Takotsubo stress cardiomyopathy and different types of stress

Sammanfattning: Myocardial infarction with normal coronary angiography (MINCA) is an important subgroup of myocardial infarction for which the prevalence, underlying pathophysiology, prognosis and optimal management are still largely unknown. Interest in and awareness of MINCA has increased in recent years due to the frequent use of coronary angiography, the description of Takotsubo stress cardiomyopathy (TSC) and new sensitive troponin assays. The purpose of this thesis was to investigate the prevalence and clinical characteristics of MINCA using cardiovascular magnetic resonance (CMR) and particularly to investigate the effect of stress on TSC using Doppler tissue imaging (DTI), heart rate variability (HRV), salivary cortisol (SC) and non-invasive coronary flow reserve (CFR). In Study I, 176 patients with MINCA were screened at five coronary care units in the Stockholm Metropolitan Area. 152 of them were investigated using CMR which showed 67% of the patients as being normal, 19% having signs of myocardial necrosis and 7% the diagnosis was myocarditis in of the patients. The remaining patients were either diagnosed with hypertrophic cardiomyopathy or were undecided. Twenty-two percent of all MINCA with a normal CMR fulfilled the Mayo Clinic criteria for TSC. In Study II, we tested the hypothesis that compared to sex- and age-matched controls TSC patients have an increased vulnerability to stress even after the acute event. Using dobutamine stress echocardiography (DSE) and DTI we investigated the TSC patients approximately 20 months (619 ± 297 days) after the acute event. At rest left ventricular myocardial performance index (LV-MPI) was significantly higher for TSC patients (p=0.01). During stress, however, there were no significant differences between the groups. Study III was in many ways similar to Study II except that mental stress was used instead of dobutamine stress. The study was performed 28 months after the acute event. In addition to DTI, HRV and SC were also studied. During mental stress there were no significant differences between TSC patients and sex- and age-matched controls for DTI, HRV and SC. There was a trend towards less increase in SC after stress in TSC patients compared to controls. A self-estimated acute stress scale (Likert-type scale from 0–6) was 2.8 and 2.6 during mental stress for TSC patients and controls, respectively. During the acute event TSC patients retrospectively estimated their acute stress level at 4.4. In Study IV, dobutamine stress was used to investigate the effect of stress on non-invasive CFR. At low-dose dobutamine, CFR was significantly lower in TSC patients compared to controls (p=0.017). There were no differences in CFR at high-dose dobutamine between the groups. Conclusion: MINCA is more common than previously thought and is associated with a normal CMR. TSC constitutes a substantial part of MINCA. Studies II and III point to a slow recovery for TSC patients measured by DTI but no sign of vulnerability was revealed by dobutamine or mental stress measured by DTI, HRV or SC. We could not confirm that the catecholamine dobutamine induced microvascular dysfunction in TSC patients. However, we found a small but significant difference in CFR at low-dose dobutamine, which implies that the role of microvascular function in TSC needs to be further explored.

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