A 65-year-old man with a history of paroxysmal atrial fibrillation, OSA, and remote cigarette smoking was referred to the Thoracic Surgery clinic for a posterior mediastinal mass in the setting of progressively debilitating neurologic symptoms of the face and neck.

A 78-year-old woman with gastroesophageal reflux disease was admitted with 2 months of progressive dyspnea on exertion and leg swelling. At baseline, she could walk 10 blocks; at presentation, she managed less than 6 steps. For a month, she had been sleeping upright in a chair. She experienced no fever, cough, palpitations, or chest pain. With prompting, she shared a several-year history of discomfort and skin changes in her fingers; she attributed these symptoms to chemical exposures as a housecleaner.

A 13-year-old boy was transferred to our institution for evaluation of a large, unexplained pleural effusion. He had a 1-month history of progressive dyspnea, accompanied by a 2-week history of fevers and a 2-kg weight loss, which was notable given his lean build. A chest CT scan performed at an outside hospital had revealed a large left-sided pleural effusion with associated low-density lesions in the sternum and vertebrae. A thoracic drainage tube had been placed, draining approximately 500 mL of turbid fluid daily. The patient's family reported no history of recent travel or exposure to pets.

Calcitonin gene-related peptide (CGRP)-targeted therapies are a recent addition to the migraine field. Monoclonal antibodies became available in 2018 and gepants in 2020, both now widely used for migraine prevention and acute treatment. CGRP is also a potent endogenous pulmonary vasodilator, and its blockade worsens pulmonary hypertension in experimental models. Yet the cardiopulmonary risks of CGRP pathway inhibition in humans have not been studied systematically. We report 3 patients with hemodynamically confirmed pulmonary arterial hypertension (PAH) diagnosed while they were receiving CGRP-targeted therapy. Two patients lacked traditional PAH risk factors; the third patient had suspected portal hypertension. All patients presented with markedly elevated pulmonary vascular resistance, and 2 patients improved after CGRP-targeted therapy was discontinued and PAH treatment was initiated. Although causality cannot be inferred from these cases, the temporal association and biologic plausibility suggest a potential safety signal deserving of further study. Clinicians should remain vigilant for cardiopulmonary symptoms in patients receiving CGRP-targeted therapies.