Hypertrophic cardiomyopathy (HCM) remains the leading cause of sudden cardiac death in the young. Early markers for HCM are important to identify individuals at risk. The aim of this study was to investigate novel serum biomarkers reflecting myocardial remodeling, microfibrosis, and vascular endotheliopathy in the early stages of familial HCM in young patients. Twenty-three HCM patients, 16 HCM-risk individuals, and 66 controls (median 15 years) underwent echocardiography and serum analysis for cathepsin S, endostatin, myostatin, type I collagen degradation marker (ICTP), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor receptor (VEGFR)-1, and vascular and intercellular adhesion molecules (VCAM, ICAM). In a subset of the population, global myocardial perfusion was performed by magnetic resonance imaging. Cathepsin S (p = 0.0009), endostatin (p < 0.0001), MMP-9 (p = 0.008), and VCAM (p = 0.04) were increased in the HCM group and correlated to left ventricular mass index and mitral E/e′ (p < 0.01). In the HCM-risk group, myostatin was decreased (p = 0.004), whereas ICAM was increased (p = 0.002). Global perfusion was decreased in the HCM group (p < 0.05) versus controls. Endostatin and mitral E/e′ correlated inversely to myocardial perfusion (p ≤ 0.05). This is the first study demonstrating adverse changes in biomarkers reflecting myocardial matrix remodeling, microfibrosis, and vascular endotheliopathy in early stage of hypertrophic cardiomyopathy in the young.

BackgroundPatients 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.MethodsNineteen 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).ResultsThere 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.ConclusionsPatients 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 individuals with HCM, but not those at risk, show decreased MP during hyperaemia compared with controls even in the absence of diastolic dysfunction or LV outflow obstruction. These results may suggest that microvascular disease contributes to the decreased MP in the investigated population.

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 AE 11 years) and healthy controls (n = 20, 62 AE 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 AE 10% of LV) had decreased ejection fraction (48 AE 8%) compared to controls (60 AE 5%, P<0Á001). Global AVPD was decreased in patients (11 AE 2 mm versus 15 AE 2 mm in controls, P<0Á001) and this held true for both infarcted and remote segments. AVPD contribution to SV was lower in patients (58 AE 9%) than in controls (64 AE 8%) (P<0Á001). There was a weak negative correlation between IS and AVPD (r 2 =0Á06) 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.