Echocardiology
Supervisor: Dr. Andrew Taylor
Email: andrew.taylor@bakeridi.edu.au
Phone: 03 90763263
The role of diffuse myocardial fibrosis in myocardial stiffness
Myocardial fibrosis is a common final pathway of many myocardial diseases; it may be regional as found in myocardial infarction due to coronary atherosclerosis, or diffuse as observed in all forms of advanced cardiomyopathy. Diffuse fibrosis may be particularly relevant in the pathogenesis of heart failure in the presence of a normal left ventricular ejection fraction (HFNEF) as well as representing a putative mechanism for the development of a more malignant phenotype in patients with left ventricular hypertrophy (LVH).
Recently, the role of diastolic dysfunction in heart failure has been highlighted. Even in the absence of overt systolic dysfunction, diastolic heart failure is a major cause of heart failure in the community, accounting for up to 50% of all cases of heart failure, with a comparable morbidity/mortality profile. Whereas the prognosis of patients with systolic heart failure has been significantly improved with new medical therapies over the past decade, the development of specific therapies for HFNEF has been less productive, and there is currently no medical therapy that has been shown to reduce mortality in patients with HFNEF. Whilst the detrimental effects of increasing myocardial fibrosis in heart failure still require further elucidation, a likely mechanism is diastolic dysfunction due to increased myocardial stiffness, which carries a poor prognosis in patients with cardiomyopathy who develop restrictive physiology.
Critical to our understanding of diffuse myocardial fibrosis and myocardial stiffness is the demonstration of a mechanistic link between these two observed phenomena. We have previously demonstrated that increasing diffuse myocardial fibrosis identified by cardiac magnetic resonance imaging (CMR) in patients with advanced heart failure is accompanied by worsening diastolic function, implying a mechanistic link between diffuse myocardial fibrosis and myocardial stiffness. However no similar study has been performed in patients with HFNEF, or those with LVH.
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A number of projects will examine the mechanistic link between whereby myocardial fibrosis might contribute to myocardial stiffness.
One study will evaluate patients with hypertension and LVH using echocardiography as well as CMR imaging to document LV volume, mass, systolic and diastolic function. Post contrast CMR imaging will also be performed to evaluate regional and diffuse fibrosis in patients with normal as well as abnormal diastolic function. In addition, serum markers of collagen turnover will be measured, and correlated with the extent of fibrosis.
In a separate study, a group of cardiac transplant recipients will undergo invasive left ventricular pressure-time measurement during routine surveillance coronary angiography. Patients will then undergo CMR scanning on the same day to non-invasively assess diffuse myocardial fibrosis, as well as ventricular volume, mass and function. Invasive measures of diastolic function and myocardial stiffness will be compared with the degree of myocardial fibrosis demonstrated by CMR.
A final project will investigate the treatment effect of the eplerenone, a drug with purported anti-fibrotic properties. Patients with HFNEF and diffuse fibrosis demonstrated by CMR will be randomised to eplerenone or placebo in addition to standard care for 12 months. Following this, patients will undergo repeat CMR and echocardiography to re-evaluate diffuse fibrosis as well as diastolic function. The effects of drug treatment on the degree of diffuse myocardial fibrosis, diastolic function and changes in markers of collagen turnover will be examined.
As the research is clinically-based, prospective applicants would be expected to have come from a clinical background, and would be best suited to someone planning a career in cardiology.
