High-sensitivity cardiac troponin T and NT-proBNP for ruling-in and ruling-out of cardiac amyloidosis

Abstract Background Cardiac amyloidosis (CA) is caused by the extracellular deposition of misfolded proteins into insoluble amyloid fibrils, the 2 most common forms being transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis. Chronic elevation of cardiac troponins and natriuretic peptides is common in CA and predicts worse outcome. The diagnostic yield of biomarkers of cardiac damage for CA has been less investigated. Purpose We aimed to evaluate the ruling-in/out values for the diagnosis of CA of high-sensitivity cardiac troponin T (hs-cTnT) and of N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP). Methods We studied 275 consecutive patients referred to two tertiary Centers in Italy (n=184) and France (n=91) with the clinical suspicion of CA due to the presence of a plasma cell dyscrasia or an unexplained left ventricular (pseudo)hypertrophy. CA was confirmed by the combination of suggestive features on imaging techniques (echocardiography, cardiac magnetic resonance, diphosphonate scintigraphy) and biopsy examination. All patients underwent a full baseline characterization including hs-cTnT and NT-proBNP. Biomarkers values corresponding to a negative likelihood ratio <0.1 or a positive likelihood ratio >10 were respectively chosen as rule-out and rule-in cut-offs for CA. Results CA was confirmed in 161 (59%) patients, who had either AL amyloidosis (n=96, 60%) or ATTR amyloidosis (n=65, 40%). At time of evaluation, 97 (35%) patients (34 CA vs. 63 controls, p=0.112) were hospitalized for decompensated heart failure. Patients with CA showed higher hs-cTnT (65 ng/L [44–122] vs. 31 [18–42], p<0.001) and NT-proBNP (4260 ng/L [2006–8911] vs. 1199 [468–3357], p<0.001) than those without CA. The area under the curve (AUC) values for hs-cTnT and NT-proBNP were 0.832 and 0.744 respectively (p=0.002 for the difference). The combination of the two biomarkers (AUC=0.836) improved discrimination over NT-proBNP (p=0.004), but not over hs-cTnT (p=0.423). A hs-cTnT value <15 ng/L (sensitivity=100%, negative predictive value=100%, true negatives=13, false negatives=0) and a NT-proBNP <550 ng/L (sensitivity=98%, negative predictive value=89%, true negatives=33, false negatives=4) were selected as rule-out cut-offs. A hs-cTnT level ≥80 ng/L (specificity=96%, positive predictive value=93%, true positives=71, false positives=5) was optimal for ruling in amyloidosis, while no rule-in cut-off could be selected for NT-proBNP. hs-cTnT values of either ≥80 or <15 ng/dL could effectively rule-in/out 89 (32%) patients. Conclusions Plasma hs-cTnT and NT-proBNP have diagnostic value in patients with suspected CA. Stand-alone hs-cTnT levels <15 or ≥80 ng/L may help to exclude or confirm the diagnosis of CA in up to one third of patients undergoing a diagnostic screening for the disease. Figure 1 Funding Acknowledgement Type of funding source: None

Download Full-text

P2729NT-proBNP and high-sensitivity cardiac troponin T to diagnose cardiac amyloidosis

European Heart Journal ◽

10.1093/eurheartj/ehz748.1046 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

V Castiglione ◽

A Aimo ◽

A Barison ◽

D Genovesi ◽

C Prontera ◽

...

Keyword(s):

Cardiac Troponin ◽

Cardiac Amyloidosis ◽

Troponin T ◽

High Sensitivity ◽

Left Ventricular ◽

Clinical Suspicion ◽

Al Amyloidosis ◽

Cardiac Troponin T ◽

Lv Mass ◽

The Difference

Abstract Background Cardiac amyloidosis (CA) is characterized by the accumulation of misfolded proteins into amyloid fibrils, leading to cardiomyocyte toxicity, extracellular volume expansion and ventricular pseudohypertrophy. As a consequence of such processes, natriuretic peptides and cardiac troponins are chronically elevated in CA and hold significant prognostic value. The diagnostic yield of these biomarkers for CA has never been explored so far. Methods Plasma levels of N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 230 patients referred to a tertiary centre with the clinical suspicion of cardiac amyloidosis. The final diagnosis was established according to current protocols, which include clinical, electrocardiographic, biohumoral, instrumental (echocardiography, cardiac magnetic resonance, diphosphonate scintigraphy), and biopsy examinations. Results Patients were aged 79 (interquartile interval 73–83) years and were predominantly males (n=147, 64%). Mean left ventricular (LV) ejection fraction was 55% (48–62%), and mean LV mass indexed was 150 (120–178) g/m2. CA was confirmed in 86 patients (37%), who had either light chain (AL) amyloidosis (n=25, 29%) or transthyretin (ATTR) amyloidosis (n=61, 71%). Alternative diagnoses were hypertensive cardiopathy (n=69, 48%), valvular disease (n=27, 19%), hypertrophic cardiomyopathy (n=18, 13%), or left ventricular hypertrophy with unknown or multifactorial mechanisms. Patients with CA showed higher NT-proBNP (5507 ng/L [2348–10326] vs. 1332 [392–3752], p<0.001) and hs-cTnT (65 ng/L [48–114] vs. 35 [21–52], p<0.001) than those without CA. The area under the curve (AUC) values for NT-proBNP and hs-cTnT were 0.712 and 0.775 respectively (p=0.062 for the difference). The combination of the two biomarkers improved discrimination over NT-proBNP alone (p=0.011), but not over hs-cTnT (p=0.470) (Figure). A NT-proBNP level <600 ng/L or a hs-cTnT level <17 ng/L were optimal for ruling out amyloidosis, with a negative predictive value of 95% in both cases. Patients with AL amyloidosis had higher NT-proBNP and hs-cTnT than those with ATTR (10809 ng/L [6292–17483] vs. 3084 [1841–7624], p=0.014; 130 ng/L [64–211] vs. 61 [48–95], p=0.006). The difference was even more prominent when biomarker levels were normalized for LV mass (NT-proBNP/LV mass, 33.9 ng/L/g [20.4–53.8] vs. 10.0 [5.8–23.5], p=0.002; hs-cTnT/LV mass, 0.48 ng/L/g [0.25–0.71] vs. 0.19 [0.14–0.26], p=0.001). NT-proBNP and hs-cTnT could effectively discriminate patients with AL amyloidosis among subjects with clinical suspicion of CA (AUC values of 0.787 and 0.805 respectively) (Figure). Figure 1 Conclusions Plasma NT-proBNP and hs-cTnT have diagnostic value in patients with suspected CA. In the subgroup with CA, both biomarkers are higher in patients with AL amyloidosis even when normalizing for LV mass, possibly because of a greater cardiotoxic effect of light-chain fibrils.

Download Full-text

3298Prehospital assessment of the one-hour rule-in/rule-out algorithm using a high-sensitivity cardiac troponin t assay in a low-prevalence population for acute coronary syndrome (OUT-ACS)

European Heart Journal ◽

10.1093/eurheartj/ehz745.0062 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T R Johannessen ◽

D Atar ◽

S Halvorsen ◽

A C Larstorp ◽

I Mdala ◽

...

Keyword(s):

Primary Care ◽

Chest Pain ◽

Predictive Value ◽

Cardiac Troponin ◽

Troponin T ◽

High Sensitivity ◽

Cardiac Troponin T ◽

Emergency Setting ◽

Coronary Syndrome ◽

Rule Out

Abstract Background The majority of patients with chest pain in Norway initially present to the primary health care system, which serves to triage them to the specialist health care services including hospitals. In some emergency primary care institutions, patients who are not hospitalised directly undergo further diagnostic testing to rule out acute myocardial infarction (AMI). Purpose Several studies have shown the advantage of using high-sensitivity assays for fast interpretation of cardiac troponins. The majority of these studies included patient populations from hospital emergency departments. In contrast, we aimed to investigate whether the 1-hour algorithm for high-sensitivity cardiac troponin T (hs-cTnT) is safe and useful for implementation in a primary care emergency setting where the patients have a much lower pre-test probability for an acute coronary syndrome. Methods In this prospective cohort study, we included 1672 patients with acute non-specific chest pain from November 2016 to October 2018 at a primary care emergency outpatient clinic in Norway. Serial hs-cTnT samples were analysed after 0, 1 and 4 hours on the Cobas 8000 e602 analyzer. We divided the results into one of three groups (rule-out, rule-in, or further observation), according to the 0/1-hour algorithm for hs-cTn from the current ESC guidelines on non-ST-elevation myocardial infarction. In the rule-out group, the 0/1-hour results were compared to the standard 4-hour hs-cTnT. Final hospital diagnoses were collected as a gold standard for the patients in the rule-in group. Results A total of 44 (2.6%) of 1672 patients were diagnosed with AMI. By applying the algorithm, 1274 (76.2%) patients were assigned to the rule-out group. One of the rule-out patients had a significant increase in hs-cTnT in the 4-hour sample. This results in a sensitivity for AMI of 97.7% (95% confidence interval [CI] 88.0–99.9) and negative predictive value of 99.9% (95% CI 99.6–100.0). There were 50 (3.0%) patients in the rule-in group, amongst whom 35 had a verified AMI. This gives a specificity for AMI of 99.1% (95% CI 98.5–99.5) and a positive predictive value at 70.0% (95% CI 55.4–82.1). Among the 348 (20.8%) patients assigned to further observation, eight patients had an AMI. The 15 rule-in patients who did not have an AMI, had other acute illnesses that required further diagnostic work-up at the hospital. Conclusions With a negative predictive value at 99.9%, the 1-hour algorithm for hs-cTnT seems safe and applicable for a faster assessment of patients with non-specific chest pain in a primary care emergency setting. Prehospital implementation of this algorithm may reduce the need for hospitalisation of these patients and hence may probably lower the costs. ClinicalTrial.gov identifier: NCT02983123 Acknowledgement/Funding Norwegian Research Fund for General Practice, The Norwegian Physicians' Association Fund for Quality Improvement and Patient Safety

Download Full-text

Outcomes of patients admitted with high-sensitive cardiac troponin T levels meeting the new rule out criteria for myocardial infarction

European Heart Journal ◽

10.1093/eurheartj/ehab724.1391 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

B C Cohen ◽

S C Cohen ◽

R T Tor ◽

S F Fuchs ◽

R K Kornowski ◽

...

Keyword(s):

Myocardial Infarction ◽

Negative Predictive Value ◽

Predictive Value ◽

Cardiac Troponin ◽

Hospital Admissions ◽

Troponin T ◽

Cardiac Troponin T ◽

Exercise Tests ◽

High Negative Predictive Value ◽

Rule Out

Abstract Background The 2020 ESC non-ST-elevation (NSTE) acute coronary syndromes (ACS) guidelines have adopted the paradigm that patients presenting with suspected NSTE-ACS and high-sensitive cardiac troponin T (hs-cTnT) values <99th percentile in a single test or small increment within 1/2 hours have a high negative predictive value for myocardial infarction (MI). Their management remains controversial. Purpose We examined the clinical outcomes and resource utilization of suspected NSTE-ACS patients who presented with hs-cTnT values meeting the early rule out criteria, but were nevertheless admitted. Methods Our single center retrospective cohort study included 4,263 visits for suspected NSTE-ACS triaged in the Emergency Room (ER), had hs-cTnT values that met the early rule-out criteria, and were admitted (Figure 1). Routine quality control and dedicated tests proved a coefficient of variance of <10% for hs-cTnT values <99th percentile (14 ng/L). Results There were no deaths in-hospital and at 30 days. Discharge diagnosis of MI was documented in 10 patients (∼0.2%). Median ER stay and hospital stay were 6 hours and 3 days, respectively. In hospital evaluation included 844 gated cardiac CT angiography (CTA), 580 SPECT heart scans, 101 ECG-exercise tests, and 178 coronary angiography, of which 70 (∼1.6% of cohort) culminated in percutaneous/surgical intervention. Conclusion Our findings highlight the high negative predictive value for MI applying the early rule out algorithm and supports a policy of ER discharge for further evaluation, sparing unnecessary and resource-consuming hospital admissions. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

Download Full-text

Evaluation of the 0 h/1 h high-sensitivity cardiac troponin T algorithm in diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI) in Han population

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0367 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Chen Dongxu ◽

Zhou Yannan ◽

Yang Yilin ◽

Yao Chenling ◽

Gu Guorong ◽

...

Keyword(s):

Cardiac Troponin ◽

Troponin T ◽

High Sensitivity ◽

Cardiac Troponin T ◽

Chinese Han ◽

Han Population ◽

St Segment Elevation ◽

Segment Elevation Myocardial Infarction ◽

St Segment ◽

Rule Out

Abstract Objectives A rapid 0 h/1 h algorithm using high-sensitivity cardiac troponin T (hs-cTnT) for rule-out and rule-in of non-ST-segment elevation myocardial infarction (NSTEMI) is recommended by the European Society of Cardiology. We aim to prospectively evaluate the diagnostic performance of the algorithm in Chinese Han patients with suspected NSTEMI. Methods In this prospective diagnostic cohort study, 577 patients presenting to the emergency department with suspected NSTEMI and recent (<12 h) onset of symptoms were enrolled. The levels of serum hs-cTnT were measured on admission, 1 h later and 4–14 h later. All patients underwent the initial clinical assessment and were triaged into three groups (rule-out, rule-in and observe) according to the 0 h/1 h algorithm. The major cardiovascular events (MACE) were evaluated at the 7-day and 30-day follow-ups. Results Among 577 enrolled patients, NSTEMI was the final diagnosis for 106 (18.4%) patients. Based on the hs-cTnT 0 h/1 h algorithm, 148 patients (25.6%) were classified as rule-out, 278 patients (48.2%) as rule-in and 151 patients (26.2%) were assigned to the observe group. The rule-out approach resulted in a sensitivity of 100% and negative predictive value of 100%. The rule-in approach resulted in a specificity of 62.9% [95% CI (58.5–67.2%)] and positive predictive value of 37.1% [95%CI (31.3–42.8%)]. No MACE was observed in the rule-out group within 30-day follow-up. Conclusions The hs-cTnT 0 h/1 h algorithm is a safe tool for early rule-out of NSTEMI, while probably not an effective strategy for accurate rule-in of NSTEMI in Chinese Han population.

Download Full-text

Abstract 15293: Increased Level of Cardiac Troponin T is a Clue of Cardiac Amyloidosis in Patients With Myocardial Hypertrophy

Circulation ◽

10.1161/circ.130.suppl_2.15293 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Seiji Takashio ◽

Megumi Yamamuro ◽

Toshihisa Anzai ◽

Hisao Ogawa

Keyword(s):

Endomyocardial Biopsy ◽

Cardiac Troponin ◽

Cardiac Amyloidosis ◽

Myocardial Hypertrophy ◽

Troponin T ◽

Area Under The Curve ◽

Al Amyloidosis ◽

Cardiac Troponin T ◽

Characteristic Analysis ◽

Precise Diagnosis

Background: Cardiac amyloidosis (CA) is an important differential diagnosis in patients with myocardial hypertrophy. The precise diagnosis of CA requires endomyocardial biopsy to demonstrate amyloid deposition, but this procedure is relatively invasive and cannot be performed routinely. Therefore, it is important to increase pretest probability of CA in patients with myocardial hypertrophy by noninvasive modalities. Because it is well known that cardiac troponin level is elevated in patients with CA, we hypothesized that increased level of cardiac troponin T contributes to diagnosis of CA in patients with myocardial hypertrophy using high sensitive assay (hs-TnT). Methods and Results: Among nonischemic patients with myocardial hypertrophy (interventricular septal thickness≧ 12 mm), hs-TnT level was measured in 28 CA patients (senile systemic amyloidosis: 13, AL amyloidosis: 14, familial amyloidosis: 1) proven amyloidosis pathologically and 29 non-CA patients proven by endomyocardial biopsy. It was significantly higher in CA patients than non-CA patients (0.075 [0.047-0.116] ng/ml vs. 0.013 [0.009-0.019] ng/ml; p<0.001: Figure). Receiver operating characteristic analysis selected 0.030 ng/ml as the best cutoff value of diagnosis for CA, with a sensitivity and specificity of 96% and 93%, respectively and area under the curve of 0.98 (95% confidence interval 0.94 to 1.00, p<0.001). Conclusions: Increased level of hs-TnT (>0.030 ng/ml) is highly suggestive of CA in patients with myocardial hypertrophy. These patients need additional diagnostic approach for CA.

Download Full-text