Utility of cardiovascular magnetic resonance in the assessment of myocardial dysfunction in pulmonary arterial hypertension

Author: Karthigesh Sree Raman

Sree Raman, Karthigesh, 2022 Utility of cardiovascular magnetic resonance in the assessment of myocardial dysfunction in pulmonary arterial hypertension, Flinders University, College of Medicine and Public Health

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Pulmonary arterial hypertension (PAH) is a pulmonary vasculature disease that predominantly involves the small pulmonary arteries and arterioles. PAH is a rare but serious disease that affects both the pulmonary vasculature and the heart. In PAH, the insult to the pulmonary vascular system causes pulmonary vascular remodelling leading to increased haemodynamic load. This leads to compensatory mechanisms of the cardiac function in response to increased right ventricle (RV) afterload. In particular, the RV adapts by increasing its force generating capacity to overcome the increase in RV afterload. As the disease progresses, the RV progresses from an adaptive to a maladaptive stage, with subsequent RV failure and death. It has been well documented that RV size and function are strong predictors of prognosis in PAH. However, in PAH the RV can negatively remodel in a clinically silent progression leading to RV failure and ultimately death. At this stage, the pathophysiological mechanisms driving this progression of the RV from adaptation to maladaptation remain unclear. Cardiovascular Magnetic Resonance (CMR) with its recent advancement of novel parametric mapping techniques have made non-invasive assessment of myocardial tissue characterisation more feasible. While these novel techniques have been comprehensively studied for various conditions in the left ventricle (LV); its use in the RV is limited.

The aims of this thesis are 1) To utilise the oxygen-sensitive CMR (OS-CMR) technique to assess the feasibility, prevalence and extent of myocardial oxygenation in response to stress and 2) to characterise the changes on myocardial extracellular matrix changes in the PAH population.

In Chapter 3, we demonstrate the feasibility of the OS-CMR technique in the RV of PAH patients, a technique previously only used for the LV myocardium. This study was followed with Chapter 4, which demonstrates the extent of myocardial oxygenation in the RV of PAH, providing new mechanistic insights into the pathophysiology of myocardial ischaemia in PAH. In Chapter 5, we demonstrate myocardial deoxygenation in the LV of PAH and with the utility of Stress/Rest T1 mapping, demonstrate concurrent myocardial perfusion abnormalities highlighting the presence of coronary microvascular dysfunction.

Furthermore, in Chapters 4 and 5, by utilising CMR parametric mapping techniques, we demonstrate changes to the myocardial extracellular matrix in PAH. However, these changes were not associated with myocardial oxygenation.

Chapters 6 and 7 examine the myocardial deformation strain changes in PAH. It demonstrates both CMR (Chapter 6), and echocardiographic (Chapter 7) strain abnormalities are associated with myocardial oxygenation and RV hypertrophy.

This thesis has advanced the mechanistic understanding into the pathophysiology of myocardial dysfunction in PAH. Further work of this nature could lead to new diagnostic, prognostic, and therapeutic possibilities for PAH patients.

Keywords: Pulmonary Hypertension, Cardiac Magnetic Resonance (CMR), coronary microvascular dysfunction, oxygen-semsitive cardiac magnetic resonance (OS-CMR), T1 mapping, stress/rest T1 mapping

Subject: Medicine thesis

Thesis type: Doctor of Philosophy
Completed: 2022
School: College of Medicine and Public Health
Supervisor: Prof. Joseph Selvanayagam