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Title: The effects of left ventricular assist devices on myocardial function and cardiac nervous system
Author: George, Robert Sobhi Bouchra
ISNI:       0000 0004 2700 2241
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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Myocardial recovery in patients with non-ischaemic end-stage dilated cardiomyopathy can occur following left ventricular assist device (LVAD) and drug combination therapy. The effects of LVAD and drug combination therapy on the cardiac nervous system have not been adequately studied. It is well recognised that contractile reserve is decreased in heart failure patients who have an increased level of circulating norepinephrine secondary to failure of the myocardial norepinephrine transporter system. The aims of this study are to examine prospectively the outcome of using continuous-flow Heart Mate (HM) II LVAD and drug combination therapy on the frequency and durability of recovery, the clinical effects of left ventricular unloading on cardiac sympathetic nervous system, and the impact on norepinephrine transporter activity and neurohormonal levels. 23 non-ischaemic end-stage heart failure patients, confirmed histologically, were implanted with a HM II LVAD between February 2006 and March 2009. The combination therapy with anti-failure reverse remodelling medication was commenced once patients were off inotropes. The first objective was to determine a cut-off point where the contribution of the continuous-flow HM II LVAD was minimal thus allowing safe and reliable assessment of the underlying left ventricular function without causing left ventricular reloading. The impacts of LVAD and drug combination therapy on myocardial function and cardiac nervous system were assessed by studying: 1) contractile reserve using a 6–minute walk exercise test; 2) norepinephrine transporter using serial nuclear 123I-mtaiodobenzylguanidine (123I-MIBG) imaging; 3) the changes in catecholamine levels using liquid chromatography mass spectrometry. Immunohistochemistry was utilised to assess norepinephrine transporter fibre concentration from the left ventricular apex biopsies taken at implantation in an attempt to correlate with myocardial recovery. Experimental and clinical studies identified 6000 rpm as an efficient and a safe "low" speed to study the underlying myocardial function. Out of the 23 patients, 15 had recovered and had significant improvement in contractile reserve (the ejection fraction has increased in the recovered patients by 7.73 ± 4.37% as compared to 1.13 ± 4.20% in non-recovered patients (p=0.012)). Recovered patients have also exhibited significant improvement in 123I-MIBG uptake parameters which were correlated significantly with changes in catecholamine levels. Further, recovered patients had higher percentage of norepinephrine transporter immunoreactive nerve fibers per total area in the left ventricular apex as compared to non-recovered patients and the concentration correlated positively with recovery. In conclusion, LVAD and drug combination therapy has a positive impact on myocardial function and the cardiac nervous system which were more enhanced in the recovered subpopulation.
Supervisor: Birks, Emma ; Yacoub, Magdi Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral