The association of left ventricular histologically verified myocardial fibrosis with pulmonary hypertension in severe aortic stenosis.

OBJECTIVES: To evaluate the association between histologically verified left ventricular (LV) myocardial fibrosis (MF) and its bio- and functional markers with pulmonary hypertension (PH) in severe aortic stenosis (AS). METHODS: About 34 patients with isolated severe AS underwent 2D echocardiography, cardiac magnetic resonance (CMR) imaging, and plasma NT-proBNP evaluation before aortic valve replacement (AVR). LV measurements were analyzed by CMR and LV strain using feature tracking software (Medis Suite QStrain 2.0). Myocardial biopsy sampled at the time of AVR was assessed by a histomorphometric analysis. PH was defined as pulmonary artery systolic pressure (PASP) ⩾ 45 mm Hg. RESULTS: Patients with severe AS and PH (mean PASP 53 ± 3.7 mm Hg) had higher extent of diffuse MF versus patients without PH (12 (10.4-12.7)% vs 6.6 (4.6-8.2)% (p = 0.00)). The extent of diffuse MF correlated with LV dilatation (r = 0.7, p = 0.02), indices of LV dysfunction (lower ejection fraction (r = -0.6, p < 0.001), global longitudinal (r = -0.5, p = 0.02) and circumferential strain (r = -0.5, p = 0.05), elevated NT-proBNP (r = 0.5, p = 0.005) and elevated PASP (r = 0.6, p < 0.001)). Histological MF > 10% (AUC 94.9%), LV global longitudinal strain > -15.5% (AUC 86.3%), and NT-proBNP > 2090 ng/l (AUC 85.1%) were independent predictors of PH in severe AS. CONCLUSIONS: The extent of diffuse myocardial fibrosis in combination with reduced longitudinal left ventricular strain and increased plasma levels of NT-proBNP relates to pulmonary hypertension in severe aortic stenosis.

Identification of Cardiac MRI and Bio-Marker Thresholds for One-Year Survival in Pre-Capillary Pulmonary Hypertension: Prospective Study.

Background and objectives: Non-invasive imaging of the heart has an important place in the diagnosis and management of pulmonary arterial hypertension (PAH). The aim of this study was to establish the thresholds of cardiac magnetic resonance imaging (CMRI)-derived biventricular deformation, function parameters, and levels of N-terminal pro brain natriuretic peptide (NT-proBNP) for the prediction of survival of pre-capillary pulmonary hypertension (PHprecap) patients. Materials and Methods: In total, 64 incident PHprecap cases, who underwent CMRI, were consecutively enrolled in a prospective cohort study. Patients underwent a systemic evaluation, including measurement of NT-proBNP, two-dimensional (2D) echocardiography, six-minute walk test (6MWT), CMRI with feature tracking (FT), and right-heart catheterization (RHC). Patients were divided into two groups according to one-year survival (survival and non-survival groups). Survival analysis was performed. Results: One-year survival was 79.6%. The distribution between age, sex, mean pulmonary artery pressure (mPAP), New York Heart Association (NYHA) functional class, and 6MWT did not differ between the groups. Survival was significantly lower in the PAH group associated with connective tissue disease (CTD-PAH), where 44% (n = 4) of patients died during the first year. Univariate analysis revealed that severely reduced right-ventricle (RV) ejection fraction (EF) <25.5%, left-ventricle global longitudinal strain (LV GLS) >-14.18%, and right pulmonary artery (RPA) relative area change (RAC) <19%, and severely increased NT-proBNP level >1738 (ng/L) indicate an increased risk of death in PHprecap patients. Conclusions: Impaired RV systolic function and LV global longitudinal strain, decrease of pulmonary artery distensibility, and CTD-PAH etiology, together with high NT-proBNP level, impair prognosis in pre-capillary PH patients. These findings are important for the risk stratification and management of pre-capillary pulmonary hypertension patients.

Left Ventricular Morphology and Function as a Determinant of Pulmonary Hypertension in Patients with Severe Aortic Stenosis: Cardiovascular Magnetic Resonance Imaging Study.

Background and Objectives: The influence of cardiac magnetic resonance (CMR) derived left ventricular (LV) parameters on the prognosis of patients with aortic stenosis (AS) was analyzed in several studies. However, the data on the relations between the LV parameters and the development of pulmonary hypertension (PH) in severe AS is lacking. Our objectives were to evaluate the CMR-derived changes of the LV size, morphology, and function in patients with isolated severe AS and PH, and to investigate the prognostic impact of these parameters on elevated systolic pulmonary artery pressure (sPAP). Materials and Methods: Thirty patients with isolated severe AS (aortic valve area ≤1 cm2) underwent a 2D-echocardiography (2D echo) and CMR before aortic valve replacement. Indices of the LV mass and volumes and ejection fraction were analyzed by CMR. The LV global longitudinal (LV LGS) and circumferential strain (LV CS) were calculated using CMR feature tracking (CMR-FT) software (Medis Suite QStrain 2.0, Medis Medical Imaging Systems B.V., Leiden, The Netherlands). The LV fibrosis expansion was assessed using a late gadolinium enhancement sequence. PH was defined as having an estimated sPAP of ≥45 mm Hg. The statistical analysis as performed using SPSS version 23.0 (SPSS, Chicago, IL, USA) Results: 30 patients with severe AS were included in the study, 23% with severe isolated AS had PH (mean sPAP 55 ± 6.6 mm Hg). More severe LV anatomical and functional abnormalities were observed in patients with PH when compared with patients without PH-a higher LV end-diastolic volume index (EDVi) (140 [120.0-160.0] vs. 90.0 mL/m² [82.5-103.0], p = 0.04), larger LV fibrosis area (7.8 [5.6-8.0] vs. 1.3% [1.2-1.5], p = 0.005), as well as lower LV global longitudinal strain (GLS; -14.0 [-14.9-(-8.9)] vs. -21.1% [-23.4-(-17.8)], p = 0.004). By receiver-operating characteristic (ROC) curve analysis, LV EDVi > 107.7 mL/m² (Area Under the Curve (AUC) 95.7%), LV GLS < -15.5% (AUC 86.3%), and LV fibrosis area >5% (AUC 89.3) were found to be robust predictors of PH in severe AS patients. Conclusions: In patients with severe aortic stenosis, a larger end-diastolic LV volume, impaired LV global longitudinal strain, and larger LV fibrosis extent can predict the development of pulmonary hypertension.

Impact of Left Ventricular Diastolic Dysfunction and Biomarkers on Pulmonary Hypertension in Patients with Severe Aortic Stenosis.

Background: Severe aortic stenosis (AS) complicated by pulmonary hypertension (PH) is associated with poor outcomes after surgical aortic valve replacement (AVR). There is still scarce information about predictors of secondary PH in this group of patients. Objectives: The aim of this study was to investigate the prognostic impact of biomarkers together with conventional Doppler echocardiographic parameters of left ventricular diastolic function on elevated pulmonary systolic pressure (PSP) in severe AS patients before surgical AVR. Methods: Sixty patients with severe isolated AS (aortic valve area <1 cm²) underwent echocardiography, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor-15 (GDF-15) measurements before AVR. PSP, left ventricular ejection fraction (LV EF), parameters of LV diastolic function (E/E' ratio, mitral valve deceleration time (MV DT) and left atrial (LA) volume) were evaluated. PH was defined as an estimated PSP ≥ 45 mmHg. Results: Of the 60 patients, 21.7% with severe isolated AS had PH with PSP ≥ 45 mmHg (58.5 ± 11.2 mmHg). LV EF did not differ between groups and was not related to an elevated PSP (50 ± 8 vs. 49 ± 8%, p = 0.58). Parameters of LV diastolic dysfunction (E/E' ratio > 14 (OR 6.00; 95% CI, 1.41⁻25.48; p = 0.009), MV DT ≤ 177.5 ms (OR 9.31; 95% CI, 2.06⁻41.14; p = 0.001), LA volume > 100 mL (OR 9.70; 95% CI, 1.92⁻49.03; p = 0.002)) and biomarkers (NT-proBNP > 4060 ng/L (OR 12.54; 95% CI, 2.80⁻55.99; p < 0.001) and GDF-15 > 3393 pg/mL (OR 18.33; 95% CI, 2.39⁻140.39; p = 0.001)) were significantly associated with elevated PSP in severe AS. Conclusions: Left ventricular diastolic dysfunction and elevated biomarkers levels could predict the development of pulmonary hypertension in patients with severe aortic stenosis. Elevation of biomarkers paired with worsening of LV diastolic dysfunction could help to stratify patients for earlier surgical treatment before the development of pulmonary hypertension.