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Aims Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) is predictive of clinical decline, however underlying mechanisms remain unclear. Cardiac diffusion tensor imaging (cDTI) allows in vivo characterization of myocardial microstructure by quantifying mean diffusivity (MD), fractional anisotropy (FA) of diffusion, and secondary eigenvector angle (E2A). In this cardiac magnetic resonance (CMR) study, we examine associations between perfusion and cDTI parameters to understand the sequence of pathophysiology and the interrelation between vascular function and underlying microstructure. Methods and results Twenty HCM patients underwent 3.0T CMR which included: spin-echo cDTI, adenosine stress and rest perfusion mapping, cine-imaging, and late gadolinium enhancement (LGE). Ten controls underwent cDTI. Myocardial perfusion reserve (MPR), MD, FA, E2A, and wall thickness were calculated per segment and further divided into subendocardial (inner 50%) and subepicardial (outer 50%) regions. Segments with wall thickness ≤11 mm, MPR ≥2.2, and no visual LGE were classified as ‘normal’. Compared to controls, ‘normal’ HCM segments had increased MD (1.61 ± 0.09 vs. 1.46 ± 0.07 × 10−3 mm2/s, P = 0.02), increased E2A (60 ± 9° vs. 38 ± 12°, P < 0.001), and decreased FA (0.29 ± 0.04 vs. 0.35 ± 0.02, P = 0.002). Across all HCM segments, subendocardial regions had higher MD and lower MPR than subepicardial (MDendo 1.61 ± 0.08 × 10−3 mm2/s vs. MDepi 1.56 ± 0.18 × 10−3 mm2/s, P = 0.003, MPRendo 1.85 ± 0.83, MPRepi 2.28 ± 0.87, P < 0.0001). Conclusion In HCM patients, even in segments with normal wall thickness, normal perfusion, and no scar, diffusion is more isotropic than in controls, suggesting the presence of underlying cardiomyocyte disarray. Increased E2A suggests the myocardial sheetlets adopt hypercontracted angulation in systole. Increased MD, most notably in the subendocardium, is suggestive of regional remodelling which may explain the reduced subendocardial blood flow.

Background:\ud \ud Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing.\ud \ud \ud Methods:\ud \ud We recruited 84 patients with LV ejection fraction ≥40% into 2 observational CMR studies. Patients (n=34) with a dual-chamber device and preserved atrioventricular conduction underwent CMR in 2 asynchronous pacing modes (atrial asynchronous and dual-chamber asynchronous) to compare intrinsic atrioventricular conduction with forced RV pacing. Patients (n=50) with high-grade atrioventricular block underwent CMR before and 6 months after pacemaker implantation to investigate the medium-term effects of RV pacing.\ud \ud \ud Results:\ud \ud The key findings were (1) initiation of RV pacing in patients with fibrosis, compared with those without, was associated with greater immediate changes in both LV end-systolic volume index (5.3±3.5 versus 2.1±2.4 mL/m2; P1.1 g of fibrosis with 90% sensitivity and 70% specificity.\ud \ud \ud Conclusions:\ud \ud Fibrosis detected on CMR is associated with immediate- and medium-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure before pacemaker implantation.

Objectives This study sought to investigate the clinical utility and the predictive relevance of absolute rest myocardial blood flow (MBF) by cardiac magnetic resonance (CMR) in acute myocardial infarction. Background Microvascular obstruction (MVO) remains one of the worst prognostic factors in patients with reperfused ST-segment elevation myocardial infarction (STEMI). Clinical trials have focused on cardioprotective strategies to maintain microvascular functionality, but there is a need for a noninvasive test to determine their efficacy. Methods A total of 64 STEMI patients post–primary percutaneous coronary intervention underwent 3-T CMR scans acutely and at 6 months (6M). The protocol included cine function, T2-weighted edema imaging, pre-contrast T1 mapping, rest first-pass perfusion, and late gadolinium enhancement imaging. Segmental MBF, corrected for rate pressure product (MBFcor), was quantified in remote, edematous, and infarcted myocardium. Results Acute MBFcor was significantly reduced in infarcted myocardium compared with remote MBF (MBFinfarct 0.76 ± 0.20 ml/min/g vs. MBFremote 1.02 ± 0.21 ml/min/g, p < 0.001), but it significantly increased at 6M (MBFinfarct 0.76 ± 0.20 ml/min/g acute vs. 0.85 ± 0.22 ml/min/g at 6M, p < 0.001). On a segmental basis, acute MBFcor had incremental prognostic value for infarct size at 6M (odds of no LGE at 6M increased by 1.4:1 [p < 0.001] for each 0.1 ml/min/g increase of acute MBFcor) and functional recovery (odds of wall thickening >45% at 6M increased by 1.38:1 [p < 0.001] for each 0.1 ml/min/g increase of acute MBFcor). In subjects with coronary flow reserve >2 or index of myocardial resistance Conclusions Acute MBF by CMR could represent a novel quantitative imaging biomarker of microvascular reversibility, and it could be used to identify patients who may benefit from more intensive or novel therapies.

Aims The co-transmitter neuropeptide-Y (NPY) is released during high sympathetic drive, including ST-elevation myocardial infarction (STEMI), and can be a potent vasoconstrictor. We hypothesized that myocardial NPY levels correlate with reperfusion and subsequent recovery following primary percutaneous coronary intervention (PPCI), and sought to determine if and how NPY constricts the coronary microvasculature. Methods and results Peripheral venous NPY levels were significantly higher in patients with STEMI (n = 45) compared to acute coronary syndromes/stable angina (n = 48) or with normal coronary arteries (NC,n = 16). Overall coronary sinus (CS) and peripheral venous NPY levels were significantly positively correlated (r = 0.79). STEMI patients with the highest CS NPY levels had significantly lower coronary flow reserve, and higher index of microvascular resistance measured with a coronary flow wire. After 2 days they also had significantly higher levels of myocardial oedema and microvascular obstruction on cardiac magnetic resonance imaging, and significantly lower ejection fractions and ventricular dilatation 6 months later. NPY (100–250 nM) caused significant vasoconstriction of rat microvascular coronary arteries via increasing vascular smooth muscle calcium waves, and also significantly increased coronary vascular resistance and infarct size in Langendorff hearts. These effects were blocked by the Y1receptor antagonist BIBO3304 (1 μM). Immunohistochemistry of the human coronary microvasculature demonstrated the presence of vascular smooth muscle Y1receptors. Conclusion High CS NPY levels immediately after reperfusion correlate with microvascular dysfunction, greater myocardial injury, and reduced ejection fraction 6 months after STEMI. NPY constricts the coronary microcirculation via the Y1receptor, and antagonists may be a useful PPCI adjunct therapy.

Background It has recently been suggested that myocardial oedema follows a bimodal pattern early post ST-segment elevation myocardial infarction (STEMI). Yet, water content, quantified using tissue desiccation, did not return to normal values unlike oedema quantified by cardiovascular magnetic resonance (CMR) imaging. We studied the temporal changes in the extent and intensity of injured myocardium using T1-mapping technique within the first week after STEMI. Methods A first group (n = 31) underwent 3 acute 3 T CMR scans (time-point (TP) Results The mean T1 relaxation time value within the AAR of the first group was reduced after 24 h (P Conclusion The intensity of oedema post-STEMI followed a bimodal pattern; while the extent of AAR did not track the same course. This discrepancy has implications for use of CMR in this context and may explain the previously reported disagreement between oedema quantified by imaging and tissue desiccation.

Contains fulltext : 202668.pdf (Publisher’s version ) (Open Access) Aims: The main aim of this study was to characterize changes in the left ventricular (LV) blood flow kinetic energy (KE) using four-dimensional (4D) flow cardiovascular magnetic resonance imaging (CMR) in patients with myocardial infarction (MI) with/without LV thrombus (LVT). Methods and results: This is a prospective cohort study of 108 subjects [controls = 40, MI patients without LVT (LVT- = 36), and MI patients with LVT (LVT+ = 32)]. All underwent CMR including whole-heart 4D flow. LV blood flow KE wall calculated using the formula: KE=12 rhoblood . Vvoxel . v2, where rho = density, V = volume, v = velocity, and was indexed to LV end-diastolic volume. Patient with MI had significantly lower LV KE components than controls (P < 0.05). LVT+ and LVT- patients had comparable infarct size and apical regional wall motion score (P > 0.05). The relative drop in A-wave KE from mid-ventricle to apex and the proportion of in-plane KE were higher in patients with LVT+ compared with LVT- (87 +/- 9% vs. 78 +/- 14%, P = 0.02; 40 +/- 5% vs. 36 +/- 7%, P = 0.04, respectively). The time difference of peak E-wave KE demonstrated a significant rise between the two groups (LVT-: 38 +/- 38 ms vs. LVT+: 62 +/- 56 ms, P = 0.04). In logistic-regression, the relative drop in A-wave KE (beta = 11.5, P = 0.002) demonstrated the strongest association with LVT. Conclusion: Patients with MI have reduced global LV flow KE. Additionally, MI patients with LVT have significantly reduced and delayed wash-in of the LV. The relative drop of distal intra-ventricular A-wave KE, which represents the distal late-diastolic wash-in of the LV, is most strongly associated with the presence of LVT.

The aim of this study was to assess the ability of stress T1 mapping to detect perfusion abnormalities and inducible ischaemia in hypertrophic cardiomyopathy (HCM).

Two-dimensional (2D) methods of assessing mitral infow velocities are pre-load dependent, limiting\ud their reliability for evaluating diastolic function. Left ventricular (LV) blood fow kinetic energy (KE)\ud derived from four-dimensional fow cardiovascular magnetic resonance imaging (4D fow CMR) may\ud ofer improvements. It remains unclear whether 4D LV blood fow KE parameters are associated\ud with physiological factors, such as age when compared to 2D mitral infow velocities. Fifty-three\ud healthy volunteers underwent standard CMR, plus 4D fow acquisition. LV blood fow KE parameters\ud demonstrated good reproducibility with mean coefcient of variation of 6±2% and an accuracy of\ud 99% with a precision of 97%. The LV blood fow KEiEDV E/A ratio demonstrated good association to the\ud 2D mitral infow E/A ratio (r=0.77, P

Introduction: There is a pressing clinical need to treat patients with acute coronary syndrome (ACS) timely and efficiently in order to improve their prognosis. Standard tools available in ED, while useful, do not comprehensively characterize ACS for either diagnosis or risk stratification. The role of CMR in ACS is emerging because it allows assessment of both myocardial composition and function. Newer CMR techniques such as: a) T2 W imaging for assessing myocardial oedema and area at risk B) pre contrast T1 mapping techniques for quantitative characterization of the tissue composition, are adding further utility for CMR in ACS. At present the clinical use of these techniques is still limited and further investigations are needed to assess their clinical applicability in ACS patients.Aims: The aims of this thesis were several. Firstly we sought to establish a CMR protocol for imaging ACS patients on a 3T CMR scanner. In order to do so, we validated a novel T2 W technique for oedema imaging (T2 prep SSFP) at 3T. Second, we aimed to perform a detailed study of the time course of oedema in ACS patients in order to establish the appropriate imaging time for the assessment of area at risk. Third, by applying T2W acute oedema imaging, we sought to investigate the functional and pathological meaning of complicated remote plaques in patients with multivessel disease. Finally, we aimed to establish whether, in comparison to standard CMR techniques, novel precontrast T1 mapping allows better characterization of the acutely injured myocardium and whether it can predict long-term functional recovery.Methods: The research studies were all performed on a 3T Trio Siemens scanner. In the initial stage of the research, we validated the T2 W technique performing phantom work and scanning both volunteers and patients to assess the uniformity of signal intensity in the myocardium and to establish a threshold based method to post process the images. We then established a CMR protocol for ACS including oedema imaging, T1 mapping imaging, perfusion, functional and late gadolinium enhancement imaging. Patients with acute myocardial infarction (both ST elevation myocardial infarction (STEMI) and non STEMI) were scanned at 4 different time points after the acute event (3 scans within 2 weeks and one at 6 months). All STEMI patients underwent primary percutaneous coronary intervention (PCI) while the non-STEMI patients underwent coronary angiography and /or PCI.Results: We validated the T2prep SSFP technique at 3T, highlighting its limitations and establishing a threshold of mean ± 2SD to assess myocardial oedema. We found that the optimal imaging window to assess the maximal expression of myocardial oedema was within 1 week from the acute event in patients with ST elevation MI. Also, our results showed a reduction of LGE over time (from acute to chronic) in segments which also showed improvement in contractile function indicating that even segments with transmural LGE assessed in the early hours post event could be viable. By applying these techniques in acute patients with bystander disease undergoing percutaneous coronary intervention, we found that: 1) T2W imaging can detect myocardial injury downstream from a vessel identified as "non culprit" 2) in 20% of NSTEMI patients, the angiographic assessment alone failed to identify the culprit vessel.Finally, we found that the diagnostic performance of acute pre-contrast T1-mapping was at least as good as that of T2W CMR for detecting myocardial injury. There was a significant relationship between the segmental damaged fraction assessed by either by LGE or T2W, and mean segmental T1 values and the likelihood of improvement of segmental function at 6 months decreased progressively as acute T1 values increased.Conclusions: In summary, we defined a stable imaging window for the retrospective evaluation of area at risk and we also indicated that acutely detected LGE does not necessarily equate with irreversible injury and may severely underestimate salvaged myocardium. Furthermore, in NSTEMI patients with multivessel disease, by revealing acute myocardial damage in territories pertaining to vessels not treated acutely, we raised the issue of the need for better tools for the correct identification of the culprit vessel and to stratify patients rather than by angiographic assessment alone.Finally, we demonstrated how pre-contrast T1 mapping allows for assessment of the extent of myocardial damage and how T1 mapping might become an important complementary technique to LGE and T2W for the identification of reversible myocardial injury and the prediction of functional recovery in acute MI.

Background—CMR T1 mapping is a quantitative imaging technique allowing the assessment of myocardial injury early after ST-segment–elevation myocardial infarction. We sought to investigate the ability of acute native T1 mapping to differentiate reversible and irreversible myocardial injury and its predictive value for left ventricular remodeling. Methods and Results—Sixty ST-segment–elevation myocardial infarction patients underwent acute and 6-month 3T CMR, including cine, T2-weighted (T2W) imaging, native shortened modified look-locker inversion recovery T1 mapping, rest first pass perfusion, and late gadolinium enhancement. T1 cutoff values for oedematous versus necrotic myocardium were identified as 1251 ms and 1400 ms, respectively, with prediction accuracy of 96.7% (95% confidence interval, 82.8% to 99.9%). Using the proposed threshold of 1400 ms, the volume of irreversibly damaged tissue was in good agreement with the 6-month late gadolinium enhancement volume (r=0.99) and correlated strongly with the log area under the curve troponin (r=0.80) and strongly with 6-month ejection fraction (r=−0.73). Acute T1 values were a strong predictor of 6-month wall thickening compared with late gadolinium enhancement. Conclusions—Acute native shortened modified look-locker inversion recovery T1 mapping differentiates reversible and irreversible myocardial injury, and it is a strong predictor of left ventricular remodeling in ST-segment–elevation myocardial infarction. A single CMR acquisition of native T1 mapping could potentially represent a fast, safe, and accurate method for early stratification of acute patients in need of more aggressive treatment. Further confirmatory studies will be needed.

Importance Among patients with suspected coronary heart disease (CHD), rates of invasive angiography are considered too high. Objective To test the hypothesis that among patients with suspected CHD, cardiovascular magnetic resonance (CMR)–guided care is superior to National Institute for Health and Care Excellence (NICE) guidelines–directed care and myocardial perfusion scintigraphy (MPS)–guided care in reducing unnecessary angiography. Design, Setting, and Participants Multicenter, 3-parallel group, randomized clinical trial using a pragmatic comparative effectiveness design. From 6 UK hospitals, 1202 symptomatic patients with suspected CHD and a CHD pretest likelihood of 10% to 90% were recruited. First randomization was November 23, 2012; last 12-month follow-up was March 12, 2016. Interventions Patients were randomly assigned (240:481:481) to management according to UK NICE guidelines or to guided care based on the results of CMR or MPS testing. Main Outcomes and Measures The primary end point was protocol-defined unnecessary coronary angiography (normal fractional flow reserve >0.8 or quantitative coronary angiography [QCA] showing no percentage diameter stenosis ≥70% in 1 view or ≥50% in 2 orthogonal views in all coronary vessels ≥2.5 mm diameter) within 12 months. Secondary end points included positive angiography, major adverse cardiovascular events (MACEs), and procedural complications. Results Among 1202 symptomatic patients (mean age, 56.3 years [SD, 9.0]; women, 564 [46.9%] ; mean CHD pretest likelihood, 49.5% [SD, 23.8%]), number of patients with invasive coronary angiography after 12 months was 102 in the NICE guidelines group (42.5% [95% CI, 36.2%-49.0%])], 85 in the CMR group (17.7% [95% CI, 14.4%-21.4%]); and 78 in the MPS group (16.2% [95% CI, 13.0%-19.8%]). Study-defined unnecessary angiography occurred in 69 (28.8%) in the NICE guidelines group, 36 (7.5%) in the CMR group, and 34 (7.1%) in the MPS group; adjusted odds ratio of unnecessary angiography: CMR group vs NICE guidelines group, 0.21 (95% CI, 0.12-0.34, P

Abnormal myocardial motion occurs in many cardiac pathologies, though in different ways, depending on the disease, some of which can result in negative clinical outcomes. Therefore, a better understanding of the contractile capability of the tissue is crucial in providing an improved and patient-specific clinical outcome [4]. Cardiovascular MagneticResonance Imaging (CMR) is considered the gold standard for the assessment of cardiac function and has the potential to also be used for routine tissue strain analysis because of its high availability in clinical practice. In this study we estimate the local strain in myocardial tissue over a cardiac cycle using cine MRI imaging to perform the analysis. To quantify the tissue displacement, we use the diffeomorphic demons registration algorithm [15] in a multi-step 3D registration, for the minimization of cumulative errors propagation. Using the displacement gradient of the deformation, individual voxel strain curves are computed. We present a novel method for parcellating the myocardium into regions based on the strain behaviour of clusters of voxels. We define the supervoxels using the Simple Linear Iterative Clustering (SLIC) algorithm [1] inside a predefined mask. The results are consistent with late gadolinium enhancement scar identification.

The immune system plays critical roles in myocardial injury and repair following acute myocardial infarction (AMI). Evidence from experimental models strongly implicates monocytes as critical to these processes and their specific targeting results in a significant reduction in infarct size and improved healing. It is currently unclear if monocytes play a similarly important role in humans. Examining changes in the patterns of gene expression can address this question. Here, we show that the peripheral blood monocyte response following AMI is conserved between species and that monocytes appear to be ‘programmed’ prior to their arrival at sites of myocardial injury. This investigation may translate to the future development of therapeutics to treat patients presenting with AMI that importantly would be effective in the hours after the onset of ischaemia., Aims Monocytes play critical roles in tissue injury and repair following acute myocardial infarction (AMI). Specifically targeting inflammatory monocytes in experimental models leads to reduced infarct size and improved healing. However, data from humans are sparse, and it remains unclear whether monocytes play an equally important role in humans. The aim of this study was to investigate whether the monocyte response following AMI is conserved between humans and mice and interrogate patterns of gene expression to identify regulated functions. Methods and results Thirty patients (AMI) and 24 control patients (stable coronary atherosclerosis) were enrolled. Female C57BL/6J mice (n = 6/group) underwent AMI by surgical coronary ligation. Myocardial injury was quantified by magnetic resonance imaging (human) and echocardiography (mice). Peripheral monocytes were isolated at presentation and at 48 h. RNA from separated monocytes was hybridized to Illumina beadchips. Acute myocardial infarction resulted in a significant peripheral monocytosis in both species that positively correlated with the extent of myocardial injury. Analysis of the monocyte transcriptome following AMI demonstrated significant conservation and identified inflammation and mitosis as central processes to this response. These findings were validated in both species. Conclusions Our findings show that the monocyte transcriptome is conserved between mice and humans following AMI. Patterns of gene expression associated with inflammation and proliferation appear to be switched on prior to their infiltration of injured myocardium suggesting that the specific targeting of inflammatory and proliferative processes in these immune cells in humans are possible therapeutic strategies. Importantly, they could be effective in the hours after AMI.

BACKGROUND It is widely accepted that edema occurs early in the ischemic zone and persists in stable form for at least 1 week after myocardial ischemia/reperfusion. However, there are no longitudinal studies covering from very early (minutes) to late (1 week) reperfusion stages confirming this phenomenon. OBJECTIVES This study sought to perform a comprehensive longitudinal imaging and histological characterization of the edematous reaction after experimental myocardial ischemia/reperfusion. METHODS The study population consisted of 25 instrumented Large-White pigs (30 kg to 40 kg). Closed-chest 40-min ischemia/reperfusion was performed in 20 pigs, which were sacrificed at 120 min (n = 5), 24 h (n = 5), 4 days (n = 5), and 7 days (n = 5) after reperfusion and processed for histological quantification of myocardial water content. Cardiac magnetic resonance (CMR) scans with T2-weighted short-tau inversion recovery and T2-mapping sequences were performed at every follow-up stage until sacrifice. Five additional pigs sacrificed after baseline CMR served as controls. RESULTS In all pigs, reperfusion was associated with a significant increase in T2 relaxation times in the ischemic region. On 24-h CMR, ischemic myocardium T2 times returned to normal values (similar to those seen pre-infarction). Thereafter, ischemic myocardium-T2 times in CMR performed on days 4 and 7 after reperfusion progressively and systematically increased. On day 7 CMR, T2 relaxation times were as high as those observed at reperfusion. Myocardial water content analysis in the ischemic region showed a parallel bimodal pattern: 2 high water content peaks at reperfusion and at day 7, and a significant decrease at 24 h. CONCLUSIONS Contrary to the accepted view, myocardial edema during the first week after ischemia/reperfusion follows a bimodal pattern. The initial wave appears abruptly upon reperfusion and dissipates at 24 h. Conversely, the deferred wave of edema appears progressively days after ischemia/reperfusion and is maximal around day 7 after reperfusion. (C) 2015 by the American College of Cardiology Foundation. Sí

Objectives This study sought to test the diagnostic performance of native T1 mapping in acute myocarditis compared with cardiac magnetic resonance (CMR) techniques such as dark-blood T2-weighted (T2W)-CMR, bright-blood T2W-CMR, and late gadolinium enhancement (LGE) imaging. Background The diagnosis of acute myocarditis on CMR often requires multiple techniques, including T2W, early gadolinium enhancement, and LGE imaging. Novel techniques such as T1 mapping and bright-blood T2W-CMR are also sensitive to changes in free water content. We hypothesized that these techniques can serve as new and potentially superior diagnostic criteria for myocarditis. Methods We investigated 50 patients with suspected acute myocarditis (age 42 ± 16 years; 22% women) and 45 controls (age 42 ± 14 years; 22% women). CMR at 1.5-T (median 3 days from presentation) included: 1) dark-blood T2W-CMR (short-tau inversion recovery); 2) bright-blood T2W-CMR (acquisition for cardiac unified T2 edema); 3) native T1 mapping (shortened modified look-locker inversion recovery); and 4) LGE. Image analysis included: 1) global T2 signal intensity ratio of myocardium compared with skeletal muscle; 2) myocardial T1 relaxation times; and 3) areas of LGE. Results Compared with controls, patients had significantly higher global T2 signal intensity ratios by dark-blood T2W-CMR (1.73 ± 0.27 vs. 1.56 ± 0.15, p < 0.01), bright-blood T2W-CMR (2.02 ± 0.33 vs. 1.84 ± 0.17, p < 0.01), and mean myocardial T1 (1,010 ± 65 ms vs. 941 ± 18 ms, p < 0.01). Receiver-operating characteristic analysis showed clear differences in diagnostic performance. The areas under the curve for each method were: T1 mapping (0.95), LGE (0.96), dark-blood T2 (0.78), and bright-blood T2 (0.76). A T1 cutoff of 990 ms had a sensitivity, specificity, and diagnostic accuracy of 90%, 91%, and 91%, respectively. Conclusions Native T1 mapping as a novel criterion for the detection of acute myocarditis showed excellent and superior diagnostic performance compared with T2W-CMR. It also has a higher sensitivity compared with T2W and LGE techniques, which may be especially useful in detecting subtle focal disease and when gadolinium contrast imaging is not feasible. © 2013 by the American College of Cardiology Foundation.