinase (CK), CK-MB, troponin T and I) in predicting infarct size and left ventricular ejection fraction (LVEF) after primary PCI. Methods: EVOLVE (Evaluation of MCC-135 for Left Ventricular Salvage in AMI) was a randomized double-blind, placebo-controlled trial comparing the efficacy of intracellular calcium modulator as an adjunct to primary PCI in patients with first large AMI. Levels of cardiac biomarkers (CK, CK-MB mass, troponin T and I) were determined in 375 patients at baseline before PCI and 2, 4, 12, 24, 48 and 72 hours thereafter. Single photon emission computed tomography imaging was performed to measure infarct size and LVEF on day 5. Results: Area under curve and peak concentrations of all cardiac markers: CK, CK-MB mass, troponin T and troponin I were significantly correlated with myocardial infarct size and LVEF determined on day 5 (Spearman correlation, all P< 0.001; Table ). Troponin I, however provided the best predictor and a single measure at 72 hr was a strong indicator of both infarct size and LVEF. Using receiver operator characteristics curve, troponin I cutoff value of >55 pg/mL at 72 hr has 90% sensitivity and 70% specificity for detection of large infarct size≥10% ( c =0.88; P< 0.001). Conclusions: Plasma levels of CK, CK-MB, troponin T and troponin I remain useful predictors of infarct size and cardiac function in the era of primary PCI for AMI. A single measurement of circulating troponin I at 72 hours can provide an effective and convenient indicator of infarct size and LVEF in clinical practice. Correlation of cardiac biomarkers with Day 5 SPECT determined infarct size and LVEF

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P1869A novel risk score to predict mortality in patients with atrial fibrillation: the BLACCK (AF) death risk score

European Heart Journal ◽

10.1093/eurheartj/ehz748.0619 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A Samaras ◽

A Kartas ◽

G Fotos ◽

D Vasdeki ◽

G Dividis ◽

...

Keyword(s):

Atrial Fibrillation ◽

Risk Score ◽

Troponin T ◽

Cox Model ◽

Cardiac Biomarkers ◽

Accurate Estimation ◽

Discriminative Ability ◽

Death Risk ◽

Risk Of Death ◽

All Cause Mortality

Abstract Background Prior risk stratification schemes for atrial fibrillation (AF) have extensively focused on stroke as the principal outcome. However, an accurate estimation of the risk of death in patients with AF has received disproportional attention. Purpose The aim of this study was to develop and validate a risk score for predicting mortality in patients with AF who underwent a hospitalization for cardiac reasons. Methods The new risk score was developed and internally validated in 887 patients with AF, who were followed up for a median of 2 years. The outcome measure was all-cause mortality. Biomarker samples, echocardiographic data and renal function values were obtained at the date closest to hospital discharge. A Cox-model that determined the variables that significantly contributed to the prediction of all-cause mortality, was adapted to a risk points system through weighting of the model coefficients. The model was internally validated by bootstrapping, assessing both discrimination and calibration. Results 311 all-cause deaths were reported during 1755 person-years of follow-up (incidence rate 17.7 events per 100 person-years). The most important predictors of death were N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin-T (hs-TnT), left atrial area indexed to body surface area (LAAi), prior cardiac arrest, kidney impairment, congestive heart failure and age, and were included in the BLACCK (AF) death risk score. The score was well-calibrated (observed probabilities adjusted to predicted probabilities) and showed good discriminative ability [c-index 0.87 (95% CI 0.85–0.90)]. The internal validation of the score reported minimal over-fitting (optimism-corrected c-index of 0.85). The 1, 2 and 3-year risk of death derived by the score's total points may be calculated immediately through the nomogram (Figure 1). BLACCK (AF) risk score nomogram Conclusions We developed a simple, well-calibrated and internally validated novel risk score for predicting 1, 2 and 3-year risk of death in patients with AF after a hospitalization for cardiac reasons. The BLACCK (AF) death risk score included both cardiac biomarkers and clinical information, performed well and may assist physicians in decision-making when treating patients with AF.

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