Quantitative Correlates of Resting Potassium-43 Perfusion Following Myocardial Infarction in Man

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Doctor of Philosophy

dissertationDespite a century of research and practice, the clinical accuracy of the electrocardiogram (ECG) to detect and localize myocardial ischemia remains less than satisfactory. Myocardial ischemia occurs when the heart does not receive adequate oxygen-rich blood to keep up with its metabolic requirements, and severe ischemia can lead to myocardial infarction and life-threatening arrhythmias. Early and accurate detection is an essential component of managing this condition. Ischemia is known to be a dynamic condition that reflects a changing imbalance between blood supply and metabolic demand so that it is natural that examination under physical stress conditions or exercise testing (ET) is in widespread clinical use. However, ET is characterized by poor sensitivity (68%) and specificity (77%), limiting its diagnostic usefulness and providing the motivation to address some gaps in our understanding of myocardial ischemia and its ECG signature. This dissertation is composed of three studies. The aim of the first study was to evaluate the conventionally held mechanisms for nontransmural ischemia using intramural electrodes to measure three-dimensional potential distributions in the ventricles of animals exposed to acute ischemia. We demonstrated that contrary to accepted dogma, the electrocar- diographic response of acute myocardial ischemia originated throughout the ventricular wall, i.e., in the subendocardium, midmyocardium, or the subepicardium, under various conditions. Our goal in the second study was to evaluate whether acute myocardial ischemia follows a similar pattern of spatial and temporal evolution as seen in myocardial infarction. Our findings show that the spatial and temporal evolution of acute ischemia is characterized by multiple distinct regions that expand in all three directions, with maximal expansion in the circumferential direction, especially in the early stages of ischemic development. Furthermore, with increased stress, these regions continue to expand and eventually merge into one another, and in the extreme become transmural. The progression of myocardial infarction, by contrast, was very quickly transmural in extent and formed a cohesive block of affected tissues. The aim of the third study was to evaluate the sensitivity of epicardial electrical markers of acute ischemia relative to direct evidence of ischemia derived from intramural electro- grams. The key finding from this study is that the epicardial T-wave is a more sensitive index of acute ischemia than epicardial ST segment changes, especially in the early stages of acute ischemia development

Coronary Angiography

In the intervening 10 years tremendous advances in the field of cardiac computed tomography have occurred. We now can legitimately claim that computed tomography angiography (CTA) of the coronary arteries is available. In the evaluation of patients with suspected coronary artery disease (CAD), many guidelines today consider CTA an alternative to stress testing. The use of CTA in primary prevention patients is more controversial in considering diagnostic test interpretation in populations with a low prevalence to disease. However the nuclear technique most frequently used by cardiologists is myocardial perfusion imaging (MPI). The combination of a nuclear camera with CTA allows for the attainment of coronary anatomic, cardiac function and MPI from one piece of equipment. PET/SPECT cameras can now assess perfusion, function, and metabolism. Assessing cardiac viability is now fairly routine with these enhancements to cardiac imaging. This issue is full of important information that every cardiologist needs to now

Nonfluoroscopic electromechanical mapping of the left ventricle: Evaluation of the technique as diagnostic tool and as guidance for novel therapeutic strategies

With his landmark paper in Nature Medicine in 1996, Shlomo Ben-Baim and coworkers introduced a novel technique into the clinical arena. In

Understanding ventricular tachycardia : towards individualized substrate-based therapy

Patients with structural heart disease - e.g. after myocardial infarction or due to a cardiomyopathy - are at increased risk for sudden cardiac death because of arrhythmia. The department of Cardiology at the Leiden University Medical Center has a strong interest for the underlying substrate and mechanisms of ventricular arrhythmias. Since 2011, research fellow Sebastiaan Piers and his supervisor prof. dr. Katja Zeppenfeld have performed innovative studies, combining advanced electrophysiological data with detailed imaging data derived from CT and MRI. These studies have led to important insights into the substrate and mechanisms of ventricular arrhythmia in patients after myocardial infarction or with a cardiomyopathy. An improved understanding may be the most important prerequisite for the development of effective, individualized and substrate-based therapies for ventricular arrhythmias in the future. Sebastiaan Piers will defend his thesis "Understanding Ventricular Tachycardia: Towards Individualized Substrate-based Therapy" on Thursday January 28th 2016.The printing of this thesis was financially supported by St. Jude Medical, Biotronik, Bayer HealthCare, Sanofi Aventis, Chipsoft, Medis Medical Imaging and Toshiba Medical Systems. Het verschijnen van dit proefschrift werd mede mogelijk gemaakt door de steun van de Nederlandse Hartstichting en de Stichting Wetenschap en Onderzoek Interne Geneeskunde Onze Lieve Vrouwe Gasthuis.UBL - phd migration 201