Although surgical and transcatheter interventions have significantly improved survival of patients with coarctation of the aorta (CoA) and interrupted aortic arch (IAA), long-term complications including left ventricular (LV) abnormalities and systemic arterial dysfunction remain issues of concern despite successful repair. While new indices of myocardial deformation that reflect diastolic and systolic function in terms of strain, strain rate, and torsion as detected by speckle tracking echocardiography have shown promise in the assessment of LV, left atrial (LA), and right ventricular (RV) mechanics, the understanding of ventricular myocardial deformation after repair of CoA is limited. In this thesis, studies were undertaken to test the hypotheses that LV, LA, and RV myocardial deformation is altered and related to structural and functional arterial alterations in adolescents and young adults late after successful intervention of CoA and IAA, and to explore the LV contractile reserve noninvasively by examining the force-frequency relationship (FFR) in these patients. The LV, LA, and RV mechanics were evaluated with tissue Doppler and speckle tracking echocardiography, while carotid arterial structure and function were determined by radiofrequency-based echocardiographic imaging and oscillometry techniques. Supine bicycle stress exercise testing was used to evaluate the FFR by tracking the changes in LV contractility with increase in heart rate. Patients after CoA and IAA repair had significantly greater carotid arterial stiffness and intima-media thickness when compared with controls. Furthermore, mitral annular systolic and diastolic velocities, LV longitudinal and radial strain and early diastolic strain rates, peak torsion and untwisting velocity, and LA peak positive and total strain, and LA strain rates at ventricular systole, early diastole, and atrial contraction were significantly lower in patients than controls. Increased arterial stiffness and intima-media thickness was associated with worse LV myocardial deformation, while LA total strain and LA strain rate at ventricular early diastole were associated with diastolic annular velocities and strain rates. Multivariate analysis further revealed arterial stiffness as an independent determinant of LA total strain. With regard to dynamic assessment of LV contractile reserve, at submaximal exercise, the systemic blood pressures were significantly greater in patients than controls, while mitral annular systolic and early diastolic velocities remained significantly reduced. The increase in LV myocardial isovolumic acceleration, a relative load independent index of contractility, with increase in heart rate during exercise stress was significantly reduced in patients compared with controls. Flattening of FFR in patients reflected impaired LV contractile reserve, which was found to be associated negatively with increment in systemic blood pressure during exercise. For RV mechanics, patients with CoA repaired exhibited significantly lower tricuspid annular systolic and early diastolic velocities, global RV systolic longitudinal strain, and strain rate during systole, early and late diastole, compared to controls. Impairment of RV deformation was further related to increased LV mass and RV thickness. In conclusion, these findings suggest arterial dysfunction, impaired LV, RV, and LA mechanics, and reduced LV contractile reserve, in patients late after CoA and IAA repair even in the absence of residual aortic narrowing and implicate abnormal arterial-LV-LA and LV-RV interactions. / published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

Renal failure in patients undergoing Aortic surgery is associated with a poor outcome. The shortcomings of serum creatinine for measuring renal function are well documented. We examined the value of alternative markers in diagnosing and predicting renal damage in patients undergoing abdominal aortic surgery and those exposed to intravascular contrast media. Cystatin C lacks some of the reservations associated with serum creatinine when used as a marker of glomerular filtration rate. The protease inhibitor alpha-glutathione Stransferase (a-GST) is recovered in urine after injury to proximal tubular cells. Urine microalbumin is a marker of glomerular permeability. Together we used all four assays to detect and characterize the nature of renal injury after surgery and contrast exposure. Cystatin C had a marginally better sensitivity than serum creatinine at detecting baseline renal impairment. It also showed earlier changes in individual patients whose renal dysfunction deteriorated over time. The urinary markers showed an earlier significant rise after the onset of surgery when compared to serum markers, but only a-GST rose significantly after contrast exposure. Patients undergoing a supra-renal cross-clamp showed significantly higher a-GST levels (and not the other three markers) when compared to the infra-renal group. Cystatin C appears to have better sensitivity and specificity for predicting the need for dialysis in patients undergoing surgery. Peak serum creatinine and cystatin C after contrast exposure show good correlation with peak values after surgery. Cystatin C is equivalent to and may be better than serum creatinine in detecting preexisting and deteriorating renal impairment. Although the urinary assays are earlier markers of renal injury, their clinical significance needs to be determined. Elevation in creatinine and cystatin C after contrast exposure parallel those after surgical intervention and may be helpful in selecting out high-risk patients prior to surgery. / Thesis (M.Med.Sc.)-University of Natal, 2003.