Comparative assessment of myocarditis and pericarditis reporting rates related to mRNA COVID-19 vaccines in Europe and the United States.

OBJECTIVES: The novel mRNA vaccines proved to be safe and effective in averting severe COVID-19. Vaccine-related complications recorded by pharmacovigilance systems, such as 'EudraVigilance' in Europe and 'VAERS' in the United States (US), rarely include myocarditis and pericarditis. Given the novelty of the platform and the increasing global-scale vaccine production needs, we assessed their reporting rates comparatively across continents. METHODS: Data of myocarditis and pericarditis cases post COVID-19 vaccination reported from week 52/2020 (December 21 to 27, 2020) to week 40/2021 (October 4 to 10, 2021) were collected for mRNA vaccines from EudraVigilance and VAERS. The corresponding administered vaccine doses were used as denominators to estimate reporting rates for comparison purposes. Cross-tabulation analysis was employed to compare the reporting rates of mRNA vaccines-associated myocarditis and pericarditis between EudraVigilance and VAERS. RESULTS: Low reporting rates of myocarditis (7.64/million vaccine doses) and pericarditis (5.32/million) were found, with higher rates of both disorders in EudraVigilance compared to VAERS; these differences were more pronounced post-mRNA-1273 (5-6-fold, p=0.000 for myocarditis and p<0.001 for pericarditis) than post-BNT162b2 vaccination (1.5-2-fold, p<0.001 for both conditions). Most myocarditis cases occurred in males <30 years. Pericarditis affected predominantly males <40 and both sexes >40 years. The extremely rare fatalities related to myocarditis (0.102/million) or pericarditis (0.017/million) were also higher in EudraVigilance versus VAERS. CONCLUSIONS: Understanding the underlying causes of the observed differences could provide guidance for the enhanced quality of mRNA vaccines that would also foster vaccine acceptance.

Benefit-risk assessment of COVID-19 vaccine, mRNA (Comirnaty) for age 16-29 years.

Since authorization of the Pfizer-BioNTech COVID-19 Vaccine, mRNA (Comirnaty), real-world evidence has indicated the vaccines are effective in preventing COVID-19 cases and related hospitalizations and deaths. However, increased cases of myocarditis/pericarditis have been reported in the United States associated with vaccination, particularly in adolescents and young adults. FDA conducted a benefit-risk assessment to determine whether the benefits of vaccination outweigh the risks among various age (16-17, 18-24, 25-29) and sex (M/F) subgroups being considered for approved use of the vaccine. We conducted a simulation study with sensitivity analysis of the benefits and risks of the vaccine across possible pandemic scenarios. The model results show benefits outweigh the risks for all scenarios including the high-risk subgroup, males 16-17 years old. Our worst-case scenario used sex and age subgroup-specific incidences for COVID-19 cases (47-98 per million per day) and hospitalizations (1-4 per million per day) which are the US COVID-19 incidences as of July 10, 2021, vaccine efficacy of 70% against COVID-19 cases and 80% against hospitalization, and unlikely, pessimistic, non-zero vaccine-attributable myocarditis death rate. For males 16-17 years old, the model predicts prevented COVID cases, hospitalizations, ICUs, and deaths of 13577, 127, 41, and 1, respectively; while the predicted ranges for excess myocarditis/pericarditis cases, hospitalizations, and deaths attributable to the vaccine are [98-196], [98-196], and 0, respectively, for the worst-case scenario. Considering the different clinical implications of hospitalization due to COVID-19 infection versus vaccine-attributable myocarditis/pericarditis cases, we determine the benefits still outweigh the risks even for this high-risk subgroup. Our results demonstrate that the benefits of the vaccine outweigh its risks for all age and sex subgroups we analyze in this study. Uncertainties exist in this assessment as both benefits and risks of vaccination may change with the continuing evolution of the pandemic.

Incidence, Clinical Presentation, and Management of Myocarditis following mRNA-Based Covid-19 Vaccines: A Brief Report.

BACKGROUND: Recent surveillance studies following nationwide mass vaccination are investigating rare complications such as myocarditis, pericarditis, and thromboembolic events related to mRNA-based Covid-19 vaccines. SUMMARY: In the current report, we present an overview of the incidence, clinical presentation and management of post-mRNA vaccine myocarditis, and pericarditis in view of the currently available data. Our main focus is directed toward myocarditis. KEY MESSAGES: Myocarditis following mRNA-based Covid-19 vaccines is rare, more frequently affects younger men <30 years and is usually of mild severity with spontaneous recovery. The overall benefit of mRNA vaccines in terms of protecting from severe Covid-19 infection and associated cardiovascular complications outweighs the risk of postvaccination myocarditis. Currently, there are no dedicated guidelines for patients with postvaccination myocarditis or pericarditis in terms of the frequency of follow-up including clinical assessment, repeated echocardiography, and cardiac resonance imaging. However, follow-up studies in terms of long-term consequences are underway.

Incidence, clinical presentation, management, and outcome of acute pericarditis and myopericarditis.

AIMS: Little is known about the epidemiology, clinical presentation, management, and outcome of acute pericarditis and myopericarditis. METHODS AND RESULTS: The final diagnoses of acute pericarditis, myopericarditis, and non-ST-segment elevation myocardial infarction (NSTEMI) of patients presenting to seven emergency departments in Switzerland with acute chest pain were centrally adjudicated by two independent cardiologists using all information including serial measurements of high-sensitivity cardiac troponin T. The overall incidence of pericarditis and myopericarditis was estimated relative to the established incidence of NSTEMI. Current management and long-term outcome of both conditions were also assessed. Among 2533 chest pain patients, the incidence of pericarditis, myopericarditis, and NSTEMI were 1.9% (n = 48), 1.1% (n = 29), and 21.6% (n = 548), respectively. Accordingly, the estimated incidence of pericarditis and myopericarditis in Switzerland was 10.1 [95% confidence interval (95% CI) 9.3-10.9] and 6.1 (95% CI 5.6-6.7) cases per 100 000 population per year, respectively, vs. 115.0 (95% CI 112.3-117.6) cases per 100 000 population per year for NSTEMI. Pericarditis (85% male, median age 46 years) and myopericarditis (62% male, median age 56 years) had male predominance, and commonly (50% and 97%, respectively) resulted in hospitalization. No patient with pericarditis or myopericarditis died or had life-threatening arrhythmias within 30 days [incidence 0% (95% CI 0.0-4.8%)]. Compared with NSTEMI, the 2-year all-cause mortality adjusted hazard ratio of pericarditis and myopericarditis was 0.40 (95% CI 0.05-2.96), being 0.59 (95% CI 0.40-0.88) for non-cardiac causes of chest pain. CONCLUSION: Pericarditis and myopericarditis are substantially less common than NSTEMI and have an excellent short- and long-term outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, number NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587.

Disease and Economic Burden Associated with Recurrent Pericarditis in a Privately Insured United States Population.

INTRODUCTION: Approximately 30% of patients with a first acute pericarditis episode experience a recurrence ≤ 18 months; ~ 15% experience multiple recurrences. This study assessed the recurrence and economic burden among patients with multiple recurrences. METHODS: Adults with idiopathic pericarditis were identified in the OptumHealth Care Solutions, Inc., database (2007-2017). Recurrent pericarditis (RP) was defined as ≥ 2 episodes of care separated by > 28 days; multiple recurrences were defined as ≥ 2 recurrences. RESULTS: Among 944 patients with RP, 375 (39.7%) experienced multiple recurrences and were propensity score-matched 1:1 to 375 patients without recurrence. Among patients with multiple recurrences, median disease duration (time from first episode to end of last recurrence, confirmed by a 1.5-year recurrence-free period) was 2.84 years. The multiple recurrences cohort had higher rates of hospitalizations per-patient-per-month (PPPM) than the no recurrence cohort (rate ratio [95% confidence interval (CI)] = 2.22 [1.35-3.65]). Mean total healthcare costs were significantly higher in the multiple recurrences versus no recurrence cohort ($2728 vs. $1568 PPPM, cost ratio [95% CI] = 1.74 [1.29-2.32]), mainly driven by higher hospitalization costs in the multiple recurrences cohort (mean: $1180 vs. $420 PPPM, cost ratio [95% CI] = 2.81 [1.80-4.66]). Mean work loss costs were higher in the multiple recurrences versus no recurrence cohort ($696 vs. $169 PPPM, cost ratio [95% CI] = 4.12 [1.64-9.61]). In patients with multiple recurrences, mean cost of the first episode was $19,189; subsequent recurrences ranged from $2089 to $7366 (second recurrence = $6222). CONCLUSION: In conclusion, among patients with multiple pericarditis recurrences, disease symptoms persisted several years, and healthcare and work loss costs were further compounded in this subset of patients.

US Database Study of Clinical Burden and Unmet Need in Recurrent Pericarditis.

Background Patients with recurrent pericarditis (RP) may develop complications, multiple recurrences, or inadequate treatment response. This study aimed to characterize disease burden and unmet needs in RP. Methods and Results This retrospective US database analysis included newly diagnosed patients with RP with ≥24 months of continuous history following their first pericarditis episode. RP was defined as ≥2 pericarditis episodes ≥28 days apart. Some patients had ≥2 recurrences, while others had a single recurrence with a serious complication, ie, constrictive pericarditis, cardiac tamponade, or a large pericardial effusion with pericardiocentesis/pericardial window. Among these patients with multiple recurrences and/or complications, some had features relating to treatment history, including long-term corticosteroid use (corticosteroids started within 30 days of flare, continuing ≥90 consecutive days) or inadequate treatment response (pericarditis recurring despite corticosteroids and/or colchicine, or other drugs [excluding NSAIDs] within 30 days of flare, or prior pericardiectomy). Patients (N=2096) had hypertension (60%), cardiomegaly (9%), congestive heart failure (17%), atrial fibrillation (16%), autoimmune diseases (18%), diabetes mellitus (21%), renal disease (20%), anxiety (21%), and depression (14%). Complications included pericardial effusion (50%), cardiac tamponade (9%), and constrictive pericarditis (4%). Pharmacotherapy included colchicine (51%), NSAIDs (40%), and corticosteroids (30%), often in combination. This study estimates 37 000 US patients with RP; incidence was 6.0/100 000/year (95% CI, 5.6‒6.3), and prevalence was 11.2/100 000 (95% CI, 10.6‒11.7). Conclusions Patients with RP may have multiple recurrences and/or complications, often because of inadequate treatment response and persistent underlying disease. Corticosteroid use is frequent despite known side-effect risks, potentially exacerbated by prevalent comorbidities. Substantial clinical burden and lack of effective treatments underscore the high unmet need.

Clinical and economic outcomes associated with hospitalizations for acute idiopathic pericarditis in the United States.

BACKGROUND: Outcomes-based data regarding the management of hospitalized U.S. patients with acute idiopathic pericarditis (AIP) are lacking. OBJECTIVES: This study sought to elucidate the clinical and economic outcomes associated with the inpatient care of AIP. METHODS: Cohort study of adults with AIP; multivariable analyses of clinical and economic outcomes (inpatient mortality, surgical or medical complications, length of stay, and medical charges). RESULTS: Surgical or medical complications, pericardiocentesis, and pericardiotomy were each independently associated with a significantly higher odds of inpatient mortality (p<0.05). Pericardiocentesis, pericardiotomy, and pericardiectomy were also independently associated with significantly higher odds for complications (p<0.001) and, overall, surgical or medical complications were associated with longer lengths of stay and higher charges (p < 0.001). A higher odds of inpatient mortality was associated with micropolitan or rural patient residence, Medicaid payor, and African American race (p<0.05). CONCLUSIONS: U.S. inpatient cases of AIP are associated with significant use of healthcare resources, disparities, morbidity, and mortality.

Voluntary monitoring systems for pig health and welfare in the UK: Comparative analysis of prevalence and temporal patterns of selected non-respiratory post mortem conditions.

Collection of abattoir data related to public health is common worldwide. Standardised on-going programmes that collect information from abattoirs that inform producers about the presence and frequency of disease that are important to them rather than public health hazards are less common. The three voluntary pig health schemes, implemented in the United Kingdom, are integrated systems which capture information on different macroscopic disease conditions detected in slaughtered pigs. Many of these conditions have been associated with a reduction in performance traits and consequent increases in production costs. The schemes are the Wholesome Pigs Scotland in Scotland, the British Pig Health Scheme in England and Wales and the Pig Regen Ltd. health and welfare checks in Northern Ireland. In this study, four post mortem conditions (pericarditis, milk spots, papular dermatitis and tail damage) were surveyed and analysed over a ten and half year period, with the aim to compare the prevalence, monthly variations, and yearly trends between schemes. Liver milk spot was the most frequently recorded condition while tail damage was the least frequently observed condition. The prevalence of papular dermatitis was relatively low compared to liver milk spot and pericarditis in the three schemes. A general decreasing trend was observed for milk spots and papular dermatitis for all three schemes. The prevalence of pericarditis increased in Northern Ireland and England and Wales; while Scotland in recent years showed a decreasing trend. An increasing trend of tail damage was depicted in Scotland and Northern Ireland until 2013/2014 followed by a decline in recent years compared to that of England and Wales with a decreasing trend over the full study period. Monthly effects were more evident for milk spots and papular dermatitis. Similarity of the modus operandi of the schemes made the comparison of temporal variations and patterns in gross pathology between countries possible over time, especially between countries with similar pig production profile. This study of temporal patterns enables early detection of prevalence increases and alerts industry and researchers to investigate the reasons behind such changes. These schemes are, therefore, valuable assets for endemic disease surveillance, early warning for emerging disease and also for monitoring of welfare outcomes.

Acute Pericarditis-Associated Hospitalization in the USA: A Nationwide Analysis, 2003-2012.

BACKGROUND AND OBJECTIVES: Epidemiologic data on hospitalizations for acute pericarditis are scarce. We sought to study the trends in these hospitalizations and outcomes in the USA over a 10-year period. METHODS: We used the 2003-2012 Nationwide Inpatient Sample database to identify admissions with a primary diagnosis of acute pericarditis. Outcomes included hospitalization rate, case fatality rate (CFR), length of stay (LOS), hospital charges, complications and diagnostic and therapeutic procedures. RESULTS: We observed an estimated 135,710 hospitalizations for acute pericarditis among patients ≥16 years during the study period (mean age 53.5 ± 18.5 years; 40.5% women). The incidence of acute pericarditis hospitalizations was significantly higher for men than for women [incidence rate ratio (IRR) 1.56; 95% confidence interval (CI) 1.54-1.58; p < 0.001]; it decreased from 66 to 54 per million person-years (p < 0.001). CFR and LOS declined significantly during the study period (CFR: 2.2% in 2003 to 1.4% in 2012; LOS: 4.8 days in 2003 to 4.1 days in 2012; p < 0.001 for both). The average inflation-adjusted health-care charge increased from USD 31,242 to 38,947 (p < 0.001). CONCLUSION: The hospitalization rate, CFR and LOS associated with acute pericarditis have declined significantly in the US population. Average charges for acute pericarditis hospitalization have increased.

Comparison of recording of pericarditis and lung disorders at routine meat inspection with findings at systematic health monitoring in Danish finisher pigs.

BACKGROUND: The use of secondary data is widespread in a range of surveillance and monitoring applications because of the low cost and high availability associated with this form of data. However, as they are often collected for quite unrelated purposes, they are not necessarily fit for the new purpose that is required of them. Routine meat inspection data were originally collected with the purpose of safeguarding food, but have been re-tasked to also include animal welfare assessment. The objective of the present study was to compare the recording of pericarditis, pleuritis and lungs with lesions at routine meat inspection (RMI) with those performed at systematic health monitoring (SHM) in Danish pigs at slaughter, in order to assess the usefulness of RMI for monitoring the prevalence of these diseases. Data originating from 165 Danish pig herds were collected in the period September 2011 to November 2013. From each herd, a batch consisting of all pigs slaughtered on a specific day from a specific farm were included as the RMI data, while lungs and hearts sampled from the batches were used for the SHM. The RMI data and SHM data included recordings related to a) chronic pericarditis, b) chronic pleuritis and c) lung lesions. The proportion of carcases with a specific disease recording was estimated for each batch of pigs, and linear regression was used to relate the RMI-proportion to the SHM-proportion for the conditions mentioned above. RESULTS: The coefficients of determination (R(2)) were estimated as R(2),pericarditis = 0.16; R(2),pleuritis = 0.67; R(2),lungs with lesions = 0.40. R(2),pericarditis changed to 0.42 when the regression analysis included inspection type at the abattoir (with purely visual inspection of the hearts versus traditional inspection including an incision into the heart). CONCLUSIONS: Overall, the results suggest that the correlation between findings at RMI and SHM was moderate for pleuritis and lungs with lesions, but poor for pericarditis. The latter could partly be explained by the type of meat inspection conducted at the abattoir. We conclude that caution should be used whenever RMI data are used for purposes other than those for which they were originally intended.

Idiopathic pericarditis and pericardial effusion in children: contemporary epidemiology and management.

BACKGROUND: Multicenter studies on idiopathic or viral pericarditis and pericardial effusion (PPE) have not been reported in children. Colchicine use for PPE in adults is supported. We explored epidemiology and management for inpatient hospitalizations for PPE in US children and risk factors for readmission. METHODS AND RESULTS: We analyzed patients in the Pediatric Health Information System database for (1) a code for PPE; (2) absence of codes for underlying systemic disease (eg, neoplastic, cardiac, rheumatologic, renal); (3) age ≥30 days and <21 years; and (4) discharge between January 1, 2007, and December 31, 2012, from 38 hospitals contributing complete data for each year of the study period. Among 11 364 hospitalizations with PPE codes during the study period, 543 (4.8%) met entry criteria for idiopathic or viral PPE. Significantly more boys were noted, especially among adolescents. No temporal trends were noted. Median age was 14.5 years (interquartile range 7.3 to 16.6 years); 78 patients (14.4%) underwent pericardiocentesis, 13 (2.4%) underwent pericardiotomy, and 11 (2.0%) underwent pericardiectomy; 157 (28.9%) had an intensive care unit stay, including 2.0% with tamponade. Median hospitalization was 3 days (interquartile range 2 to 4 days). Medications used at initial admission were nonsteroidal anti-inflammatory drugs (71.3%), corticosteroids (22.7%), aspirin (7.0%), and colchicine (3.9%). Readmissions within 1 year of initial admission occurred in 46 of 447 patients (10.3%), mostly in the first 3 months. No independent predictors of readmission were noted, but our statistical power was limited. Practice variation was noted in medical management and pericardiocentesis. CONCLUSIONS: Our report provides the first large multicenter description of idiopathic or viral PPE in children. Idiopathic or viral PPE is most common in male adolescents and is treated infrequently with colchicine.

A systematic review of validated methods to capture myopericarditis using administrative or claims data.

PURPOSE: To identify algorithms that can capture incident cases of myocarditis and pericarditis in administrative and claims databases; these algorithms can eventually be used to identify cardiac inflammatory adverse events following vaccine administration. METHODS: We searched MEDLINE from 1991 to September 2012 using controlled vocabulary and key terms related to myocarditis. We also searched the reference lists of included studies. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria. Two reviewers independently extracted data regarding participant and algorithm characteristics as well as study conduct. RESULTS: Nine publications (including one study reported in two publications) met criteria for inclusion. Two studies performed medical record review in order to confirm that these coding algorithms actually captured patients with the disease of interest. One of these studies identified five potential cases, none of which were confirmed as acute myocarditis upon review. The other study, which employed a search algorithm based on diagnostic surveillance (using ICD-9 codes 420.90, 420.99, 422.90, 422.91 and 429.0) and sentinel reporting, identified 59 clinically confirmed cases of myopericarditis among 492,671 United States military service personnel who received smallpox vaccine between 2002 and 2003. Neither study provided algorithm validation statistics (positive predictive value, sensitivity, or specificity). CONCLUSIONS: A validated search algorithm is currently unavailable for identifying incident cases of pericarditis or myocarditis. Several authors have published unvalidated ICD-9-based search algorithms that appear to capture myocarditis events occurring in the context of other underlying cardiac or autoimmune conditions.

The impact of race and ethnicity on disease severity in systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) can result in comorbidities and high disease severity. The aim of this study was to evaluate the effects of age, sex, race, ethnicity, cost of hospitalization, length of stay, and payor source on SLE disease severity scores. DESIGN: Epidemiological study. SETTING: Hospital discharge data were obtained from the DFW Hospital Council (DFWHC), for 65,535 patients hospitalized in the North Texas Dallas-Fort Worth (DFW) Metropolitan Statistical Area (MSA) from 1999-2005 with at least one autoimmune disease. PATIENTS: Of the 65,535 autoimmune patients, 14,829 patients had SLE as a diagnosis. The sample was assessed for disease severity according to the SLE comorbidity Index. MAIN OUTCOME: Disease severity, SLE comorbidities. RESULTS: SLE patients were younger and more than five times more likely to have multiple autoimmune diseases. More than one third of Hispanic patients were on Medicaid or self-pay and more likely to have higher disease severity. Race (Caucasian), sex (female), and payor source (PPO/POS) predicted lower disease severity scores. SLE was predictive of eight of the fourteen SLE-CI diseases, with greatest effects observed for nephritis (OR = 3.30, P < .0001), chronic renal failure (OR = 3.36, P < .0001), pericarditis (OR = 3.2, P < .0001), and pleuritis (OR = 2.06, P < .0001). Non-Caucasian patients were more likely to have chronic renal failure, nephritis, congestive heart failure, pericarditis and pleuritis. CONCLUSIONS: The comorbidities that exist in SLE vary according to ethnicity. It is paramount for physicians to be cognizant of these disparities and make appropriate referrals.

Contemporary trends in the epidemiology and management of cardiomyopathy and pericarditis in sub-Saharan Africa.

Heart failure in sub-Saharan Africans is mainly due to non-ischaemic causes, such as hypertension, rheumatic heart disease, cardiomyopathy and pericarditis. The two endemic diseases that are major contributors to the clinical syndrome of heart failure in Africa are cardiomyopathy and pericarditis. The major forms of endemic cardiomyopathy are idiopathic dilated cardiomyopathy, peripartum cardiomyopathy and endomyocardial fibrosis. Endomyocardial fibrosis, which affects children, has the worst prognosis. Other cardiomyopathies have similar epidemiological characteristics to those of other populations in the world. HIV infection is associated with occurrence of HIV-associated cardiomyopathy in patients with advanced immunosuppression, and the rise in the incidence of tuberculous pericarditis. HIV-associated tuberculous pericarditis is characterised by larger pericardial effusion, a greater frequency of myopericarditis, and a higher mortality than in people without AIDS. Population-based studies on the epidemiology of heart failure, cardiomyopathy and pericarditis in Africans, and studies of new interventions to reduce mortality, particularly in endomyocardial fibrosis and tuberculous pericarditis, are needed.