A 48-year-old man with a history of granulomatosis with polyangiitis (GPA) and hypertension presents with a 4-week history of shortness of breath (SOB) and progressive lower extremity edema. He endorses increased abdominal distension, decreased appetite, and daily episodes of epistaxis that have been unchanged for several years.

His pertinent rheumatologic history is notable for a diagnosis of GPA 15 years before presentation. His initial clinical presentation involved migratory joint pain of multiple joints followed by persistent ankle and knee swelling, bilateral scleritis, and intermittent hemoptysis, and laboratory data were notable for a high-titer anti–proteinase 3 (PR3) antineutrophil cytoplasmic antibody (c-ANCA). He was initially treated with cyclophosphamide followed by methotrexate, then was off therapy for an extended period. His last treatment included rituximab 11 months earlier while traveling abroad. He is not currently taking any immunosuppression therapy.

Physical examination shows blood pressure 138/62 mm Hg, heart rate 90 bpm, temperature 36.8°C, and oxygen saturation 100%. Cardiac auscultation demonstrates a loud diastolic murmur at the right upper sternal border, elevated jugular venous filling pressure, and bilateral pitting edema.

Laboratory workup findings include an elevated N-terminal pro–B-type natriuretic peptide level of 5323 pg/mL (reference range <450 pg/mL) and high-sensitivity troponin level of 35 ng/L (reference range <14 ng/L). Complete blood count values are notable for white blood cell count 7100 cells/mcL (reference range 4,000-10,000 cells/mcL) with 10.5% eosinophilia and mildly elevated eosinophil count of 740/mcL (reference range 0-500/mcL). Complete metabolic panel values are unremarkable (serum creatinine level 0.85 mg/dL [reference range 0.5-1.2 mg/dL]). Erythrocyte sedimentation rate is 37 mm/hour (reference range <15 mm/hour) and high-sensitivity C-reactive protein level is 14.1 mg/L (reference range <10 mg/L). c-ANCA is positive with an anti-PR3 titer of 856 CU (reference range <19 CU). A transthoracic echocardiogram has findings of severe aortic insufficiency (AI) (Video 1). A transesophageal echocardiogram has findings of a tricuspid aortic valve (AoV). Leaflets are mildly thickened with central malcoaptation (Videos 2a, b, c, d). Severe aortic regurgitation (AR) with centrally directed jet and holodiastolic flow reversal in the descending aorta are evident (Image 1). The left ventricle is mildly dilated and left ventricular function is 50%.

Video 1: Severe Aortic Regurgitation by Color Doppler

Video 2a: Echocardiographic Images Showing Tricuspid Aortic Valve With Mildly Thickened Leaflets and Central Malcoaptation

Video 2b: Echocardiographic Images Showing Tricuspid Aortic Valve With Mildly Thickened Leaflets and Central Malcoaptation

Video 2c: Echocardiographic Images Showing Tricuspid Aortic Valve With Mildly Thickened Leaflets and Central Malcoaptation

Video 2d: Echocardiographic Images Showing Tricuspid Aortic Valve With Mildly Thickened Leaflets and Central Malcoaptation

Image 1

During his hospital admission, he is managed with intravenous diuresis, with significant improvement in SOB and lower extremity edema. Multiple sets of blood cultures have negative findings. He undergoes extensive workup for eosinophilia with infectious disease and hematology including flow cytometry and cytogenetics; workup findings are unrevealing.

Further cardiac imaging is obtained. Cardiac computed tomography findings confirm diffuse thickening of the AoV leaflets with significant central malcoaptation (Video 3). Cardiac magnetic resonance imaging (MRI) has findings of thickening of the AoV and severe AI (Video 4). There is no evidence of late gadolinium enhancement, and native T1 and T2 times are normal, ruling out myocardial edema, inflammation, or scar. Whole-body positron emission tomography scan does not have findings of any abnormal fluorodeoxyglucose uptake surrounding the AoV or signs of active extracardiac GPA.

Video 3: Cardiac Computed Tomography Showing Tricuspid Aortic Valve With Mildly Thickened Leaflets and Central Malcoaptation

Video 4: Cardiac Magnetic Resonance Images Showing Aortic Insufficiency