Abstract Background Recurrent pericarditis (RP) is a chronic autoinflammatory disease mediated by IL-1 that requires long-term treatment. While the 2015 European Society of Cardiology Guidelines position IL-1 pathway inhibition only after corticosteroids, complications associated with long-term steroid use underscore the importance of steroid-sparing strategies. Rilonacept, an IL-1α and IL-1β cytokine trap, is the only FDA-approved treatment for RP (available since April 2021). RESONANCE, an ongoing 5-year non-interventional US registry of patients (pts) with RP, has collected real-world data from pts cared for by cardiologists with a focus on pericardial disease, with a goal of informing contemporary RP clinical management. Purpose Analysis of temporal trends in RP management from RESONANCE. Methods From a database cut-off (DCO) on 21 December 2023, patient demographics and disease characteristics are reported for 242 active RP pts (excluding RHAPSODY prior participants) at 20 US sites (median [Q1:Q3] 2.1 [1.5:2.6] years and 556 patient-years [PY] of observation). Complete medication class use data were available for 239 pts (total 546 PY). Proportional medication class use prior to initiating rilonacept was analyzed annually across the observation period. Results Mean (standard deviation) age at DCO was 50.2 (16.6) years; 58.1% were female. Median [Q1:Q3] disease duration at DCO from index pericarditis episode was 3.1 [2.2:5] years. Median [Q1:Q3] number of prior recurrences at enrollment was 3 [2:5]. Prior to rilonacept availability, NSAIDs/Colchicine/Aspirin represented the highest proportion of treatment (73% of PY); steroid use was 9% of PY, IL-1 pathway inhibition (anakinra) was 13% of PY, and conventional synthetic disease modifying antirheumatic drugs (csDMARDs) were 0.46% PY (no RP-specific treatment was 5% of PY) (Fig 1). In the years since rilonacept availability, proportional IL-1 pathway inhibition use has increased, from 13% of PY in 2020-21 to 26% of PY in 2023, driven by an increase in rilonacept use (6%, 13%, 16% of PY in 2021, 2022, and 2023, respectively). Over that same period, proportional NSAIDs/Colchicine/Aspirin use (57%-63% of PY) has been consistently 6-times more than proportional steroid use (10%-11% of PY). Among pts who initiated rilonacept (n=81), similar proportions transitioned from NSAIDs/Colchicine/Aspirin as from corticosteroids (Fig 2), a robust trend observed each year. Of those pts transitioning from corticosteroids, 1/3 had used corticosteroids for <30 days and 1/3 for >6 months. Conclusions Real-world data from the RESONANCE registry reveal a temporal shift in RP management in US centers with RP-focused cardiologists, with increased proportional IL-1 pathway inhibition use since rilonacept availability in 2021. Advancing beyond 2015 guideline recommendations, IL-1 pathway inhibition is often being used as steroid-sparing treatment, i.e., after colchicine instead of chronic corticosteroids.

Abstract Background Recurrent pericarditis (RP) is a chronic disease mediated by IL-1 often lasting for years, and specific tools to guide treatment duration with IL-1 pathway inhibition at the individual patient (pt) level are limited. The Phase 3 trial RHAPSODY and 2-year long-term extension (LTE) demonstrated that rilonacept reduced risk of recurrence over long-term treatment (1,2). At the conclusion of the LTE, after a median of 28 months of rilonacept treatment (non-US pts), Italian pts returned to standard management because rilonacept was not commercially available. Clinical outcomes after rilonacept cessation and washout were followed to inform disease persistence and time to recurrence. Purpose Multicentric analysis of RP event rates in Italian pts after stopping long-term rilonacept. Methods Clinical records from Italian RHAPSODY pts were examined for the 18-month period post-LTE (To). Primary outcome: pericarditis recurrence (defined by tertiary-center experts as pericarditis pain plus c-reactive protein [CRP] elevation). Secondary outcomes: time to recurrence and proportion of pts requiring re-initiation of IL-1 pathway inhibition. Safety outcomes: serious adverse events (SAEs). Results 17 Italian pts were observed (Table 1). At To, median [Q1-Q3] disease duration (time from index episode) was 48 [41-56] months, during which pts had received a median 28 [27-30] months of continuous rilonacept treatment (all were in Clinical Response, i.e., no pain, normalized CRP, and on rilonacept monotherapy). After rilonacept cessation at To, no pts received prophylactic treatment. 82.4% (14/17) of pts experienced confirmed pericarditis recurrences, with time to recurrence 8 [6-9] weeks. Half of these pts (n=7) were given oral medications (NSAIDS, colchicine [n=3] and/or steroids [n=4], of whom 1 steroid-treated pt failed and resumed IL-1 pathway inhibition). The other half (n=7) resumed IL-1 pathway inhibition directly upon recurrence. The remaining 17.6% (3/17) of pts had no pericarditis recurrences after To and remained off treatment during the observation period. No pts experienced SAEs. Neither recurrence frequency nor time to recurrence was significantly related to baseline disease characteristics or demographics. Conclusions This exploratory analysis shows that in pts with RP of even 4-years’ duration (including a median 28-months’ rilonacept treatment), the 80% recurrence rate after treatment cessation was indicative of severe persistent underlying disease. Time to pericarditis recurrence after rilonacept cessation (median 8 weeks) was consistent with the predicted gradual pharmacokinetic washout and previously-reported 8.6-week time to flare in RHAPSODY (1). Pericarditis recurrences in these pts with long disease duration and systemic inflammation were severe enough to necessitate re-initiation of advanced therapy. Further studies could quantify optimal treatment duration for pts achieving prolonged remission on IL-1 pathway inhibition.

Cross modality 1377Conclusion: The combination of echo and CMRI indices improved the stratification of the risk in LVNC patients.Also, our findings showed the importance of biventricular assessment to detect the severity of this cardiomyopathy.

Introduction: There are no known pathognomonic ECG findings in constrictive pericarditis (CP). Increased pericardial thickness in CP is associated with low QRS voltage secondary to thickening and calcification. We sought to study the correlation between pericardial thickness identified by cardiac magnetic resonance (CMR) and ECG changes pre and post pericardiectomy. Methods and results: 80 consecutive patients with proven constriction underwent pericardiectomy at a Cleveland Clinic between 2009 and 2011. Baseline characteristics, CMR, and pathological specimens were reviewed retrospectively (Table one). Paired t-test and McNemar test were used to analyze pre and post ECG changes for continuous and categorical variables, respectively. There were significantly less patients with Afib, LBBB, RBBB or 1st degree AVB post-pericardiectomy (table1). Also, significant increase in limb and precordial R-wave voltage postop (ΔR 8.2±3.7 and 9±4.3, respectively, p <0.001). On multivariate linear logistic regression, pericardial thickness (β 0.3 [0.078-0.52], p 0.009), low preop R wave voltage (β -0.54 [-1.1 to -0.60], p0.001) and age (β 0.18 [0.002-0.09] p=0.04) were predictors of R wave recovery postop. there was statistically significant correlation between pericardial thickness and mean R wave recovery (r 0.34, p 0.002) (figure 1). ECG Pre and Post surgery Values are expressed as means ± SD or n (%). Conclusion: In patient with CP, rhythm and electrical conduction improve post pericardiectomy. Thickened pericardium on CMR is an independent predictor of improvement of R wave with significant correlation.

We aimed to determine the incidence, risk factors and complications of RSV in- fections in infants with CHD. Our second goal was to determine the efficacy of monoclonalantibody (palivizumab) prophylaxis. Methods: The study population constituted of 419 patients less than 2 years of age with the diagnosis of LRTI. 241 (57%) of those patients had the diagnosis of CHD and they were hemodynamically unstable and required continuous medical therapy. 178 (43%) patients did not have CHD.RSVwas diagnosed by Respi Strip in samples obtained with nasopharyngeal swab. Results: In CHD patients with LRTI, the rate of hospitalization due to RSV was 14% and the average length of stay was 9.9 days (5- 17 days). 30% of these infants had to be treated in the pediatric intensive care unit and 18% required mechanical ventilation.These rates were significantly higher when compared with patients without CHD and who were infected with RSV (p=0.01). 15 mg/kg/dose monoclonalantibody (palivizumab) was applied monthly during RSV season to 29 CHD patients. The rate of in-patient treatment before prophylaxis was 59% and it reduced to 14% after prophylaxis (p=0.001). Only one patient with CHD died due to RSV infection (2%). Conclusion: RSV is an important virus leading to mortality and morbidity for infants with CHD, also in developing countries like Turkey. Prophylaxis with monoclonalantibody (palivizumab) is effective forthese patients. Since in 20% of infants with LRTI, the causative agent was RSV; this necessitates the utility of diagnostic methods for RSV to prevent useless antibiotic therapies and to enable isolation precautions to be taken more effectively. Introduction: Lyme boreliosis is a disease induced by a sting of an infected tick, leading to various systemic body manifestations. Initially it can be asymptomatic, and after incubation period it can clinically present itself in different forms, de- pending on the organ system affected. Heart is rarely a target for boreliosis, and if it does happen, usually it is manifested in some forms of myocarditis. Methods and results: Over the period of four years in our facility, there were 5 cases of boreliosis with the existence of conductive interference. These patients were followed by an infectious disease specialist and controlled by the cardiol-ogist. In 2 cases the interference was a part of the later disease manifestation. However, in 3 cases with younger patients after diagnosing conductive interference ranging from AV block grade II Mobitz I to AV block grade III, it was first epidemiologically and then serologically determined the presence of boreliosis, connected to the initial disease manifestation. All patients received adequate an- tibiotic therapy, and after appropriate monitoring and follow up they came out of the block within7 to10 days. A complete non-invasive cardio diagnostics was per- formed, including documented 24h Holter mintoring ECG for each patient at least twice: initially when administering the patients and after stopping of the block. Conclusion: Although not in typical forms, myocardial conductive disorder could be a manifestation of Lyme disease. Thus in cases where a conductive disor- der is diagnosed, it would be wise to exclude it, as a possible etiological factor. Furthermore, these disorders are transient with the adequate antibiotic therapy. Purpose: The optimal treatment of neoplastic pericarditis (NP) in lung cancer (LC) is still a clinical challenge. Various treatment methods are used: pericardiocentesis (P), pericardial window (W), systemic chemotherapy (CT), local (in- trapericardial) CT, combined systemic and local CT. Aim of this study is to com-pare 4 different approaches, all including CT, using an objective scoring system to assess the outcome. No such studies are available so far. Methods: We retrospectively reviewed the data of 146 LC patients (pts) (106 males, 40 females) with NP requiring drainage and confirmed by cytology. A neo-plasticscore (intrapericardial effusion and masses) was used to assess the sever- ity of pericardial involvement at diagnosis and at the last available follow-up or when a new intervention (drainage or window) was necessary. The outcome was classified as: Complete response (CR) if no effusion or masses were detectable at follow-up; partial response (PR) if the neoplastic score was reduced and no more intervention were necessary, stable disease (SD) or progression (PD) if the score was unchanged or worsened. Results: Pericardiocentesis plus: local CT (P+L) was performed in 24 pts; systemic CT (P+S) in 44; combined (P+S+L) therapy in 55. Twenty three pts had pericardial window plus systemic CT (W+S). A complete response was obtained in 67% of pts treated with local CT (alone or withsystemic CT).A complete or par- tial response was obtained in 96% of pts P+S+L, in 91% of those underwent W+S, and in 88% of those with P+L; CR or PR was obtained in 64% with P+S (p < 0.001). A significantly longer survival was obtained with combined CT (ANOVA test p=0.001). comes and presents a high rate of recurrence after pericardiocentesis. Various approaches have been reported for prevention of recurrences. However most of them are associated with significant morbidity or even mortality and required un- necessarily prolonged hospital stay. We sought to confirm the efficacy of percutaneous balloon pericardiotomy (PPB) as the initial treatment of choice for MPE. Methods: Retrospective analysis of the clinical, echocardiographic and follow-up characteristics of a consecutive series of PPB carried out in a single center in patients with advanced cancer. Results: Twenty-one PPB were performed in 19 patients with a mean age of 65 ± 15 years. Seventeen patients had pathologically confirmed metastatic neoplastic disease and in another two patients there was a high radiological suspi- cion of it. Three patients had previously required pericardiocentesis, and in the remaining patients PPB constituted the first treatment for the MPE. All patients had a severe ( > 20mm) circumferential effusion and only one patient did not have evidence of hemodynamic compromise on echocardiography. In allcases the pro- cedure was initiallysuccessful, there were no acute complications, and it was well tolerated at the first attempt. There were no infectious complications, and just one patient developed a large pleural effusion that did not require treatment. During the follow-up (median 74 [IQR 31.5-207.5] days), four patients required a new pericardial procedure: 2 elective pericardial window surgeries and 2 new PPB. Conclusions: PPB is a simple, safe procedure that can be effective in the pre- vention of recurrences in many patients with MPE. Based on the results and the poor prognosis of these patients we believe that PPB might be considered the initial treatment of choice for most MPE. Both endoplasmic reticulum stress (ER stress) and autophagy are essential for cellular homeostasis and stress responsiveness. In response to cellular stress, ER stress and autophagy are activated to degrade misfolding/unfolding proteins, therefore re-establish cellular homeostasis and alleviate the inciting stress. However, if the stress cannot be resolved, the cell dies by apoptosis. Emerging ev- idences show that ER stress and autophagy play a critical role in the progress of cardiovascular disease. The purpose of this study was focused on the role of ER stress and autophagy against the progress of dietary-induced hypertrophic cardiomyopathy. Materials: Male mice of 6 to 7 wk old were fed ad libitum with a standard chow diet (CON) or else a high-fat/sucrose diet (HFSD) for 2, 4, 8, 16, and 24 wk, respectively. At the end of experiment, mice were sacrificed and tissues were collected for the analysis. Results: The body weight and heart weight were increased with the advanced HFSD stimulation. After receiving the 4 wk HFSD, mice were induced hyper-glycemia and hypercholesteromia. ER stress sensor, cardiac Perk protein ex- pression was similar between CON and HFSD mice for the 2 wk feeding, while its expression was suppressed after receiving more than 4 wk HFSD. In addition, cardiac procaspase-12 and its activation were induced in mice receiving more than 8 wk HFSD. These results demonstrated that ER stress was activated to alleviate the stress after the 2 wk HFSD stimulation, but it failed to protect the heart and leaded to ER stress-induced apoptosis after receiving the 8 wk HFSD. Mediator of autophagy initiation, cardiac AMPK activation was elevated after receiving the 8 wk HFSD, but was inhibited after receiving more than 16 wk HFSD. The ratio of LC3II to LC3I in the heart did not increase until receiving the 24 wk HFSD. These autophagic data demonstrated that autophagic Conclusions: for caridoprotection autophagy after long-term HFSD stimulation. value (SUVmax). We compared reductions of SUVmax in response to therapy in both groups. Furthermore, the relationship between the 18F-FDG uptake pattern and prognosis was examined. Results: Aftersteroid therapy, SUVmax wassignificantly reduced inboth the G(+) group (from 8.0 ± 0.9 to 4.0 ± 0.4, p=0.04) and the G(-) group (from 8.3 ± 3.4 to 6.2 ± 3.2, p < 0.01). Neither the absolute value of SUVmax nor the (cid:2) SUVmax after steroid therapy were significantly correlated with event-free survival. After steroid therapy, ten patients showed diffuse uptake on 18F-FDG PET and five patients showed focal uptake. Major cardiac events (sudden cardiac death, ventricular arrhythmia, heart failure and complete AV block) occurred in 60% of patients with diffuse and 20% of those with focal uptake. Ten patients relapsed after reducing the dose of prednisolone. 18F-FDG uptake was significantly increased with low-dose prednisolone (mean 9.3 ± 4.8 mg) compared with high-dose prednisolone. Conclusions: This study suggests that some cases ofcardiac sarcoidosis cannot be diagnosed by current guidelines, and HL 18F-FDG PET might be useful for diagnosis of cardiac s

Background: Constrictive pericarditis is a debilitating disease and reversible constriction is a well-described phenomenon. However, factors which predict reversibility remain unknown. No study has shown factors that might predict reversibility and thus preclude these patients from pericardiectomy which has its own host of debilitating sequelae. In this study we sought to look into factors which predict constriction reversibility in CP patients. Method: We evaluated 48 consecutive patients who developed CP following the first attack of pericarditis in year 2011. All patients were treated with NSAIDs, colchicine and steroids as first treatment. Demographics, etiology, laboratory, echocardiograpic and outcome data were collected retrospectively using electronic medical record offline echocardiograms films. Results: 27 patients had reversibly constriction with medical therapy only and 19 patients underwent pericardiectomy who were identified as irreversible. Those who had surgery had normal inflammatory marker (ERS, 11.8±7 vs. 40±25, CRP 2.5±2 vs. 6.9±3.1, p=0.001), more septal bounce (17 vs. 7, p=0.001), and more dilated inferior vena cava (2.69±0.4 vs. 2.12±0.35, p=0.001) and less inspiratory collapse (3 vs. 20, p=0.001). Furthermore, patient who had surgery had thicker pericardium on echo confirmed with cardiac MRI (0.74 vs. 0.45 vs. 0.41±0.5, p=0.28). Using tissue doppler, septal and lateral E/e' were higher among those who had reversible disease (11.36±4.8 vs. 7.25±1.9 p=0.001 and 9.8±3.9 vs. 5.9±2.4, p=0.001), respectively. On multivariate analysis, septal bounce correlated with need for surgery (p<0.05). High ESR and high E/e' lateral correlated with resolution (p<0.05). Conclusion: In CP, pericardiectomy can be the ultimate treatment in advanced cases. In few cases CP can be reversible and respond to medical therapy only. In this study we identified septal bounce, increased pericardial thickness, and normal inflammatory markers as predictors for pericardiectomy, which represent less inflammation and more fibrosis as pathology of pericardial constriction. On the other hand, higher inflammatory markers, and mitral valve annular velocity, as predictors for reversibility and potential to response to medical therapy. Knowing features that describe reversible disease will be helpful in pursuing aggressive medical management for those who will benefit and avoiding unnecessary surgery.

Using Doppler-echocardiography, diastolic dysfunction (DD) can be differentiated: normal (grade 0), abnormal relaxation (grade 1), pseudonormal (grade 2) and restrictive filling (grade 3). Although grade 3 DD is associated with worse survival, limited prognostic data exist regarding other grades. MeRGE is an individual patient meta-analysis evaluating DD and mortality in patients (pts) with heart failure (HF) and post-AMI. This analysis compares outcome by grade of DD.

BACKGROUND:Restrictive mitral filling pattern (RFP), the most severe form of diastolic dysfunction, is a predictor of outcome after acute myocardial infarction (AMI). Low power has precluded a definite conclusion on the independent importance of RFP, especially when overall systolic function is preserved. We undertook an individual patient meta-analysis to determine whether RFP is predictive of mortality independently of LV ejection fraction (LVEF), end-systolic volume index, and Killip class in patients after AMI. METHODS AND RESULTS:Twelve prospective studies (3396 patients) assessing the relationship between prognosis and Doppler echocardiographic LV filling pattern in patients after AMI were included. Individual patient data from each study were extracted and collated into a single database for analysis. RFP was associated with higher all-cause mortality (hazard ratio, 2.67; 95% CI, 2.23 to 3.20; P<0.001) and remained an independent predictor in multivariate analysis with age, gender, and LVEF. The overall prevalence of RFP was 20% but was highest (36%) in the quartile of patients with lowest LVEF (<39%) and lowest (9%) in patients with the highest LVEF (>53%; P<0.0001). RFP remained significant within each quartile of LVEF, and no interaction was found for RFP and LVEF (P=0.42). RFP also predicted mortality in patients with above- and below-median end-systolic volume index (1575 patients) and in different Killip classes (1746 patients). Importantly, when diabetes, current medication, and prior AMI were included in the model, RFP remained an independent predictor of outcome. CONCLUSIONS:Restrictive filling is an important independent predictor of mortality after AMI regardless of LVEF, end-systolic volume index, and Killip class.

BACKGROUND:Electrical cardioversion in patients with atrial fibrillation (AF) is associated with an increased risk of stroke. We compared a transesophageal echocardiography (TEE)-guided strategy with a conventional strategy in patients with AF > 2 days' duration undergoing electrical cardioversion over a 6-month follow-up. METHODS:The ACUTE study was a multicenter, randomized, clinical trial, with 1222 patients. Six-month follow-up was available in 1034 patients (85%), 525 in the TEE group and 509 in the conventional group. The primary composite end points were cerebrovascular accident, transient ischemic attack, and peripheral embolism at 6 months, which was a prespecified time point. Secondary end points were hemorrhage, mortality, and sinus rhythm. RESULTS:At 6 months, there was no difference in composite embolic events between the TEE group and the conventional group (10 [2%] vs 4 [0.8%]; risk ratio (RR) 2.47, 95% CI 0.78-7.88; P = .11). However, the hemorrhagic rate was significantly lower in the TEE group (23 [4.4%] vs 38 [7.5%]; RR 0.58, 96% CI 0.35-0.97; P = .04). There was no difference between the 2 treatment groups in all-cause mortality (21 [4%] vs 14 [2.8%]; RR 1.48, 95% CI 0.76-2.92; P = .25) and in the occurrence of normal sinus rhythm between the 2 groups (305 [62.2%] vs 280 [58.1%]; P = .51). Sinus rhythm at 6 months was more common in the TEE-guided group, in those patients who had direct current cardioversion (238 [62.5%] vs 151 [53.9%]; P = .03). CONCLUSION:The TEE-guided strategy may be considered a clinically effective alternative to a conventional anticoagulation strategy for patients with AF of > 2 days' duration undergoing electrical cardioversion over a 6-month period.

The prognostic values of tissue Doppler imaging and color M-mode diastolic indexes were studied in 225 patients who had symptomatic systolic heart failure in the ADEPT study. The primary end point of death, transplantation, or hospitalization due to heart failure occurred in 65 patients and was independently predicted by shorter deceleration time, lower ratio of pulmonary vein systolic to diastolic velocity, and increasing levels of the ratios of early transmitral velocity to early annular velocity or velocity of propagation. For the ratio of early transmitral velocity to early annular velocity, this prediction was additive to deceleration time. Newer diastolic indexes provide an independent prediction of clinical outcomes.