Does beta-blockade improve cardiopulmonary exercise testing variables and other related static cardiac function measures? : systemic review, meta-analysis and prospective interventional drug trial : improving cardiac function in high-risk surgical patients (ICAF-beta) : cardiopulmonary exercise testing, biomarkers and beta-blockade

Williams, Murray Richard

September 2019

Thesis or dissertation

© 2019 Murray Richard Williams. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

Background: Beta-blocking agents have demonstrated : an increased survival, improved ventricular contractility and provide symptomatic relief in chronic heart failure (CHF). Cardiopulmonary exercise testing (CPET) has prognostic value for event-free survival in CHF and surgical populations. Therefore, it is reasonable to assume that the improvement seen with beta-blockers would be measurable with CPET. However, debate continues around the effect of beta-blockade on CPET variables, exercise capacity and perioperative outcomes. The objectives were to assess the effect of de novo beta-blockade on CPET variables and related static cardiac function measures in all populations and on a targeted high risk population scheduled to have non-cardiac surgery.

Method: Literature searches were conducted using the MeSH terms: adrenergic beta- antagonists, exercise and clinical trials. Stud ies were eligible if they were interventional trials investigating de novo beta-blockade and included before and after treatment breath-to-breath CPET analysis. Meta-analysis was conducted using a random effects model.
We also designed a prospective proof-of-concept case series study with MHRA and ethical approval. Baseline and post-treatment CPET, echocardiogram and NT- proBNP were conducted on high risk surgical patients treated with a minimum of 10 days bisoprolol 2.5mg

Results: 16 of 222 potentially relevant studies met the inclusion criteria with a total of 795 patients. VE/V̇ CO₂ changed by -1.17 (CI -2.33-0.0), anaerobic threshold changed by 0.35ml/kg/min (CI -0.26-0.97), peak oxygen consumption changed by 0.67ml/kg/min (CI -0.14-1.48), and ejection fraction improved by 6.72% (CI 4.93- 8.51).

Conclusions: Disparity exists between improved cardiac function and symptoms after beta-blockade compared to static objective functional capacity assessment with CPET. These CPET variables may be inadequate to assess the effect of beta-blockade. Perhaps beta-blockade improvements are weighted to disease severity and therefore targeted therapy is desirable. The ongoing case study will conclude whether beta- blocker treatment can effect VE/V̇ CO₂ in high risk patients undergoing non-cardiac surgery.

Hull York Medical School, The University of Hull and the University of York
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