The lack of widely accepted objective measures of cardiac dysfunction other than left ventricular ejection fraction (LVEF) has hampered, and continues to hamper, clinical research in patients with heart failure (HF). Identifying patients at higher risk of adverse outcome would allow better targeting of therapy to those with most to gain.The thesis is divided in three parts.In the first part, I report the results of studies of the association between echocardiographic measures of right atrial pressure (by measuring the inferior vena cava (IVC) diameter) and outcome in ambulatory patients with HF. I also studied the associations with prognosis of a newer echocardiographic method (global longitudinal strain, GLS) to assess left ventricular systolic function in patients with normal LVEF on conventional imaging. In the second part, I report the results of studies of the associations of left atrial function by cardiac magnetic resonance (cMRI) with outcome in ambulatory patients with HF. I also studied the relationship between QRS morphology on ECG with cardiac structure and function measured by cMRI in ambulatory patients with HF.In the third part, I report the results of developing and prospectively evaluating an ultrasound method to measure the internal jugular vein diameter (as an objective estimate of the right atrial pressure) and its changes with respiratory manoeuvres.I studied the association between the jugular vein diameter, clinical and echocardiographic variables, and its relations with outcome in ambulatory patients with HF and controls.My results showed that upstream consequences of a dysfunctional left ventricle, such as impaired left atrial function measured by cMRI, a distended IVC or internal jugular vein by ultrasound, provide powerful prognostic information, similar to that obtained by measuring N-terminal pro-B-type natriuretic peptide plasma levels, in individuals with HF regardless of whether they have a reduced or normal LVEF.As residual congestion (dilated IVC or jugular vein) and impaired left atrial function appear strongly related to an adverse outcome, tailoring treatment to minimise congestion or improving left atrial function is an attractive concept worth testing.Published articles:1) Pellicori P, Carubelli V, Zhang J, Castiello T, Sherwi N, Clark AL, Cleland JG. IVC diameter in patients with chronic heart failure: relationships and prognostic significance. JACC Cardiovasc Imaging. 2013;6:16-28.http://doi.org/10.1016/j.jcmg.2012.08.012http://www.sciencedirect.com/science/article/pii/S1936878X120087902) Pellicori P, Kallvikbacka-Bennett A, Khaleva O, Carubelli V, Costanzo P, Castiello T, Wong K, Zhang J, Cleland JG, Clark AL. Global longitudinal strain in patients with suspected heart failure and a normal ejection fraction: does it improve diagnosis and risk stratification? Int J Cardiovasc Imaging. 2014;30:69-79.http://doi.org/10.1007/s10554-013-0310-yhttps://link.springer.com/article/10.1007/s10554-013-0310-y3) Pellicori P, Zhang J, Lukaschuk E, Joseph AC, Bourantas CV, Loh H, Bragadeesh T, Clark AL, Cleland JG. Left atrial function measured by cardiac magnetic resonance imaging in patients with heart failure: clinical associations and prognostic value. Eur Heart J. 2015;36:733-42.https://doi.org/10.1093/eurheartj/ehu405https://academic.oup.com/eurheartj/article/36/12/733/2293211/Left-atrial-function-measured-by-cardiac-magnetic?searchresult=14) Pellicori P, Joseph AC, Zhang J, Lukaschuk E, Sherwi N, Bourantas CV, Loh H, Clark AL, Cleland JG. The relationship of QRS morphology with cardiac structure and function in patients with heart failure. Clin Res Cardiol. 2015;104:935-45.http://doi.org/10.1007/s00392-015-0861-0https://link.springer.com/article/10.1007/s00392-015-0861-05) Pellicori P, Kallvikbacka-Bennett A, Zhang J, Khaleva O, Warden J, Clark AL, Cleland JG. Revisiting a classical clinical sign: jugular venous ultrasound. Int J Cardiol. 2014;170:364-70.http://doi.org/10.1016/j.ijcard.2013.11.015http://www.sciencedirect.com/science/article/pii/S01675273130198766) Pellicori P, Kallvikbacka-Bennett A, Dierckx R, Zhang J, Putzu P, Cuthbert J, Boyalla V, Shoaib A, Clark AL, Cleland JG. Prognostic significance of ultrasound-assessed jugular vein distensibility in heart failure. Heart. 2015;101:1149-58.http://dx.doi.org/10.1136/heartjnl-2015-307558http://heart.bmj.com/content/101/14/114
