Rick Wage

Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis.

OBJECTIVES The goal of this study was to assess the prognostic significance of midwall and infarct patterns of late gadolinium enhancement (LGE) in aortic stenosis. BACKGROUND Myocardial fibrosis occurs in aortic stenosis as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in a range of other cardiac conditions. METHODS Between January 2003 and October 2008, consecutive patients with moderate or severe aortic stenosis undergoing cardiovascular magnetic resonance with administration of gadolinium contrast were enrolled into a registry. Patients were categorized into absent, midwall, or infarct patterns of LGE by blinded independent observers. Patient follow-up was completed using patient questionnaires, source record data, and the National Strategic Tracing Service. RESULTS A total of 143 patients (age 68 ± 14 years; 97 male) were followed up for 2.0 ± 1.4 years. Seventy-two underwent aortic valve replacement, and 27 died (24 cardiac, 3 sudden cardiac deaths). Compared with those with no LGE (n = 49), univariate analysis revealed that patients with midwall fibrosis (n = 54) had an 8-fold increase in all-cause mortality despite similar aortic stenosis severity and coronary artery disease burden. Patients with an infarct pattern (n = 40) had a 6-fold increase. Midwall fibrosis (hazard ratio: 5.35; 95% confidence interval: 1.16 to 24.56; p = 0.03) and ejection fraction (hazard ratio: 0.96; 95% confidence interval: 0.94 to 0.99; p = 0.01) were independent predictors of all-cause mortality by multivariate analysis. CONCLUSIONS Midwall fibrosis was an independent predictor of mortality in patients with moderate and severe aortic stenosis. It has incremental prognostic value to ejection fraction and may provide a useful method of risk stratification.

Fully automatic segmentation and objective assessment of atrial scars for long‐standing persistent atrial fibrillation patients using late gadolinium‐enhanced MRI

Purpose Atrial fibrillation (AF) is the most common heart rhythm disorder and causes considerable morbidity and mortality, resulting in a large public health burden that is increasing as the population ages. It is associated with atrial fibrosis, the amount and distribution of which can be used to stratify patients and to guide subsequent electrophysiology ablation treatment. Atrial fibrosis may be assessed noninvasively using late gadolinium‐enhanced (LGE) magnetic resonance imaging (MRI) where scar tissue is visualized as a region of signal enhancement. However, manual segmentation of the heart chambers and of the atrial scar tissue is time consuming and subject to interoperator variability, particularly as image quality in AF is often poor. In this study, we propose a novel fully automatic pipeline to achieve accurate and objective segmentation of the heart (from MRI Roadmap data) and of scar tissue within the heart (from LGE MRI data) acquired in patients with AF. Methods Our fully automatic pipeline uniquely combines: (a) a multiatlas‐based whole heart segmentation (MA‐WHS) to determine the cardiac anatomy from an MRI Roadmap acquisition which is then mapped to LGE MRI, and (b) a super‐pixel and supervised learning based approach to delineate the distribution and extent of atrial scarring in LGE MRI. We compared the accuracy of the automatic analysis to manual ground truth segmentations in 37 patients with persistent long‐standing AF. Results Both our MA‐WHS and atrial scarring segmentations showed accurate delineations of cardiac anatomy (mean Dice = 89%) and atrial scarring (mean Dice = 79%), respectively, compared to the established ground truth from manual segmentation. In addition, compared to the ground truth, we obtained 88% segmentation accuracy, with 90% sensitivity and 79% specificity. Receiver operating characteristic analysis achieved an average area under the curve of 0.91. Conclusion Compared with previously studied methods with manual interventions, our innovative pipeline demonstrated comparable results, but was computed fully automatically. The proposed segmentation methods allow LGE MRI to be used as an objective assessment tool for localization, visualization, and quantitation of atrial scarring and to guide ablation treatment.

Late gadolinium enhancement cardiovascular magnetic resonance for sudden cardiac death risk stratification in hypertrophic cardiomyopathy.

Background Although myocardial fibrosis identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) may predict adverse outcomes among patients with hypertrophic cardiomyopathy (HCM), its precise role in risk stratification for sudden cardiac death (SCD) remains unresolved. Previous studies have relied on broad surrogate composite endpoints and were underpowered to assess SCD risk or to adjust for confounding variables. To address this, we studied the prognostic significance of LGE in a large HCM cohort with long-term follow-up. Methods

The relationship between interstitial fibrosis and contractile function in HCM: a combined T1-mapping and CSPAMM tagging study

Background Interstitial fibrosis is a pathological hallmark of hypertrophic cardiomyopathy (HCM) and is thought to contribute to the abnormal myocardial mechanics seen in this patient group. T1-mapping now allows interstitial fibrosis to be detected non-invasively. Replacement fibrosis as identified by late gadolinium enhancement imaging has been associated with abnormal cardiac mechanics in HCM. However, the relationship between interstitial fibrosis and contractile function in HCM has not been previously explored. We assessed the association between interstitial fibrosis as assessed by T1-mapping and contractile function as determined by continuous spatial modulation of magnetisation (CSPAMM) tagging, hypothesising that increased fibrosis would correlate with abnormal myocardial strain. Methods Twelve HCM patients free of significant comorbidity and 16 controls were studied. CMR was undertaken on a 1.5T Siemens Avanto (Siemens, Erlangen, Germany). Tagged images were acquired at the mid-ventricle using aC SPAMM sequence (Field of View: 300mm, slice thickness 6mm, tag separation 7mm, typical TR/TE 30/ 1.26ms, Flip Angle 20°, 20 phases). Peak circumferential (Ecc) and radial (Err) strains were determined using inTag (Creatis, Lyon, France). Mid-ventricular short-axis T1 maps were acquired using the Modified Look-Locker Inversion Recovery sequence pre-gadolinium bolus and then at 5, 7, 9, 11, 15, 20 and 25 minutes. Signal intensity-time curves for myocardial and blood pool regions of interest were used to determine T1 relaxation times through a non-linear curve-fit (CMR42, Circle Cardiovascular Imaging, Calgary, Canada). The partition coefficient at equilibrium, an index of fibrosis, was determined by plotting the reciprocal of myocardial T1 times at equilibrium against those for the blood pool and calculating the slope of the resultant linear regression line. Results HCM patients were older than the controls and there was a preponderance of men. In keeping with their diagnosis, HCM patients had significantly higher indexed LV mass and wall thickness than controls (Table 1). The partition coefficient was significantly higher in HCM patients than controls (mean ±SD: 0.439 ±0.230 for HCM vs 0.281 ±0.071 for controls, P=0.02). Whilst peak global Ecc was significantly lower in the HCM group relative to the controls (0.173 ±0.041 vs 0.226 ±0.025, P<0.001), there was no significant difference with respect to peak global Err (0.154 ±0.06 vs 0.134 ±0.051, P=0.25). No significant association was found between the partition coefficient and either circumferential or radial strain. Conclusions The partition coefficient for gadolinium was significantly raised in patients with HCM relative to controls, however, no association was found between this and local contractile function. This implies that interstitial fibrosis alone may not account for the perturbations in myocardial mechanics seen in patients with HCM and that alternative mechanisms should be explored.

Cardiac effects of anabolic steroid use amongst recreational body builders - a CMR study

Background Abuse of anabolic steroids to induce skeletal muscle hypertrophy is widespread amongst recreational bodybuilders, however, the cardiac effects of such drugs have not been systematically documented. The ability of cardiovascular magnetic resonance (CMR) to image the myocardium in any plane and achieve full myocardial coverage renders it the gold standard for assessing LV volumes and mass.We sought to investigate the cardiac effects of anabolic steroid use with CMR hypothesising that significant hypertrophy and distinct LV remodelling would be seen in steroid users relative to non-users. Methods

Diffusion Tensor Cardiovascular Magnetic Resonance of Microstructural Recovery in Dilated Cardiomyopathy

Diffusion tensor cardiovascular magnetic resonance (DT-CMR) evaluates myocardial microstructure, using helix angle (HA) and absolute angulation of the second eigenvector (E2A) to assess cardiomyocyte and sheetlet orientation respectively. In health, sheetlets align more wall-parallel in diastole and

T2 mapping by cardiovasular magnetic resonance in acute and recovered myocarditis: potential role in clinical surveillance

Doxorubicin induced cardiotoxicity is a well-recognized complication of chemotherapy, and its prevention remains an important challenge in cancer survivorship. An angiogenic hormone prokineticin via its receptor PKR1 promotes angiogenesis, differentiation of cardiac stem cells, and survival of the cardiomyocytes. PKR1 has been recently shown to protect heart against myocardial infarction in mice model. Thus, we hypothesized that PKR1 agonist can be a promising target to prevent doxorubicin-mediated cardiotoxicity. Methods and Results: In vitro, we showed that IS20 attenuates apoptosis induced by DOX treatment in H9c2 cardiomyocytes and human epicardial derived progenitor cells. However, IS20 does not interfere DOX-mediated cytotoxicity in cancer cell line. In vivo, IS20 administration in juvenile mice model promotes survival, proliferation and differentiation of WT1+EPDCs into vasculogenic cells. Similarly, IS20 on chronic mice model preserves vascular structure, reduces apoptosis and inflammation. IS20 also improves systolic and diastolic parameters that impaired by DOX. Conclusions: Multi effects of IS20 on the activation of cardiac progenitor cells, cardiac cells survival, vascular stability and cardiac parameters show a strong cardioprotective potential of PKR1 agonist that can be used in cancer patients during anthracyclines chemotherapy. P2008 Growth differentiation factor 15 as a predictor of acute kidney injury formation IR Vishnevskaya1; HF Barahmeh2 1Government institution “L.T. Malaya Therapy National institute of the National academy of medical sci”, Kharkiv, Ukraine; 2V.N. Karazin Kharkiv National University, Kharkiv, Ukraine The development of acute kidney injury (AKI) in patient with acute coronary syndrome (ACS), especially in those who underwent angiography, is an actual problem, because it worsens the prognosis. In order to diagnose this condition in time the search for biomarkers is going. Stress-induced marker growth differentiation factor 15 (GDF 15), a member of the transforming growth factor-β cytokine superfamily is being actively studied. Purpose: to determine the prognostic significance of GDF 15 and other markers in development of AKI in patients with ACS. Methods: 73 patients were enrolled with different forms of ACS (55 male and 18 female), mean age was 61, 8± 1, 3 years. All patients underwent a baseline investigation which includes: standard electrocardiography, echocardiography, angiography and determination of marker of myocardial necrosis – cardiac troponin T. Based on the results of the examination glomerular filtration rate (GFR) was calculated by Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). A group of patients has been selected (n=54), their creatinine level was determined during the first 24 hours and after 48 hours. All patients were divided into two groups according to acute kidney injury network classification (AKIN): 21 patient in the first group with negative dynamic (1st stage AKIN and higher), 33 patient in the second group without creatinine dynamic. In addition, the level of GDF 15 was determined during the first day of hospitalization (normal range of GDF 15< 1200 pg / ml). Results: By comparing selected groups significant difference was found in creatinine level and GFR in both groups (p< 0.001; p< 0.01, respectively). The effects of various variables were assessed on formation of AKI in patients with different level of GFR. To identify the main risk factors for AKI, we have used logistic regression (LR): ejection fraction of left ventricle (area under curve (AUC) 0.7; p< 0.01; 95% confidence interval (CI): 0.560 – 0,842), GDF 15 (AUC 0.77; p< 0.03; 95% CI: 0.53 – 0.92) and age (AUC 0.77; p< 0.01) were main risk factors for predicting development of AKI. During the statistical analysis the predictive value for estimated parameters was calculated: GDF 15 > 2200 pg/ml (specificity (Spe) 87%, sensitivity (Se) 65%), ejection fraction of left ventricle >46% (Spe 80 %, Se 71 %), age >55 year (Spe 39 %, Se 96 %) We have developed a prognostic model to predict reduced kidney function formation (AUC 0.8; p < 0.001). This model with 96% of Se and 68% of Spe can predict development of AKI in patients with different levels of GFR after ACS. Conclusion: the prognostic multifactor model can be used in clinical practice to improve risk stratification in patients with ACS to prevent formation of AKI. P2009 Neladenoson, a partial adenosine A1-receptor agonist, improves mitochondrial function in skeletal muscle of dogs with chronic heart failure HN Hani Sabbah1; RC Gupta1; V Singh-Gupta1; K Zhang1; J Xu1; B Albrecht-Kuepper2 1Henry Ford Hospital, Detroit, United States of America; 2Bayer AG, Wuppertal, Germany Funding Acknowledgements: Bayer AG Background: Exercise intolerance (Ex-Int) is a feature of chronic heart failure (HF) and in particular, HF with preserved ejection fraction (HFpEF) and attributable, in part, to skeletal muscle (SM) abnormalities of fiber type composition and mitochondrial (MITO) dysfunction. In patients and dogs with HF, SM aerobic, MITO-dependent, type-I fibers decrease in number while anaerobic type-II fibers increase; a maladaptation that contributes to Ex-Int. We previously showed that chronic therapy with capadenoson, a partial adenosine A1-receptor agonist (pA1RA), improves LV function in HF dogs and therapy with neladenoson (NELA), a novel pA1RA, normalizes MITO function in failing cardiomyocytes. This study examined the effects of NELA on MITO function in SM biopsies from normal (NL) dogs and dogs with microembolization-induced HF. Methods: Fresh SM open biopsies ( ̃6 grams) were obtained from the hind leg Vastus Lateralis muscle of 6 NL and 6 HF anesthetized dogs. Samples were cut into thin sections, divided into 4 equal portions, and one portion each incubated in 0 (vehicle), 3, 10, and 30 nM concentration of NELA respectively for one hour at 37∘C. At end of incubation, MITO were isolated from SM and their function assessed. MITO ADP-stimulated state-3 respiration (ADPresp) was measured using a Strathklein respirometer, MITO complex-IV (COX-IV) activity was measured polarographically and MITO maximum rate of ATP synthesis (ATPsyn) was measured using the bioluminescent ApoSENSOR assay kit. Results: Increasing concentration of NELA had no effect on measures of MITO function in SM from NL dogs (Table). In SM from HF dogs, depressed levels of MITO ADPresp, ATPsyn, and COX-IV activity increased significantly in a dose-dependent manner after exposure to NELA (Table). Conclusions: The results indicate that NELA improves MITO function of SM of dogs with HF. These improvements can potentially reduce/reverse Ex-Int in HF. MITO Function Measures Vehicle 3 nM NELA 10 nM NELA 30 nM NELABackground and purpose: To estimate healthcare resource utilization among patients with heart failure (HF) with preserved (HFpEF) versus reduced (HFrEF) ejection fraction using population data from ...

Cardiovascular magnetic resonance of acute myocardial infarction following traumatic coronary artery dissection

Traumatic coronary artery dissection is a very rare cause of myocardial infarction. Occurrence of this condition late in the posttraumatic period is extremely uncommon. We present a case of a young patient with acute myocardial infarction 4 weeks after blunt chest trauma. Coronary angiography showed left anterior descending artery dissection as well as thrombus formation, and multiple small infarctions were shown by cardiovascular magnetic resonance.

Effects of anabolic steroid use on myocardial perfusion in body-builders: a quantitative cardiovascular magnetic resonance Study

Methods Twenty one body-builders were studied 14 anabolic steroid users and 7 controls matched for age and training history. First pass CMR perfusion imaging was performed on a 1.5T Avanto (Siemens, Erlangen, Germany) after adenosine-induced hyperemia (140 mcg/kg/min) and at rest using a hybrid echo-planar imaging sequence. Images of the base, mid-ventricle and apex were acquired and the myocardium was divided into 16 segments as well as endocardial and epicardial layers. After image registration, a modified Fermi-constrained deconvolution algorithm was applied pixel-wise to quantify absolute MBF. Late gadolinium enhancement (LGE) imaging was performed as well as standard assessment of ventricular volumes, function and LV mass. Data were analysed using a linear mixed effects model.

Cardiovascular magnetic resonance assessment of left atrial volumes and function in patients with persistent atrial fibrillation before and after ablation therapy

Methods A Siemens scanner (Avanto, 1.5T) was used to study 13 patients (mean age 65 ± 9, 4 females and 9 males) with persistent AF before and 3 months after ablation therapy. Images of the LA were acquired in the two-chamber and four-chamber orientation using a breath-hold ECG-gated steady state free precession cine sequence. Biplane arealength method was used to measure the LA end-systolic (ESV) and end-diastolic (EDV) volumes[1]. LA function was determined by its calculated ejection fraction (EF=(EDV-ESV)/EDV) [1]. Seven-day rhythm tape was used to assess patients’ rhythm 3 months after ablation. All 13 patients underwent either surgical or catheter ablation therapy successfully, achieving sinus rhythm post procedure. Only 2 patients reverted to AF at 3 months.