T-vector and T-loop morphology analysis of ventricular repolarization in ischemic heart disease

Sammanfattning: Background Sudden cardiac death (SCD) is responsible for about half of all cardiovascular deaths in the western world. Heterogeneous ventricular repolarization (VR) is a common denominator in the genesis of malignant ventricular arrhythmias responsible for SCD and the presence of coronary artery disease (CAD) is an aggravating factor. A non-invasive method reliably reflecting VR heterogeneity could therefore play a significant role in the preventive strategy against SCD. This thesis focuses on VR in CAD and acute ischemia. Aims To study VR abnormalities in patients with CAD using 3-dimensional (3-D) vectorcardiography (VCG). To assess VR at rest and during acute ischemia in patients with/without major co-morbidities, including hypertension and left ventricular hypertrophy (LVH), applying recently developed VCG parameters. To assess VR alterations in relation to the amount of the ischemic myocardium. To explore the prognostic value of these parameters in terms of cardiovascular (CV) mortality and morbidity during long-term follow-up. Studies I-II As a first step, VR measures at rest and during acute ischemia were analyzed in a subgroup of 56 CAD patients selected to create a relatively homogeneous group without obvious confounders affecting the VR response, e.g. previous myocardial infarction (MI) or LVH. They were identified from a cohort of 187 patients planned for an elective single-vessel percutaneous coronary intervention (PCI). In the next step, the electrophysiological consequences of myocardial hypertrophy were assessed in all 187 CAD patients, including 33 with LVH and 54 with a history of hypertension. VR was examined in terms of the maximum T-vector orientation in space by azimuth and elevation and the angular relationship with the main depolarization vector, the QRS-T angle. The planarity of the T loop (Tavplan), its shape and roundness (Teigenv) and the area under the 3-D T-wave (Tarea) were analyzed as well. At rest, the Tarea and Teigenv differed significantly between CAD patients and healthy controls. Acute ischemia most consistently reduced T-loop planarity and increased its roundness and area under the T-wave. Only occlusion of the left anterior descending artery (LAD) significantly changed the T-vector orientation. Patients with LVH had not only the most abnormal VR at rest but also a significantly more pronounced VR response during coronary occlusion. Patients with a history of hypertension (without LVH) had mean parameter values between the LVH patients and those with neither hypertension nor LVH. Study III The relationship between the size and location of the myocardium at risk (MAR) and the VR response during ischemia was studied during elective PCI in another cohort of 35 CAD patients. Tc-99m-sestamibi was administered intravenously immediately after coronary occlusion. The perfusion defect severity and MAR were quantified by automated software. The VR measures during maximum ischemia was compared with baseline and the changes (delta) were related to the MAR and the occluded artery. There were significant correlations between MAR size and ST-segment alterations (STC-VM, deltaST-VM), as previously shown, but also with deltaTavplan and deltaTeigenv, although they were most prominent during LAD occlusion, which induced the largest MAR size. Study IV In a longitudinal cohort study, the 187 CAD patients (Study II) were followed for 8±1 years. There were 16 CV deaths, 19 new MIs and more then 70 additional revascularizations. CV death was independently predicted by a prolonged QRS duration and a widened QRS-T angle, along with left ventricular dysfunction or hypertrophy. MI was most consistently predicted by increased Tavplan. Repeat revascularization was predicted by the presence of diabetes and the absence of stent implantation. Conclusion CAD patients displayed changes in VR compared with the healthy controls, even in the absence of major co-morbidities. Short-lasting LAD occlusion induced the most pronounced VR changes, which were associated with the largest amount of jeopardized myocardium compared with the other coronary arteries. Myocardial hypertrophy was associated not only with the most abnormal VR at baseline but also with the most exaggerated VR response during ischemia. These observations are consistent with epidemiological, experimental and autopsy data showing a predominance of LAD disease and/or myocardial hypertrophy in SCD victims. A widened QRS-T angle was independently associated with the CV deaths, which is consistent with previous studies, and an increased distortion of the T-loop (Tavplan) with subsequent MI, which is a novel finding. VCG-based VR analysis might prove to be a useful tool in assisting the identification of risk individuals and for following the effects of preventive therapies.