Yvonne Tan

Reperfusion Hemorrhage Following Acute Myocardial Infarction: Assessment with T2* Mapping and Effect on Measuring the Area at Risk

Research ethics committee approval and informed consent were obtained. The purpose of this study was to assess the feasibility of multiecho T2* mapping of the heart for detecting reperfusion hemorrhage following percutaneous primary coronary intervention (PPCI) for acute myocardial infarction, and to measure the effect of hemorrhage on quantifying the ischemic area at risk (IAR) on T2-weighted magnetic resonance images. Fifteen patients (mean age, 59 years; 13 men, two women) were imaged a mean of 3.2 days following PPCI. The mean area of hemorrhage, indicated by a T2* decay constant of less than 20 msec, was 5.0% +/- 4.9 (standard deviation) at the level of the infarct and this correlated with the infarct (r(2) = 0.76, P < .01) and microvascular obstruction (r(2) = 0.75, P < .01) volumes. When 5% or less hemorrhage was present, the IAR was underestimated by 50% at a standard deviation threshold level of five, compared with a boundary detection tool (21.8% vs 44.0%, P < .05). T2* mapping is feasible for quantifying post-reperfusion hemorrhage and boundary detection is required to accurately assess the IAR when hemorrhage is present.

Assessment of severe reperfusion injury with T2* cardiac MRI in patients with acute myocardial infarction

Background In patients with acute myocardial infarction, restoration of coronary flow by primary coronary intervention (PCI) can lead to profound ischaemia-reperfusion injury with detrimental effects on myocardial salvage. Non-invasive assessment of interstitial myocardial haemorrhage by T2* cardiac MRI (T2*-CMR) provides a novel and specific biomarker of severe reperfusion injury which may be of prognostic value. Objective To characterise the determinants of acute ischaemia-reperfusion injury following ST elevation myocardial infarction (STEMI) using CMR. Methods and results Fifty patients with acute STEMI who had been successfully treated by PCI were studied. T2*-CMR was used to identify the presence of reperfusion haemorrhage and contrast enhancement was used to measure microvascular obstruction (MVO) and infarct size. Haemorrhagic ischaemia-reperfusion injury was present in 29 patients (58%) following PCI and occurred despite rapid revascularisation (mean 4.2±3.3 h). Haemorrhage was only present when the infarct involved at least 80% (mean±SD 91±5.3%) of the left ventricular wall thickness. There was a strong association between the extent of MVO and reperfusion haemorrhage (r2=0.87, p<0.001). Transmural infarcts (n=43) showed significantly impaired systolic wall thickening at the infarct mid point when reperfusion haemorrhage was present (21.5±16.7% vs 3.7±12.9%), p<0.0001) compared with non-haemorrhagic infarcts. Conclusions Severe reperfusion injury may occur when there is near-transmural myocardial necrosis despite early and successful revascularisation. Reperfusion haemorrhage is closely associated with the development of MVO. These findings indicate that, once advanced necrosis has developed, the potential for severe myocardial reperfusion injury is significantly enhanced.

The use of next-generation sequencing in clinical diagnosis of familial hypercholesterolemia

Purpose:Familial hypercholesterolemia is a common Mendelian disorder associated with early-onset coronary heart disease that can be treated by cholesterol-lowering drugs. The majority of cases in the United Kingdom are currently without a molecular diagnosis, which is partly due to the cost and time associated with standard screening techniques. The main purpose of this study was to test the sensitivity and specificity of two next-generation sequencing protocols for genetic diagnosis of familial hypercholesterolemia.Methods:Libraries were prepared for next-generation sequencing by two target enrichment protocols; one using the SureSelect Target Enrichment System and the other using the PCR-based Access Array platform.Results:In the validation cohort, both protocols showed 100% specificity, whereas the sensitivity for short variant detection was 100% for the SureSelect Target Enrichment and 98% for the Access Array protocol. Large deletions/duplications were only detected using the SureSelect Target Enrichment protocol. In the prospective cohort, the mutation detection rate using the Access Array was highest in patients with clinically definite familial hypercholesterolemia (67%), followed by patients with possible familial hypercholesterolemia (26%).Conclusion:We have shown the potential of target enrichment methods combined with next-generation sequencing for molecular diagnosis of familial hypercholesterolemia. Adopting these assays for patients with suspected familial hypercholesterolemia could improve cost-effectiveness and increase the overall number of patients with a molecular diagnosis.Genet Med 15 12, 948–957.Genetics in Medicine (2013); 15 12, 948–957. doi:10.1038/gim.2013.55

Cardiac MRI of myocardial salvage at the peri-infarct border zones after primary coronary intervention

The purpose of this study was to use cardiac MRI to define the morphology of the reversibly injured peri-infarct border zone in patients treated with primary percutaneous coronary intervention (PPCI) for acute ST elevation myocardial infarction. In 15 patients, T2-weighted myocardial edema imaging was used to identify the ischemic bed or area at risk (AAR), and late gadolinium enhancement imaging was used to measure infarct size. Images were coregistered, and the boundaries of edema and necrosis were defined using an edge-detection methodology. We observed that infarction always involved the subendocardium but showed variable transmural extension within the AAR. The mean infarct size was 22 +/- 19% (range: 8-48%), and the mean AAR was 34 +/- 12% (range: 20-57%). The infarcted myocardium was always smaller than the ischemic AAR and involved between 34% and 99% (mean 72 +/- 21%) of the ischemic bed primarily due to variation in transmural infarct extension. Although a lateral border zone of potentially viable myocardium was often present, its extent was limited (range: 0-11 mm, mean: 5 +/- 4 mm). As a result of this, infarcts occupied the majority (range: 70-100%, mean: 82 +/- 13%) of the width of the AAR. The mean fractional wall thickening in the infarcted, peri-infarcted, and remote myocardium was 3.6 +/- 16.0%, 40.5 +/- 26.4%, and 88.2 +/- 39.3%, respectively. These findings demonstrate that myocardial salvage is largely determined by epicardial limitation of the infarct within the ischemic AAR after PPCI. The lateral boundaries of necrosis approximate to the lateral extent of the ischemic bed and systolic wall motion abnormalities extend well beyond the infarct border zone.

The ischemic area-at-risk on T2-weighted MRI shows recovery of systolic strain at 1 year

Animal models have demonstrated a recovery in systolic strain following reperfusion of acutely ischemic myocardium, however this has not been shown in clinical practice.

Microvascular obstruction following PCI is associated with reperfusion hemorrhage and chronic left ventricular impairment

Introduction Myocardial hemorrhage occurs when severely ischemic myocardium is reperfused and is a potential marker for subsequent LV remodeling. The relationship between reperfusion hemorrhage (RH) and microvascular obstruction (MVO) is poorly understood. Although gross hemorrhage is detectable on T2-weighted imaging, the true incidence of hemorrhagic transformation in acute myocardial infarction is unknown.