ECHOCARDIOGRAPHY AND EVALUATION OF CARDIAC PHYSIOLOGY

Introduction: Pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) assessment are fundamental for cardiac disease diagnosis and management. Right heart catheterization (RHC) provides accurate PCWP and RAP measurement, but it is invasive and impractical for widespread use. The left atrial expansion index (LAEI), measured by either transthoracic echocardiography (TTE) or cardiovascular magnetic resonance (CMR), and the right atrial expansion index (RAEI), measured by TTE, estimate the LA and RA compliance by describing the relative LA and RA volume increase during the atria reservoir phase. This thesis aimed to assess and validate LAEI and RAEI as non-invasive parameters for PCWP and RAP estimation. Methods: We performed four observational, cross-sectional, single-center studies. The 1st study retrospectively enrolled 649 patients with various chronic cardiac diseases divided into derivation (n=509) and validation (n=140) cohorts. The 2nd study retrospectively enrolled 167 patients with mitral valve (MV) stenosis, prosthesis, and repair. In the 3rd study, we included 126 patients with dilated cardiomyopathy (DCM) divided into derivation (n=92, retrospective) and validation (n=34 prospective) cohorts. Finally, in the 4th study, we included 586 patients with various chronic cardiac diseases divided into derivation (n=406, retrospective) and validation (n=180, prospective) cohorts. All patients underwent clinically indicated RHC and either TTE (1st, 2nd, 4th study) or CMR (3rd study) within 24 hours. PCWP and RAP were measured during RHC, whereas TTE/CMR parameters were measured offline, blinded to RHC results. Results: In the 1st study, we found that TTE-measured LAEI had a strong logarithmic association with PCWP (lnLAEI-PCWP:r=-0.73, p<0.001); lnLAEI showed an independent and added predictive value for PCWP estimation over clinical and diastolic dysfunction (DD) parameters. In the validation cohort, lnLAEI<4.02 identified PCWP>12mmHg with higher accuracy than 2016 DD algorithm (88% vs. 74%) and PCWP=38.3-6.2xlnLAEI predicted invasively measured PCWP (0.4±5.4mmHg). In the 2nd study, TTE-measured LAEI maintained the logarithmical association with PCWP (lnLAEI-PCWP:r=-0.616; p<0.001). lnLAEI was an independent determinant of PCWP and provided added predictive value over clinical and TTE parameters. Moreover, lnLAEI discriminated elevated PCWP better than other TTE parameters, and PCWP=36.8-5.5xlnLAEI could estimate invasive PCWP (0.0±6.1mmHg). In the 3rd study, CMR-measured LAEI was also logarithmically associated with PCWP (lnLAEI-PCWP:r=-0.81, p<0.001), and lnLAEI provided added and independent predictive value over clinical and CMR parameters for PCWP estimation. In the validation cohort, lnLAEI≤3.85 identified PCWP≥15mmHg with 85.3% accuracy and PCWP=52.33-(9.17xlnLAEI) predicted PCWP (-0.1±5.7mmHg). In the 4th study, TTE-measured RAEI was logarithmically correlated to RAP (lnRAEI-RAP:r=-0.64, p<0.001), and lnRAEI provided independent and added predictive value for RAP assessment over clinical and TTE parameters, including inferior vena cava (IVC) diameter and collapsibility index. In the validation cohort, lnRAEI<3.57 was more accurate than IVC assessment for the identification of RAP≥10mmHg (81.7% vs. 71.7%), and RAP=18.9-3.2xlnRAEI predicted invasive RAP (0.31±2.9mmHg) more accurately than guidelines recommended IVC assessment (1.73±4.4mmHg). Conclusions: TTE-measured LAEI outperformed the 2016 DD algorithm for PCWP estimation in a large cohort of patients with various cardiac diseases and also allowed non-invasive PCWP assessment in patients with MV stenosis, prosthesis, and repair. Furthermore, CMR-measured LAEI resulted in an accurate and straightforward parameter for PCWP assessment in DCM patients. Finally, TTE-measured RAEI resulted in a novel and fast parameter more accurate than IVC assessment for RAP estimation.