Echocardiographic, Biochemical, and Electrocardiographic Correlates Associated With Progressive Pulmonary Arterial Hypertension

Abstract

Background: Pulmonary arterial hypertension (PAH) is a progressive proliferative vasculopathy associated with mechanical and electrical changes, culminating in increased vascular resistance, right ventricular (RV) failure, and death. With a main focus on invasive tools, there has been an underutilization of echocardiography, electrocardiography, and biomarkers to non-invasively assess the changes in myocardial and pulmonary vascular structure and function during the course of PAH.Methods: A SU5416-hypoxia rat model was used for inducing PAH. Biventricular functions were measured using transthoracic two-dimensional (2D) echocardiography/Doppler (echo/Doppler) at disease onset (0 week), during progression (3 weeks), and establishment (5 weeks). Similarly, electrocardiography was performed at 0, 3, and 5 weeks. Invasive hemodynamic measurements and markers of cardiac injury in plasma were assessed at 0, 3, and 5 weeks.Results: Increased RV systolic pressure (RVSP) and rate of isovolumic pressure rise and decline were observed at 0, 3, and 5 weeks in PAH animals. EKG showed a steady increase in QT-interval with progression of PAH, whereas P-wave height and RS width were increased only during the initial stages of PAH progression. Echocardiographic markers of PAH progression and severity were also identified. Three echocardiographic patterns were observed: a steady pattern (0–5 weeks) in which echo parameter changed progressively with severity [inferior vena cava (IVC) expiratory diameter and pulmonary artery acceleration time (PAAT)], an early pattern (0–3 weeks) where there is an early change in parameters [RV fractional area change (RV-FAC), transmitral flow, left ventricle (LV) output, estimated mean PA pressure, RV performance index, and LV systolic eccentricity index], and a late pattern (3–5 weeks) in which there is only a late rise at advanced stages of PAH (LV diastolic eccentricity index). RVSP correlated with PAAT, PAAT/PA ejection times, IVC diameters, RV-FAC, tricuspid systolic excursion, LV systolic eccentricity and output, and transmitral flow. Plasma myosin light chain (Myl-3) and cardiac troponin I (cTnI) increased progressively across the three time points. Cardiac troponin T (cTnT) and fatty acid-binding protein-3 (FABP-3) were significantly elevated only at the 5-week time point.Conclusion: Distinct electrocardiographic and echocardiographic patterns along with plasma biomarkers were identified as useful non-invasive tools for monitoring PAH progression.

Ethanol‐induced lung and cardiac right ventricular inflammation and remodeling underlie progression to pulmonary arterial hypertension

“…The ethanol-induced RV hypertrophy, which is expressed as a higher RV/body weight ratio and Fulton index (RV/LV+ Septum) (Figure 1B,C), likely resulted from increased RV afterload, a hallmark cardiac phenotype of PAH (Ryan & Archer, 2014). As discussed earlier, elevated RV afterload is supported by ethanol-induced: (1) progressive reductions in both PAAT and PAAT/PET (Figure 2A,B), which are inversely related to RVSP derived from right ventricle catheterization (Spyropoulos et al, 2020;Zaky et al, 2021), and (2) elevation in mPAP (Figure 2D). Our echocardiographic findings of ethanolinduced progressive increases in RV chamber size (Figure 2C) likely F I G U R E 3 Ethanol causes pulmonary arteriole thickening and RV cardiomyocyte hypertrophy.…”

“…Rat chest hair was removed using Veet® hair removal cream. Echocardiography data analysis was conducted using VivoLab Software (Zaky et al., 2021).…”

Inhibition of KIR2.1 decreases pulmonary artery smooth muscle cell proliferation and migration

“…PAAT is the time interval between the onset of systolic pulmonary arterial flow and peak flow velocity. Previous studies have demonstrated that PAAT is inversely proportional to pulmonary vascular resistance (28)(29)(30). If the pulmonary vascular resistance increases, the pulmonary artery pressure also increases.…”

Quercetin regulates pulmonary vascular remodeling in pulmonary hypertension through TGF-β1-Smad2/3 pathway

“…PAAT was measured near the pulmonary valve on the left chest. According to the current guidelines of the American Society of Echocardiography, mPAP can be calculated according to the following formula: mPAP = 72-(0.42×PAAT, PAAT < 120 ms) [23,25]. After the detection, the rats were sacri ced under deep anesthesia (I.P.…”