Biomarkers and Personalized Medicine in Cardiovascular Disease Symposium

Trends and Disparities in Cardiac Magnetic Resonance Utilization During Index Hospitalization for Myocarditis (2015–2025)

Oscar P. Levine, MD¹; Ido Avivi²; Mattheus Ramsis²; Ori Ben-Yehuda, MD²

Affiliations:

¹ Division of General Internal Medicine, Department of Medicine, University of California San Diego

402 Dickinson St, Ste 380

San Diego, CA 92103, USA

² Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego

9434 Medical Center Drive

San Diego, CA 92037, USA

Background: Cardiac magnetic resonance (CMR) is a key tool in the diagnosis of myocarditis and provides valuable prognostic information. However, real-world utilization and variation in access remain incompletely characterized. We sought to evaluate temporal trends in CMR use and characterize variation in utilization across patient subgroups.

Methods: We conducted a retrospective cohort study using Epic Cosmos, a large, multicenter electronic health record database, to identify patients hospitalized with myocarditis in the U.S. between 2015 and 2025. The study population included index hospitalizations for myocarditis, defined by billed ICD-10 diagnosis codes (I40.x, B33.22, I51.4). CMR during index hospitalization was identified using billed procedure codes (CPT 75557, 75561, 75565). Temporal trends in CMR utilization were assessed using logistic regression with year modeled as a continuous variable. Variation in CMR use across patient characteristics (age, sex, race, ethnicity, insurance status, social vulnerability index [SVI], and ICU admission) was assessed using chi-square testing.

Results: A total of 61,791 index hospitalizations for myocarditis were identified. Overall, CMR was performed in 27.4% of cases. CMR utilization increased from 24.8% in 2015 to 32.2% in 2025 and was significantly associated with calendar year (OR per year 1.05, 95% CI 1.04–1.06; p < 0.001), with a transient decline in 2020 followed by increased use thereafter. CMR use differed across age groups (p < 0.001), peaking in patients aged 18–29 years (35.0%) and declining with older age. Use was modestly higher in males than females (28.2% vs 25.9%; p < 0.001). CMR use was similar across race groups, ranging from 25.4% (Asian) to 28.6% (Other), and did not differ significantly by ethnicity. CMR use differed across SVI quartiles, with lower use in the highest versus lowest quartile (25.3% vs 30.2%; p < 0.001), and by insurance, ranging from 19.6% in Medicare beneficiaries to 33.0% in privately insured patients (p < 0.001). CMR use was lower among patients with ICU admission (25.8% vs 28.4%; p < 0.001).

Conclusions: Despite increasing use over time, CMR use during index hospitalization for myocarditis remains limited and varies by demographic, clinical, and socioeconomic factors. Lower use among older, socially vulnerable, publicly insured, and critically ill patients suggests potential disparities in access to advanced cardiac imaging. Efforts to expand access to CMR may improve diagnostic evaluation and prognostication.

Keywords: Myocarditis, cardiac magnetic resonance, imaging biomarkers, health disparities

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

Nocturnal Respiratory Rate: a Stable, Heritable Trait that Predicts All-Cause Mortality

Raimon Padrós-Valls, MS1,2, Mijia Ma, MS3, Keshav Gupta, MBBS, MS1, Nicholas Harrington, PhD1, Jeremy E. Orr, MD4, Robert L. Owens, MD4, Rany Salem, PhD5, Kevin R. King, MD, PhD1,6

1.Department of Bioengineering, Jacobs School of Engineering, UC San Diego; 2.Bioinformatics and Systems Biology Graduate Program, UC San Diego; 3.Department of Biostatistics, Harvard T.H. Chan School of Public Health; 4.Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, UC San Diego; 5.Herbert Wertheim School of Public Health and Longevity Science, UC San Diego; 6.Department of Medicine, Division of Cardiovascular Medicine, UC San Diego.

Abstract:

Respiratory rate is a fundamental vital sign controlled by brainstem circuits, yet its determinants and prognostic potential remain poorly defined. Because activity and conscious modulation confound waking measurements, we hypothesized that nocturnal respiratory rate (NRR) could serve as a stable, passively measurable trait suitable for longitudinal monitoring and population-scale study. Using non-contact home bed sensors, we found that NRR was highly consistent within and between nights for a given individual but varied substantially across individuals, consistent with a subject-specific set point. In a survival analysis of 5,679 older adults from the Sleep Heart Health Study, individuals in the high NRR group exhibited nearly 5-fold higher all-cause mortality, with an adjusted hazard ratio of 2.15 (95% CI 1.30–3.55) after controlling for major clinical covariates. To investigate genetic determinants, we combined polysomnography from the National Sleep Research Resource with dbGaP genotyping data from four cohorts to perform the first genome-wide association study of respiratory rate (N=14,277). We identified significant loci implicating ion-channel (DPP10), neuronal (PIRT), structural (TNR, DACH1), and immune/cardiac (NFATC1) genes, with SNP-based heritability of 0.247 (SE 0.035). Together, these results establish NRR as a stable, heritable, and prognostic biomarker with inherited and acquired determinants.

Title: Association of Lipoprotein(a) with ASCVD Risk in Women by Menopausal Status: the UK Biobank

Author names: Mikaila P. Reyes¹, Alexander C. Razavi², Harpreet S. Bhatia³

Affiliations:

¹University of California San Diego School of Medicine, San Diego, CA, USA; mpr006@health.ucsd.edu

²Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA; alexander.c.razavi@emory.edu

³Division of Cardiovascular Medicine, University of California San Diego, CA, USA; hsbhatia@health.ucsd.edu 

ABSTRACT

Introduction: Lipoprotein(a) [Lp(a)] is a predominantly genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD); however, menopause is one of the few conditions that can lead to an increase in Lp(a). We aimed to investigate whether menopause status modifies the association between Lp(a) and ASCVD risk.

Methods: A total of 153,890 pre- and post-menopausal women free of prior ASCVD were studied using data from the UK Biobank. Menopause status was based on self-report while ASCVD was a composite outcome based on ICD10-coded myocardial infarction, stroke or cardiovascular death. Multivariable Cox proportional hazards models evaluated the association between Lp(a) and incident ASCVD events stratified by menopause status.

Results: The median age was 56.1 years, with 60% of women post-menopausal. Median Lp(a) was 22.5 [10.1, 62.1] nmol/L, 21% had Lp(a) >75 nmol/L, and 12% had Lp(a) ≥125 nmol/L. There were 5,160 (3.4%) incident ASCVD events during a median follow up of 13.7 years. Standard deviation increases in Lp(a) were associated with higher risk of ASCVD events among pre-menopausal (HR 1.06, 95% CI 1.00-1.12, p = 0.041) and post-menopausal women (HR 1.06, 95% CI 1.03 - 1.09, p <0.001). Among post-menopausal women, Lp(a) between 75-125 nmol/L (HR 1.13, 95% CI 1.01, 1.25, p = 0.03) and >125 nmol/L (HR 1.15, 95% CI 1.05, 1.26, p = 0.003) were associated with increased ASCVD risk when compared to Lp(a) < 75 nmol/L. The association between Lp(a) and ASCVD risk did not vary with menopause status (p-interactions >0.05).

Conclusion: Lp(a) is an independent risk factor for ASCVD events for both pre- and post-menopausal women.

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.

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.

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.

Serial Lipoprotein(a) Measurements in Heart Transplant Recipients

Andrew S. Kao MD ¹, Antoinette Birs MD ², Jose Cruz Rodriguez MD ²

¹Department of Medicine, UC San Diego Health, La Jolla, CA, USA

²Division of Cardiovascular Medicine, UC San Diego Health, La Jolla, CA, USA

Introduction: Lipoprotein (a), a genetically determined lipid carrier molecule consists of low-density lipoprotein with apolipoprotein B-100 and apolipoprotein (a), is a well-established biomarker with casual association to development of atherosclerotic cardiovascular disease (ASCVD) events.¹ ACC/AHA guidelines recommend lipid lowering therapy for Lp(a) level >50 mg/dL,²  as Lp(a) has a positive association with intima thickening leading to coronary allograft vasculopathy (CAV).^3-4 The following case demonstrates the utility in serial Lp(a) level as a critical biomarker for CAV development in conjunction with surveillance cardiac catheterization.

Case: A 49-year-old man with T2DM, Stage 4 CKD, hyperlipidemia, and a history of end stage ischemic cardiomyopathy with HeartMate 3 LVAD device as a bridge to orthotopic heart transplant (OHT, month 0). His A1c was 8.4% at the time of OHT. Lipoprotein (a) level was 113 mg/dL (Month -10) pre-OHT while on high intensity statin. Aggressive management of his baseline risk factors was continued post-transplant. Maximal intimal thickness (MIT) at post-transplant year 1 (Month 12) catheterization demonstrated left main (LM) 0.23mm, proximal LAD (pLAD) 0.25mm, and mid-LAD 0.22mm; at year 2 (Month 24): LM 0.31 mm, pLAD 0.28mm, and mid-LAD 0.24mm. Both surveillance catheterization showed no angiographically significant CAV with ISHLT class 0 and normal LVEDP. Graft function remained intact (Month 23) and post-transplant Lp(a) level was 37 mg/dL (Month 26).

Discussion: Based on ISHLT classification, CAV may be detected with angiography in 8% of HTx recipients within first year post-transplant, 32% in the first 5 years, and 43% in the first 8 years.⁵ Current data on role on Lp(a) utility as a surveillance biomarker in CAV remain scarce. One recent study of 150 HTx patients at a tertiary center observed that Lp(a) ≥ 30 mg/dL portends a higher risk of early CAV development.³ Our case demonstrates a significant decrease in post-transplant Lp(a) level with aggressive management of cardiovascular risk factors, and a favorable clinical outcome with MIT < 0.5mm on both surveillance angiography. However, it is crucial to acknowledge that immunosuppressive agents have been observed to decrease serum Lp(a) level.^6-7

Conclusion: Lp(a) is a highly prognostic biomarker that informs the risk of future cardiovascular events. In addition to surveillance angiography, we support serial assessment of Lp(a) level to assess for CAV development, and risk stratify for further interventions among cardiac transplant recipients.

References:

1. Bhatia HS, Wilkinson MJ. Lipoprotein(a): Evidence for Role as a Causal Risk Factor in Cardiovascular Disease and Emerging Therapies. J Clin Med. 2022 Oct 13;11(20):6040.

2. Grundy SM, Stone NJ, Bailey AL et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;73:e285-e350.

3. González-Quijano M, Grande-Trillo A, Esteve-Ruiz I, Aranda-Dios A, Sobrino-Márquez JM, Rangel-Sousa D. Elevated Lipoprotein A Levels and Development of Moderate or Severe Cardiac Allograft Vasculopathy in Patients with Heart Transplants. Transplant Proc. 2023 Dec;55(10):2295-2298.

4. Parameshwar J, Foote J, Sharples L, Wallwork J, Large S, Schofield P. Lipids, lipoprotein (a) and coronary artery disease in patients following cardiac transplantation. Transpl Int. 1996;9(5):481-5.

5. Taylor DO, Edwards LB, Boucek MM, Trulock EP, Waltz DA, Keck BM, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-third official adult heart transplantation report: 2006. J Heart Lung Transplant. 2006;25:869 – 879

6. Farmer JA, Ballantyne CM, Frazier OH, Radovancevic B, Payton-Ross C, Patsch W, Morrisett JD, Gotto AM Jr, Young JB. Lipoprotein(a) and apolipoprotein changes after cardiac transplantation. J Am Coll Cardiol. 1991 Oct;18(4):926-30.

7. DeNofrio D, Desai S, Rader DJ, Chang G, Kelley MP, Acker MA, Loh E. Changes in lipoprotein(a) concentration after orthotopic heart transplantation. Am Heart J. 2000 Apr;139(4):729-33.

Disclosures: All authors have no competing interests to declare.

A Case of Olanzapine-Induced Dyslipidemia

Andrew S. Kao MD¹, Harpreet S. Bhatia MD, MAS²

¹Department of Medicine, UC San Diego Health, La Jolla, CA, USA

²Division of Cardiovascular Medicine, UC San Diego Health, La Jolla, CA, USA

Introduction: Elevation in lipid biomarkers, specifically total cholesterol (TC), LDL-C, and triglyceride levels, can be observed within 4 weeks of initiation of atypical anti-psychotic medications without significant HDL-C alteration. Olanzapine use is associated with a five-fold risk increase in risk of developing dyslipidemia and higher predisposition to an ASCVD event. Routine assessment of lipid profile is crucial to minimize cardiovascular risk among patients with psychiatric comorbidities in need of long-term anti-psychotics.

Case: A 51-year-old woman with history of breast cancer on adjuvant hormonal therapy was prescribed olanzapine 5mg daily with venlafaxine and lithium due to an acute manic episode (Month 0). Her lipid profile pre- and post- 3 months of olanzapine initiation: TC 224 to 296 mg/dL, LDL-C 129 to 198 mg/dL, HDL-C 63 to 68 mg/dL, Triglyceride 162 to 138 mg/dL, respectively. She did not have a prior history of cardiac disease, diabetes, hypertension, or family history of hypercholesterolemia. Upon initiation of high intensity statin (Month 16) and discontinuation of olanzapine (Month 17), lipid profile (Month 18) improved as follows: TC 115 mg/dL, LDL-C 47 mg/dL, Triglyceride 76 mg/dL, HDL-C 55mg/dL. She was transitioned from high to moderate intensity statin (Month 18), and follow-up lipid profile (Month 22) was: TC 163 mg/dL, LDL-C 72 mg/dL, Triglyceride 104 mg/dL, HDL-C 70 mg/dL.

Discussion: Among commonly used atypical anti-psychotics, olanzapine and clozapine have the highest efficacy, but also confer the greatest risk for metabolic derangements. Elevation in TC and triglyceride levels are well described with quetiapine, olanzapine, and clozapine. The highest elevation in LDL-C is seen with olanzapine, whereas no strong correlation with HDL-C alteration has been established. The temporal relationship between marked dyslipidemia with olanzapine initiation and resolution upon discontinuation in our case demonstrates the importance of routine lipid profile surveillance in this population. Current guidelines recommend periodic measurement at baseline prior to initiation, followed by 3 and 12 months, then annual screening. This is particularly critical among patients with pre-existing cardiovascular risk factors and prior ASCVD events.

Conclusion: Overall, treatment with anti-psychotics is associated with lower cardiac and all-cause mortality compared to placebo. While psychotropic-induced dyslipidemia is an associated risk, the benefits of long-term control of psychotic symptoms must be weighed. If continuation of anti-psychotics is warranted, clinicians should consider concomitant lipid lowering therapy and lifestyle modifications.

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

Cardiac magnetic resonance imaging paralleled recurrent pericarditis clinical response to rilonacept treatment over 18 months: a RHAPSODY subgroup analysis

Authors:

Paul C. Cremer, MD¹, Antonio Brucato, MD², Antonella Insalaco, MD³, David Lin, MD⁴, Sushil A. Luis, MBBS, PhD⁵, Deborah H. Kwon, MD¹, Christine L. Jellis, MD, PhD¹, JoAnn Clair, PhD, MBA⁶, Allison Curtis, PhD⁶, Sheldon Wang, PhD⁶, Allan L. Klein, MD¹, Massimo Imazio, MD⁷, John F. Paolini,MD, PhD⁶, for the RHAPSODY investigators. 

¹Department of Cardiovascular Imaging, Center for the Diagnosis and Treatment of Pericardial Diseases, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio, USA;  

²Department of Biomedical and Clinical Science, University of Milano, Fatebenefratelli Hospital, Milano, Italy;  

³Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy;  

⁴Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, Minnesota, USA;  

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

⁶Kiniksa Pharmaceuticals, Lexington, Massachusetts, USA;  

⁷Cardiothoracic Department, University Hospital "Santa Maria della Misericordia", ASUFC, Udine, Italy;  

Background: Rilonacept treatment in RHAPSODY resolved active pericarditis recurrences, and long-term treatment led to sustained risk reduction. Prior analysis linked greater baseline Late Gadolinium Enhancement (LGE), with more rapid recurrence upon rilonacept suspension after 12 weeks of treatment.  Serial cardiac magnetic resonance (CMR) imaging (T2-STIR, LGE) enabled longitudinal assessment for tracking clinical improvement, guiding decision-making, and predicting patient outcomes after treatment cessation.

Methods: At the long-term extension (LTE) 18-month decision milestone (18MDM), investigators chose, based on clinical status, to continue rilonacept, suspend rilonacept/observe, or discontinue the LTE.  An imaging core lab blinded to clinical data measured pericardial thickness and graded pericardial edema (T2-STIR) and LGE at baseline and 18MDM. Pericarditis recurrence was assessed clinically following rilonacept suspension. 

Results: Baseline and 18MDM CMRs were available for 13 patients.  Reductions in pericardial thickness, T2-STIR, and LGE from baseline to 18MDM were measured while on treatment.  CMRs were obtained in 7/8 patients suspending rilonacept at 18MDM: LGE was none/trace, and T2-STIR was negative; yet, 5/7 (71%) had pericarditis recurrence within 1-4 months of rilonacept suspension despite prophylactic colchicine (n=2).

Conclusions: Continued clinical improvement during prolonged rilonacept treatment corresponded with improvement on CMR, including reduced pericardial thickness, resolution of pericardial edema on T2-STIR, and resolution of LGE. Negative/trace LGE at 18MDM while on treatment did not predict absence of pericarditis recurrence upon subsequent rilonacept suspension in this size-limited subgroup. Larger prospective studies examining CMR parameters in guiding RP treatment duration decisions and informing associated clinical outcomes are warranted.

Disclosure Statement: PC: grants and personal fees from Kiniksa Pharmaceuticals; grants from Novartis Pharmaceuticals; and personal fees from SOBI Pharmaceuticals outside the submitted work. AB: unrestricted research grant from SOBI and ACARPIA; travel and accommodation for advisory committee from SOBI and Kiniksa. AI: travel and accommodation for advisory committee from SOBI. DL: advisory board for Kiniksa Pharmaceuticals. SAL: consultant for Kiniksa Pharmaceuticals, Cardiol Therapeutics and Medtronic. DHK: funding from the National Heart, Lung, and Blood Institute of the National Institute of Health. CJ: none. MI: scientific advisory board for Kiniksa Pharmaceuticals. ALK: research grant and scientific advisory boards for Kiniksa Pharmaceuticals and Cardiol Therapeutics, scientific advisory board for Pfizer, consultant to Kiniksa Pharmaceuticals. AC, JC, SW, AK: employees and shareholders of Kiniksa Pharmaceuticals. JFP: Employee and shareholder of Kiniksa Pharmaceuticals; inventor on patents/patent applications covering the use of rilonacept for the treatment of recurrent pericarditis.