Yarnykh, Svetlana

Introduction: Heart failure (HF) affects interstitial lung structure and function. AI-assisted quantitative computed tomography (qCT) offers possibility of objective assesment of lung structure, allowing to detect the presence and the severity of HF. Hypothesis: Can automated qCT analysis discriminate HF from controls and identify tissue structures most linked to degree of congestion ? Methods: Subjects underwent right heart catheterization (RHC), native CT chest imaging (full inspiration/expiration) by Naeotom-α photon-counting CT scanner (Siemens), lab testing, echocardiography. Automated AI-based analysis (VIDA Diagnostics) was employed to evaluate lung volumes, densities and tissue texture. Image series were used in mediastinal and lung window reconstruction with slice thickness 0,8 mm and increments 0,5 mm. Results: 186 HF patients (85% HFrEF, NYHA 2.8±0.5, 58 y, 80% males, NTproBNP 4491 pg/ml, LVEF 26%) and 43 controls of similar sex and BMI were analyzed; both groups free of primary lung disease. In HF, 85 % had PH (mPAP>20mmHg). HF patients had comparable inspiratory lung volume, reduced air volume and increased lung tissue volume, compared to controls. Mean lung density (-782±50 vs -832±25 HU, p<0.0001), density variability and estimated lung fluid content (21.3 vs 16.7%, p<0.0001) were all higher in HF compared to controls. Across various density cut-offs, the most notable difference was at lung tissue density < -856 HU at inspiration. Lung tissue density corelated with mean PA pressure (r=0.49, p<0.0001), and less with pulmonary vascular resistance (r=0.21, p=0.006). Insp/exp scan analysis showed no difference in air trapping, but reduced lung tissue compliance (Jacobian strain: 1.8±0.4 vs 1.6±0.3, p=0.0005) in HF. Lung texture analysis showed increased ground-glass opacity (GGO) mass (48.8 g vs 9.1 g; p < 0.001), reticulation (42.2 g vs. 8.4 g; p < 0.001) and consolidation (0.5 g vs 0.2 g; p=0.0011) in HF compared to controls, with no difference in honeycombing. GGO mass correlated strongly with pulmonary capillary wedge pressure (PCWP) (r=0.48, p<0.001) and mitral regurgitation grade (r=0.28,<0.0001), but not with inflammation (hsCRP, IL6, WBC), smoking exposure or oncotic pressure. Conclusions: qCT distinguished HF patients from controls by increased lung tissue mass, reduced air volume, increased lung density and increased mass of GGO and reticulation. GGO mass in HF strongly reflects increased hydrostatic pressure, but not inflammation.

BACKGROUND: Some, but not all, patients with heart failure (HF) develop pulmonary vascular disease (PVD), which contributes to poor prognosis. Mechanisms leading to PVD in HF are poorly understood. We aimed to analyze transpulmonary gradients of proteins consumed or elaborated across the lungs to identify mediators of PVD by unbiased proteomics. METHODS: Overall, 21 controls and 160 patients with HF with reduced ejection fraction underwent pulmonary artery catheterization with blood sampling from postcapillary (wedged balloon) and precapillary (unwedged) position to obtain transpulmonary gradients. The samples from controls and HF from the highest (Q4, n=40) and lowest quartile (Q1, n=40) of pulmonary vascular resistance (PVR) were analyzed using the proteomic proximity extension assay (Olink) of 275 proteins. Venous blood concentrations or transpulmonary gradients were analyzed to identify biomarkers or potential mediators of PVD. RESULTS: Comparison of Q1 and Q4 of PVR identified PSP-D (pulmonary surfactant-associated protein D) as a marker of PVD. Examination of gradients across the lungs in high PVR HF revealed significant uptake of 18 proteins, mostly associated with inflammation (chemokines, oncostatin-M, MMP9 [matrix metalloproteinase 9]) or with TGF (transforming growth factor)/activin pathway (GDF2 [growth differentiation factor 2]/BMP9 [bone morphogenic protein 9]), and release of 5 proteins, notably IL (interleukin) 6 and IL33. In contrast, these protein gradients were negligible in controls and low PVR patients with HF. Active pulmonary release of IL6 contributed to systemic elevation of IL6 and correlated with right ventricular function. CONCLUSIONS: The lungs of patients with HF with high PVR display abnormal uptake and release of proinflammatory cytokines from IL6/gp130 family (IL6, IL33, oncostatin-M), along with increased transpulmonary uptake of GDF2/BMP9. The study shows that proteins orchestrating inflammation or pulmonary vessel remodeling in group 1 pulmonary hypertension, are also operating in patients with PVD due to HF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06331208.