| 1. |
- Fernlund, Eva I., et al.
(author)
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Serum biomarkers of early stages of hypertrophic cardiomyopathy in a young population
- 2015
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In: Journal of the American College of Cardiology. - 0735-1097. ; 65:10S, s. 787-787
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Conference paper (peer-reviewed)abstract
- 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.
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| 2. |
- Gyllenhammar, Tom
(author)
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Cardiac Microvascular Disease Quantified with CMR
- 2021
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Doctoral thesis (other academic/artistic)abstract
- 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 phantom
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| 3. |
- Gyllenhammar, Tom, et al.
(author)
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Decreased global myocardial perfusion at adenosine stress as a potential new biomarker for microvascular disease in systemic sclerosis : A magnetic resonance study
- 2018
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In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 18:1
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Gyllenhammar, Tom, et al.
(author)
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Myocardial perfusion by CMR coronary sinus flow shows sex differences and lowered perfusion at stress in patients with suspected microvascular angina
- 2022
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In: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 42:3, s. 208-219
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
- Lundin, Magnus, et al.
(author)
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Left ventricular global wall thickness is easily calculated, detects and characterizes hypertrophy, and has prognostic utility
- 2019
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Conference paper (other academic/artistic)abstract
- BACKGROUND: Cardiovascular magnetic resonance (CMR) can be used to measure left ventricular end-diastolic volume (LVEDV) and left ventricular mass (LVM). However, there is currently no good way to measure the normality of LVM in relation to a given LVEDV. We hypothesized that a simple measure of left ventricular global wall thickness (GWT) would be accurate, beneficial for detecting and characterizing hypertrophy, and have prognostic significance.METHODS: Subjects underwent CMR at 1.5T, including healthy volunteers (n=99) and patients assessed for heart disease (n=2828).RESULTS: GWT calculated from LVEDV and LVM had excellent agreement with measured mean end-diastolic wall thickness of the entire left ventricle (bias 0.01±0.23mm). GWT was most predictive of death or hospitalization for heart failure in patients with normal findings by CMR (n=326, log-rank 26.8, p<0.001, median [interquartile range] follow-up 5.8 [5.0–6.7] years). GWT indexed to body surface area (GWTi) was most predictive of outcomes in patients with normal LVEDV index (n=1352, log-rank 36.4, p<0.001, follow-up 5.5 [4.1–6.5] years). Patients with concentric remodeling had worse prognosis than the normal patients (p=0.02), and the patients with hypertrophy had worse prognosis than both normal patients (p<0.001) and patients with concentric remodeling (p=0.045), see Figure 1. Of patients with suspected heart disease but normal CMR findings regarding left ventricular volumes, function, mass, and scar, 22% were found to have increased mean GWTi corresponding to concentric remodeling, see Figure 2.CONCLUSIONS: Left ventricular GWT is an intuitive measure that can be easily calculated from mass and volume with high accuracy, and has prognostic utility in patients with normal CMR findings. Also, GWTi classifies hypertrophy as concentric or eccentric, and detects concentric remodeling in a substantial portion of patients with otherwise normal findings.
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| 8. |
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| 9. |
- Lundin, Magnus, et al.
(author)
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Prognostic utility and characterization of left ventricular hypertrophy using global thickness
- 2023
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In: Scientific Reports. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Cardiovascular magnetic resonance (CMR) can accurately measure left ventricular (LV) mass, and several measures related to LV wall thickness exist. We hypothesized that prognosis can be used to select an optimal measure of wall thickness for characterizing LV hypertrophy. Subjects having undergone CMR were studied (cardiac patients, n = 2543; healthy volunteers, n = 100). A new measure, global wall thickness (GT, GTI if indexed to body surface area) was accurately calculated from LV mass and end-diastolic volume. Among patients with follow-up (n = 1575, median follow-up 5.4 years), the most predictive measure of death or hospitalization for heart failure was LV mass index (LVMI) (hazard ratio (HR)[95% confidence interval] 1.16[1.12-1.20], p < 0.001), followed by GTI (HR 1.14[1.09-1.19], p < 0.001). Among patients with normal findings (n = 326, median follow-up 5.8 years), the most predictive measure was GT (HR 1.62[1.35-1.94], p < 0.001). GT and LVMI could characterize patients as having a normal LV mass and wall thickness, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy, and the three abnormal groups had worse prognosis than the normal group (p < 0.05 for all). LV mass is highly prognostic when mass is elevated, but GT is easily and accurately calculated, and adds value and discrimination amongst those with normal LV mass (early disease).
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| 10. |
- Pahlm, Ulrika, et al.
(author)
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Longitudinal left ventricular function is globally depressed within a week of STEMI
- 2018
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In: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961. ; 38:6, s. 1029-1037
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Journal article (peer-reviewed)abstract
- Sixty percent of stroke volume (SV) is generated by atrioventricular plane displacement (AVPD) in a healthy left ventricle (LV). The aims were to determine the effect of ST-elevation myocardial infarction (STEMI) on AVPD and contribution of AVPD to SV and to study the relationship between AVPD and infarct size (IS) and location. Patients from CHILL-MI and MITOCARE studies with cardiovascular magnetic resonance within a week of STEMI (n = 177, 59 ± 11 years) and healthy controls (n = 20, 62 ± 11 years) were included. Left ventricular volumes were quantified in short-axis images. AVPD was measured in six locations in long-axis images. Longitudinal contribution to SV was calculated as AVPD multiplied by the short-axis epicardial area. Patients (IS 17 ± 10% of LV) had decreased ejection fraction (48 ± 8%) compared to controls (60 ± 5%, P<0·001). Global AVPD was decreased in patients (11 ± 2 mm versus 15 ± 2 mm in controls, P<0·001) and this held true for both infarcted and remote segments. AVPD contribution to SV was lower in patients (58 ± 9%) than in controls (64 ± 8%) (P<0·001). There was a weak negative correlation between IS and AVPD (r2=0·06) but no differences in global AVPD linked to infarct location. Decrease in global and regional AVPD occur even in remote myocardium within 1 week of STEMI. Global AVPD decrease is independent of MI location, and MI size has only minor effect. Longitudinal pumping is slightly lower compared to controls but remains to be the main component to SV even after STEMI. These results highlight the difficulty in determining infarct location and size from longitudinal measures of LV function.
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