Myocardial Work Assessment by Non-Invasive Pressure-Strain Relations

Abstract

Background. Left ventricular (LV) dysfunction, which is the inability of the LV to pump blood effectively, constitutes the final common pathway for a host of cardiac disorders. The morbidity, mortality and healthcare cost associated with heart failure make the detection and prevention an attractive option before irreversible myocardial damage occurs. Initial diagnosis of LV dysfunction is through echocardiography, which, predominately relies on two-dimensional ejection fraction (EF) however, is fraught with limitation. Global longitudinal strain (GLS) is an established method for subclinical diagnosis of heart disease, however, is sensitive to changes in afterload leading to misinterpretation of true contractile function. Myocardial work (MW) is a recent echocardiographic modality derived from non-invasive LV pressure-strain loops and addresses the afterload limitation of GLS. Aims. The thesis investigates the use of MW against conventional echocardiographic parameters in hypertensive heart disease, ischaemic and non-ischaemic cardiomyopathy and ischaemic heart disease. It is hypothesised that MW indices will be more sensitive than GLS and provide a new dimension in the clinical evaluation of LV dysfunction. Methods. Patients enrolled in the CATHARSIS research program performed at The Prince Charles Hospital who have comprehensive echocardiographic studies followed by invasive coronary angiography will be investigated. All echocardiographic measurements were performed in according to the current echocardiographic guidelines. GLS and MW analysis was calculated utilising speckle tracking echocardiography via vendor specific modules (EchoPAC Version 202, GE Vingmed Ultrasound, Norway). MW was derived from derived from non-invasive LV pressurestrain loops indexed to brachial systolic blood pressure. MW indices obtained include: Global myocardial work index (GWI) – a global representation of MW; Constructive MW (CW) – the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation; Wasted MW (WW) – energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation; Myocardial work efficiency (GWE) – derived from the percentage ratio of CW to the sum of CW and WW. Results. The first research paper demonstrated that patients with early-stage hypertensive heart disease have seemingly normal EF and GLS, however, MW revealed that the LV is functioning at a higher energy level to overcome the resistance of higher arterial pressures. If there is a long-term and sustained increase in MW caused by hypertension, eventual remodelling of the myocardium will occur with heart failure the major consequence. MW provides an ability to detect increased work of the heart in order to prevent the sequalae of events through modification of therapy. Coexistent with low EF and GLS, patients with ischaemic and nonischaemic cardiomyopathy have significantly lower levels of MW which was due to a combination of decreased CW along with increase WW. This is indicative of LV remodelling characterised by ventricular dilatation and contractile dysfunction. The second research paper demonstrated the ability of MW to identify patients with single and multi-vessel coronary artery disease (CAD). This was possible despite the absence of visually detectable regional wall motion abnormalities and no prior history of ischaemic heart disease. In patients with CAD, GWI along with CW were both reduced while WW was increased reflecting the metabolic adaptation of the myocardium in the presence of CAD. The third research paper facilitated the delineation of patients with a false-positive from a true-positive exercise stress echocardiogram, despite normal resting LV systolic function and the absence of visually detectable resting regional wall motion abnormalities. This was possible despite single or multi-vessel CAD. Patients with a positive exercise stress echo and significant CAD on coronary angiography had a reduction in GLS and GWI from a combination of reduced CW and increased WW. The fourth research paper demonstrated the contractile reserve response to exercise and revealed a compromised contractile reserve assessed by myocardial deformation and work. Interestingly, as a result of more significant coronary lesions, patients that were treated using surgical bypass demonstrated a greater deterioration in MW indices at peak exercise compared to those that could be managed using percutaneous options. Conclusions. The work contained within this thesis has contributed to the diagnostic capabilities of ultrasound in the subclinical diagnosis of LV dysfunction. MW provides a more detailed assessment of intrinsic myocardial function and is an additional technique to assist in the detection of early cardiovascular disease under different loading conditions. This may be important in the future evaluation of patients with heart failure, hypertension and those with ischaemic heart disease where the EF is normal or at the lower limit of normal.