| Summary: | In recent years, an increasing body of evidence has emerged postulating that right ventricular (RV) - pulmonary artery (PA) ventriculoarterial coupling may offer insight into the transition from RV adaptation to RV maladaptation in different cardiopulmonary disorders and heart failure. RV-PA ventriculoarterial coupling is a matching between RV contractility (Ees – End-Systolic Elastance) and afterload (Ea – Effective Arterial Elastance). While ventriculoarterial coupling has been extensively described in the LV and used to determine optimal conditions for the efficient transfer to blood from the ventricle into the aorta, it remains unclear whether this relationship can be translated to the thinner walled RV that pumps at lower pressures against a more compliant pulmonary vascular system. Therefore, the pressure-volume (PV)-loop studies in this thesis were undertaken to assess whether ventriculoarterial uncoupling due to pressure overload or sub-optimal contractility contributed to further RV diastolic dysfunction. An in-vivo porcine model of RV-PA ventriculoarterial coupling was developed to define optimal conditions. This animal model was used to provide insights into two clinical patient groups that have RV dysfunction due to: i) long-term RV pressure overload in patients with a clinical diagnosis of chronic thromboembolic disease (CTED) / pulmonary hypertension (CTEPH); and ii) aortic valve stenosis transmitted by ventricular interdependence and septal wall reconfiguration in patients treated with transcatheter aortic valve implantation (TAVI). The animal model determined an ventriculoarterial coupling ratio at maximal stroke work (Ees/Eamax sw = 0.68±0.23) threshold, below which cardiac output and RV stroke work fell. In the first clinical study this threshold was used to reclassify 25% of a cohort of patients with CTED or CTEPH. Two patients with CTED were identified with an EesEa below 0.68 suggesting occult RV dysfunction whilst three patients with CTEPH demonstrated Ees/Ea≥0.68 suggesting residual RV energetic reserve. In the second clinical study ventricular interdependence phenomena caused septal reconfiguration and increased RV volumes after valve deployment, due to the reduction in LV afterload. However, the rapid pacing (RP) protocol used to stabilise the aortic valve during deployment also caused RP-induced ischemia and stunning. This resulted in the reduction of Ees and led to Ees/Ea uncoupling and further diastolic dysfunction. This work has demonstrated that: Low Ees/Ea aligns with features of RV maladaptation in CTED. Characterization of Ees/Ea in CTED may allow for better identification of occult RV dysfunction in patients with otherwise normal pulmonary hemodynamics; and a reduction in Ees following TAVI correlates with increased RV diastolic dysfunction, due to RP-induced ischemia and stunning.
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