The right ventricular response to lung resection

Lung cancer is the most common cause of cancer death in the UK and although the best opportunity for cure is provided by lung resection, surgery is associated with high rates of cardiorespiratory complications and long-term morbidity. Existing studies indicate right ventricular dysfunction occurs following lung resection and may be implicated in any post-op deterioration. Evaluation of right ventricular function is challenging, with its complex shape, marked load dependence and retrosternal position meaning there is no reliable, non-invasive method of assessment. The majority of previous work examining right ventricular function in the lung resection population has been performed using the volumetric pulmonary artery catheter, the reliability of which has been challenged. The first section of this thesis reviews the right ventricle in terms of anatomy, physiology and assessment, providing context for future investigations (Chapter 1). A review of the literature examining the right ventricular / pulmonary vascular response to lung resection is then presented, along with the rationale for further investigations (Chapter 2). As there is a high frequency of complications in this population, often requiring critical care support, the first investigation (Chapter 3) of this thesis characterises those patients admitted to intensive care following surgery. It also examines the incidence of right ventricular dysfunction in this population. Given the methodological concerns regarding the techniques previously used to assess right ventricular function following lung resection, cardiovascular magnetic resonance imaging was used to sequentially assess the right ventricular response to surgery (Chapter 5). Cardiovascular magnetic resonance is a reference method for assessment of right ventricular function and has not previously been used sequentially in this population. This investigation demonstrates right ventricular function (measured by right ventricular ejection fraction) deteriorates following lung resection with impairment still evident two months following surgery. There were no changes in left ventricular function over the same period. With the difficulties associated with cardiovascular magnetic resonance imaging in this population and its limited use outside of research settings, an alternative method for assessment of right ventricular function would have utility in this population. Trans-thoracic echocardiography is the most commonly used non-invasive method for assessment of right ventricular function with widespread availability and low cost. Chapters 6 and 7 attempt to validate conventional and novel echocardiographic methods for assessment of right ventricular function in this population. The main finding is that established echocardiographic methods; fractional area change, tricuspid annular plane systolic excursion and S' wave velocity at the tricuspid annulus, are not suitable for assessment of right ventricular function in this population. Speckle tracked strain echocardiography is a novel method of assessing right ventricular function that has shown promising results in other patient groups. Chapter 7 demonstrates that right ventricular global strain is not useful, but that right ventricular free-wall strain may have value in this population. Biomarkers of myocardial dysfunction (B-type natriuretic peptide and high sensitivity troponin-t) were measured contemporaneously with the imaging studies (Chapter 8). This investigation demonstrates that both biomarkers increase following lung resection and that their plasma concentration two days following surgery are associated with right ventricular function. There was no association with parameters of left ventricular function suggesting the biomarkers are released in response to changes affecting the right ventricle. On an exploratory basis the association between the peri-operative biomarkers and functional capacity following surgery is also assessed. Finally, potential mechanisms of right ventricular dysfunction following lung resection are explored (Chapter 9). This demonstrates that as pulmonary artery acceleration time (a surrogate measure of right ventricular afterload) increases, right ventricular ejection fraction deteriorates. Using a cardiovascular magnetic resonance surrogate, a deterioration in the matching of right ventricular function with right ventricular afterload (coupling) is also demonstrated. In combination these studies provide a robust answer to the question "what happens to right ventricular function following lung resection?" It provides validated methods for future work in this population and suggests an association between post-operative right ventricular function and right ventricular afterload