Clinical implications of microvascular obstruction and intramyocardial haemorrhage in acute myocardial infarction using cardiovascular magnetic resonance imaging

OBJECTIVES: To investigate the clinical implications of microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) in acute myocardial infarction (AMI). METHODS: Ninety patients with a first AMI undergoing primary percutaneous coronary intervention (PCI) were studied. T2-weighted, cine and late gadolinium-enhanced cardiovascular magnetic resonance imaging was performed at 5 ± 2 and 103 ± 11 days. Patients were categorised into three groups based on the presence or absence of MVO and IMH. RESULTS: MVO was observed in 54% and IMH in 43% of patients, and correlated significantly (r = 0.8, p < 0.001). Pre-PCI thrombolysis in myocardial infarction 3 flow was only observed in MVO(−)/IMH(−) patients. Infarct size and impairment of systolic function were largest in MVO(+)/IMH(+) patients (n = 39, 23 ± 9% and 47 ± 7%), smallest in MVO(−)/IMH(−) patients (n = 41, 8 ± 8% and 55 ± 8%) and intermediate in MVO(+)/IMH(−) patients (n = 10, 16 ± 7% and 51 ± 6%, p < 0.001). LVEF increased in all three subgroups at follow-up, but remained intermediate in MVO(+)/IMH(−) and was lowest in MVO(+)/IMH(+) patients. Using random intercept model analysis, only infarct size was an independent predictor for adverse LV remodelling. CONCLUSIONS: Intramyocardial haemorrhage and microvascular obstruction are strongly related. Pre-PCI TIMI 3 flow is less frequently observed in patients with MVO and IMH. Only infarct size was an independent predictor of LV remodelling

Bicuspid Aortic Valve Stenosis and the Effect of Vitamin K2 on Calcification Using F-Sodium Fluoride Positron Emission Tomography/Magnetic Resonance:The BASIK2 Rationale and Trial Design

BASIK2 is a prospective, double-blind, randomized placebo-controlled trial investigating the effect of vitamin K2 (menaquinone-7;MK7) on imaging measurements of calcification in the bicuspid aortic valve (BAV) and calcific aortic valve stenosis (CAVS). BAV is associated with early development of CAVS. Pathophysiologic mechanisms are incompletely defined, and the only treatment available is valve replacement upon progression to severe symptomatic stenosis. Matrix Gla protein (MGP) inactivity is suggested to be involved in progression. Being a vitamin K dependent protein, supplementation with MK7 is a pharmacological option for activating MGP and intervening in the progression of CAVS. Forty-four subjects with BAV and mild–moderate CAVS will be included in the study, and baseline 18F-sodiumfluoride (18F-NaF) positron emission tomography (PET)/ magnetic resonance (MR) and computed tomography (CT) assessments will be performed. Thereafter, subjects will be randomized (1:1) to MK7 (360 mcg/day) or placebo. During an 18-month follow-up period, subjects will visit the hospital every 6 months, undergoing a second 18F-NaF PET/MR after 6 months and CT after 6 and 18 months. The primary endpoint is the change in PET/MR 18F-NaF uptake (6 months minus baseline) compared to this delta change in the placebo arm. The main secondary endpoints are changes in calcium score (CT), progression of the left ventricularremodeling response and CAVS severity (echocardiography). We will also examine the association between early calcification activity (PET) and later changes in calcium score (CT)

Visualization of Coronary Wall Atherosclerosis in Asymptomatic Subjects and Patients with Coronary Artery Disease Using Magnetic Resonance Imaging

Background: Magnetic resonance imaging (MRI) is sensitive to early atherosclerotic changes such as positive remodeling in patients with coronary artery disease (CAD). We assessed prevalence, quality, and extent of coronary atherosclerosis in a group of healthy subjects compared to patients with confirmed CAD. Methodology: Twenty-two patients with confirmed CAD (15M, 7F, mean age 60.4±10.4 years) and 26 healthy subjects without history of CAD (11M, 15F, mean age 56.1±4.4 years) underwent MRI of the right coronary artery (RCA) and vessel wall (MR-CVW) on a clinical 1.5T MR-scanner. Wall thickness measurements of both groups were compared. Principal Findings: Stenoses of the RCA (both < and ≥50% on CAG) were present in all patients. In 21/22 patients, stenoses detected at MRI corresponded to stenoses detected with conventional angiography. In 19/26 asymptomatic subjects, there was visible luminal narrowing in the MR luminography images. Fourteen of these subjects demonstrated corresponding increase in vessel wall thickness. In 4/26 asymptomatic subjects, vessel wall thickening without luminal narrowing was present. Maximum and mean wall thicknesses in patients were significantly higher (2.16 vs 1.92 mm, and 1.38 vs 1.22 mm, both p<0.05). Conclusions: In this cohort of middle-aged individuals, both patients with stable angina and angiographically proven coronary artery disease, as well as age-matched asymptomatic subjects. exhibited coronary vessel wall thickening detectable with MR coronary vessel wall imaging. Maximum and mean wall thicknesses were significantly higher in patients. The vast majority of asymptomatic subjects had either positive remodeling without luminal narrowing, or non-significant stenosis. Trial registration ClinicalTrials.gov NCT00456950

The Maastricht Acquisition Platform for Studying Mechanisms of Cell–Matrix Crosstalk (MAPEX):An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5–5.5 cm or shows a growth rate of &gt;0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold of &lt;55 mm. Moreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue–cell crosstalk (MAPEX). The explicit scientific focus of the platform is on the dynamic interactions between vascular smooth muscle cells and extracellular matrix (i.e., cell–matrix crosstalk), which play an essential role in aortic wall mechanical homeostasis. Accordingly, we consider pathophysiological influences of wall shear stress, wall stress, and smooth muscle cell phenotypic diversity and modulation. Co-registrations of hemodynamics and deep phenotyping at the histological and cell biology level are key innovations of our platform and are critical for understanding aneurysm formation and dissection at a fundamental level. The MAPEX platform enables the interpretation of the data in a well-defined clinical context and therefore has real potential for narrowing existing knowledge gaps. A better understanding of aortic mechanical homeostasis and its derangement may ultimately improve diagnostic and prognostic possibilities to identify and treat symptomatic and asymptomatic patients with existing and developing aneurysms.</p

The role of cardiovascular magnetic resonance imaging and computed tomography angiography in suspected non-ST-elevation myocardial infarction patients:Design and rationale of the CARdiovascular Magnetic rEsoNance imaging and computed Tomography Angiography (CARMENTA) trial

BackgroundAlthough high-sensitivity cardiac troponin (hs-cTn) substantially improves the early detection of myocardial injury, it lacks specificity for acute myocardial infarction (MI). In suspected non–ST-elevation MI, invasive coronary angiography (ICA) remains necessary to distinguish between acute MI and noncoronary myocardial disease (eg, myocarditis), unnecessarily subjecting the latter to ICA and associated complications. This trial investigates whether implementing cardiovascular magnetic resonance (CMR) or computed tomography angiography (CTA) early in the diagnostic process may help to differentiate between coronary and noncoronary myocardial disease, thereby preventing unnecessary ICA.Study DesignIn this prospective, single-center, randomized controlled clinical trial, 321 consecutive patients with acute chest pain, elevated hs-cTnT, and nondiagnostic electrocardiogram are randomized to 1 of 3 strategies: (1) CMR, or (2) CTA early in the diagnostic process, or (3) routine clinical management. In the 2 investigational arms of the study, results of CMR or CTA will guide further clinical management. It is expected that noncoronary myocardial disease is detected more frequently after early noninvasive imaging as compared with routine clinical management, and unnecessary ICA will be prevented. The primary end point is the total number of patients undergoing ICA during initial admission. Secondary end points are 30-day and 1-year clinical outcome (major adverse cardiac events and major procedure-related complications), time to final diagnosis, quality of life, and cost-effectiveness.ConclusionThe CARMENTA trial investigates whether implementing CTA or CMR early in the diagnostic process in suspected non–ST-elevation MI based on elevated hs-cTnT can prevent unnecessary ICA as compared with routine clinical management, with no detrimental effect on clinical outcome

Detection and characteristics of microvascular obstruction in reperfused acute myocardial infarction using an optimized protocol for contrast-enhanced cardiovascular magnetic resonance imaging

Several cardiovascular magnetic resonance imaging (CMR) techniques are used to detect microvascular obstruction (MVO) after acute myocardial infarction (AMI). To determine the prevalence of MVO and gain more insight into the dynamic changes in appearance of MVO, we studied 84 consecutive patients with a reperfused AMI on average 5 and 104 days after admission, using an optimised single breath-hold 3D inversion recovery gradient echo pulse sequence (IR-GRE) protocol. Early MVO (2 min post-contrast) was detected in 53 patients (63%) and late MVO (10 min post-contrast) in 45 patients (54%; p = 0.008). The extent of MVO decreased from early to late imaging (4.3 ± 3.2% vs. 1.8 ± 1.8%, p < 0.001) and showed a heterogeneous pattern. At baseline, patients without MVO (early and late) had a higher left ventricular ejection fraction (LVEF) than patients with persistent late MVO (56 ± 7% vs. 48 ± 7%, p < 0.001) and LVEF was intermediate in patients with early MVO but late MVO disappearance (54 ± 6%). During follow-up, LVEF improved in all three subgroups but remained intermediate in patients with late MVO disappearance. This optimised single breath-hold 3D IR-GRE technique for imaging MVO early and late after contrast administration is fast, accurate and allows detection of patients with intermediate remodelling at follow-up