EXPRESS: Echocardiographic markers of pulmonary hemodynamics and right ventricular hypertrophy in rat models of pulmonary hypertension

Echocardiography is the gold standard non-invasive technique to diagnose pulmonary hypertension (PH). It is also an important modality used to monitor disease progression and response to treatment in patients with PH. Surprisingly, only few studies have been conducted to validate and standardize echocardiographic parameters in experimental animal models of PH. We sought to define cut-off values for both invasive and non-invasive measures of pulmonary hemodynamics and right ventricular (RV) hypertrophy that would reliably diagnose PH in three different rat models. The study was designed in two phases: (1) a derivation phase to establish the cut-off values for invasive measures of RV systolic pressure (RVSP), Fulton’s index (RV weight/Left ventricle+Septum weight), RV to body weight ratio (RV/BW) and non-invasive echocardiographic measures of pulmonary arterial acceleration time (PAAT), PAAT to ejection time (ET) ratio and RV wall thickness in diastole (RVWTd) in the hypoxic and monocrotaline rat models of PH and (2) a validation phase to test the performance of the cut-off values in predicting PH in an independent cohort of rats with Sugen/Hypoxia induced PH. Our study demonstrates that RVSP ≥ 35.5 mmHg and FI ≥ 0.34 are highly sensitive (>94%) and specific (> 91%) cut-offs to distinguish animals with PH from controls. When PAAT/ET and RVWTd were both measured, a result of either PAAT/ET ≤ 0.25 or RVWTd ≥ 1.03 mm detected RVSP ≥ 35.5 mmHg or FI≥0.34 with a sensitivity of 88 % and specificity of 100%. With properly validated non-invasive echocardiography measures of RV performance in rats that accurately predict invasive measures of pulmonary hemodynamics, future studies can now utilize these markers to test the efficacy of different treatments with preclinical therapeutic modeling.