A 34-year-old man with debilitating polyneuropathy and monoclonal gammopathy presents with progressive lower extremity edema, pericardial effusion and dyspnea. Pulmonary edema, elevated jugular venous pressure and peripheral edema suggested right heart failure, and dyspnea responded initially to diuresis. Echocardiography revealed occult pericardal effusion, right heart dysfunction and estimated right ventricular systolic pressure of 54 mmHg. The differential diagnosis included pulmonary hypertension secondary to chronic pulmonary or left heart processes, pericardial constriction, restrictive myopathy or a syndromic condition capturing his neurologic and hematologic findings. Chest CT and VQ-scan were negative for acute and chronic pulmonary thromboembolic disease, respectively. Cardiac magnetic resonance imaging was most consistent with amyloidosis. Pericardial enhancement was normal, arguing against constriction. Amyloidosis was thought to be unlikely given preserved left ventricular size and function, increase in both serum free κ and λ light chains, and was ultimately excluded by fat pad biopsy. The paraneoplastic disease Crow-Fukase or POEMS syndrome, classically described as polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes explained the patient’s constellation of signs and symptoms. Pulmonary hypertension subsequent to cor pulmonale is common and reversible with treatment of the underlying gammopathy. Diagnosis of the POEMS syndrome was confirmed by the presence of sclerotic bone lesions and markedly elevated vascular endothelial growth factor (VEGF) level of 1028 pg/mL (ref. range 31-86 pg/mL). VEGF is highly induced in the POEMS syndrome and correlates closely with disease activity. VEGF-mediated microangiopathy, neovascularization, and vasopermeability likely underlie multiple clinical sequelae of extravascular volume overload such as pericardial effusion and peripheral edema. The patient responded to sildenafil for pulmonary arterial hypertension and immunomodulatory therapy for the monoclonal gammopathy. At six months of treatment, the patient has recovered substantial strength, heart failure has not reoccurred and repeat VEGF level reduced to 383 pg/mL.
PATHOPHYSIOLOGY IN PULMONARY HEART DISEASES, WITH SPECIAL REFERENCE TO ROLE OF PULMONARY HYPERTENSION, HYPOXEMIA AND RIGHT VENTRICULAR HYPERTROPHY ON RIGHT HEART FAILURE
