Orthostatic Hypotension in Continuous-Flow LVADs: Baroreflex Unloading, Preload Dependence, and a Phenotype-Specific Framework

Orthostatic hypotension (OH) is an underrecognized consequence of continuous-flow left ventricular assist device (CF-LVAD) therapy, affecting 12–30% of patients. Reduced arterial pulsatility during CF support creates a distinct autonomic environment characterized by impaired baroreceptor stimulation, defective sympathetic vasoconstriction, exaggerated venous pooling, and extreme preload dependence. Traditional blood pressure assessments often fail to identify OH in this population, and resting hemodynamics rarely reveal the underlying mechanism. In this perspective piece, we propose a two-phenotype, physiology-based framework for OH specific to CF-LVAD patients. We synthesize current knowledge of baroreflex biology, vascular capacitance, and pump dynamics to describe how reduced pulsatility disrupts cardiovascular responses to upright posture. Within this framework, we define two dominant mechanistic phenotypes: (1) autonomic dysfunction-predominant failure, where impaired reflexes drive orthostatic venous pooling and LV underfilling, and (2) right ventricular (RV) failure–limited forward flow, where RV dysfunction constrains preload delivery to the pump despite preserved autonomic tone. We outline how integrating autonomic data with LVAD hemodynamics and posture-linked imaging—specifically dynamic changes in venous capacitance, inferior vena cava behavior, left ventricular end-diastolic dimension, and pump performance—forms a coherent diagnostic and management pathway. This physiology-first approach allows clinicians to distinguish between preload failure and RV-limited flow at the bedside and tailor therapy accordingly. A mechanistic understanding of OH in CF-LVAD patients is essential for accurate diagnosis, preventing suction events, optimizing device settings, and reducing morbidity through targeted, mechanism-specific management.