Dyspnea in heart failure: pathophysiology, clinical assessment, and evidence from clinical trials

Dyspnea is a key symptom of heart failure (HF), particularly in its acute form, where it represents the most common cause of hospitalization. Although traditionally attributed to pulmonary congestion, dyspnea in HF is a multidimensional phenomenon resulting from complex interactions among elevated cardiac filling pressures, hemodynamic alterations, fluid redistribution, impaired gas exchange, activation of mechano- and chemoreceptors, and maladaptive neurohormonal activation. Comorbidities, including chronic lung disease, obesity, cachexia, renal dysfunction, anemia, and chronic inflammation, further modulate symptom perception and lower the threshold for its occurrence. In this review, we synthesize current knowledge on the pathophysiological mechanisms underlying dyspnea in HF, emphasizing its heterogeneity and the complex interplay between hemodynamics, ventilatory regulation, and peripheral factors. We discuss available dyspnea assessment tools, highlighting their strengths and methodological limitations in clinical practice and randomized trials. Despite the use of standardized scales, dyspnea remains a subjective and dynamically evolving symptom. Data from large clinical trials in acute HF indicate that early improvement in dyspnea is common but does not translate into reduced mortality or rehospitalization, whereas residual dyspnea identifies patients at higher risk of adverse events. A better understanding of its multidimensional pathophysiology, measurement limitations, and prognostic significance has important implications for the interpretation of clinical trial results and for optimizing the assessment and management of this fundamental symptom.