Myocardial inflammation drives right ventricular dysfunction following lung resection surgery

Introduction Lung cancer is the third commonest cancer in the United Kingdom.1 After surgery, a reduction in cardio-respiratory function appears to influence patient reported functional capacity. Our research group have demonstrated a reduction in right ventricular (RV) function following lung resection with alterations in both pulmonary afterload and contractility.2-4 Animal models of pulmonary embolism, which are functionally analogous to lung resection surgery and one lung ventilation with transient clamping of the pulmonary artery, have widely described an RV inflammatory injury. We hypothesise RV inflammation also plays a key role in the pathophysiology of peri-operative myocardial injury and RV dysfunction following lung-resection. Cardiovascular magnetic resonance (CMR) offers the ability to assess myocardial inflammation using CMR T1-mapping techniques. Methods We conducted a single-centre, prospective, observational cohort study at a tertiary referral cardiothoracic centre. Fifteen patients undergoing lung-resection underwent serial CMR imaging. T1 mapping was performed both pre and post-contrast. T1 and extracellular volumes (ECV) were calculated using circle(cv142) software (Calgary, Canada). Changes in T1 and ECV over time were assessed using Friedman's test and appropriate pairwise comparisons. Association was sought between T1, ECV and CMR measures of RV function using analysis of covariance(ANCOVA). Results Thirty-eight pre-contrast and 39 post-contrast T1 maps were available for analysis. There was a significant rise in T1 at post-operative day two (POD2) from pre-operative values in both the RV insertion point (RVIP) (p=0.002, Figure 1) and septum (p=0.03) with no change in the left ventricle (p=0.64). There was a significant rise in RVIP ECV at POD2 from baseline (p=0.005). Both increased RVIP T1 and ECV were associated with a reduction in RVEF at POD2 (r = -0.91, p<0.001 and r= -0.77, p=0.008 respectively). Increased ECV at two-months was associated with a reduction in RVEF at two-months (r=-0.82, p=0.004). Discussion This is the first study to demonstrate both T1 and ECV are markedly increased in the RVIPs and septum in the post-operative period in patients undergoing lung resection surgery. These changes suggest lung resection triggers an early inflammatory response within the myocardium in response to surgery. Increases in T1 in the early post-operative period suggests acute inflammation results in acute RV impairment whilst increases in ECV at two-months represents scarring of the myocardium resulting in chronic RV impairment. Better understanding of the pathophysiology of RV dysfunction following lung resection has the potential to identify and protect high-risk patients and ameliorate post-operative functional limitation.