Echocardiographic assessment of acute and chronic effects of exercise on cardiac function – from physiology to clinical practice
Dorobantu, D
Date: 13 May 2024
Thesis or dissertation
Publisher
University of Exeter
Degree Title
Doctor of Philosophy in Sport and Health Sciences
Abstract
Assessing the cardiorespiratory response to exercise, be it acute, such as during a stress test, or chronic, such as related to sports or rehabilitation is central to cardiovascular research and clinical care. Peak oxygen uptake (V̇O2 peak), obtained through a cardiopulmonary exercise test (CPET) is a key measure of fitness, and critical ...
Assessing the cardiorespiratory response to exercise, be it acute, such as during a stress test, or chronic, such as related to sports or rehabilitation is central to cardiovascular research and clinical care. Peak oxygen uptake (V̇O2 peak), obtained through a cardiopulmonary exercise test (CPET) is a key measure of fitness, and critical in the diagnosis and prognosis of cardiovascular disease. One important limitation of conventional CPET is that it cannot provide comprehensive or disease specific measurements of cardiac function. Exercise stress echocardiography (ESE) is better suited for this purpose as it provides detailed insight into an array of cardiac function pathways.
The central theme of this thesis was how modern ultrasound techniques, such as speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI) can be used to characterise cardiac responses to exercise. The main aim was to enhance understanding of the cardiorespiratory mechanisms governing normal and pathological responses to exercise and apply these onto the emergent framework for integrative exercise testing. This approach resulted in three inter-connected sections, each with a distinct focus: 1. The role of chronic exposure to exercise in athlete cardiac screening, 2. Normal and pathological cardiac reserve mechanisms underlying acute response to exercise and 3. Translational use of exercise response physiology in diagnostic testing and cardiac rehabilitation.
The first section of the thesis sought to explore the role of STE in evaluating cardiomyopathies in children, by first conducting a systematic review and meta-analysis of the existing literature (Chapter 4.1). Cardiomyopathies are rare inherited conditions often difficult to diagnose, associated with sudden cardiac death. The review revealed that STE derived left ventricular (LV) function can differentiate cardiomyopathy, such as LV non-compaction (LVNC) from healthy controls. In contrast, only one study investigated STE in arrhythmogenic cardiomyopathy (ACM). This highlighted the role STE could play in screening athletes, where chronic exposure to exercise leads to structural changes overlapping those of the pathological (“athlete’s heart”). Healthy adolescent elite footballers meeting echocardiographic criteria for LVNC (Chapter 5.1) and ACM (Chapter 5.2) were compared to those without such disease criteria. Longitudinal strain (Sl) and strain rate (SRl) were not found to be worse in those with suspect structural changes. STE could thus be used in screening and in characterising the “athlete’s heart”. To further investigate the effects of sports on cardiac function, a subgroup of these healthy athletes underwent CPET and ESE before and after the football season (Chapter 5.3). This was to explore whether detrimental effects of intense training (“cardiac fatigue”) exists in footballers. There were no changes in biventricular function at rest, or during exercise seen post-season, compared to pre-season, while peak HR and work rate increase, and peak V̇O2 remained constant. This shows that current elite football training programmes are not associated with “cardiac fatigue”. In addition, this study established a first framework for STE with ESE in athlete screening to comprehensively assess acute and chronic response to exercise in this group.
The second section of the thesis investigates the use of modern imaging in complex and severe paediatric cardiac conditions. A systematic review and meta-analysis on the prognostic role of STE in congenital heart disease (CHD) was performed (Chapter 4.2), which showed that throughout the spectrum of defects, worse ventricular Sl and SRl were prognostic of outcomes. The importance of STE was further explored in the context of characterising pathological exercise responses in Chapter 6. Three paediatric groups with right ventricular (RV) diseases were included: pulmonary arterial hypertension (PAH), which is a severe condition leading to considerable exercise limitation, corrected tetralogy of Fallot, which is a CHD characterised by gradual right ventricular (RV) failure, which is less severe in childhood, and elite athletes, serving as healthy controls. All participants underwent exercise testing, with STE and TDI measurements of the RV function. The results were that ESE can differentiate pathological responses to exercise, compared to the absence of marked dysfunction that is present at rest. Patients with PAH had exercise induced RV dysfunction at high intensity, while patients with ToF had preserved cardiac response through exercise but reduced systolic and diastolic cardiac reserve compared to athletes. Importantly, the methodological framework highlighted the challenges of comparing exercise responses in strikingly different patient groups and established the value of standardisation using exercise intensity domains, rather than work rate alone.
The third and final section was dedicated to implementing the findings and lessons learned in the previous two sections into two pilot studies on exercise testing and cardiac rehabilitation. In the first study, cardiac reserve measured with stress STE was compared between high intensity interval exercise (HIIE) and moderate intensity interval training (MIIE). A total of 19 healthy children participated, and it was found that biventricular Sl and SRl response was greater in HIIE compared to MIIE, while enjoyment during the session was similar. Importantly, this was maintained during active recovery periods, highlighting a possible role of the interval nature of exercise in the clinical benefits of HIIE. The benefits of HIIE on cardiac response were greater for SRl, which relates more to contractility, than they were for Sl, which relates more to stroke volume. This pilot study provided valuable mechanistic information, which can potentially guide how we deliver cardiac rehabilitation, and also how we evaluate positive cardiac remodelling as an outcome of this intervention. The second study evaluated the feasibility of a single step, high intensity CPET-ESE. Twenty-one healthy adults underwent a maximal CPET, and two high intensity ESE sessions (CPET-hiESE), at a work rate based on the gas exchange threshold and peak heart rate. These were compared with the standard maximal protocol (smESE), where measurements are conducted at 85% of predicted peak heart rate. It was found that both CPET-hiESE approaches resulted in better image quality and data completeness compared to smESE, while achieving similar STE and TDI cardiac function measurements and reproducibility. This pilot study established that a true combined CPET-ESE, using physiological testing data to guide ESE acquisition can be a superior alternative to current testing protocols.
In conclusion, this thesis established that modern echocardiographic modalities have a role in evaluating cardiac responses to acute exercise and remodelling after chronic exercise. In addition, it provided novel practical, methodological and mechanistic insights into how ESE use can be further improved, through integration on physiological and clinical knowledge into one common multimodal approach. The lessons learned throughout were translated into an original CPET-ESE methodological framework which can be further explored in future clinical populations.
Doctoral Theses
Doctoral College
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