Acute and Complicated Inflammatory Pericarditis: A Guide to Contemporary Practice.

Inflammatory disease of the pericardium represents a relatively common presentation, especially among the young. For the most part, inflammatory pericardial disease can be expeditiously and effectively managed without significant sequelae. However, some individuals present with severe and recurrent illness, representing significant therapeutic challenges. During the past decade, there have been great strides made in developing an evidence-based approach to management of inflammatory pericardial disease, the result of which has been the development of (1) a systematic, protocoled approach to initial care; (2) targeted therapeutics; and (3) specialized, collaborative, and integrated care pathways. Herein we present a review of the current state of the art as it pertains to the diagnostic evaluation and therapeutic considerations in inflammatory pericardial disease with a focus on acute and complicated pericarditis.

Impact on Kidney Function and Medium-Term Outcomes of Transcatheter Aortic Valve Replacement in Patients With Chronic Kidney Disease.

Transcatheter aortic valve replacement (TAVR) is now widely approved for the treatment of aortic stenosis, regardless of the patients' surgical risk. However, the outcomes of TAVR and their determinants in patients with chronic kidney disease (CKD) beyond 1 year of follow-up are unknown. We aimed to assess the medium-term outcomes of TAVR in CKD, develop a risk score to estimate the 2-year mortality in patients with CKD, and evaluate the changes in kidney function at discharge after TAVR. Adults who underwent TAVR were retrospectively identified. The CKD stage was determined using the Chronic Kidney Disease Epidemiology 2021 creatinine formula. Improved kidney function was defined as post-TAVR creatinine ≤50% of pre-TAVR creatinine or decrease in creatinine of ≥0.3 mg/100 ml compared with pre-TAVR creatinine. Overall, 1,523 patients (median age 82 years; 59% men; 735 with CKD stage II or less, 661 with CKD III, 83 with CKD IV, and 44 with CKD V [of whom 40 were on dialysis]) were included. The all-cause mortality was higher in CKD stages IV and V on the multivariable analysis (p <0.001) at median follow-up of 2.9 (interquartile range 2.0 to 4.2) years. Moderate or severe tricuspid regurgitation, anemia, right ventricular systolic pressure >40 mm Hg and CKD stages IV and V were independent predictors of 2-year mortality and were used to develop a risk score. At hospital discharge, persisting acute kidney injury after TAVR occurred in 88 of 1,466 patients (6%), whereas improved kidney function occurred in 170 of 1,466 patients (12%). In conclusion, CKD stage was an independent determinant of mortality beyond 2 years after TAVR. Kidney function was more likely to improve than worsen at the time of hospital discharge after TAVR.

The Evolving Etiologic and Epidemiologic Portrait of Pericardial Disease.

Pericardial disease includes a variety of conditions, including inflammatory pericarditis, pericardial effusions, constrictive pericarditis, pericardial cysts, and primary and secondary pericardial neoplasms. The true incidence of this varied condition is not well established, and the causes vary greatly across the world. This review aims to describe the changing pattern of epidemiology of pericardial disease and to provide an overview of causative etiologies. Idiopathic pericarditis (assumed most often to be viral) remains the most common etiology for pericardial disease globally, with tuberculous pericarditis being most common in developing countries. Other important etiologies include fungal, autoimmune, autoinflammatory, neoplastic (both benign and malignant), immunotherapy-related, radiation therapy-induced, metabolic, postcardiac injury, postoperative, and postprocedural causes. Improved understanding of the immune pathophysiological pathways has led to identification and reclassification of some idiopathic pericarditis cases into autoinflammatory etiologies, including immunoglobulin G (IgG)4-related pericarditis, tumour necrosis factor receptor-associated periodic syndrome (TRAPS), and familial Mediterranean fever in the current era. Contemporary advances in percutaneous cardiac interventions and the recent COVID-19 pandemic have also resulted in changes in the epidemiology of pericardial diseases. Further research is needed to improve our understanding of the etiologies of pericarditis, using the assistance of contemporary advanced imaging techniques and laboratory testing. Careful consideration of the range of potential causes and local epidemiologic patterns of causality are important for the optimization of diagnostic and therapeutic approaches.

Interleukin-1 blockers for the treatment of recurrent pericarditis: pathophysiology, patient reported outcomes and perspectives.

ABSTRACT: Recurrent pericarditis (RP) is the most troublesome complication of acute pericarditis reflecting an unresolving inflammation of the pericardial sac around the heart and associated with significant morbidity. Recent studies have shown interleukin-1 (IL-1) signaling to be central to the pathophysiology of cases of RP with evidence of activation of systemic inflammation. We herein review the literature and clinical trials discussing the utility of IL-1 blockade for RP. The early experience of IL-1 blockade with anakinra (Kineret) and its favorable safety profile paved the way for the clinical development of rilonacept (Arcalyst) and subsequent approval by the US FDA for RP. In patients with RP who have become colchicine-resistant and glucocorticoid-dependent, IL-1 blockade with rilonacept or anakinra effectively treats recurrences and prevents future flares, and significantly improves quality of life.

Perioperative management of aortic stenosis in patients undergoing non-cardiac surgery.

Aortic stenosis is one of the most common cardiac valve pathologies in the world and its prevalence increases with age. Although previously associated with increased perioperative mortality, more recent studies suggest that mortality rates may be decreasing. Recent guidelines suggest that major non-cardiac surgery can be performed safely in asymptomatic severe aortic stenosis patients with close hemodynamic monitoring. Among symptomatic patients, the guidelines recommend aortic valve intervention prior to major non-cardiac surgery because of a reduction in the incidence of postoperative heart failure and improved rates of long-term overall survival. This review provides a comprehensive and contemporary review of the perioperative management of patients with severe aortic valve stenosis.

Transition to rilonacept monotherapy from oral therapies in patients with recurrent pericarditis.

OBJECTIVE: Polypharmacy management of recurrent pericarditis (RP) often involves long-term therapies, often with negative effects. Slow tapering of oral therapies is often required to avoid recurrence. A post hoc analysis of the phase III trial Rilonacept inHibition of interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal Symptomatology and Outcomes Study (RHAPSODY) evaluated investigator approaches to transitioning to IL-1 blockade monotherapy with rilonacept, which was hypothesised to allow accelerated withdrawal of common multidrug pericarditis regimens. METHODS: RHAPSODY was a multicentre (Australia, Israel, Italy, USA), double-blind, placebo-controlled, randomised-withdrawal trial in adults and adolescents with RP. Investigators initiated rilonacept at the labelled dose level and discontinued oral pericarditis therapies during the 12-week run-in; randomised patients received study drug as monotherapy. Time to rilonacept monotherapy was quantified in patients receiving multidrug regimens at baseline who achieved rilonacept monotherapy during run-in. RESULTS: In 86 enrolled patients, mean time to rilonacept monotherapy was 7.9 weeks, with no recurrences. Of these, 64% (n=55) entered on multidrug regimens: non-steroidal anti-inflammatory drugs (NSAIDs) plus colchicine (44% (24/55)), colchicine plus glucocorticoids (24% (13/55)), or NSAIDs, colchicine, plus glucocorticoids (33% (18/55)). Investigators transitioned patients receiving colchicine and glucocorticoids at baseline to rilonacept monotherapy without recurrence regardless of taper approach: sequential (n=14; median, 7.7 weeks) or concurrent (n=17; median, 8.0 weeks). Median time to rilonacept monotherapy was similar regardless of glucocorticoid dose and duration: ≤15 mg/day (n=21): 7.3 weeks; >15 mg/day (n=18): 8.0 weeks; long-term (≥28 days): 7.6 weeks. CONCLUSIONS: Rapid discontinuation of oral RP therapies while transitioning to rilonacept monotherapy was feasible without triggering pericarditis recurrence. TRIAL REGISTRATION NUMBER: NCT03737110.

Interleukin-1 Trap Rilonacept Improved Health-Related Quality of Life and Sleep in Patients With Recurrent Pericarditis: Results From the Phase 3 Clinical Trial RHAPSODY.

Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health-related quality of life. RHAPSODY (rilonacept inhibition of interleukin-1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL-1α and -ß cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient-reported outcome questionnaire score change during the trial. Methods and Results Participants completed 5 patient-reported outcome (PRO) questionnaires assessing pericarditis pain, health-related quality of life, general health status, sleep impact, and overall symptom severity. PRO score changes during the treatment run-in period (12 weeks) and the blinded randomized withdrawal period (up to 24 weeks) were evaluated using descriptive statistics and mixed model repeated measures analyses. Participants with PRO data from the run-in period (n=84) and the randomized withdrawal period (n=61; 30 rilonacept, 31 placebo) were included in analyses. Run-in baseline PRO scores indicated that pericarditis symptoms during pericarditis recurrence impacted health-related quality of life. All PRO scores significantly improved (P<0.001) on rilonacept treatment during the run-in period. For the randomized withdrawal period, PRO scores were maintained for participants receiving rilonacept. For those receiving placebo and who experienced a recurrence, PRO scores deteriorated at the time of recurrence and then improved following rilonacept bailout. At randomized withdrawal Week 24/End of Study, scores of participants who received bailout rilonacept were similar to those of participants who had continued rilonacept. Conclusions These results demonstrate the burden of pericarditis recurrences and the improved physical and emotional health of patients with recurrent pericarditis while on rilonacept treatment. These findings extend prior rilonacept efficacy results, demonstrating improvements in patient-reported health-related quality of life, sleep, pain, and global symptom severity while on treatment. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.

Estimating the US pericarditis prevalence using national health encounter surveillance databases.

OBJECTIVE: To obtain a nationally representative annualized estimate of the prevalence of pericarditis (inflammation of the pericardium) in the United States (US) in order to better understand the potential burden on the health care system. METHODS: Three nationally representative datasets were used to estimate the annualized period prevalence and prevalence rate of pericarditis from 2007 to 2016: the National Ambulatory Medical Care Survey (NAMCS), the National Hospital Ambulatory Medical Care Survey (NHAMCS), and the Nationwide Inpatient Sample (NIS). Across all data sources, ICD-9/10 codes were used to identify healthcare encounters with ≥1 primary or secondary diagnosis related to pericarditis irrespective of duration or etiology. The prevalence of pericarditis in 2020 was extrapolated by multiplying the average annualized prevalence rate from 2007 to 2016 by the total US population as of March 2020. RESULTS: Data from NAMCS/NHAMCS (2007-2016) yielded an average annualized estimate of 125,209 patients with pericarditis, resulting in a pooled average annualized prevalence estimate of 40 patients with pericarditis per 100,000 persons. Data from NIS (2007-2016) yielded an average annualized estimate of 34,441 patients with pericarditis, resulting in a pooled average annualized prevalence estimate of 11 hospitalized patients with pericarditis per 100,000 persons. Extrapolation of these results based on the March 2020 population estimates from the US Census Bureau of 329,436,928 resulted in an estimated US prevalence of pericarditis to be approximately160,000. CONCLUSION: Despite certain methodologic limitations, our analysis of data from nationally representative sources support that pericarditis is a rare disease affecting substantially fewer than 200,000 persons in the US.

Outcomes and periprocedural management of cardiac implantable electronic devices in patients with carcinoid heart disease.

BACKGROUND: Carcinoid heart disease (CHD) is a rare complication of hormonally active neuroendocrine tumors that often requires surgical intervention. Data on cardiac implantable electronic device (CIED) implantation in patients with CHD are limited. OBJECTIVE: The purpose of this study was to evaluate the experience of CIED implantation in patients with CHD. METHODS: Patients with a diagnosis of CHD and a CIED procedure from January 1, 1995, through June 1, 2020, were identified using a Mayo Clinic proprietary data retrieval tool. Retrospective review was performed to extract relevant data, which included indications for implant, procedural details, complications, and mortality. RESULTS: A total of 27 patients (55.6% male; mean age at device implant 65.6 ± 8.8 years) with cumulative follow-up of 75 patient-years (median 1.1 years; interquartile range 0.4-4.6 years) were included for analysis. The majority of implanted devices were dual-chamber permanent pacemakers (63%). Among all CHD patients who underwent any cardiac surgery, the incidence of CIED implantation was 12%. The most common indication for implantation was high-grade heart block (66.7%). Device implant complication rates were modest (14.8%). No patient suffered carcinoid crisis during implantation, and there was no periimplant mortality. Median time from implant to death was 2.5 years, with 1-year mortality of 15%. CONCLUSION: CHD is a morbid condition, and surgical valve intervention carries associated risks, particularly a high requirement for postoperative pacing needs. Our data suggest that CIED implantation can be performed relatively safely. Clinicians must be aware of the relevant carcinoid physiology and take appropriate precautions to mitigate risks.

Prognostic Value of Cardiac Magnetic Resonance Imaging in Acute Coronary Syndrome Patients With Troponin Elevation and Nonobstructive Coronary Arteries.

OBJECTIVE: To define the diagnostic yield of cardiac magnetic resonance (CMR) in differentiating the underlying causes of myocardial infarction with nonobstructive coronary arteries (MINOCA) and to determine the long-term prognostic implications of such diagnoses. METHODS: Cardiac magnetic resonance evaluation was performed in 227 patients (mean age, 56.4±14.9 years; 120 [53%] female) with a "working diagnosis" of MINOCA as defined by presentation with a troponin-positive acute coronary syndrome (troponin I >0.04 µg/L) and nonobstructed coronary arteries between January 1, 2007, and February 28, 2013. Follow-up was performed to assess the primary composite end point of myocardial infarction, heart failure, and all-cause mortality. RESULTS: Cardiac magnetic resonance identified nonstructural cardiomyopathies in 97 (43%) patients, myocardial infarction in 55 (24%) patients, structural cardiomyopathies in 27 (12%) patients, and pulmonary embolism in 1 patient. No CMR abnormalities were identified in the remaining patients. Kaplan-Meier analysis demonstrated the ability of a CMR diagnosis to predict the risk of the primary composite end point (P=.005) at 5-year follow-up. Worse outcomes were seen among patients with "true" MINOCA and a normal CMR image compared with those with CMR-confirmed myocardial infarction (P=.02). Use of antiplatelets (78% [37/45] vs 95% [52/55]; P=.01), beta blockers (56% [25/45] vs 82% [45/55]; P=.004), and statins (64% [29/45] vs 85% [47/55]; P=.01) was significantly lower in patients with true MINOCA with normal CMR imaging compared with those with CMR-confirmed myocardial infarction. CONCLUSIONS: Cardiac magnetic resonance carries a high diagnostic yield in patients with MINOCA and predicts long-term prognosis. Patients with MINOCA with normal CMR imaging had an increased rate of major adverse cardiac events and lower use of guideline-recommended myocardial infarction therapy compared with those with CMR-confirmed myocardial infarction.

Health-related quality of life in patients with recurrent pericarditis: results from a phase 2 study of rilonacept.

BACKGROUND: Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1ß cytokine trap) to treat RP. METHODS: Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n = 16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n = 9). All participants received rilonacept weekly during a 6-week base treatment period (TP) plus an optional 18-week extension period (EP). Tapering of concomitant medications, including corticosteroids (CS), was permitted during EP. HRQoL was assessed using the PROMIS GH, and patient-reported pain and blood levels of c-reactive protein (CRP) were collected at Baseline and follow-up periods. A secondary, descriptive analysis of the Phase 2 trial efficacy results was completed using HRQoL measures to characterize both the impact of RP and the treatment effect of rilonacept. RESULTS: Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline (mean PROMIS Global Physical Health [GPH] and Global Mental Health [GMH], were lower than population norm average). In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved during EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP). CONCLUSION: This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to CS. TRIAL REGISTRATION: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522 .

Catheter Ablation in Patients With Neuroendocrine (Carcinoid) Tumors and Carcinoid Heart Disease: Outcomes, Peri-Procedural Complications, and Management Strategies.

OBJECTIVES: This report describes a series of patients with neuroendocrine tumors with or without carcinoid heart disease undergoing catheter ablation at the authors' institution. BACKGROUND: Neuroendocrine (carcinoid) tumors are a rare form of neoplasm with the potential for systemic vasoactive effects and cardiac valvular involvement. These tumors can create peri-operative management challenges for the electrophysiologist. However, there are few data regarding ablation outcomes, periprocedural complications, and management of these patients. METHODS: All patients with neuroendocrine tumors undergoing catheter ablation at the Mayo Clinic, Rochester, Minnesota over a 25-year period were retrospectively reviewed. From this cohort, the type of arrhythmias ablated, the recurrence of arrhythmia, perioperative complications, and mortality were reviewed and analyzed. RESULTS: A total of 17 patients (52.9% male; mean age 62.4 ± 9.3 years) with neuroendocrine tumors underwent catheter ablation during the study period. Primary tumor sites included the gastrointestinal tract (n = 11), lung (n = 4), ovary (n = 1), and lymph node (n = 1). Nine patients had metastatic disease, 5 of whom were on somatostatin analog therapy at the time of ablation. Three patients had active symptoms of carcinoid syndrome at the time of ablation, and 2 of those patients had carcinoid heart disease. Ablations were performed mainly for atrial arrhythmias (76.5%): atrioventricular nodal re-entry tachycardia (n = 7), atrial fibrillation (n = 4), and atrial flutter (n = 2). Four patients underwent ablation of ventricular arrhythmias. During a mean follow-up of 19.2 ± 26.2 months, arrhythmia recurred in 35.3% of patients. Three patients (17.6%) had periprocedural complications: pericardial effusion (n = 1), groin site hematoma (n = 1), and carcinoid crisis (n = 1). No deaths were noted in the peri-operative period. CONCLUSIONS: In a unique cohort of patients with neuroendocrine tumors, catheter ablation was feasible in patients with or without carcinoid syndrome. Carcinoid crisis may occur during the periprocedural period, which can be life-threatening, and a specified protocol for management is important to mitigate this risk.

Discriminative Ability and Reliability of Transesophageal Echocardiography in Characterizing Cases of Cardiac Device Lead Vegetations Versus Noninfectious Echodensities.

BACKGROUND: Approximately one-third of cases of cardiovascular implantable electronic device (CIED) infection present as CIED lead infection. The precise transesophageal echocardiographic (TEE) definition and characterization of "vegetation" associated with CIED lead infection remain unclear. METHODS: We identified a sample of 25 consecutive cases of CIED lead infection managed at our institution between January 2010 and December 2017. Cases of CIED lead infection were classified using standardized definitions. Similarly, a sample of 25 noninfected patients who underwent TEE that showed a defined lead echodensity during the study period was included as a control group. TEEs were reviewed by 2 independent echocardiologists who were blinded to all linked patient demographic, clinical, and microbiological information. Reported echocardiographic variables of the infected vs noninfected cases were compared, and the overall diagnostic performance was analyzed. RESULTS: Descriptions of lead echodensities were variable and there were no significant differences in median echodensity diameter or mobility between infected vs noninfected groups. Among infected cases, blinded echocardiogram reports by either reviewer correctly made a prediction of infection in 6 of 25 (24%). Interechocardiologist agreement was 68%. Sensitivity of blinded TEEs ranged from 31.5% to 37.5%. CONCLUSIONS: Infectious vs noninfectious lead echodensities could not be reliably distinguished on the basis of size, mobility, and general shape descriptors obtained from a retrospective blinded TEE examination without knowledge of clinical and microbiological parameters. Therefore, a reanalysis of criteria used to support a diagnosis of CIED lead infection may be warranted.

Association of Left Ventricular Volume in Predicting Clinical Outcomes in Patients with Aortic Regurgitation.

BACKGROUND: Aortic regurgitation (AR) is a common valvular lesion associated with increased mortality once the left ventricle enlarges significantly or develops systolic dysfunction (ejection fraction < 50%). Valve guidelines recommend aortic valve repair or replacement (AVR) for left ventricular (LV) linear end-systolic dimension ≥ 50 mm or end-diastolic dimension ≥ 65 mm. However, chamber quantification guidelines recommend using LV volume for LV size determination because linear measurements may not accurately reflect LV remodeling. The aim of this study was to evaluate the correlation of LV volumes with linear dimensions, interobserver variability in the estimation of volumes, and the association of volumes with outcomes in patients with AR. METHODS: A total of 1,100 consecutive patients with chronic moderate to severe and severe AR on echocardiography between 2004 and 2019 were retrospectively analyzed. The modified Simpson disk summation method was used for LV volume estimation. The primary outcome was all-cause mortality; the secondary outcome was mortality censored at AVR. RESULTS: Patients' age was 60 ± 17 years, and 198 were women (18%). Volumes were measured using the biplane method in 939 patients (85%) and the monoplane method in 161 (15%); end-systolic volume was normal in 169 (11%). Correlations between volumes and linear dimensions were 0.5 for end-diastolic volume and 0.6 for end-systolic volume. At median follow-up of 5.4 years (interquartile range, 2.4-10.0 years), 216 patients had died and 539 had undergone AVR. Indexed LV end-systolic volume (iLVESV) and indexed left ventricular end-systolic dimension were both associated with mortality and symptoms, but the association of iLVESV was stronger. iLVESV, age, male gender, Charlson comorbidity index, New York Heart Association functional class III or IV, and time-dependent AVR were independently associated with all-cause mortality. Interobserver variability in the estimation of LV volumes in 200 patients included intraclass coefficients of 0.94 (95% CI, 0.92-0.95) for end-diastolic volume and 0.88 (95% CI, 0.78-0.93) for end-systolic volume. Patients with iLVESV ≥ 45 mL/m2 had lower survival and a higher prevalence of symptoms than those with volumes < 45 mL/m2. CONCLUSIONS: Echocardiographic LV volume assessment had good reproducibility in patients with moderate to severe and severe AR. The correlation between linear dimensions and volumes was limited. Both iLVESV and indexed left ventricular end-systolic dimension were associated with worse outcomes, but the association of iLVESV was stronger. iLVESV ≥ 45 mL/m2 was associated with worse outcomes.