CARDIOVASCULAR MECHANICS AND HEMODYNAMICS EVALUATION ACROSS THE SPECTRUM OF HEART FAILURE: FROM DIAGNOSTIC AND PROGNOSTIC ASSESSMENT TO TREATMENT GUIDANCE

Background. Cardiopulmonary hemodynamic assessment is central in heart failure (HF), enabling diagnosis, phenotyping, prognostic evaluation and treatment guidance across the disease spectrum. Right heart catheterization (RHC) remains the gold standard for assessing pressures and flows, while echocardiography allows non-invasive hemodynamic evaluation with increasing accuracy. However, important knowledge gaps persist, resulting in heterogeneous clinical application and uncertainty. Aims. This thesis aimed to bridge key gaps in invasive and non-invasive hemodynamic assessment across the HF spectrum, focusing on: the clinical relevance of flow and pressure assessment and trajectories in acute and chronic HF; the accuracy and prognostic value of non-invasive hemodynamics; the hemodynamic effects of HF therapies; and the use of hemodynamics to optimize advanced HF and left ventricular assist device (LVAD) management. Methods. Prospective and retrospective studies were conducted across cardiac intensive care units and ambulatory HF clinics. Patients with chronic HF, advanced HF, LVAD support or cardiogenic shock (CS) underwent comprehensive invasive and/or echocardiographic hemodynamic assessment, including flow, cardiovascular power, filling pressures, pulmonary pressures, and right ventricular (RV) load and adaptation. Longitudinal changes were assessed at predefined intervals. Outcomes included mortality, LVAD implantation, heart transplantation (HT), and HF hospitalization. Multivariable models, ROC analyses, agreement testing, and trajectory-based stratification were applied. Results. In >1200 patients, several key findings emerged. In CS, 24-hour invasive hemodynamic reassessment improved prognostic discrimination over baseline values, with pulmonary artery elastance (PaE) as the strongest independent predictor of inhospital mortality. Non-invasive echo-dynamics showed good agreement with invasive assessment across most parameters, enabling reliable hemodynamic phenotyping despite limitations in wedge pressure estimation. Longitudinal echo-dynamic trajectories further refined risk stratification, with persistent abnormalities in cardiovascular power, 4 pulmonary pressures and filling pressures identifying the highest-risk patients. RV–PA coupling assessed by TAPSE/PaE provided a robust non-invasive marker of RV– pulmonary interaction, outperforming isolated RV or pulmonary metrics. In advanced HF, vasodilator challenge during RHC improved prediction of post-LVAD RV failure, reflecting impaired RV reserve. In LVAD recipients, integrated hemodynamic profiling identified optimal circulatory states and enabled classification of hemodynamic complications with prognostic implications. In chronic HF, an optimal echo-dynamic profile integrating flow and filling pressures improved risk stratification and reclassified patients beyond clinical assessment. In advanced HF patients awaiting HT, SGLT2 inhibitors were safe and associated with improved clinical stability, likely mediated by more favorable and stable hemodynamic profiles. Conclusions. Across the HF spectrum, hemodynamic assessment emerged as a unifying framework for diagnosis, risk stratification and treatment guidance. In acute settings, hemodynamic trajectories—both invasive and non-invasive—provided incremental prognostic value and enabled identification of distinct pathophysiological phenotypes. In advanced HF and LVAD support, hemodynamics guided assessment of circulatory adequacy and therapy optimization. In chronic HF, integrated flow- and pressure-based profiling improved patient stratification. These findings collectively demonstrate that hemodynamic assessment - whether invasive or echocardiographic - offers a unifying physiological framework to phenotype patients, refine prognosis, and inform individualized treatment across all stages of HF