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Title: Novel contractility assessments in the evaluation of cardiac function : applications to common clinical practice and cardiac device therapy
Author: McIntosh, Robert A.
ISNI:       0000 0004 7427 1321
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2018
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Background Commonly employed assessments of systolic cardiac function are limited by their emphasis on two-dimensional assessment of chamber volume or dimension at end-systole and end- diastole. Such measures are poorly reproducible and are sensitive to limitations in image quality and changes in haemodynamic loading. In performing examinations only at rest, we also fail to assess the ability of the myocardium to augment in its contraction. These limitations may explain why such assessments often correlate poorly with patient symptoms and exercise capacity. By developing enhanced assessment techniques we may improve the relevance of our investigations and allow for detection of cardiac disease at an earlier stage than is currently possible. Methods Standard echocardiographic measures of systolic function (left ventricular ejection fraction (LVEF), left ventricular outflow tract velocity time integral (LVOT VTI) and cardiac output (CO)); measures of left ventricular contractility obtained by pulsed-wave tissue Doppler examination (LV Vmax) and measures of contractility derived from sensor-derived peak-endocardial acceleration (PEA1) or closed loop (CLS) assessments were obtained during rest, exercise and/or dobutamine stress. Groups studied included healthy subjects, patients with heart failure and reduced left ventricular ejection fraction (HFREF), subjects undergoing mitral valve repair, patients with implanted cardiac devices and subjects with persistent atrial fibrillation. During exercise assessments, cardiopulmonary gas exchange analysis was performed allowing for calculation of peak oxygen uptake (pVCh). PEA1 and femoral artery dP/dTmax measures were also obtained in subjects undergoing invasive electrophysiology studies in both sinus rhythm and during arrhythmia. Results In a resting comparison between heart failure (N=20) and healthy control subjects (N=10), both LVEF (P=<0.01) and LV Vmax (P=<0.01) were significantly lower in the heart failure population. There was no difference in resting PEA measures between the groups. During exercise significant differences in LVEF (P=<0.01), LV Vmax (P=<0.01), LVOT VTI (P=<0.01), CO (P=<0.01) and PEA1 (P=<0.01) were identified. LV Vmax during both rest (R=0.535, P=0.006) and exercise (R=0.774, P=<0.001) was the parameter most strongly related to pVO2. There was no significant relationship between pVO2 and any other resting contractility parameter. Of other parameters on exercise, only LVEF (R=0.412 P=0.04) and change in PEA1 (R=0.409, P=0.04) showed a significant association with pVO2. In 10 subjects undergoing mitral valve repair, no PEA1 or echocardiographic contractility parameter during either rest or stress was significantly related to postoperative functional outcome as judged by change in pVO2 post-operatively. Change in LV Vmax (R=0.61, P=0.08) and change in PEA1 amplitude (R=0.6, P=0.09) during dobutamine stress displayed non­significant associations with post-operative change in pVO2. During invasive electrophysiology assessment in 57 subjects, change in PEA amplitude was found to be significantly related to change in femoral artery dP/dtmax during rhythm transition from sinus rhythm to both supraventricular tachycardia (R=0.52, P=0.069) and atrial fibrillation (R=0.68, P=0.005). PEA data extraction was not possible during rapid ventricular tachycardia (heart rate 255 ± 89bpm) due to described methodological constraints. Echocardiographic assessment of aortic VTI was conducted in 19 patients during cardiac resynchronisation therapy in states of rest, low-level exercise and atrial overdrive pacing. The effect of adjustment in atrio-ventricular (AV) and ventriculo-ventricular (VV) delay on mean aortic VTI was examined. There was substantial inter-subject variability in the haemodynamic response to adjustment of AV and VV delay within each state. Assessed across all states of testing, adjustment in VV delay was found to have no consistent independent impact on aortic VTI. Across all states adjustment in AV delay was found to have a significant independent impact on aortic VTI (P=0.02) with long (166±39ms) and medium (120±21ms) AV delays being associated with a higher AoVTI compared to short (78±8 ms) AV delays. In 22 atrio-ventricular (AV) node-ablated and paced subjects, tissue Doppler-derived electromechanical delay following a right ventricular pacing stimulus was assessed in relation to the CLS contractility waveform. At both three (R=0.518, P=0.019) and twelve months of follow-up (R=0.457, P=0.049), there was a significant association between electromechanical delay and the time between pacing stimulus delivery to trough CLS impedance. An analysis of 101 subjects undergoing cardiopulmonary exercise echocardiography included subjects from a range of cardiac patient groups. Of the echocardiographic parameters assessed, pVO2 was strongly related to LV Vmax on exertion (R=0.84, P < 0.001). The strength of this relationship was greater than that observed with any other echocardiographic measure of cardiac function either during rest or during exercise. Conclusion Of the echocardiographic measures of cardiac function that were assessed, LV Vmax was more strongly related to exercise capacity than any other assessment of systolic function. Examination on exertion increased the strength of the relationship and LV Vmax on exertion was the best echocardiographic indicator of functional capacity. Contractility data derived from the PEA and CLS sensors provides a means to incorporate haemodynamic measures of cardiac function into implantable device diagnostic monitoring or treatment algorithms. Such sensor-derived assessments may assist in improving technology in areas such as contractility monitoring, arrhythmia discrimination or pacing-interval optimisation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available