BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Heart Supplementary Table E. Valvular and myopericardial disease in the literature. Report Comments Reference VALVULAR DISEASE 1 A 55-year-old man presented for evaluation of a diffuse erythematous maculopapular Komatsuzaki et al., rash. Biopsy showed fibrosing lesions with marked IgG infiltrate and an IgG4/IgG ratio 2019 of almost 100%. This prompted workup for IgG4-RD. Serum IgG4 was high and PET-CT showed scattered lymphadenopathy; physical exam revealed cardiac murmur which PMID: 31773746 prompted echocardiography. Patient was found to have aortic stenosis. 2 A 62-year-old man with suspected IgG4-RD (history of pancreatitis, lacrimal gland Kosugi et al., 2018 enlargement, and retroperitoneal fibrosis; already on steroids) presented with dyspnea and bradycardia. EKG revealed complete atrioventricular block. Echocardiography and CT PMID: 31020164 chest revealed new severe aortic regurgitation with valve thickening extending to the left ventricular outflow tract. He was empirically treated for presumed IgG4-related valve disease with pulse steroids. AV block quickly resolved, but patient eventually developed worsening aortic regurgitation and heart failure that ultimately required valve replacement. Intraoperatively, the valve thickening was noted to have regressed. Pathology of the excised aortic valve leaflets confirmed IgG4-RD. 3 A 74-year-old man with prior suspicion of IgG4-RD (elevated serum IgG4 and CT Hourai et al., 2018 concerning for retroperitoneal fibrosis) was later found to have severe aortic stenosis and admitted. EKG was notable for complete right bundle branch block and anterior ST- PMID: 30101853 segment depressions. Coronary angiography showed LAD and RCA obstructive CAD, so he underwent CABG with aortic valve replacement. Native valve was found to have IgG4-positive plasmacytic infiltrate and patient had markedly elevated serum IgG4. This led authors to presume, but not completely confirm, IgG4-RD. 4 A 72-year-old woman presented with dyspnea and near-syncope. She was found to have Tiong et al., 2018 3-vessel CAD and severe mitral stenosis, so underwent CABG with mitral valve replacement. PMID: 29437558 5 An 82-year-old man with a history of aortic stenosis was admitted with systemic Bruls et al., 2017 symptoms concerning for lymphoma. PET-CT showed diffuse FDG-avid lymphadenopathy. Lymph node biopsy findings were consistent with IgG4-RD. Despite PMID: 28219556 steroid therapy, patient developed dyspnea and echocardiogram showed progression of aortic stenosis. Surgical replacement was performed and excised native aortic valve was found to have IgG4-positive plasmacytic infiltrate. 6 An asymptomatic 64-year-old man was incidentally found to have a systolic murmur, so Ishida et al., 2017 underwent echocardiogram which showed a mass attached to the pulmonary valve and right ventricular outflow tract. The mass was FDG-avid on PET-CT. Resection was PMID: 28219555 performed and pathology showed IgG4-RD. The mass was found to be regrowing a year later, so steroids were initiated and it regressed again. 7 A 64-year-old woman with history of orbital fibrosclerosis developed new-onset heart Besik et al., 2015 failure. Echocardiogram revealed a pathologic mass-like infiltrate that began in the anterior leaflet of the mitral valve and continued to the left ventricular outflow tract and PMID: 26434439 left coronary cusp of the aortic valve. She had resulting severe aortic regurgitation and moderate mitral stenosis and regurgitation. She did not improve with medical therapy, so partial surgical excision of the mass with aortic and mitral valve replacement was performed. Pathology showed dense lymphoplasmacytic infiltrate with elevated IgG/IgG4 ratio. 8 2 separate cases that were the first report of aortic valve involvement: Malaszewski et al., A 60-year-old woman with chest tightness and shortness of breath underwent 2015 echocardiogram and was found to have thickened aortic valve leaflets with moderate aortic stenosis, moderate to severe aortic regurgitation, and thickened mitral valve leaflets PMID: 25283128 with severe regurgitation. Aortic valve replacement was performed and excised native valves were noted to have IgG4-heavy lymphoplasmacytic infiltrate. Shakir A, et al. Heart 2021;0:1–9. doi: 10.1136/heartjnl-2020-318041 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Heart The second case was a 70-year-old man with prior history of submandibular mass and CAD status-post stent, who developed exertional dyspnea and dizziness. Echo showed severe aortic stenosis so he underwent valve replacement with pathology showing similar findings to the woman above. PET-CT was done to rule out other IgG4-RD lesions and he was found to have a pancreatic tail mass. Fine needle aspiration confirmed IgG4-RD. 9 A 58-year-old woman presented with syncope and was found to have a systolic murmur Kouzu et al., 2014 over the pulmonic valve area on exam. Transesophageal echocardiogram revealed a mass on the anterior semilunar cusp of the pulmonic valve; CT chest showed that it expanded PMID: 24369180 to obstruct the right ventricular outflow tract. Surgical resection and valvuloplasty were performed. A diagnosis of inflammatory myofibroblastic tumor was made, but IgG4/IgG ratio was elevated enough to meet criteria for IgG4-RD so this diagnosis was considered “probable.” 10 (Previously cited in Supplementary Table A – comorbid periaortitis) Hwang et al., 2013 A 70-year-old woman presented with dyspnea which prompted echocardiogram. This PMID: 24339717 revealed a mass attached to the anterior leaflet of the mitral valve, with resulting functional mitral stenosis and pulmonary hypertension. Cardiac MRI showed that the mass extended throughout the mitral valve, into the left atrial wall and interatrial septum. CT abdomen showed periaortitis; both the mitral valve and abdominal aortic lesions were FDG-avid on PET-CT. Excisional biopsy of the aortic wall mass confirmed IgG4-RD. Dyspnea resolved and valvular lesion shrunk after steroid administration. 11 A 59-year-old woman was admitted for dyspnea and leg edema. She was found to have Yamauchi et al., pleural effusions on chest X-ray and 2:1 AV block on EKG. Echocardiogram showed a 2013 mass attached to the anterior leaflet of the mitral valve and severe aortic regurgitation. She underwent aortic valve replacement. IgGR-RD diagnosis was made based on PMID: 23706467 pathology of the tumorous valve infiltrate, which was lymphoplasmacytic with high IgG4/IgG ratio. 12 (Previously cited in Supplementary Table A – comorbid periaortitis) Yang et al., 2013 54-year-old man admitted for syncope was found to have idiopathic ventricular PMID: 24776336 tachycardia requiring defibrillator implantation. Echocardiogram and PET-CT done as part of workup were suggestive of periaortitis. Patient developed worsening dyspnea and repeat PET-CT showed severe thickening of the aortic valve and anterior leaflet of the mitral valve. Aortic biopsy showed fibrosis and lymphoplasmacytic infiltrate, so IgG4- RD was tentatively diagnosed. This was presumed to be the cause of the valvular infiltrate as well. MYOCARDIAL DISEASE 1 A 47-year-old man was admitted after being shocked in the field for nonischemic cardiac Pestana et al., 2019 arrest caused by high-degree AV block. He went into torsades de pointes inpatient requiring a second shock. Echocardiogram revealed a large tumorous mass in the PMID: 29551702 interatrial septum. Echo-guided percutaneous biopsy was done and showed a benign fibro-inflammatory neoplasm. Permanent pacemaker was implanted but the mass was not resectable. Histopathology confirmed IgG4-RD. 2 A 69-year-old woman was worked up for exophthalmos and was found to have elevated Yano et al., 2018 serum IgG4. PET-CT showed high FDG uptake in bilateral orbits and mediastinal lymph nodes; it also incidentally revealed a large FDG-avid intracavitary mass in the right PMID: 30012925 atrium. EKG showed ectopic atrial rhythm. Percutaneous transcatheter biopsy was performed and revealed an IgG4-positive lymphoplasmacytic infiltrate. After 4 weeks on steroid therapy, both mass size and serum IgG4 had decreased, and EKG showed normal sinus rhythm. 3 (Previously cited in Supplementary Table A – comorbid periaortitis) Li et al., 2016 A 52-year-old man presented with acute chest pain. Echocardiogram showed a mass in PMID: 27263808 the right ventricular wall near the apex. CT angiogram redemonstrated the mass and additionally showed an ascending aortic intramural hematoma. He underwent surgical Shakir A, et al. Heart 2021;0:1–9. doi: 10.1136/heartjnl-2020-318041 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Heart exicision of the mass and replacement of the ascending aorta. Pathology of both mass and resected aortic wall was consistent with IgG4-RD. 4 (Previously cited in Supplementary Table D – comorbid phlebitis) Song et al., 2013 A 55-year-old woman with syncope and dizziness was found to have 1st-degree AV PMID: 23918583 block on EKG with multiple sinus pauses and episodes of atrial fibrillation on Holter