Is Close Really Close Enough? Immune Check Inhibitor Resulting in Pulmonary Hypertension and Congestive Heart Failure

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Abstract Introduction: Nivolumab (NV) is widely recognized as a treatment for various cancers, including non-small cell lung cancer (NSCLC). While it has demonstrated efficacy in prolonging survival, it is associated with immune-related adverse events (irAEs), one of which is pneumonitis. Here, we present the case of a 69-year-old male with stage IV NSCLC who developed grade 3 pneumonitis after receiving nivolumab, subsequently progressing to pulmonary hypertension (PAH) and right-sided heart failure. Clinical Presentation: The patient, with history of NSCLC and Chronic Obstructive Pulmonary Disease was switched to NV due to disease progression. After completing several cycles of NV, the patient experienced fatigue and worsening non-productive cough. No fever or other signs of infection reported. Physical examination revealed tachypnea, low oxygen saturation (83% on room air), and bilateral inspiratory crackles. A chest X-ray showed bilateral interstitial infiltrates, prompting a Chest CT revealing “crazy paving” patterns and ground-glass opacities in bilaterally. Imaging raised concerns for pulmonary edema vs pulmonary alveolar proteinosis vs drug-induced pneumonitis. An arterial blood gas confirmed hypoxemia, with a requirement of FiO2 35%. NV was discontinued and intravenous methylprednisolone were started for suspected pneumonitis. Empiric antibiotics were given initially, though no infection was identified. Eventually oxygen therapy was changed to High Flow nasal cannula. Over the following days his symptoms gradually improved and patient discharged with a tapering steroid regimen, and long-term oxygen therapy (LTOT).Despite LTOT, the patient continued to experience dyspnea with worsening shortness of breath. Two months later, peripheral edema, ascites, and fatigue were seen with heart failure in differential. Cardiac catheterization revealed mixed PAH, right ventricular dilation, reduced systolic function, and mean Pulmonary Artery Pressure at 38 mmHg. These findings were thought to be due to PAH secondary to chronic hypoxemia from nivolumab-induced pneumonitis. Discussion: This case illustrates the potential severe complications associated with immune checkpoint inhibitor (ICI) therapy. While NV effectively extends survival in patients with advanced malignancies, it can lead to significant irAEs like pneumonitis. In this case, persistent hypoxemia resulted in PAH and right-sided heart failure, complicating the clinical trajectory. Managing ICI-induced pneumonitis may require long-term oxygen support, and patients should be closely monitored for complications like PAH and CHF. A multidisciplinary approach involving oncologists, pulmonologists, and cardiologists is crucial for managing both acute irAEs and their chronic consequences. Early detection and management of PAH are essential, as failure to do so can significantly increase morbidity and mortality.

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