Cremer, Paul C

Background: Corticosteroids are widely used in pericarditis despite guideline recommendations reserving them for select indications. Observational studies have reported inconsistent associations between corticosteroid use and pericarditis recurrence, and optimal dosing and tapering strategies remain unclear. We conducted a systematic review of oral corticosteroids for acute or recurrent pericarditis to characterize patterns of treatment and evaluate the association between corticosteroids and pericarditis recurrence across different disease contexts. Methods: MEDLINE, EMBASE, CENTRAL, and Scopus were searched from inception to November 26, 2025. Studies enrolling adults with acute or recurrent pericarditis treated with oral corticosteroids were included. Randomized trials, cohort studies, and case–control studies reporting clinical outcomes were eligible. Risk of bias was assessed using the Newcastle–Ottawa Scale (NOS). Data were synthesized descriptively due to anticipated clinical and methodological heterogeneity. Results: Ten studies (2 prospective, 8 retrospective) including 2632 patients (800 corticosteroid-treated) met inclusion criteria. Prednisone was most frequently studied, with heterogeneous dosing (0.25–1.0 mg/kg/day) and non-standardized tapering strategies. Follow-up ranged from 1 to 6.7 years, and overall risk of bias was moderate with limited adjustment for confounding. Findings on recurrence were inconsistent in acute idiopathic and post-procedure pericarditis, while most studies in recurrent pericarditis reported higher recurrence with corticosteroid exposure. Conclusions: Evidence evaluating oral corticosteroids in pericarditis is limited by heterogeneity, confounding, and inconsistent reporting of treatment strategies. Observational data show variable associations with recurrence across clinical contexts. High-quality randomized trials stratified by pericarditis etiology and acuity are needed to define the optimal use of corticosteroids in pericarditis.

Background Recurrent pericarditis may be mediated through inappropriate activation of the NACHT, leucine‐rich repeat, and pyrin domain‐containing protein 3 inflammasome. Pharmaceutically manufactured cannabidiol is an oral formulation that inhibits NACHT, leucine‐rich repeat, and pyrin domain‐containing protein 3 inflammasome activation and development of pericarditis in a preclinical model. Methods This Phase 2, open‐label, multicenter trial included adult patients with symptomatic recurrent pericarditis: pericarditis chest pain ≥4 on an 11‐point numerical rating scale with an elevated C‐reactive protein (≥1 mg/dL) or at least mild pericardial inflammation on cardiac magnetic resonance imaging. At enrollment, patients were on stable doses of non‐steroidal anti‐inflammatory drugs, colchicine, and/or corticosteroids. Cannabidiol was administered during an 8‐week treatment period and an optional 18‐week extension period when background therapy was tapered and discontinued. The primary efficacy end point was change in patient‐reported pericarditis pain. Secondary end points included normalization of C‐reactive protein and percentage of patients with recurrences. Results Among 27 patients (18 women, mean age 53 years), baseline maximal numerical rating scale pain score was 5.8±1.7, and 10 patients had elevated C‐reactive protein. At Week 8, maximal numerical rating scale pain score was 2.1±1.8, and median time to numerical rating scale score ≤2 was 5 days. Among the 10 patients with baseline C‐reactive protein elevation, C‐reactive protein was normal at Week 8 in 8 patients (80%). During the extension period, 17 (71%) of 24 patients remained free of pericarditis recurrence. A serious adverse event leading to cannabidiol discontinuation occurred in 1 patient. Conclusions In symptomatic patients with recurrent pericarditis, pharmaceutically manufactured cannabidiol appears safe and associated with reductions in pericarditis pain and systemic inflammation. Registration URL: clinicaltrials.gov ; Unique Identifier: NCT05494788.

Abstract Background Recurrent pericarditis (RP) predominantly shows features consistent with IL-1-mediated chronic autoinflammatory disease (1-4). A recent analysis suggested that supplementing anakinra with colchicine incrementally reduced pericarditis recurrence vs. anakinra alone (5). Rilonacept (a weekly IL-1α and IL-1β cytokine trap with 6-week washout) prevents engagement with IL-1 receptor, inhibiting both IL-1α and IL-1β activity (6). The Phase 3 trial RHAPSODY demonstrated rilonacept efficacy in two independent analyses: Randomized Withdrawal (RW) and Long-Term Extension (LTE) periods (7,8). Purpose Assess long-term recurrence-free persistence with rilonacept as monotherapy in pts with RP during the combined RW and LTE periods of RHAPSODY. Methods Post-hoc analysis. Freedom from recurrence on rilonacept monotherapy was quantified using the Kaplan-Meier (KM) method from RW start (if randomized to rilonacept) or from initiation of bailout rilonacept (if randomized to placebo) until the end of treatment. Prespecified recurrence adjudication criteria were pericarditis pain (numerical rating scale [NRS]) ≥4 plus C-reactive protein (CRP) ≥1 mg/dL. Per RHAPSODY protocol, background therapies were discontinued during the Run-In Period before randomization. In pts treated with rilonacept, concomitant colchicine was not added during the RW period. In the LTE, 6.8% (5/74) of pts added colchicine: one for 2 days of chest pain without CRP elevation, 4 in the absence of chest pain, CRP elevation, or recurrence; these 5 pts were censored in the KM curve at 6 days after last rilonacept dose or at colchicine initiation (whichever was first). One additional pt added colchicine prophylactically before an intentional rilonacept treatment interruption for elective cardiac surgery and experienced a recurrence after this interruption; this pt was not censored from the recurrence-free persistence analysis at colchicine initiation in order to capture this event. Results 74 pts (mean [SD] age 43.9 [15.7] years, 83.8% idiopathic pericarditis, mean [SD] disease duration 2.5 [3.2] years) were analyzed over three years. Rilonacept was well tolerated. Recurrence-free persistence was 95.9% (n=71/74) while receiving rilonacept as monotherapy (Figure 1). The three observed adjudicated recurrences were each associated with temporary interruptions of 1-3 doses of rilonacept. Conclusions Rilonacept as monotherapy provided recurrence-free persistence over the three-year trial duration when used continuously without interruption; pericarditis recurrences occurred only after interruptions. These findings support evidence-based use of rilonacept as monotherapy, minimizing the need for adjunctive treatments and reducing polypharmacy in long-term RP management. Further investigations are warranted to address how to assess pts as candidates for long-term treatment with rilonacept and when to cease rilonacept treatment.

Abstract Background Recurrent pericarditis (RP) is an IL-1-mediated chronic autoinflammatory disease (1,2). The phase 3 trial RHAPSODY demonstrated that rilonacept (IL-1α and IL-1β cytokine trap), the first and only FDA-approved treatment for RP, was effective in treating RP not only as a third-line agent (3L; after corticosteroids) but also as a second-line agent (2L; instead of corticosteroids) and reduced recurrence risk as monotherapy (3). The REgiStry Of the NAtural history of recurreNt periCarditis in pEdiatric and adult patients (RESONANCE) has been collecting long-term combined prospective and retrospective data from US-based pericardial-disease-dedicated programs since 2020 (4). Purpose To assess the efficacy of rilonacept in RP in a real-world setting, extending the clinical trial findings of RHAPSODY. Methods Database cut-off (DCO) was 05 February 2025. Data on RP management were collected and analyzed from pts with ≥2 years of observation in RESONANCE. Disease duration at DCO was defined as time from RP diagnosis to either disease resolution (no disease flares while off all RP treatments for ≥6 months before DCO) or last follow-up (for pts with ongoing treatment at DCO). Pericarditis recurrences (investigator-assessed) were confirmed based on RP symptom data and/or objective findings. Annualized recurrence rates were calculated per RP treatment regimen as total pericarditis recurrences divided by total patient-years (PY) while receiving that treatment. Wilcoxon signed-rank test was utilized to analyze the significance in change of annualized recurrence rates before and after rilonacept initiation. Results At DCO, 81 pts had ≥2 years of follow-up data in RESONANCE; mean (SD) age was 51.0 (16.8) years; most (66.7%) were female; 84% had idiopathic etiology; median (Q1-Q3) disease duration was 3.1 (2.6-3.7) years; and median observation was 2.93 (2.54-3.38) years. Patient-year treatment exposures per treatment were: NSAIDS ± colchicine (n=79; 187.8 PY), corticosteroids (n=30; 61.1 PY), anakinra (n=1; 1.2 PY) and rilonacept (n=35; 72.8 PY). Of the 35 pts treated with rilonacept for any duration (median observation: 3.2 years; median time on rilonacept: 2.08 years), the most common reason for rilonacept initiation was chest pain/recurrence on prior treatment (n=28). The annualized recurrence rate while receiving rilonacept was significantly lower versus all combined prior lines of treatment (4.00 vs. 0.02 events per PY; p=0.002); this outcome was consistent across line of treatment for rilonacept use (2L: 3.73 vs. 0.06 events per PY, p=0.02; 3L: 4.14 vs. 0 events per PY, p<0.001; Table 1). Conclusions This first report of real-world outcomes from RESONANCE shows that rilonacept-containing regimens for RP as 1st, 2nd, or 3rd line therapy reduced recurrence risk over long- term (>2 year) treatment, supporting prolonged management during RP natural history.

Abstract Background Nearly 40,000 people in the U.S. experience recurrent pericarditis with up to 90% of cases having no identifiable cause, often making the journey to diagnosis arduous. Understanding the challenges that patients and health care professionals (HCP) face will help address gaps and barriers in patient diagnosis and care. In addition, the lack of U.S. based guidelines for recurrent pericarditis clinical care, coupled with the time lapse from the last published European guideline, has created an opportunity to discover workflow solutions for U.S. based healthcare professionals. Purpose The American Heart Association’s (AHA) Addressing Recurrent Pericarditis Initiative is a three-year effort utilizing a quality improvement approach to address gaps/barriers in patient care, educate HCPs, and develop patient education resources to improve diagnosis, treatment, and quality of life. To accomplish this, the lived experiences and challenges patients face on their journey to diagnosis was integrated into the qualitative research process. Methods To assess quality improvement opportunities, the AHA engaged HCPs with recurrent pericarditis experience from 15 diverse health systems to participate in a learning collaborative strategy for quality improvement and implementation to share successful strategies, provide input on professional education topics, and participate in process mapping. Data collection strategies include 1:1 consultations, quarterly learning collaborative calls, surveys and questionnaire completion. To assess patient education needs, the AHA Market Research Team held 1-hour video interviews with ten diverse patients. Results AHA-led HCP interviews produced process maps of clinical workflows and identified opportunities for standardization to improve clinical workflow and patient outcomes (Figure 1). From these data collection methods, preliminary results include care coordination across clinical settings, exploring treatment options, standardization of follow-up cadence, and provider awareness of misdiagnoses/underdiagnosis rates. The patient interviews revealed that there is a lack of symptom recognition, persistent rate of misdiagnosis, delay in accurate diagnosis and treatment, and discrepancies in diagnosis and treatment for various demographics including female and younger adult patients (Figure 2). Conclusion(s) In Year 2 of this three-year initiative, we will continue to refine identified areas of opportunities to improve patient outcomes by creating and disseminating educational materials and launch awareness campaigns, while also producing a national education series for HCPs that provide guidance for system-level quality improvement to emphasize consistency in care and reductions in health inequities. Key findings from this study highlight the care coordination involved in the treatment of patients with recurrent pericarditis and the need to provide multidiscipline educational approaches to achieve this goal.Figure. 1 Summary of care pathway Figure. 2 Summary of patient interviews

Prosthetic heart valve (PHV) dysfunction is increasingly seen due to the increase in the number of PHV that are being implanted worldwide. Cardiac CT imaging has emerged as a valuable tool to assess PHVs and determine the cause of dysfunction. This consensus document first summarizes the available techniques for PHV assessment. Then the use of CT in PHV (dys)function assessment is discussed in detail including consensus statements for correct indications and patient selection for CT assessment of PHVs, image acquisition, reconstruction and measurement protocols and how to interpret and report the CT findings for specific types of PHV dysfunction. This article was published in Journal of Cardiovascular Computed Tomography, Budde RPJ et al, Cardiac computed tomography for prosthetic heart valve assessment: An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Cardiology (ACC), the European Society of Cardiovascular Radiology (ESCR), the North American Society for Cardiovascular Imaging (NASCI), the Radiological Society of North America (RSNA), the Society for Cardiovascular Angiography & Interventions (SCAI), and the Society of Thoracic Surgeons (STS). The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation may be used when referencing this document. © 2025 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. on behalf of the Society of Cardiovascular Computed Tomography. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Keywords: Computed Tomography, Valve, Cardiac, Imaging, Dysfunction, Prosthetic

BACKGROUND: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), VALOR-HCM trial (Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [URL: https://clinicaltrials.gov ; Unique identifier: NCT04349072]) reported that mavacamten reduced the short-term need for septal reduction therapy (SRT). The current report examined the longer-term effect of mavacamten through end of treatment at week 128. METHODS: A double-blind randomized placebo-controlled multicenter trial at 19 sites in the United States included symptomatic obstructive HCM patients referred for SRT (enrollment July 2020 through October 2021). The group initially randomized to mavacamten continued the drug for 128 weeks and the placebo to mavacamten group from week 16 to 128 (112-week exposure). Dose titrations were performed using echocardiographic left ventricular outflow tract gradient and left ventricular ejection fraction measurements. The principal end point was proportion of patients proceeding with SRT or remaining guideline-eligible at week 128. RESULTS: At week 128, 17 of 108 (15.7%) patients in the total study sample met the composite end point (7 underwent SRT, 1 was SRT-eligible, and 9 SRT-status unevaluable). Additionally, 87 of 108 (80.5%) patients demonstrated ≥1 New York Heart Association class improvement by week 128, and 52 of 108 (48.1%) demonstrated ≥2, with a sustained reduction in resting and Valsalva left ventricular outflow tract gradients of 38.2 mm Hg and 59.4 mm Hg, respectively. Ninety-five of 108 (88%) patients transitioned to commercial mavacamten. Overall, 15 of 108 (13.8%) patients (5.41 per 100 patient-years) had an left ventricular ejection fraction <50% (2 with left ventricular ejection fraction ≤30%; 1 death). Of these, 12 of 15 (80%) continued treatment. New-onset atrial fibrillation occurred in 11 (10.2%) patients (4.55 per 100 patient-years). CONCLUSIONS: In severely symptomatic obstructive HCM patients, sustained freedom from SRT was observed at 128 weeks, with nearly 90% patients remaining on long-term mavacamten. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04349072.

Background: Recurrent pericarditis results from inflammasome activation and is associated with significant morbidity. Cannabidiol has been shown to block numerous inflammasome signaling pathways, including reducing transcription of pro-IL-1β and NLRP3, and inhibiting secretion of IL-1β and IL-6. Aim: To assess the impact of oral pharmaceutically manufactured (P-)cannabidiol in recurrent pericarditis patients (pts). Methods: Adult pts (≥18 years) with symptomatic, recurrent pericarditis (≥2 recurrences) were eligible for this open-label, multicenter study. Eligible pts had pericarditis chest pain with a numerical rating scale (NRS) pain score ≥4 within 7 days prior to enrollment, together with either elevated (≥1.0 mg/dL) C-reactive protein (CRP) within the prior 7 days or prior pericardial late gadolinium enhancement (LGE) on cardiac imaging. Pts had to be on chronic treatment with NSAIDs, colchicine or corticosteroids (any combination) with stable baseline (BL) doses. Oral P-cannabidiol was uptitrated to 10 mg/kg twice daily (BID), or maximum tolerated dose. The primary efficacy endpoint was improvement in NRS pain score at week 8 (WK8). A secondary efficacy endpoint among pts with elevated BL CRP was the percentage of pts with CRP normalization (≤0.5 mg/dL) at WK8. Results: 27 pts, mean age of 53 years (range 24-77), 18 of female sex, with a median of 3 prior pericarditis episodes were enrolled. CRP was ≥1.0 mg/dL in 10 pts (37%) at BL. Prior evidence of LGE was present in 21 pts (78%). At BL, 41% of pts were receiving corticosteroid therapy. The highest tolerated study medication dose was BID 10 mg/kg in 20 pts (74.1%), 7.5 mg/kg in 4 pts (14.8%), and 5 mg/kg in 3 pts (11.1%). All 27 pts (100%) completed the WK8 visit. Mean NRS score decreased by 3.7, from 5.8 at BL to 2.1 at WK8. In those with CRP elevation at BL, CRP normalized in 8 pts (80%) by WK8, with mean CRP decreasing from 5.71 to 0.31 mg/dL. Study medication was discontinued due to AEs in 2 pts (7.4%). 24 pts (89%) tolerated P-cannabidiol with a treatment response and proceeded into the 18-week extension period (EP) where background therapy is weaned. Conclusions: Among pts with symptomatic pericarditis recurrence, oral administration of P-cannabidiol led to a clinically relevant reduction in pericarditis chest pain (measured by NRS score) and in CRP. P-cannabidiol was shown to be safe and generally well tolerated, with the majority of pts reaching the target dose and continuing into the study EP.

Abstract Background In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM phase 3 randomized, double-blind, placebo-controlled clinical trial demonstrated that mavacamten, reduces the need for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients and symptoms. As a cardiac myosin inhibitor, mavacamten’s mechanism of action reduces myocardial hypercontractility. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function and can complement left ventricular ejection fraction (LVEF). Objective We sought to assess serial changes in LV and right ventricular (RV)-GLS in patients enrolled in the VALOR-HCM study. Methods VALOR-HCM included 112 symptomatic obstructive HCM patients (mean 60 years, 51% male, LVEF 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo crossed over to mavacamten (n=52) from week 16-56 (40-week exposure). LV and RV-GLS assessment was performed according to the current American and European guideline recommendations using a vendor-neutral post processing software. Non-foreshortened apical (4, 3 and 2-chamber) views were used to obtain peak value of LV-GLS. For RV-GLS, RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. Results Serial changes in LVEF, average LV-GLS, and RV-GLS (4-chamber and free wall) from baseline to week 56 are shown in the Figure. Despite preserved LVEF at baseline, average baseline LV-GLS was abnormal. There were significant and continued improvements in LV-GLS in the total group from baseline to week 56. 12 patients had transient reduction in LVEF (&lt;50%) requiring temporary drug interruption (permanent discontinuation in 3). The LV-GLS in this subgroup was worse at baseline compared to the total study population, with no significant worsening from baseline through week 56. In the overall population, excluding these 12 patients, LV-GLS demonstrated an improvement sustained through week 56. Both free wall and 4-chamber RV-GLS were abnormal at baseline and remained unchanged from baseline to week 56. Conclusions In the VALOR-HCM trial, despite hypercontractile LVEF at baseline, average baseline LV-GLS was worse than normal reference values. Treatment with mavacamten resulted in an improvement in LV-GLS from baseline through Week 56 (with no significant worsening of LV-GLS in the subgroup who experienced any reduction in LVEF &lt;50%), suggesting a favorable long-term impact on regional LV systolic function due to the reduction of cardiac hypercontractility. Additionally, there was no significant detrimental impact on RV systolic function on serial GLS assessment.Serial changes in LV and RV GLS in VALOR