The term coronary "artery vasculitis" is used for a diverse group of diseases with a wide spectrum of manifestations and severity. Clinical manifestations may include pericarditis or myocarditis due to involvement of the coronary microvasculature, stenosis, aneurysm, or spontaneous dissection of large coronaries, or vascular thrombosis. As compared to common atherosclerosis, patients with coronary artery vasculitis are younger and often have a more rapid disease progression. Several clinical entities have been associated with coronary artery vasculitis, including Kawasaki's disease, Takayasu's arteritis, polyarteritis nodosa, ANCA-associated vasculitis, giant-cell arteritis, and more recently a Kawasaki-like syndrome associated with SARS-COV-2 infection. This review will provide a short description of these conditions, their diagnosis and therapy for use by the practicing cardiologist.

Coronary Vasculitis

The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes.

/pdf/elevated-cytokines-and-chemokines-in-peripheral-blood-of-4efsbid6kk.pdf

Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

Immunoglobulin G4-Related Aortitis and Severe Aortic Valve Stenosis Treated With Transcatheter Aortic Valve Replacement and Immunosuppression.

Constrictive pericarditis remains a problematic diagnosis and a thorough investigation is critical. Among possible aetiologies, immunoglobulin-G4 (IgG4)-related pericardial disease is an unusual cause of pericardial constriction. We report a challenging diagnostic case of pericardial constriction due to IgG4-related disease.A 68-year old male with a history of inferior myocardial infarction with right ventricle (RV) involvement was thrice-hospitalized due to marked ascites and peripheral oedema. Systemic congestion was initially attributed to RV dysfunction due to previous infarction. Yet, at the final admission, a re-assessment echocardiogram followed by cardiac computed tomography, magnetic resonance and right heart catheterization raised a possible diagnosis of constrictive pericarditis with a finding of abnormal pulmonary venous return. Patient therefore underwent pericardiectomy and surgical correction of pulmonary venous return. Pericardium histology revealed an IgG4-related pericardial constriction. Patient was later discharged on corticosteroids with marked symptomatic improvement.IgG4-related disease remains a rare cause of pericardium constriction while also presenting a challenging diagnosis in everyday clinical practice. This case exemplifies the difficulties faced by clinicians when reviewing a possible case of constrictive pericarditis, while highlighting the importance of a multimodality assessment. 

/pdf/immunoglobulin-g4-related-constrictive-pericarditis-and-the-11rn45pn.pdf

Immunoglobulin G4-related constrictive pericarditis and the importance of a thorough workup: a case report

IgG4-related disease (IgG4-RD) is a systemic disease characterized by serum IgG4 upregulation, massive infiltration of IgG4-positive plasma cells, and storiform fibrosis, which results in nodules or thickening of the involved organs. Cardiologists have recently recognized that IgG4-RD can be complicated by coronary artery events (CAEs); however, the mechanisms and clinical characteristics of this phenomenon are unknown. We evaluated the clinical signs of patients with coronary periarteritis (CP), aortic periarteritis (AP), and pericardial thickening, which are complications of IgG4-RD, to determine the contributing factors.We retrospectively examined 19 patients with IgG4-RD who attended or consulted a cardiologist in our department at the University of Tokyo Hospital between January 1, 2004, and December 31, 2021.The frequency of CAEs was significantly higher in the CP group than in the non-CP group. Furthermore, the CP group had significantly lower event-free survival than the non-CP group (log-rank test, P = 0.008). However, the frequency of incidents and event-free survival for CAEs after IgG4-RD diagnosis did not differ significantly between the AP and non-AP groups. Although no statistically significant difference was present between the frequency of CAEs for those with vs without pericardial thickening, the group with pericardial thickening had significantly worse event-free survival than the group without pericardial thickening (log-rank test, P = 0.017).The incidence and clinical course of CAEs complicated by IgG4-RD could be predicted by identifying CP and pericardial thickening in IgG4-RD but not AP.La maladie liée aux immunoglobulines de type G4 (ML-IgG4) est une maladie généralisée caractérisée par une augmentation du taux sérique d’IgG4, par une infiltration massive de plasmocytes exprimant les IgG4 et par une fibrose storiforme, qui produit des nodules ou un épaississement des organes touchés. Les cardiologues ont récemment reconnu que la ML-IgG4 peut être compliquée par des événements coronariens; les mécanismes et caractéristiques cliniques de ce phénomène demeurent cependant inconnus. Nous avons évalué les signes cliniques chez des patients atteints de périartérite coronarienne (PC), de périaortite (PA) et d’épaississement du péricarde, des complications de la ML-IgG4, pour tenter d’établir les facteurs contributifs.Nous avons examiné de manière rétrospective les dossiers de 19 patients atteints de ML-IgG4 qui ont été admis à notre service de l’Hôpital de l’Université de Tokyo ou qui ont consulté un cardiologue du service entre le 1er janvier 2004 et le 31 décembre 2021.La fréquence des événements coronariens était significativement plus élevée dans le groupe PC que dans les autres groupes. Par ailleurs, le groupe PC avait une survie sans événement significativement plus courte que les autres groupes (test logarithmique par rangs; p = 0,008). En outre, la fréquence des événements coronariens et la survie sans événement coronarien après un diagnostic de ML-IgG4 ne variaient pas de manière significative entre le groupe PA et les autres groupes. Bien qu’aucune différence statistiquement significative n’ait été constatée quant à la fréquence des événements coronariens entre les patients présentant un épaississement du péricarde et les autres patients, le premier groupe affichait une survie sans événement significativement plus courte que l’autre (test logarithmique par rangs; p = 0,017).L’incidence et le déroulement clinique des événements coronariens compliqués par la ML-IgG4 pouvaient être anticipés dans les cas de ML-IgG4 en présence de PC et d’un épaississement du péricarde, mais pas de PA. 

https://doi.org/10.1016/j.cjco.2023.03.008

Coronary Periarteritis and Pericardial Thickening Could Be Predictors for Coronary Artery Events Complicated by IgG4-Related Disease

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disease characterised by multiorgan lymphoplasmacytic infiltration, obliterative phlebitis and storiform fibrosis. It can be associated with cardiovascular pathology. The objective of this narrative review is to summarise the published literature on cardiovascular manifestations of IgG4-RD and to provide a basis for diagnosis and management of the condition by the practising cardiologist.We propose the following categorisations of cardiovascular IgG4-RD: aortitis, medium-vessel arteritis, pulmonary vascular disease, phlebitis, valvulopathy, pericarditis, myocardial disease and antineutrophilic cytoplasmic antibody-associated vasculitis. We also review herein developments in radiological diagnosis and reported medical and surgical therapies. Cardiovascular lesions frequently require procedural and/or surgical interventions, such as aortic aneurysm repair and valve replacement. IgG4-RD of the cardiovascular system results in serious complications that can be missed if not evaluated aggressively. These are likely underdiagnosed, as clinical presentations frequently mimic cardiovascular disease due to more common aetiologies (myocardial infarction, abdominal aortic aneurysm and so on). While systemic corticosteroids are the mainstay of IgG4-RD treatment, biological and disease-modifying agents are becoming more widely used. Cardiologists should be aware of cardiovascular IgG4-RD as a differential diagnosis, and understand the roles of corticosteroids, disease-modifying agents and biologicals, as well as their integration with surgical approaches. There are several knowledge gaps, including diagnosis, risk factors, pathogenesis and appropriate management in Ig4-RD of the cardiovascular system. Areas lacking well-conducted randomized trials include safety of steroids in the setting of vascular aneurysms and the role of disease-modifying drugs and biological agents in patients with established cardiovascular complications of this multifaceted enigmatic disease.

https://heart.bmj.com/content/heartjnl/early/2021/01/18/heartjnl-2020-318041.full.pdf

Yurong Wheeler

Papers

The enigmatic immunoglobulin G4-related disease and its varied cardiovascular manifestations.