Cardiac Microvascular Disease Quantified with CMR

This thesis has investigated three different diagnoses where cardiac microvascular disease is suspected: hypertrophic cardiomyopathy (HCM), systemic sclerosis (SSc), and patients with suspected microvascular angina (MVA).Study I of this thesis investigated patients with HCM. We investigated the myocardial perfusion (MP) using cardiac magnetic resonance imaging (CMR) in young patients with HCM or the risk of developing the disease. The investigation found that the patients had lower blood flow of the heart muscle than a reference group with healthy volunteers. This finding was interpreted as a sign of cardiac microvascular disease.Study II investigated patients with SSc, which is a complex rheumatic disease with multiorgan involvement. The investigation showed that the patients had lower blood flow through the heart muscle than a reference group with healthy volunteers. This finding was interpreted as a sign of cardiac microvascular disease.Study III Investigated patients with suspected MVA. The investigation showed that these patients had lower global MP than a reference group of healthy volunteers, but not as low as another reference group with patients with known coronary artery disease. The finding was interpreted as a sign of cardiac microvascular disease in this group of patients.Study IV aimed to collect reference values for coronary sinus (CS) flow derived global MP and to validate the method against a flow phantom. The study showed that global MP was lower in men than women, which needs to be recognized when interpreting a quantitative assessment of global MP. The study also showed that the CS flow method is accurate compared to a flow phanto

Myocardial perfusion by CMR coronary sinus flow shows sex differences and lowered perfusion at stress in patients with suspected microvascular angina

Background: Patients with chest pain may have normal coronary arteries and suffer from microvascular angina (MVA). The aim of this study was to determine if patients with suspected MVA have lower global myocardial perfusion (global MP) during adenosine stress compared with healthy controls and coronary artery disease (CAD) patients and to determine if there are sex differences in global MP. Methods: Twenty-three patients with suspected MVA (66 ± 11 years), 19 CAD patients (69 ± 5 years) with stress-induced ischaemia and 24 healthy controls (61 ± 10 years) underwent cardiac magnetic resonance (CMR) including coronary sinus flow measurements and first-pass perfusion at rest and during adenosine stress. Global MP was quantified as coronary sinus flow normalized to left ventricular mass. Results: Global perfusion was lower during stress in patients with suspected MVA (2.9 ± 1.0 ml/min/g) compared with healthy volunteers (3.7 ± 1.1 ml/min/g, p = 0.018), but higher compared with CAD patients (2.0 ± 0.9 ml/min/g, p = 0.019). Female controls had higher global MP than male controls both at rest (1.0 ± 0.3 vs. 0.7 ± 0.2 ml/min/g, p = 0.003) and during stress (4.4 ± 1.0 vs. 3.1 ± 0.6 ml/min/g, p = 0.001). Furthermore, females with suspected MVA showed higher global MP than males with suspected MVA (3.3 ± 1.0 vs. 2.4 ± 0.7, p = 0.04). Conclusions: Patients with suspected MVA have lower global MP at stress than healthy volunteers but higher than patients with CAD. Furthermore, there seems to be a sex difference in global MP at stress both in healthy volunteers and in patients with suspected MVA, with higher global MP in females, which implies a need for sex-specific normal limits when assessing quantitative MP

Decreased global myocardial perfusion at adenosine stress as a potential new biomarker for microvascular disease in systemic sclerosis : A magnetic resonance study

Background: Patients with systemic sclerosis (SSc) have high cardiovascular mortality even though there is no or little increase in prevalence of epicardial coronary stenosis. First-pass perfusion on cardiovascular magnetic resonance (CMR) have detected perfusion defects indicative of microvascular disease, but the quantitative extent of hypoperfusion is not known. Therefore, we aimed to determine if patients with SSc have lower global myocardial perfusion (MP) at rest or during adenosine stress, compared to healthy controls, quantified with CMR. Methods: Nineteen SSc patients (17 females, 61 ± 10 years) and 22 controls (10 females, 62 ± 11 years) underwent CMR. Twelve patients had limited cutaneous SSc and 7 patients had diffuse cutaneous SSc. One patient had pulmonary arterial hypertension (PAH). MP was quantified using coronary sinus flow (CSF) measurements at rest and during adenosine stress, divided by left ventricular mass (LVM). Results: There was no difference in MP at rest between patients and controls (1.1 ± 0.5 vs. 1.1 ± 0.3 ml/min/g, P = 0.85) whereas SSc patients showed statistically significantly lower MP during adenosine stress (3.1 ± 0.9 vs. 4.2 ± 1.3 ml/min/g, P = 0.008). Three out of the 19 SSc patients showed fibrosis in the right ventricle insertion points despite absence of PAH. None had signs of myocardial infarction. Conclusions: Patients with SSc have decreased MP during adenosine stress compared to healthy controls. Thus hypoperfusion at stress may be a sensitive marker of cardiac disease in SSc patients possibly signifying microvascular myocardial disease

Young patients with hypertrophic cardiomyopathy, but not subjects at risk, show decreased myocardial perfusion reserve quantified with CMR.

To determine if myocardial perfusion (MP) during hyperaemia is decreased in young patients with hypertrophic cardiomyopathy (HCM). Also, to determine if an MP decrease is associated with diastolic dysfunction, and to investigate if young subjects at risk of HCM show differences in MP compared with controls

Serum biomarkers of early stages of hypertrophic cardiomyopathy in a young population

Background: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disorder and the leading cause of sudden cardiac death in the young. Although in a majority of HCM cases there are gene mutations coding for sarcomere proteins, the onset for the clinical consequences of these mutations are difficult to predict, as these mutations do not show any clear relationship to the degree of myocardial hypertrophy. Hence identification of early markers for this disease is important. The aim of this study was to investigate novel serum biomarkers reflecting myocardial remodeling, microfibrosis and coronary endotheliopathy in young presymtomatic HCM patients and in individuals at risk for developing HCM. Methods: Eighty-nine participants (18 HCM patients, 14 HCM-risk individuals, and 57 healthy controls) with median age of 15 (range 0-30) years underwent assessment with echocardiography and serum analysis for myostatin, cathepsin S, endostatin, type I collagen degradation marker (ICTP), matrix metalloproteinase (MMP) 9, vascular (VCAM) and intercellular adhesion molecules (ICAM). In some individuals, myocardial perfusion was measured both at rest and after adenosine via magnetic resonance. Results: Both cathepsin S and endostatin were increased in the HCM group (p0.3) and diastolic function, expressed as E/e' (p0.3). In the HCM-risk group, myostatin was decreased (p0.1). Conclusion: To the best of our knowledge, this is the first study to suggest early onset changes in biomarkers of myoblast regulation, endothelial function and matrix remodeling in young presymptomatic HCM patients and in HCM-risk individuals