Coronavirus disease-19 and cardiovascular disease: A risk factor or a risk marker?

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to provide a succinct review about the pathophysiology and cardiac manifestations of COVID-19, as well as treatment considerations and the various adaptations made to the current healthcare structure as a result of the pandemic.

[Oral administration of TRPV4 inhibitor improves atrial calcium handling abnormalities in sterile pericarditis rats].

Atrial Ca2+ handling abnormalities, mainly involving the dysfunction of ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+-ATPase (SERCA), play a role in the pathogenesis of atrial fibrillation (AF). Previously, we found that the expression and function of transient receptor potential vanilloid subtype 4 (TRPV4) are upregulated in a sterile pericarditis (SP) rat model of AF, and oral administration of TRPV4 inhibitor GSK2193874 alleviates AF in this animal model. The aim of this study was to investigate whether oral administration of GSK2193874 could alleviate atrial Ca2+ handling abnormalities in SP rats. A SP rat model of AF was established by daubing sterile talcum powder on both atria of Sprague-Dawley (SD) rats after a pericardiotomy, to simulate the pathogenesis of postoperative atrial fibrillation (POAF). On the 3rd postoperative day, Ca2+ signals of atria were collected in isolated perfused hearts by optical mapping. Ca2+ transient duration (CaD), alternan, and the recovery properties of Ca2+ transient (CaT) were quantified and analyzed. GSK2193874 treatment reversed the abnormal prolongation of time to peak (determined mainly by RyR activity) and CaD (determined mainly by SERCA activity), as well as the regional heterogeneity of CaD in SP rats. Furthermore, GSK2193874 treatment relieved alternan in SP rats, and reduced its incidence of discordant alternan (DIS-ALT). More importantly, GSK2193874 treatment prevented the reduction of the S2/S1 CaT ratio (determined mainly by RyR refractoriness) in SP rats, and decreased its regional heterogeneity. Taken together, oral administration of TRPV4 inhibitor alleviates Ca2+ handling abnormalities in SP rats primarily by blocking the TRPV4-Ca2+-RyR pathway, and thus exerts therapeutic effect on POAF.

Epidemiology and Clinical Features of Myocarditis/Pericarditis before the Introduction of mRNA COVID-19 Vaccine in Korean Children: a Multicenter Study.

BACKGROUND: Korean health authority plans to vaccinate adolescents against coronavirus disease 2019 (COVID-19) starting high school seniors during the summer vacation of 2021. However, the myocarditis/pericarditis following COVID-19 vaccine has been reported recently in adolescents and young adults. This study was performed to answer the urgent questions about the basic epidemiology and clinical course of myocarditis/pericarditis in hospitalized patients prior to the introduction of COVID-19 vaccines in pediatric population. METHODS: A retrospective medical record analysis including frequency, clinical characteristics, etiology and outcome of myocarditis/pericarditis was conducted in 17 years and younger patients who were hospitalized in two referral hospitals in Korea between 2010 and 2019. RESULTS: Total 142 patients with myocarditis (n = 119) and/or pericarditis (n = 23) were identified. Median age was 5.4 years (interquartile range, 0.6-12.9 years; range, 11 days-17.8 years), and male was 61%. In adolescents aged 12-17 years, the male to female ratio was 3.2. Myocarditis/pericarditis occurred 0.70 per 1,000 in-patients during the study period: 0.96 (< 1 year), 0.50 (1-5 years), 0.67 (6-11 years) and 1.22 (12-17 years) per 1,000 in-patients, respectively. There was an increasing tendency for the annual frequency from 0.34 in 2010 to 1.25 per 1,000 in-patients in 2019 (P = 0.021). Among the 56 (40%) proven pathogens at admission, Mycoplasma pneumoniae (n = 11, 8%) and enterovirus (n = 10, 7%) were most common. Of the 142 patients, 99 (70%) required pediatric intensive care unit care and 10 (7%) received heart transplantation. In addition, 61 patients (61/131, 47%) without heart medication at admission needed heart medication when they were discharged. Eleven (7.7%) patients died, of which five patients were previously healthy. The median age of deceased patients was lower than the survival group (0.8 vs. 6.3 years, P = 0.014). CONCLUSION: The frequency of myocarditis/pericarditis was highest among male adolescent in-patients; however, the outcome was favorable in this group without any mortality.

Inflammation and pericarditis: Are neutrophils actors behind the scenes?

The morbidity of acute pericarditis is increasing over time impacting on patient quality of life. Recent clinical trials focused especially on clinical aspects, with a modest interest in pathophysiological mechanisms. This narrative review, based on papers in English language obtained via PubMed up to April 2018, aims at focusing on the role of the innate immunity in pericarditis and discussing future potential therapeutic strategies impacting on disease pathophysiology. In developed countries, most cases of pericarditis are referred to as idiopathic, although etiological causes have been described, with autoreactive/lymphocytic, malignant, and infectious ones as the most frequent causes. Apart the known impairment of the adaptive immunity, recently a large body evidence indicated the central role of the innate immune system in the pathogenesis of recurrent pericarditis, starting from similarities with autoinflammatory diseases. Accordingly, the "inflammasome" has been shown to behave as an important player in pericarditis development. Similarly, the beneficial effect of colchicine in recurrent pericarditis confirms that neutrophils are important effectors as colchicine, which can block neutrophil chemotaxis, interferes with neutrophil adhesion and recruitment to injured tissues and abrogate superoxide production. Anyway, the role of the adaptive immune system in pericarditis cannot be reduced to a black or white issue as mechanisms often overlap. Therefore, we believe that more efficient therapeutic strategies have to be investigated by targeting neutrophil-derived mediators (such as metalloproteinases) and disentangling the strict interplay between neutrophils and platelets. In this view, some progress has been done by using the recombinant human interleukin-1 receptor antagonist anakinra.

A novel therapy for an unusual problem: IL-1 receptor antagonist for recurrent post-transplant pericarditis.

Heart transplant (HTx) recipients are at increased risk of pericardial disease. Idiopathic recurrent pericarditis has not been previously described following HTx. We describe a 35-year-old male who was admitted with pericarditis and moderate pericardial effusion 10 months after HTx. Two weeks before his admission, his prednisone had been tapered off. A thorough infectious workup and endomyocardial biopsy was unrevealing. He was started on colchicine with the addition of tapering prednisone regimen of 40 mg daily due to unresolved pain. Over the next several years, he had three recurrent episodes of pericarditis requiring re-initiation of prednisone with extensive investigations negative for rejection, autoimmune, and infectious causes. Cardiac MRI confirmed pericardial inflammation. Due to his recurrent course and inability to wean off prednisone, anakinra, an IL-1 receptor antagonist, was started at 100 mg sc daily. This allowed successful discontinuation of prednisone. He is now 34 months post-transplant without recurrence on anakinra and colchicine maintenance. Due to the overlap between idiopathic recurrent pericarditis and auto-inflammatory diseases, there is growing evidence for utilizing IL-1 receptor antagonists in this condition. While pericarditis is common in the HTx population, this is the first report of successful use of an IL-1 receptor blocker for pericarditis in this population.

Cardiac involvement in trypanosomiasis in sheep experimentally infected by Trypanosoma vivax (Ziemman, 1905).

The objective of the present study was to evaluate the clinical signs, electrocardiographic signs and evolution of histopathological lesions in the heart of sheep experimentally infected by Trypanosoma vivax during the acute and chronic phases of infection as well as to investigate the presence of parasitic DNA in the heart using polymerase chain reaction (PCR). Twenty-two male sheep were divided into the following four groups: G1, which consisted of six sheep infected by T. vivax that were evaluated until 20 days post-infection (dpi; acute phase); G2, which consisted of six sheep infected by T. vivax that were evaluated until 90 dpi (chronic phase); and G3 and G4 groups, which each consisted of five uninfected sheep. At the end of the experimental period, electrocardiographic evaluations and necroscopic examinations were performed. Fragments of the heart were collected and stained by Hematoxylin-Eosin and Masson's trichrome, and the fragments were also evaluated by PCR for T. vivax. G2 animals presented clinical signs suggestive of heart failure and electrocardiogram alterations characterized by prolonged P, T and QRS complex durations as well as by a cardiac electrical axis shift to the left and increased heart rate. In these animals, mononuclear multifocal myocarditis and interstitial fibrosis were also observed. PCR revealed positivity for T. vivax in two G1 animals and in all G2 animals. Thus, these findings suggested that T. vivax is responsible for the occurrence of cardiac lesions, which are related to heart failure, electrocardiographic alterations and mortality of the infected animals.

Nonrheumatoid Fibrinous Pericarditis: A Medical Examiner Algorithm for the Diagnosis of Viral Myocarditis and Use of Molecular Diagnostic Techniques.

Classic "bread-and-butter" appearance of fibrinous pericarditis had been described in rheumatic disease and other immunologic diseases such as systemic lupus erythematosus, post-myocardial infarct, uremia, tuberculosis, radiation effects, bacterial, and viral etiology. In most of the described cases, pericarditis occurs as a delayed complication. We present a case of a 21-year-old white woman who was seen in the emergency department to rule out pulmonary embolism for shortness of breath, chest pain, and lightheadedness. The autopsy showed a collection of serous fluid into the pericardial sac with bread-and-butter appearance. Microscopically, the pericardium showed acute inflammation with fibrinous exudates. Sections of the heart showed areas of lymphocytic infiltration with acute fibrinous inflammation of the pericardium. Vasculitis was seen in small blood vessels in the heart and was negative in other organs. No granuloma or necrotizing lesion was seen in microscopic sections of all organs including the heart, ruling out rheumatologic disease. The present study highlights the quest and design of an algorithm for a nonrheumatic disorder as the cause of pericarditis. Molecular studies were performed on heart tissue blocks for identification of cardiotropic viruses. Human parvovirus B19 was isolated from heart tissue blocks. The present case study highlights on updates in pathophysiology and diagnostic criteria for myocarditis along with the use of new molecular techniques for detection of idiopathic cardiomyopathies in a medical examiner setup.

Characteristics of Pericardial Biopsy: 100 Cases in a Single Center.

BACKGROUND: Pericardial biopsies are rarely performed during the diagnosis and management of pericardial diseases. The circumstances and clinical profile of patients undergoing pericardial biopsies are largely uncharacterized. OBJECTIVES: To examine the circumstances in which pericardial biopsies are obtained and to evaluate their diagnostic yield. METHODS: We studied a total of 100 cases (71% males, mean age 60.8 years, range 8.1-84.5 years) of surgically resected pericardium specimens obtained from 2000 to 2015 at Sheba Medical Center, the largest medical center in Israel. Patients were classified into groups according to four major histological etiologies: idiopathic pericarditis, constrictive pericarditis, malignant pericarditis, and post-cardiac injury syndrome (PCIS). The clinical history and course, laboratory, echocardiography, and histological results were reviewed retrospectively. RESULTS: Causes of pericarditis according to histological definitions included idiopathic pericarditis (29%), constrictive pericarditis (29%), PCIS (9%), and malignant pericarditis (26%). Overall sensitivity of the pericardial biopsy in patients with malignancy was 57.7%. During the study period, we found a trend toward an increased number of biopsies due to constrictive pericarditis and PCIS, along with a decrease in the number of biopsies performed in patients with malignant or idiopathic pericarditis. The diagnosis following biopsy did not change for any of the patients. CONCLUSIONS: Our findings suggest a low diagnostic yield from pericardial biopsies, especially in malignant pericarditis. This conclusion, along with novel therapies, resulted in the infrequent use of pericardial biopsy in recent years.

Characteristics of cellular composition in malignant pericardial effusion and its association with the clinical course of carcinomatous pericarditis.

To date, the cellular composition of malignant pericardial effusion (MPE) and its association with the clinical course of carcinomatous pericarditis remain unclear. We aimed to determine the MPE cellular composition and its association with carcinomatous pericarditis. Forty-four cases indicated for pericardial drainage due to symptomatic carcinomatous pericarditis were retrospectively reviewed; the blood cell count and composition of MPE were examined. The most dominant cells in MPE were neutrophils. The appearance ratio of an atypical cell in cytologically positive MPE was 95.5%. Low neutrophil and high lymphocyte counts were significantly associated with good effusion failure-free survival at 1 month. The survival after pericardial drainage was significantly shorter when the neutrophil/lymphocyte ratio was 3.5 or more (P = 0.041). Patients whose performance status improved due to drainage had significantly high leukocyte counts in MPE (P = 0.02). Prediction of the course of drainage through basic examination of MPE cellular composition might be beneficial in clinical practice.

Uremic pericarditis in patients with End Stage Renal Disease: Prevalence, symptoms and outcome in 2017.

The prevalence of uremic pericarditis (UP) used to range from 3% to 41%. More recently, it has decreased to about 5%-20% and to <5% in the last decades, as hemodialysis techniques have become widely used and dialysis quality improved. The objective of this work is to determine the initial clinical picture and the prognosis of patients presenting End Stage Renal Disease (ESRD) with UP. MATERIALS: This is a retrospective study (May 2015-September 2017). Inclusion criteria targeted patients who had uremic pericarditis defined as pericarditis occurring in a patient with ESRD before initiation of renal replacement therapy, or within eight weeks of its initiation. RESULTS: 16 patients met the inclusion criteria. The median age of patients was 54 [24, 71] years and 56.2% were male. Pericardial effusion was small, moderate and large in 31.2%, 37.6% and 31.2% of cases respectively. One pericardiocentesis was performed in view of a clinical picture of impending cardiac tamponade and three pericardial drainages were performed given presentation of tamponade. Hemodialysis was initiated for all the patients and continued for 2 to 3weeks until complete regression of the pericardial effusion. The mean number of dialysis sessions was 11±3.5. One patient died of septic shock that developed three weeks after diagnosis of uremic pericarditis. CONCLUSION: UP is considered a rare but fatal complication of ESRD because of the risk of tamponade and its prognosis remains dependent on early diagnosis and adequate treatment of ESRD.

Fulminant Cryptococcus neoformans infection with fatal pericardial tamponade in a patient with chronic myelomonocytic leukaemia who was treated with ruxolitinib: Case report and review of fungal pericarditis.

Cryptococcus neoformans is a saprophytic fungal pathogen that can cause serious illness in immune-compromised hosts and it presents with a wide variety of clinical symptoms. We present a fatal case of fulminant C. neoformans infection presenting as pericardial tamponade in a 71-year-old male with chronic myelomonocytic leukaemia undergoing chemotherapy with the JAK-STAT inhibitor ruxolitinib. We also review the published cases of fungal pericarditis/tamponade. In addition to illustrating an atypical presentation of C. neoformans, this case highlights the risk for opportunistic fungal infections in patients with haematological malignancies, especially the ones treated with small molecule kinase inhibitors.

Prognostic implications of epicardial fat volume quantification in acute pericarditis.

BACKGROUND: The pathophysiology of acute pericarditis remains largely unknown, and biomarkers are needed to identify patients susceptible to complications. As adipose tissue has a pivotal role in cardiovascular disease pathogenesis, we hypothesized that quantification of epicardial fat volume (EFV) provides prognostic information in patients with acute pericarditis. MATERIALS AND METHODS: Fifty (n = 50) patients with first diagnosis of acute pericarditis were enrolled in this study. Patients underwent a cardiac computerized tomography (CT) scan to quantify EFV on a dedicated workstation. Patients were followed up in hospital for atrial fibrillation (AF) development and up to 18 months for the composite clinical endpoint of development of constrictive, recurrent or incessant pericarditis or poor response to nonsteroidal anti-inflammatory drugs. RESULTS: Patients presenting with chest pain had lower EFV vs. patients without chest pain (167·2 ± 21·7 vs. 105·1 ± 11·1 cm3 , respectively, P < 0·01); EFV (but not body mass index) was strongly positively correlated with pericardial effusion size (r = 0·395, P = 0·007) and associated with in-hospital AF. At follow-up, patients that reached the composite clinical endpoint had lower EFV (P < 0·05). After adjustment for age, EFV was associated with lower odds ratio for the composite clinical endpoint point of poor response to NSAIDs or the development of constrictive, recurrent or incessant pericarditis during follow-up (per 20 cm3 increase in EFV: OR = 0·802 [0·656-0·981], P < 0·05). CONCLUSIONS: We report for the first time a significant association of EFV with the clinical features and the outcome of patients with acute pericarditis. Measurement of EFV by CT may have important prognostic implications in these patients.

Clinical evaluation of myocardial involvement in acute myopericarditis in young adults.

BACKGROUND: Myocardial involvement in young adults has various causes. Acute myopericarditis is one of the myocardial involvements in young adults. It is easy to confuse with acute ST-elevation myocardial infarction because of the electrocardiographic features. This study aims to investigate a number of imaging techniques and clinical features for acute myopericarditis in young adults (<30 years of age). METHODS: This retrospective study included 147 patients selected from the 2147 patients at the age of <30 with acute chest pain admitted into emergency service between 2010 and 2016. Of 147 patients, 77 patients were diagnosed with acute myopericarditis (group I) (between 18 and 30 aged) and 70 patients had ST-elevation myocardial infarction (group II). The echocardiographic pictures and information of the patients in both groups were rechecked in terms of impaired segmental wall-motion abnormalities, pericardial effusion, and additional features. RESULTS: The patients in group I had focal echobright, which was defined as myocardial brightness in the left ventricle regions, especially in posterior and lateral wall. Focal echobright was observed in the 75 of 77 cases of acute myopericarditis in transthoracic echocardiogram. This sign was confirmed by cardiac magnetic resonance imaging. Focal echobright sensitivity was 95%; its specificity was 93%; its predictive was 95.2%. Pericardial effusion (83%) was observed in group I behind posterior wall. Its specificity was 81%; its sensitivity was 65%; predictivity was 73%. CONCLUSIONS: Pericardial effusion and myocardial focal echobright in echocardiography can be quite sensitive indicators for acute myopericarditis in young adults.

Arteriosclerosis in the ventral aorta and epicarditis in the bulbus arteriosus of Atlantic salmon (Salmo salar L).

Spontaneous mortality of seemingly healthy, farmed Atlantic salmon (Salmo salar L) is an increasing problem in Norwegian aquaculture. In this study, we present a morphological study of the previously undescribed syndrome of arteriosclerosis of the ventral aorta and epicarditis of the adjacent bulbus arteriosus found in farmed Atlantic salmon, with wild-captured fish as a control group. Both the ventral aorta and epicardium are vital for correct arterial compliance and vascular resistance in the respiratory capillaries of the gills. We discuss the possible implications of ventral aorta arteriosclerosis and epicarditis for blood vascular health and in particular for the increasing frequency of spontaneous gill bleeding in farmed salmon. As both these conditions primarily occur in farmed salmon, we suggest that they should be considered pathological.

A case of fatal perimyocarditis due to a rare disease.

Although myocarditis is caused by viral infections in about 50% of cases in European countries, various other causative agents are known. We report the case of a 51-year-old man who died several months after being diagnosed with asthma by his general practitioner. This diagnosis had been confirmed by a pulmonologist approximately 6 weeks before the man's death. To rule out the possibility of medical malpractice the prosecuting authority ordered a forensic autopsy. At autopsy macroscopic indicators for perimyocarditis and pneumonia were found. Microbiological and histological examination of tissue samples confirmed a diagnosis of Churg-Strauss syndrome, also known as Eosinophilic Granulomatosis with Polyangiitis (EGPA). The cause of death was determined to be cardiac involvement in Churg-Strauss syndrome. The presence of this disease also accounted for the man's recent medical history. There were no findings to indicate that a medical error had been made. The reported case illustrates why accessory histological and microbiological examinations should always be performed when macroscopic findings at autopsy suggest myocarditis. Determining the etiology of myocarditis is a necessary step to prevent overlooking rare diseases with inflammatory myocardial involvement, especially in the clarification of alleged medical malpractice.

[A Case of Chronic Myelogenous Leukemia That Developed Fibrous Pericarditis Owing to Nilotinib Use].

A 64-year-old man was diagnosed with chronic-phase chronic myelogenous leukemia(CML)in May 2009. He was treated with imatinib and achieved complete cytogenetic response(CCyR)in 2 months. After 4 months of treatment, he developed interstitial pneumonia and became intolerant to imatinib. He was then switched to nilotinib from October of the same year. In June 2013, he was diagnosed with drug-induced pericarditis resulting from nilotinib use, and thus, nilotinib was discontinued. Subsequently, he was followed up without specific treatment for CML. In January 2014, he was admitted to the Dept. of Cardiovascular, Renal and Metabolic Medicine at our hospital because of heart failure. After examinations of cardiac function, he was diagnosed with constrictive pericarditis. Therefore, pericardiolysis was performed by the Dept. of Cardiovascular Surgery at our hospital. Pathologic findings showed hyaline-like fibrous tissue proliferation in the pericardium, which was diagnosed as fibrous pericarditis induced by nilotinib. We report a case of chronic myelogenous leukemia that developed fibrous pericarditis owing to nilotinib use.

F-18 FDG PET/CT imaging of cardiac and vascular inflammation and infection.

INTRODUCTION: Inflammation forms an important core of the aetiopathogenic process involved in many diseases affecting the heart and the blood vessels. These diseases include infections as well as inflammatory non-infectious cardiovascular conditions. The common feature of this is invasion of the heart or blood vessel by inflammatory cells. F-18 2-fluoro 2-deoxy-D glucose (FDG) is an analogue of glucose and like glucose it is taken up by activated inflammatory cells that accumulate at the site of infection. This has formed the basis of the use of F-18 FDG PET/CT in the non-invasive evaluation of human inflammatory diseases. SOURCES OF DATA: This review is based on the published academic articles as well as our clinical experience. AREAS OF AGREEMENT: F-18 FDG PET/CT is a useful imaging modality in the evaluation of cardiovascular inflammatory disorders. Accumulation and distribution of F-18 FDG at the site of inflammation/infection corresponds to severity of the inflammation/infection and extent of involvement. AREAS OF CONTROVERSY: Most studies evaluating utility of F-18 FDG PET/CT in imaging cardiovascular inflammation are small observational studies hence are potentially prone to bias. GROWING POINTS: Being a hybrid metabolic and morphologic imaging technique, F-18 FDG PET/CT offers combined advantage of complementary anatomic and metabolic information in disease process. This makes it a useful modality in the diagnosis, determination of extent of disease, prognostication as well as treatment monitoring. AREAS TIMELY FOR DEVELOPING RESEARCH: Larger prospective studies are needed to validate the superiority of F-18 FDG PET/CT imaging over conventional anatomic imaging modalities.