
 Introduction:
 Insulin like growth factor binding proteins (IGFBPs) are a family of growth factor modifiers, some of which are known to be independently associated with PAH survival. IGFBP7 is a unique low-affinity IGFBP that, independent of IGF, stimulates prostacyclin production.
 
 
 Hypothesis:
 Elevated IGFBP7 is associated with worse disease severity and survival in PAH.
 
 
 Methods:
 Using enzyme-linked immunosorbent assays (ELISA), we evaluated serum IGFBP7 in a multicenter PAH cohort, the NHLBI PAHBiobank (N=2583), and healthy controls (N=99). Hemodynamic and functional measures were used to assess IGFBP7’s association to PAH severity and survival. Kruskal Wallis was used for comparison and Spearman’s rank correlation for correlations. Linear and logistic regressions performed for associations. IGFBP7 was dichotomized at the median and analyzed by Kaplan-Meier survival and Cox proportional Hazard regression.
 
 
 Results:
 Serum IGFBP7 levels were significantly elevated in patients with PAH compared to controls. After adjustment, logarithmic increases in IGFBP7 were associated with a 38 meter shorter six-minute walk distance (6MWD; -37.7, 95%CI -54 to -21, p=<0.001), a higher mean right atrial pressure (2.18mmHg, 95%CI 1.51-2.89, p<0.001) and a higher REVEAL risk score (1.10, 95%CI 0.88-1.33, p <0.001). Logarithmic increases in IGFBP7 were also associated with a two-times higher likelihood of having PAH associated with Portopulmonary disease (2.39, 95%CI 1.95-2.84, p<0.001). Kaplan Meier analysis demonstrated significant survival effects of IGFBP7 above the median (see Figure 1) and an adjusted (age, sex, functional class, and 6MWD) Cox proportional hazards model (HR 3.1, 95% CI 2.2-4.4, p<0.001).
 
 
 Conclusions:
 Higher circulating IGFBP7 levels were significantly associated with worse PAH severity and decreased survival. Given its role of as a prostacyclin stimulant, IGFBP7 may also serve as a therapeutic target for disease modulation.
 
 
 


Abstract 13688: Low-Affinity Insulin-Like Growth Factor Binding Protein 7 and Its Association With Pulmonary Arterial Hypertension Severity and Survival

Application of Deep Convolutional Neural Networks in Determining Chronicity of Pulmonary Nodules in Patients with Nontuberculous Mycobacterial Lung Infection

Association of Clinical and Imaging Characteristics With Pulmonary Function Testing in Patients With Long-COVID


 Introduction:
 Right ventricular (RV) diastolic dysfunction in pulmonary arterial hypertension (PAH) remains poorly understood. In this study, we used RV pressure-volume (PV) loops to assess RV diastology as a function of afterload in PAH.
 
 
 Methods:
 RV PV loops were prospectively measured in control (n=9) and PAH (n=39) patients at rest and during supine bike exercise. PAH patients were stratified by effective arterial elastance (Ea), a lumped measure of total afterload, into two groups: high afterload (HA, n=20) and severe afterload (SA, n=19).
 
 
 Results:
 PAH groups were matched with respect to age, sex, and PAH medication usage. Ea at rest and exercise was higher in SA PAH (1.8 vs. 0.6 mmHg/ml, P <0.0001 at rest; 2.3 vs 0.8 mmHg/ml, P < 0.0001 with exercise). In the SA group, RV end-diastolic pressure (RVEDP) was higher at rest (13.3 vs 7.6 mmHg, P = 0.0017) and rose markedly with exertion (23.4 vs 13.1 mmHg, P=0.0001). Because RV volumes changed similarly in both groups, SA patients exhibited stiffer RVs (dP/dV 0.30 vs 0.11 mmHg/mL, P=.024). To understand pericardial-interventricular interactions, we calculated the RVEDP-to-pulmonary capillary wedge pressure (PCWP) ratio and the left ventricular (LV) transmural filling pressure (LVTMFP). RVEDP/PCWP was substantially higher in SA (2.1 vs 1.0, P=.005). Therefore, even though PCWP rose considerably in SA (mean 16 mmHg), exercise LVTMFP was significantly reduced in SA vs HA PAH (-7.5 vs 2.55 mmHg, P=0.002). Along with reduced LV size seen by concomitant echo, we thus revealed blunted LV filling specifically in SA PAH. Accordingly, exercise cardiac index, stroke volume index, and LV stroke work index were all markedly reduced in SA PAH.
 
 
 Conclusions:
 Severe afterload in PAH results in high RV diastolic pressures and RV stiffening, which in turn blunt LV filling and LV output with exertion. Due to ventricular interactions, exercise PCWP may rise considerably in PAH, thus reducing its ability to differentiate from left heart disease.
 
 
 


Abstract 10899: Excessive Right Ventricular Afterload in Pulmonary Arterial Hypertension: Effects on Diastolic Function and the Left Ventricle

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Abstract 13688: Low-Affinity Insulin-Like Growth Factor Binding Protein 7 and Its Association With Pulmonary Arterial Hypertension Severity and Survival

Application of Deep Convolutional Neural Networks in Determining Chronicity of Pulmonary Nodules in Patients with Nontuberculous Mycobacterial Lung Infection

Association of Clinical and Imaging Characteristics With Pulmonary Function Testing in Patients With Long-COVID

Abstract 10899: Excessive Right Ventricular Afterload in Pulmonary Arterial Hypertension: Effects on Diastolic Function and the Left Ventricle