Institutionen för medicin / Department of Medicine
Abstract
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