Biomarkers and Personalized Medicine in Cardiovascular Disease Symposium

Evaluating Pediatric High-Sensitivity Troponin Thresholds and Testing Trends: A Multicenter Retrospective Cohort Study

Alexander J F Thurston^1*, Eirik Å. Røys^2,3*, Ragnhild Røysland^4,5, Øyvind Skadberg⁶, Dorien M Kimenai⁷, Nicholas L Mills^7,8, Kristin M Aakre^2,3,9

¹ Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK² Department of clinical science, University of Bergen, Bergen, Norway³ Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway⁴ Multidisciplinary Laboratory Medicine and Medical Biochemistry, Division of Diagnostics and Technology, Akershus University Hospital, Lørenskog, Norway ⁵ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway⁶ Laboratory of Medical Biochemistry, Stavanger University Hospital, Stavanger, Norway⁷ BHF Centre of Research Excellence, University of Edinburgh, Edinburgh, UK⁸ Usher Institute, University of Edinburgh, Edinburgh, UK⁹ Department of Heart Disease, Haukeland University Hospital, Bergen, Norway

^*Both authors contributed equally to this paper

Background: There are no clear clinical recommendations regarding use of high-sensitivity cardiac troponin (hs-cTn) measurements in children and young adults. Upper reference limits (URL) are known to be age dependent in pediatric patients but there is an ongoing debate if the 97.5 or 99^th percentile should be recommended as URL. This retrospective cohort study, conducted across four hospitals in Norway and the United Kingdom from 2013 to 2023, aimed to; 1) analyze trends in hs-cTn testing, 2) compare pediatric- and adult-derived cutoffs including the 97.5^th and 99^th percentile URL and 3) assess associations with clinical outcomes such as myocarditis and pericarditis.

Methods: We identified 9,669 pediatric patients (≤18 years) who underwent hs-cTn testing, retaining only the first measurement per individual. Troponin assays included high-sensitivity cardiac troponin T (Roche) and I (Abbott), with values below detection limits assigned half the reporting threshold. The proportion of patients with elevated troponin levels was evaluated using the local URL, adult sex-specific 99^th percentiles, and pediatric-derived URLs (99^th and 97.5^th percentiles). Trends in hs-cTn test volumes were normalized towards concurrent creatinine measurements, while clinical diagnoses of myocarditis and pericarditis were retrieved from hospital records (United Kingdom) or health care registers (Norway).

Results: Troponin testing increased at some sites while remaining stable at others, with the most marked rise occurring during the COVID-19 pandemic. Overall, 18.1% of patients had troponin levels exceeding the adult sex-specific 99^th percentile, compared with 18.0% using the pediatric 99th percentile. By contrast, the sex-specific pediatric 97.5^th percentile identified 23.2% of patients as having elevated troponin (relative increase of 28%). Infants (<1 year) had notably higher rates of elevated hs-cTn, in line with recognized physiological elevations in early life. Despite increased testing at select locations, the incidence of myocarditis and pericarditis remained low, and no clear link emerged between testing volume and disease prevalence.

Conclusions: In this multicenter retrospective cohort, pediatric-specific reference intervals had minimal impact on the proportion of patients identified with elevated hs-cTn levels compared to adult thresholds, except when using the paediatric sex-specific 97.5^th percentile, which significantly increased the classification of myocardial injury. The variability in testing trends suggests that local clinical practices influence hs-cTn utilization, but increased troponin testing did not lead to a corresponding rise in myocarditis or pericarditis diagnoses.

Keywords: multi-site retrospective study, pediatric, high-sensitivity cardiac troponin

Disclosure Statement:

N.L.M reports receiving honoraria or consultancy with Roche Diagnostics, Abbott Laboratories and Siemens Healthineers.

K.M.A. has served on advisory board for Roche Diagnostics, Siemens Healthineers, Radiometer and SpinChip, consultant honoraria form CardiNor, lecturing honorarium from Siemens Healthineers, Roche Diagnostics, Mindray and Snibe Diagnostics and research grants from Siemens Healthineers and Roche Diagnostics, she is Associate Editor of Clinical Biochemistry and Chair of the IFCC Committee of Clinical Application of Cardiac Biomarkers.

The remaining authors report that they have no competing interests to declare. 

Contemporary Recurrent Pericarditis Management – Real-World Evidence of Limited Cardiac Magnetic Resonance Imaging Prior to Initiating Rilonacept 

Brittany Weber, MD, PhD¹, Paul C. Cremer, MD², Michael S. Garshick, MD^3,4, Sushil A. Luis, MBBS, PhD⁵, Ajit Raisinghani, MD⁶, Vidhya Parameswaran, MPH⁷, Allison Curtis, PhD^7*, Allan L. Klein, MD⁸, John F. Paolini, MD, PhD⁷, on behalf of the RESONANCE Study Group.

Presenter: Corina Grancorvitz⁷

*Corresponding author:

¹Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women‘s Hospital, Harvard Medical School, Boston, MA, USA;

²Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA;

³Cardio-Rheumatology Program, Center for the Prevention of Cardiovascular Disease, NYU Langone Health, New York, NY, USA;

⁴Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA;

⁵Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA;

⁶Division of Cardiology, Department of Medicine, Sulpizio Cardiovascular Center, University of California San Diego, San Diego, California, USA;

⁷Kiniksa Pharmaceuticals, Lexington, Massachusetts, USA; 

⁸Department of Cardiovascular Imaging, Center for the Diagnosis and Treatment of Pericardial Diseases, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio, USA 

Word count: (287/375) words (NO FIGURES)

Background: Recurrent pericarditis (RP) is a chronic autoinflammatory disease mediated by IL-1. Cardiac magnetic resonance (CMR) imaging characterizes pericardial inflammation and may inform RP management. Rilonacept, an IL-1α and IL-1β cytokine trap, is the only FDA-approved treatment for RP. We analyzed all CMR use prior to rilonacept initiation in RESONANCE, a US observational RP registry.

Methods: CMR use data were analyzed from 103 active pts at 22 sites (19 academic medical centers [AMCs], n=97; 3 non-AMC sites, n=6) who initiated rilonacept during RESONANCE up to Sep 9, 2024 (223.9 pt-yrs in median [Q1:Q3] 2.2 [1.4, 3.0] yrs). 

Results: In 103 pts initiating rilonacept (mean [SD] age 49.7 [17.0] yrs, 56% female; median observation 0.8 [0.4, 1.0] yrs), median disease duration was 1.0 [0.4, 2.9] yr, with 1.5 [1, 2] prior recurrences. 45% (46/103) of pts had CMR before rilonacept initiation, 98% (45/46) of whom were managed at AMCs; 59% (27/46) showed pericardial inflammation.  54% (52/97) of rilonacept initiators at AMCs and 83% (5/6) at non-AMCs did not have CMR. Those having CMR had similar disease duration (1.0 [0.5,2.9] yr) but more prior recurrences (2 [1, 3]) and more prior steroid use (52%) than those not having CMR (0.9 [0.4, 2.9] yrs; 1 [1, 2]; 32%).  

Conclusion: Recurrent pericarditis is a chronic disease that requires long-term treatment, and selection of therapy is guided by multiple factors. While CMR has utility amongst expert cardiologists in diagnosis, pericardial characterization, and monitoring, it was obtained in more clinically complex RP pts; real-world data indicate that pericardial imaging with CMR prior to rilonacept initiation was performed primarily at AMCs but in less than half of AMC patients (pericardial inflammation was present in approximately half); clinical criteria informed rilonacept initiation in the remainder.

Keywords: autoinflammatory disease; interleukin‐1; recurrent pericarditis; rilonacept; imaging; magnetic resonance imaging

Disclosures:B. Weber: consultant fees from Kiniksa Pharmaceuticals, Novo Nordisk, Horizon Therapeutics, and BMS; P.C. Cremer: grants and consultant fees from Kiniksa Pharmaceuticals, grants and personal fees from Sobi; M. S. Garshick: consultant fees from BMS, Agepha, Kiniksa Pharmaceuticals; S.A. Luis: consultant fees from Kiniksa Pharmaceuticals, Cardiol Therapeutics, and Medtronic; A. Raisinghani: consultant fees from Kiniksa Pharmaceuticals; C. Grancorvitz, V. Parameswaran, A. Curtis, and J. F. Paolini: shareholders and employees of Kiniksa Pharmaceuticals; A.L. Klein: grants and consultant fees from Kiniksa Pharmaceuticals, Cardiol Therapeutics, and Pfizer.

Management of Uncomplicated Myocarditis in a Young Athlete

Oscar Levine, Masihullah Barat, David Torres Barba, Ori Ben-Yehuda¹

¹UC San Diego Health

Background: A 17-year-old previously healthy male competitive soccer player presented to the emergency department with chest pain.

History: The patient woke up with sharp, pleuritic, substernal chest pain radiating to his right shoulder. One week prior, he had fever and myalgias, was diagnosed with influenza, and was treated with oseltamivir. He had no cardiac history, no family history of premature coronary artery disease, and denied alcohol, tobacco, or drug use.

Exams and images: Vital signs and physical exam were unremarkable. Lab work was notable for troponin T generation 5 initially at 169 ng/L and peaking at 493 ng/L (normal: <22 ng/L), with corresponding creatine kinase-myocardial band (CK-MB) elevations peaking at 22.0 ng/mL (normal: 0-4.8 ng/mL). Electrocardiogram demonstrated sinus bradycardia with prominent ST upsloping and peaked T waves diffusely, but no definitive ST changes. Transthoracic echocardiogram (TTE) demonstrated a borderline depressed left ventricular ejection fraction of 55% without wall motion abnormalities. Cardiac magnetic resonance (CMR) revealed subepicardial late gadolinium enhancement (LGE) in the basal anteroseptal and distal inferoseptal walls.

Treatment plan: The patient was diagnosed with myopericarditis. He was treated with ibuprofen (800mg every 8 hours for 1 week) and colchicine (0.6mg daily for 6 months). He was advised to avoid full training until follow-up troponin, TTE, and stress echocardiogram were obtained, with repeat CMR planned for a later assessment.

Patient outcome: The patient’s chest pain resolved by hospital day four. One-week follow-up troponins, TTE, and stress echocardiogram were normal. He resumed gradual cardiovascular activity over two weeks post-hospitalization, prior to resumption of full training. He participated in a college showcase soccer tournament one month post-hospitalization without symptoms. CMR at four and seven months post-hospitalization showed improved LGE with minimal residual enhancement in the basal anteroseptum.

Clinical implications: This case highlights several questions regarding the management of uncomplicated myocarditis, including when follow-up tests such as cardiac troponins and CMR should be obtained, how these tests should be used to guide return-to-exercise recommendations, and the prognostic significance of residual LGE on CMR.

Disclosures: The authors report there are no competing interests to declare.

Impact of Polygenic Risk Scoring on Lipid-Lowering Therapy in Primary Prevention for Coronary Artery Disease

Matthew Sangoi, Pranav Mellacheruvu, Nawaz Safdar, Rishitha Penmetsa, Skyler Burke, Maxwell Ambrosino, Nasser Monzer, Deepak Vedamurthy, Daniel Soffer, Douglas Jacoby

Corresponding Author: Rishitha Penmetsa, 9729889664, rishitha.penmetsa@utsouthwestern.edu

Pennsylvania Hospital of the University of Pennsylvania, Philadelphia, PA, United States

Perelman School of Medicine, Philadelphia, PA, United States

UT Southwestern School of Medicine, Dallas, TX, United States

Background: Polygenic risk scores (PRS) estimate inherited risk for coronary artery disease (CAD) by aggregating multiple genetic variants. Emerging data suggest PRS can enhance traditional risk models, particularly in younger or borderline-risk patients, before clinical risk factors develop. As validation across diverse populations advances, PRS may guide early preventive strategies such as lipid-lowering therapy (LLT).

Methods: A one-year, single-center retrospective study was conducted at a Preventive Cardiology clinic. Patients without known cardiovascular disease who consented to PRS testing (Allelica, Inc.) were included. High genetic risk was defined as PRS ≥90th percentile. Pre- and post-PRS data were collected on lipid profiles, biomarkers, and LLT (statins, ezetimibe, PCSK9 inhibitors, bempedoic acid, icosapent ethyl).

Results: Among 107 patients (median age 51; 37.2% female; 82.2% White), 20.6% had a high-risk PRS. In this group, 54.5% had a change in LLT—36.4% initiated and 18.2% intensified therapy. Statin prescriptions increased by 18.2% (RR 1.25; 95% CI: 0.94–1.67; p=0.13), and non-statin prescriptions by 22.7% (RR 1.63; 95% CI: 0.85–3.12; p=0.15). High-risk patients were more likely to be prescribed statins than low-risk patients (RR 1.36; 95% CI: 1.11–1.65; p<0.01).

Conclusion: PRS testing identified high genetic risk in one-fifth of patients, with over half of these experiencing changes in LLT. Increased statin and non-statin use among high-risk patients suggests PRS may influence lipid management in primary prevention. Further research is needed to confirm its clinical impact.

Keywords: Polygenic risk score, lipid-lowering therapy, primary prevention

Disclosure Statement: The authors report there are no competing interests to declare.

Background/Synopsis:

Lipoprotein(a) [Lp(a)] is an inherited pro-atherogenic lipoprotein associated with cardiovascular diseases. Lp(a) acts as a carrier of oxidized phospholipids, which activate inflammatory response and promote formation of atherosclerotic plaques. The OxPL-apoB method quantifies the content of oxidized phospholipids on apolipoprotein B-100 containing particles, particularly Lp(a) and LDL-C. Cardiac allograft vasculopathy (CAV) is characterized by progressive coronary intimal thickening in heart allografts. This study aims to investigate the association of Lp(a) and OxPL-apoB with early CAV development in cardiac transplant (HTx) recipients.

Methods:   A single-center, retrospective study analyzed 99 HTx recipients between 2015 to 2025 with measured Lp(a) and at least one post-HTx coronary angiogram with highly sensitive intravascular ultrasound (IVUS). We defined elevated Lp(a) as >50 mg/dL and OxPL-apoB levels as >3 nmol/L. The primary endpoint was CAV quantified by maximal intimal thickness (MIT) of 0.5, 1, and 1.5mm. Cox proportional hazard models were used to evaluate the association of MIT and Lp(a) >50 mg/dL, OxPL-ApoB levels >3 nmol/L. Covariates included treated cytomegalovirus infection, AMR rejection, average LDL-C level of two years post-HTx, mTOR inhibitor use, donor ischemic time, BMI, and sex.  

Results: 

A total of 26 (26.2%) of HTx recipients had an Lp(a) > 50 mg/dL and 21 (21.2%) with OxPL-apoB levels >3 nmol/L. The median follow-up after HTx was 2.02 years [1.23, 4.01]. The median Lp(a) level <50 mg/dL was 15 [7, 32.5] and >50mg/dL was 101.5 [72.25, 142]. The median OxPL-ApoB level <3 nmol/L was 1.1 [0, 1.8] and >3 nmol/L was 4.5 [3.53, 6.8].

In multivariate analysis, higher Lp(a) (>50 mg/dL) and OxPL-apoB (>3 nmol/L) levels were associated with numerically increased hazard of CAV, though these associations did not reach statistical significance. The strongest association for Lp(a) was observed at the MIT 1.5 mm threshold (HR 1.07; 95% CI, 0.32–3.45; p=0.92), and for OxPL-apoB at MIT 1.0 mm (HR 1.96; 95% CI, 0.85–4.52; p=0.11).

Conclusion:

In our study, elevated level of Lp(a) >50 mg/dL and OxPL-apoB >3 nmol/L showed a nonsignificant trend towards increased risk for the early development of CAV as determined by IVUS. While these thresholds have been linked to long-term atherosclerotic disease in the general population, their implications in the post-transplant setting remain unclear. Further investigation is warranted to understand how cumulative exposure contributes to CAV development after cardiac transplantation.