Cardiac Involvement in Cryoglobulinemia: Clinical Characteristics, Radiological Features, and Outcomes

Background: Cardiac involvement in cryoglobulinemia (CG) is rare but potentially fatal, and its clinical spectrum remains poorly characterized. Methods: This retrospective study enrolled 11 patients with cardiac involvement among 885 patients with CG at Peking Union Medical College Hospital between January 2015 and March 2026. We analyzed its clinical characteristics, radiological features and management. Results: Among 885 CG patients, 11 (1.2%; 4 type I, 7 type II) had cardiac involvement. Cardiac symptoms included dyspnea (n = 6), chest tightness (n = 4), edema (n = 3), and orthopnea (n = 1). All patients had elevated N-terminal pro-B-type natriuretic peptide (median 29,799 pg/mL). Echocardiography, performed in all 11 patients, revealed left heart enlargement (n = 9), reduced left ventricular ejection fraction (n = 7), myocardial disease (n = 6), pericardial effusion (n = 4), and pulmonary hypertension (n = 3). Cardiac magnetic resonance in 5 of 11 patients showed non-ischemic late gadolinium enhancement in two cases. For first-line therapy, 6 of 11 patients received rituximab-based regimens, 3 of 11 received bortezomib-based regimens, and 1 of 11 received antiviral therapy with corticosteroids; 1 patient declined treatment. All 10 treated patients achieved initial cardiac improvement, with 5 relapsing and 2 dying during a median follow-up of 57 months (range 9–130 months). The estimated 4-year overall and progression-free survival rates were 77.9% (95% CI: 0.546–1.000) and 50.0% (95% CI: 0.269–0.929), respectively. Conclusions: Cardiac involvement in CG is rare and associated with diverse structural and functional abnormalities. Cardiac involvement should be considered in CG patients presenting with unexplained cardiac manifestations after excluding alternative causes. B-cell-targeted therapy induced an initial response, but relapse is common. Early intervention is essential given the substantial relapse burden and potential for severe morbidity.