The role of novel echocardiographic methods in patients with pulmonary hypertension

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve various clinical conditions and may be associated with numerous respiratory and/or cardiovascular diseases, causing an increase in pulmonary pressure. Measuring mean pulmonary artery pressure by the right-heart catheterization is the gold standard for PH diagnosis. The hemodynamic definition further distinguishes PH into precapillary and postcapillary PH. There is no alternative non-invasive method to reliably distinguish between those two aetiologies. A progressive increase in pulmonary pressure causes pressure overload of the right ventricle, leading to structural and functional adaptation or remodelling of the right heart. If PH or the underlying disease is untreated, death usually occurs because of right ventricular failure. A comprehensive analysis of the role of novel echocardiographic methods in the diagnosis of PH, the understanding of the adaptive changes of the right heart and the prognostic value of newer echocardiographic parameters of right ventricle is not yet available. The proposed research aims are the following: 1) to assess the diagnostic value of non-invasive stress tests during echocardiography for defining the aetiology of PH compared to gold standard invasive measurements; 2) to analyse the pathophysiological mechanism of right ventricular adaptation and remodelling to increased afterload in patients with precapillary and postcapillary PH; 3) to investigate the association between novel echocardiographic parameters of right ventricular function (strain, myocardial work, ventricular-arterial coupling) and clinical outcome in patients with precapillary and postcapillary PH. The research project will be divided into 3 sub-studies. In the first study, we will include consecutive patients over one and half year who undergo clinically indicated right heart catheterisation. The reference invasive method, right heart catheterisation, will be compared with parameters of left ventricular diastolic function and pulmonary hemodynamics obtained during echocardiographic non-invasive stress tests (supine bicycle test, handgrip test and passive leg raising). In the second part, we will identify the study group of 20 patients with precapillary PH (pulmonary arterial hypertension/chronic thromboembolic PH) and 20 patients with isolated postcapillary PH (PH due to heart failure with preserved left ventricular ejection fraction) and 20 healthy subjects who will have echocardiography and cardiac magnetic resonance imaging. We will investigate the differences in the structural and functional changes of the right heart between the groups and identify underlying pathophysiological mechanism. In the final part of the project, we will prospectively analyse echocardiographic images of patients with precapillary and postcapillary PH who underwent echocardiographic examination in 2018-2021. We will focus on novel echocardiographic parameters of right ventricular function (parameters of myocardial deformation and myocardial work) and parameters of ventricular-arterial coupling. Patients will be followed-up over time for combined clinical endpoint (death, lung/heart transplantation, hospitalisation for failure and surgical pulmonary endarterectomy). We will investigate the clinical relevance of novel echocardiographic parameters and compare prognostic value of echocardiographic parameters between precapillary and postcapillary PH. We expect that we will be able to identify non-invasive stress tests that could more reliably determine the aetiology of PH during echocardiographic examination. We expect that we will be able to identify the right ventricular phenotype associated with pre- and postcapillary PH and to explain the pathophysiological background of right ventricular remodelling in specific PH subgroups. We also expect to identify novel echocardiographic parameters associated with the clinical outcome in patients with PH.