Background.
In patients with coronary artery disease (CAD), multi-parametric cardiovascular magnetic resonance (CMR) provides detailed information about the myocardial tissue composition and its function. This thesis aims to investigate how myocardial tissue composition characteristics influence its function. Additionally, this thesis aims to develop methods for time-resolved, three-dimensional flow imaging in-vitro and in health. 
Methods. 
We have prospectively recruited and conducted multi-parametric CMR in 76 patients with ST-elevation myocardial infarction (STEMI), 44 patients with stable chest pain and 35 healthy volunteers. 
Results. 
Study 1 and 2 evaluated if CMR derived function parameters are associated with the presence of microvascular obstruction (MVO) or intramyocardial haemorrhage (IMH) in STEMI patients. Study 1 demonstrated the diagnostic accuracy of mitral annular plane systolic excursion (MAPSE) to detect MVO/IMH. Study 2 demonstrated that peak global longitudinal strain (GLS) is most strongly associated with MVO/IMH when compared to other myocardial deformation parameters. Study 3 demonstrated that during first-pass perfusion stress CMR, at peak hyperemic stress, GLS is reduced in the presence of a perfusion defect in patients being investigated for CAD. Study 4 demonstrated that acute ECV-maps can reliably quantify area at risk and final infarct size (at 3-month follow) in reperfused STEMI patients. Study 5 investigated 3 main acceleration methods for 4-dimensional flow (4D Flow) in phantoms and healthy volunteers. In phantoms, all 4D Flow methods underestimated peak velocity but their mean errors were within reasonable limits for clinical applications. In volunteers, 4D echo planer imaging (EPI) method had the shortest acquisition time, best agreement with 2-dimensional phase contrast, best internal consistency between mitral and aortic valve flows.
Conclusions.
CMR derived longitudinal functional parameters of the left ventricle are associated with pathologies predominantly in the sub-endocardium and could be used as a surrogate imaging markers. ECV-maps offer an alternative to IS quantification. 4D EPI is the most robust acceleration method for whole-heart flow assessment.

Established and Emerging Techniques of Cardiovascular Magnetic Resonance Imaging in Coronary Artery Disease

As with many large-scale long-term outcome trials, more questions have been posed than answered regarding the potential role of angiotensin II receptor blockers as first-line agents in chronic heart failure. Given the present data, in patients with left ventricular systolic dysfunction, ACE inhibitors must remain the treatment of choice, owing to the large body of data supporting their use in this clinical syndrome. However, ARBs seems a reasonable alternative for renin-angiotensin axis blockade in the significant number of heart failure patients who are genuinely intolerant of ACE inhibitors. The pendulum has now swung back in favour of ACE inhibition for chronic heart failure, although one can only await with great expectation the results of the ongoing trials comparing not only angiotensin II receptor blockers with ACE inhibitors but a combination of the two with regards tolerability and survival. Whether this potentially useful class of drugs will ultimately become the cornerstone of heart failure therapy in place of, or in addition to, ACE inhibitors is still in debate, but hopefully we should not have to wait too long for the definitive answers.

https://journals.sagepub.com/doi/pdf/10.3317/jraas.2000.003

Angiotensin II receptor blockers in chronic heart failure--not as ELITE as expected!

Heart failure is a major cause of death, hospital admissions and poor quality of life. It affects some 1-2% of the general population, increasing to up to 8% in people over 75 years of age. Although treatment with angiotensin-converting enzyme (ACE) inhibitors reduces symptoms and mortality, 50-70% of patients with heart failure still die within 5 years of diagnosis. There is thus clear scope for improving the treatment of patients with this condition. The CHARM programme is designed to define the clinical benefits of the long-acting angiotensin II type 1 (AT 1 ) receptor blocker, candesartan cilexetil, in a wide variety of patients with symptomatic heart failure. Candesartan cilexetil will be evaluated in three double-blind, randomized studies involving patients grouped according to left ventricular function and ACE inhibitor tolerance/intolerance.

G B Granger

Papers

Candesartan in Heart Failure - Assessment of Reduction in Mortality and Morbidity (CHARM) Study Programme.