Pulmonary Hypertension Complicating Multiple Myeloma

Abstract

Pulmonary hypertension (PH) is an infrequently reported complication of multiple myeloma (MM). PH has been more commonly associated with amyloidosis, myeloproliferative diseases, and the POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome. PH in MM is typically mild to moderate and may be secondary to a variety of conditions, which include left ventricular dysfunction, high-output cardiac failure, chronic kidney disease, treatment-related toxicities, and precapillary involvement. We describe 3 patients with MM and severe PH. Each patient underwent right heart catheterization. All patients demonstrated elevated pulmonary pressures, transpulmonary gradients, and pulmonary vascular resistance. Each patient was ultimately treated with pulmonary vasodilator therapy with improvement in cardiopulmonary symptoms. Additional studies are needed to define the prevalence, prognosis, and pathogenesis of PH in this complex population and to help clarify who may benefit from targeted PH therapy.Keywords: pulmonary hypertension, multiple myeloma, pulmonary vasculature, amyloidosis. Multiple myeloma (MM) is a hematological malignancy characterized by the neoplastic proliferation of plasma cells within bone marrow and extramedullary sites. It is distinguished from other disorders of plasma cell proliferation by the presence of CRAB features, defined as hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. 1 Although cardiovascular pathology has been frequently associated with MM, pulmonary hypertension (PH), which is characterized by elevated pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR), is not a commonly recognized complication. We report the clinical and hemodynamic features of 3 patients with established MM and severe PH. We also provide a review of the literature and discuss the different pathways for development of PH in this mixed population. CASE DESCRIPTION Case 1Patient 1 was a 72-year-old man who presented to the PH clinic with exertional dyspnea. His medical history was significant for immunoglobulin A (IgA) κ MM treated with hematopoietic autologous stem cell transplantation (HSCT) 3 years earlier. At the time of presentation, the patient was receiving maintenance chemotherapy with lenalidomide to help extend clinical remission. In addition, he had a history of permanent atrial fibrillation and severe aortic stenosis. Physical examination revealed a 3/6 crescendo-decrescendo murmur at the upper sternal base radiating to the carotids and a soft 1/6 holosystolic murmur at the lower sternal base. Transthoracic echocardiography (TTE) revealed an ejection fraction (EF) of 62%, a dilated left atrium (LA), pulmonary artery systolic pressure (PASP) of 83 mmHg, flattening of the interventricular septum, a severely dilated right ventricle (RV) and right atrium (RA), mildly reduced RV function, and an aortic valve area of 0.73 cm 2 . A right heart catheterization (RHC) showed PAP of 96/32 mmHg (mean, 53 mmHg) with a left ventricular (L...

Gamma heavy chain disease complicated by pulmonary hypertension, which was successfully treated with lenalidomide

“…10 Some cases of pulmonary hypertension are complicated by multiple myeloma, and the aetiology may not involve a single mechanism, but rather a combination of mechanisms, such as immunoglobulin light chain (AL) amyloid deposition, high cardiac output states, or renal disease. 11 AL amyloidosis often involves the heart, and elevated left atrial pressure may cause pulmonary hypertension. Furthermore, a previous case report of pulmonary hypertension was due to pulmonary vascular amyloid deposition in a patient with multiple myeloma.…”

Carfilzomib‐associated pulmonary arterial hypertension in multiple myeloma

“…Prior reports have described heart failure, hypertension and ischemic heart disease related to carfilzomib 2,3 . While there are several mechanisms for pulmonary hypertension in multiple myeloma 4 , including thromboembolic disease and amyloidosis, drug-associated pulmonary arterial hypertension may become increasingly common, especially as novel medications are emerging. These two cases demonstrate that in addition to ruling out other causes of pulmonary hypertension related to multiple myeloma, drug therapy for myeloma should be carefully monitored.…”

Pulmonary Hypertension in an Oncologic Intensive Care Unit

“…Attributing PH solely to chronic myeloproliferative disease is difficult, as many of the reported cases did not have a right heart catheterization (RHC) needed to definitively diagnose PAH and rule out other causes such as left heart disease [54]. Multiple myeloma has also been associated with PH with potential etiologies that include concomitant amyloidosis, left heart dysfunction, chronic kidney failure, and treatment-related toxicities [50]. Other etiologies of PH in group 5 may be from obstruction of pulmonary vasculature from metastatic disease or primary tumors of the pulmonary vasculature (e.g., pulmonary artery sarcoma), or fibrosing mediastinitis due to previous radiation therapy or fungal infection such as histoplasmosis.…”