Modification of left ventricular geometry and function during healing after acute myocardial infarction

Jugdutt, Bodh I. (2006) Modification of left ventricular geometry and function during healing after acute myocardial infarction. MD thesis, University of Glasgow.

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Abstract

Increased left ventricular (LV) size and deformation of LV geometry are associated with LV dysfunction. Regional shape distortion (RSD), detected on two-dimensional echocardiography (2D-Echo) after acute myocardial infarction (MI), is associated with poor outcome. Two hypotheses were tested: i) early RSD of the asynergic infarct zone after MI is followed by progressive global LV dilatation, remodelling towards a spheroidal shape, and more LV dysfunction; and ii) the progressive remodelling of LV geometry spans the phases of early infarction and healing and may be modified by early and prolonged therapies applied over the phases of infarction and healing. A bench to bedside approach was used, with concurrent studies in a dog model of healing over 6 weeks after MI and patients with first MI's. Computer- assisted analysis of the 2D-Echo images with 3D reconstruction was used to quantify LV asynergy (akinesis + dyskinesis), LV volumes, LV ejection fraction, RSD bulge and global LV shape. The animal studies showed that collagen deposition during healing after MI increases progressively, reaching a plateau around 2 weeks, and deposition of collagen in already dilated infarct zones is followed by late thinning and further RSD associated with LV aneurysms. Importantly, serial 2D-Echo tracked the in- vivo changes in LV geometry and function and showed greater RSD and LV dysfunction with anterior than inferior MI, and with transmural MI than nontransmural MI. Other studies showed: i) lower LV resistance to distension and rupture in infarcted hearts; ii) marked extracellular matrix (ECM) disruption and RSD in transmural MI; ill) delayed effects on LV remodelling after infarct-limiting therapies given during acute MI; iv) loss of beneficial effects of the vasodilator nitroglycerin (NTG) with hypotension induced by high doses during acute MI; v) decreased wall stress by prolonged LV unloading after MI, with nitrates (eccentric dosing) and angiotensin-converting enzyme (ACE) inhibitors, limited early RSD and progressive LV remodelling and dysfunction; this effect was greater with therapy over 6-weeks than just over the first 2 weeks; vi) late reperfusion limited early RSD and adverse LV remodelling, and preserved ECM in the epicardial rim; vii) the resistance of the healed left ventricle to distension and rupture was further reduced by prolonged anti-inflammatory therapy (ibuprofen); viii) prolonged ACE inhibitor therapy decreases infarct collagen, which may be harmful under certain conditions. The clinical studies with serial 2D-Echo showed that systematic tomographic imaging could provide quantitative data on regional and global LV geometry and function including the degree of RSD (depth, area, and volume). An early 2D-Echo not only provided diagnostic data on LV thrombi and complications of MI, but the extent of LV asynergy on the initial 2D-Echo predicted outcome at 3 months and 1 year. Importantly, the degree of RSD on the initial 2D-Echo predicted patients at high risk of adverse remodelling with infarct expansion, greater LV dysfunction, progressive LV dilatation, and poor outcome at 1 year. Survivors of MI with > 18% LV asynergy and significant RSD on a baseline 2D Echo were at increased risk of topographic deterioration on exercise programs. Anti-inflammatory therapy after MI resulted in more RSD and adverse remodelling. Short-term LV unloading with low-dose intravenous NTG therapy during the acute MI, as well as prolonged nitrate (eccentric dosing) and captopril therapy during healing over 6 weeks after MI, improved 2D-Echo indexes of LV geometry and function, decreased complications and improved outcome. Acute thrombolytic therapy also limited LV remodelling after MI. In all these studies, the degree of RSD and severity of LV dysfunction were greater with anterior than inferior MI, and with Q-wave than non-Q wave MI. In Conclusion, the overall results indicate that early RSD in the infarct zone leads to progressive global LV dilatation, LV dysfunction and poor outcome and the changes in LV geometry and function can be quantified by serial quantitative 2D-Echo imaging. Marked RSD is associated with early ECM disruption and aneurysm formation after transmural MI. During healing, infarct zones may be thinned and dilated before the collagen plateau, and collagen deposition into these zones result in further RSD and chronic aneurysms. Prolonged anti-remodelling therapy during healing, with agents that decrease wall stress without damaging the ECM, or decreasing infarct collagen, or causing infarct thinning, or impairing healing, might be more effective for reducing RSD, LV aneurysm, global dilatation and poor outcome. The 2D-Echo measurement of RSD early after MI might be potentially important for stratifying patients according to their topographic status and for the objective assessment of the effects of anti-remodelling strategies during healing after MI.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: List of 46 original contributions and papers published as a result of the work: p. xiii-xvii. Where available, DOIs and PMC links listed in related URLs.
Subjects: R Medicine > RC Internal medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences
Funder's Name: UNSPECIFIED
Supervisor's Name: Supervisor, not known
Date of Award: 2006
Depositing User: Mrs Marie Cairney
Unique ID: glathesis:2006-8341
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 Aug 2017 13:22
Last Modified: 10 Aug 2017 13:34
URI: http://theses.gla.ac.uk/id/eprint/8341
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