A New Non-Invasive Approach for Accessing Pulmonary Arterial Stiffness in Patients with Pulmonary Hypertension

Arcus-Med, Llc, Raleigh NC

Investigators

Abstract

Pulmonary hypertension (PH) is a disease affecting approximately 10-20% of the general population that is characterized by abnormally elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR). If left untreated, PH can ultimately lead to right heart failure and death. Current diagnostic approaches utilize invasive right heart catheterization (RHC) to measure mPAP and PVR. Early detection of PH leads to improved prognosis. An increase in pulmonary arterial stiffness is the earliest physiological manifestation of PH and precedes an increase in mPAP. PA impedance describes opposition to blood flow and consists of pulsatile and resistive components. It accurately quantifies PA stiffness under both normal and pathological conditions, including the early stages of PH. PA impedance is not usually measured in clinical practice because it requires simultaneous invasive pressure and flow measurements. A reliable non-invasive procedure to assess the stiffness of pulmonary arteries that can be used in a large group of patients would be extremely useful in early diagnosis of PH and could improve clinical outcomes. A novel, non-invasive technique is proposed based on a transfer function between velocities measured by standard phase-contrast MRI that measures a quantity related to PA stiffness. The compliance of the PA causes frequency-dependent changes in an input velocity waveform as it travels through the artery thereby producing an output velocity waveform. The frequency-dependent relationship between the input and output velocity waveforms are described by a transfer function, called the velocity transfer function (VTF), which is the ratio of the frequency spectra of input and output waveforms. Results from a study of 20 consecutively enrolled patients recently published in the Journal of the American Heart Association demonstrate that the VTF has a strong association with invasive PA impedance independent of elevation in pulmonary capillary wedge pressure and accurately assesses PA stiffness and elevated PVR. This study demonstrated that VTF is an accurate and reliable non-invasive surrogate of PA impedance and thus, can potentially be used as a screening tool for pre-capillary pulmonary hypertension before more expensive or invasive tests are considered. Development and validation of a commercial quality software package is proposed that inputs phase- contrast MRI data and calculates the VTF with the ultimate goal of obtaining Food and Drug Administration (FDA) approval. We do not anticipate that the VTF will totally replace a RHC, but it could reduce the number of RHCs by allowing patients to be screened for PH with more accuracy earlier in the diagnostic process and to be followed non-invasively over time.