  Pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure
(mPAP) mmHg higher than 20 mmHg, is caused by vascular remodeling, increasing
pulmonary vascular resistance and decreasing pulmonary compliance. The disease
is progressive with a low 5-year survival rate. There are few measurable
biomarkers of PH progression, and conclusive diagnosis of the disease requires
invasive right heart catheterization (RHC). This study develops a systems-level
model calibrated to RHC data, providing a noninvasive tool for identifying
disease progression indicators. The model is formulated using an electrical
circuit analog, including all four heart chambers and the pulmonary and
systemic circulations. We calibrate the model considering two quantities of
interest: systolic, diastolic, and mean RHC pressure measurements and a
combination of static RHC data and time-varying pressure waveforms. Local and
global sensitivity analyses are applied to determine influential, identifiable
parameter subsets estimated to fit the model to data from five PH patients,
three with chronic thromboembolic PH (CTEPH) and two with pulmonary arterial
hypertension (PAH). From the calibrated model, we compute relevant outcomes,
including cardiac power, resistance and compliance ratios, and a pulsatility
index, and compare predictions between PH patients and normotensive controls.
Results show that both CTEPH and PAH patients have elevated pulmonary vascular
resistance and decreased compliance relative to normotensive patients. Both the
pulsatility index and right ventricular cardiac power increase in PH. Lastly,
we simulate treatment strategies for all five PH patients. Consistent with
clinical knowledge, treatment predictions show that CTEPH is curable, whereas
PAH is not.
