High-altitude pulmonary edema (HAPE) represents one of the most severe and potentially fatal forms of high-altitude illness encountered in individuals ascending to elevations typically above 2,500 meters. Despite advances in preventive strategies and clinical management, HAPE continues to pose diagnostic and therapeutic challenges, particularly in acclimatized individuals and in settings where overlapping cardiopulmonary conditions may obscure its recognition. The condition is characterized by non-cardiogenic pulmonary edema associated with exaggerated hypoxic pulmonary vasoconstriction, heterogeneous pulmonary blood flow, and capillary stress failure. Recent clinical and physiological research has expanded understanding of its pathophysiology, electrocardiographic manifestations, biomarker profiles, and therapeutic responses, yet important gaps persist in distinguishing HAPE from mimicking conditions such as pulmonary embolism and acute coronary syndromes at altitude. This review synthesizes contemporary evidence on the epidemiology, pathophysiological mechanisms, diagnostic criteria, electrocardiographic changes, and management strategies for HAPE, with particular emphasis on objective diagnostic frameworks and treatment modalities including oxygen therapy, pharmacological interventions, and non-invasive ventilatory support. By integrating clinical observations with physiological insights, this manuscript aims to provide a comprehensive and updated perspective on HAPE for clinicians practicing in high-altitude and expeditionary environments, while highlighting unresolved questions and directions for future research.

High-altitude pulmonary edema, hypoxic pulmonary vasoconstriction, electrocardiography, altitude illness, oxygen therapy, nifedipine

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