James Rj Foley

Effect of Care Guided by Cardiovascular Magnetic Resonance, Myocardial Perfusion Scintigraphy, or NICE Guidelines on Subsequent Unnecessary Angiography Rates: The CE-MARC 2 Randomized Clinical Trial

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 < .001); CMR group vs the MPS group, 1.27 (95% CI, 0.79-2.03, P = .32). Positive angiography proportions were 12.1% (95% CI, 8.2%-16.9%; 29/240 patients) for the NICE guidelines group, 9.8% (95% CI, 7.3%-12.8%; 47/481 patients) for the CMR group, and 8.7% (95% CI, 6.4%-11.6%; 42/481 patients) for the MPS group. A MACE was reported at a minimum of 12 months in 1.7% of patients in the NICE guidelines group, 2.5% in the CMR group, and 2.5% in the MPS group (adjusted hazard ratios: CMR group vs NICE guidelines group, 1.37 [95% CI, 0.52-3.57]; CMR group vs MPS group, 0.95 [95% CI, 0.46-1.95]). CONCLUSIONS AND RELEVANCE In patients with suspected angina, investigation by CMR resulted in a lower probability of unnecessary angiography within 12 months than NICE guideline-directed care, with no statistically significant difference between CMR and MPS strategies. There were no statistically significant differences in MACE rates. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT01664858.

Acute Infarct Extracellular Volume Mapping to Quantify Myocardial Area at Risk and Chronic Infarct Size on Cardiovascular Magnetic Resonance ImagingCLINICAL PERSPECTIVE

Background— Late gadolinium enhancement (LGE) imaging overestimates acute infarct size. The main aim of this study was to investigate whether acute extracellular volume (ECV) maps can reliably quantify myocardial area at risk (AAR) and final infarct size (IS). Methods and Results— Fifty patients underwent cardiovascular magnetic resonance imaging acutely (24–72 hours) and at convalescence (3 months). The cardiovascular magnetic resonance protocol included cines, T2-weighted imaging, native T1 maps, 15-minute post-contrast T1 maps, and LGE. Optimal AAR and IS ECV thresholds were derived in a validation group of 10 cases (160 segments). Eight hundred segments (16 per patient) were analyzed to quantify AAR/IS by ECV maps (ECV thresholds for AAR is 33% and IS is 46%), T2-weighted imaging, T1 maps, and acute LGE. Follow-up LGE imaging was used as the reference standard for final IS and viability assessment. The AAR derived from ECV maps (threshold of >33) demonstrated good agreement with T2-weighted imaging–derived AAR (bias, 0.18; 95% confidence interval [CI], −1.6 to 1.3) and AAR derived from native T1 maps (bias=1; 95% CI, −0.37 to 2.4). ECV demonstrated the best linear correlation to final IS at a threshold of >46% (R=0.96; 95% CI, 0.92–0.98; P<0.0001). ECV maps demonstrated better agreement with final IS than acute IS on LGE (ECV maps: bias, 1.9; 95% CI, 0.4–3.4 versus LGE imaging: bias, 10; 95% CI, 7.7–12.4). On multiple variable regression analysis, the number of nonviable segments was independently associated with IS by ECV maps (&bgr;=0.86; P<0.0001). Conclusions— ECV maps can reliably quantify AAR and final IS in reperfused acute myocardial infarction. Acute ECV maps were superior to acute LGE in terms of agreement with final IS. IS quantified by ECV maps are independently associated with viability at follow-up.

Comparison of fast acquisition strategies in whole‐heart four‐dimensional flow cardiac MR: Two‐center, 1.5 Tesla, phantom and in vivo validation study

To validate three widely‐used acceleration methods in four‐dimensional (4D) flow cardiac MR; segmented 4D‐spoiled‐gradient‐echo (4D‐SPGR), 4D‐echo‐planar‐imaging (4D‐EPI), and 4D‐k‐t Broad‐use Linear Acquisition Speed‐up Technique (4D‐k‐t BLAST).

Ventricular longitudinal function is associated with microvascular obstruction and intramyocardial haemorrhage

Background Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) are associated with adverse prognosis, independently of infarct size after reperfused ST-elevation myocardial infarction (STEMI). Mitral annular plane systolic excursion (MAPSE) is a well-established parameter of longitudinal function on echocardiography. Objective We aimed to investigate how acute MAPSE, assessed by a four-chamber cine-cardiovascular MR (CMR), is associated with MVO, IMH and convalescent left ventricular (LV) remodelling. Methods 54 consecutive patients underwent CMR at 3T (Intera CV, Philips Healthcare, Best, The Netherlands) within 3 days of reperfused STEMI. Cine, T2-weighted, T2* and late gadolinium enhancement (LGE) imaging were performed. Infarct and MVO extent were measured from LGE images. The presence of IMH was investigated by combined analysis of T2w and T2* images. Averaged-MAPSE (medial-MAPSE+lateral-MAPSE/2) was calculated from 4-chamber cine imaging. Results 44 patients completed the baseline scan and 38 patients completed 3-month scans. 26 (59%) patients had MVO and 25 (57%) patients had IMH. Presence of MVO and IMH were associated with lower averaged-MAPSE (11.7±0.4 mm vs 9.3±0.3 mm; p<0.001 and 11.8±0.4 mm vs 9.2±0.3 mm; p<0.001, respectively). IMH (β=−0.655, p<0.001) and MVO (β=−0.567, p<0.001) demonstrated a stronger correlation to MAPSE than other demographic and infarct characteristics. MAPSE ≤10.6 mm demonstrated 89% sensitivity and 72% specificity for the detection of MVO and 92% sensitivity and 74% specificity for IMH. LV remodelling in convalescence was not associated with MAPSE (AUC 0.62, 95% CI 0.44 to 0.77, p=0.22). Conclusions Postreperfused STEMI, LV longitudinal function assessed by MAPSE can independently predict the presence of MVO and IMH.

Assessment of stable coronary artery disease by cardiovascular magnetic resonance imaging: Current and emerging techniques

Coronary artery disease (CAD) is a leading cause of death and disability worldwide. Cardiovascular magnetic resonance (CMR) is established in clinical practice guidelines with a growing evidence base supporting its use to aid the diagnosis and management of patients with suspected or established CAD. CMR is a multi-parametric imaging modality that yields high spatial resolution images that can be acquired in any plane for the assessment of global and regional cardiac function, myocardial perfusion and viability, tissue characterisation and coronary artery anatomy, all within a single study protocol and without exposure to ionising radiation. Advances in technology and acquisition techniques continue to progress the utility of CMR across a wide spectrum of cardiovascular disease, and the publication of large scale clinical trials continues to strengthen the role of CMR in daily cardiology practice. This article aims to review current practice and explore the future directions of multi-parametric CMR imaging in the investigation of stable CAD.

4 Four-dimensional left ventricular blood flow energetics independently predict adverse remodelling post st-elevation myocardial infarction

Introduction Myocardial infraction (MI) leads to complex changes in left ventricular (LV) haemodynamics. It remains unknown how four-dimensional (4D) acute changes in LV-cavity blood flow kinetic energy (KE) affect LV remodelling. We hypothesised that LV blood flow energetics is independently associated with adverse LV-remodelling. Methods We recruited 69 revascularised ST-elevation MI patients. All patients underwent cardiovascular magnetic resonance (CMR) at 1.5 T within 48 hours and at 3 months. CMR included cines, early/late gadolinium enhancement and whole-heart 4D flow. CMR analysis included: LV volumes, infarct size (IS,%), microvascular obstruction (MVO,%), two-dimensional, retrospective valve tracking derived mitral inflow metrics and 4D KE components. KE was derived using novel, semi-automated method by using endocardial contours on short-axis cines to extract intra-cavity velocity profile. Adverse LV-remodelling was defined as increase in LV end-diastolic volume by 15%. Results Thirteen (19%) patients developed adverse LV-remodelling. Demographics were comparable between patients with/without remodelling. Baseline CMR in adverse LV-remodelling-group showed significantly lower EF, LV KE, Systolic, A-wave, in-plane KEs and increased MVO (p<0.05). In stepwise-regression analysis, only acute MVO (beta=0.17±0.06, p<0.05) and acute A-wave KE (beta=−0.17±0.08, p<0.05) independently predicted adverse remodelling at 3 months. A regression-model comprising of acute MVO and A-wave KE had high predictive value for adverse LV-remodelling (area under the curve=0.82, 95% confidence interval=0.7–0.9, p<0.001). Conclusion LV haemodynamic assessment by novel, semi-automated, 4D KE mapping adds incremental value to predict adverse LV-remodelling. A-wave KE and MVO size early after acute MI are independently associated with adverse LV-remodelling.

Left ventricular thrombus formation in myocardial infarction is associated with altered left ventricular blood flow energetics

Abstract 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 ρblood . Vvoxel . v2, where ρ = 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.

Impact of Age and Diastolic Function on Novel, 4D flow CMR Biomarkers of Left Ventricular Blood Flow Kinetic Energy

Two-dimensional (2D) methods of assessing mitral inflow velocities are pre-load dependent, limiting their reliability for evaluating diastolic function. Left ventricular (LV) blood flow kinetic energy (KE) derived from four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) may offer improvements. It remains unclear whether 4D LV blood flow KE parameters are associated with physiological factors, such as age when compared to 2D mitral inflow velocities. Fifty-three healthy volunteers underwent standard CMR, plus 4D flow acquisition. LV blood flow KE parameters demonstrated good reproducibility with mean coefficient of variation of 6 ± 2% and an accuracy of 99% with a precision of 97%. The LV blood flow KEiEDV E/A ratio demonstrated good association to the 2D mitral inflow E/A ratio (r = 0.77, P < 0.01), with both decreasing progressively with advancing age (P < 0.01). Furthermore, peak E-wave KEiEDV and A-wave KEiEDV displayed a stronger association to age than the corresponding 2D metrics, peak E-wave and A-wave velocity (r = −0.51 vs −0.17 and r = 0.65 vs 0.46). Peak E-wave KEiEDV decreases whilst peak A-wave KEiEDV increases with advancing age. This study presents values for various LV blood flow KE parameters in health, as well as demonstrating that they show stronger and independent correlations to age than standard diastolic metrics.

49 Reduced myocardial perfusion reserve in systolic heart failure a therapeutic target

Background Left ventricular systolic dysfunction (LVSD) is associated with reduced myocardial perfusion reserve (MPR) even in the absence of proven ischaemic heart disease and patients may have typical angina symptoms, despite the lack of obstructive coronary artery disease. The severity of MPR reduction has been suggested as a prognostic marker in both ischaemic and non-ischaemic cardiomyopathy. We hypothesised that reduction in MPR was associated with worsening symptomatology (NYHA class) and systolic dysfunction (ejection fraction, EF). Methods 40 patients referred from cardiology clinics with LVSD of unknown cause underwent adenosine stress perfusion CMR (Siemens 3T). First pass stress and rest myocardial perfusion CMR data were acquired in three short axis slices with 0.05 mmol/kg intravenous Gadovist using a recently reported free-breathing motion corrected Method with in-line quantification of perfusion maps. For stress, adenosine was administered at 140 mcg/kg/min over 5 min. Segments showing regional perfusion defects or containing scar were excluded from further quantitative analysis. Myocardial blood flow (MBF) was calculated globally for the remaining left ventricle. Patients with no evidence of LVSD (EF-55%) were excluded from analysis. NYHA class was recorded at the time of CMR scan. EF was calculated from a short axis cine data set and classified as: mild (45%), moderate (3544%) and severe (34%) impairment. ANOVA with post hoc Bonferroni correction was used to compare means of the three groups. Results Patients were grouped both by NYHA class and by EF severity, comparisons of these groups are shown in Table 1. No significant difference was seen between groups with respect to age, resting heart rate and resting MBF. Abstract 49 Table 1 Comparison of patient groups NYHA I NYHA II NHYA III P N 15 12 7 Age 65.7±7.7 71.4±12.9 68.4±11.2 0.39 EF% 35.1±10.7 30.0±11.4 27.9±5.9 0.24 Resting HR 67.0±12.3 70.5±9.7 70.6±18.8 0.81 Rest MBF (ml/g/min) 0.67±0.28 0.77±0.34 0.67±0.30 0.68 Stress MBF (ml/g/min) 1.92±0.96 1.49±0.57 1.00±0.62 0.04 MPR 2.90±0.96 2.05±0.61 1.45±0.45 < 0.01 Mild Moderate Severe N 4 8 22 Age 60.4±7.12 71.1±6.36 68.7±11.7 0.242 Rest HR 67.5±10.6 61.8±8.52 72.2±13.6 0.139 Rest MBF(ml/g/min) 0.56±0.18 0.83±0.44 0.68±0.25 0.314 Stress MBF (ml/g/min) 1.78±0.658 1.89±1.06 1.43±0.76 0.379 MPR 3.21±0.86 2.38±0.91 2.11±0.91 0.093 *significant at level p=0.05, ** significant at level p=0.01 MPR was associated with NYHA class (figure 1). A greater reduction in MPR was associated with a higher NYHA class and there was a significant decrease in MPR between asymptomatic patients and those with exercise limitation (Mean MPR 2.90±0.96, 2.05±0.61, 1.45±0.45 for classes I, II and III respectively, p<0.01). No significant difference was seen between NYHA II and III (2.05 vs 1.45, p=0.32) although a trend to decreasing MPR was observed. Myocardial perfusion reserve did not correlate with severity of LV dysfunction (figure 2). Abstract 49 Figure 1 Abstract 49 Figure 2 Conclusion A reduction in MPR is associated with NYHA class in systolic heart failure, independent of ejection fraction. These findings suggest potential therapeutic targets for symptomatic improvement, including use of vasodilators, even in the absence of coronary disease.

Quantitative deformation analysis differentiates ischaemic and non-ischaemic cardiomyopathy: sub-group analysis of the VINDICATE trial

Aims To test the hypothesis that patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM) have different torsion and strain parameters, and compare to healthy, age-matched controls. VINDICATE investigated efficacy of high-dose vitamin D on patients with heart failure (HF) secondary to left ventricular (LV) systolic dysfunction of any aetiology. It is important to differentiate ICM and NICM as treatment and prognosis varies significantly. Cardiovascular magnetic resonance (CMR) reliably determines aetiology of HF and tissue tagging techniques are recognized as the reference standard measures of strain and torsion. Methods and results Fifty three patients (31 ICM, 22 NICM) from VINDICATE and 25 controls underwent CMR at 3.0T, including cine imaging in multiple planes and tissue tagging by spatial modulation of magnetization. CMR data were analysed blinded, by quantitatively reporting circumferential strain and torsion from tagged images and global longitudinal strain from feature tracking. HF patients had larger ventricles indexed to body surface area, lower left ventricular ejection fraction (LVEF), LV torsion, twist, and strain parameters compared to controls. There were no significant differences between ICM and NICM in age, blood pressure, heart rhythm, or NYHA status. There was no significant difference in LV dimensions, EF, and strain parameters between ICM and NICM. NICM patients had significantly lower LV twist (6.0 ± 3.7° vs. 8.8 ± 4.3°, P = 0.023) and torsion (5.9 ± 3.5° vs. 8.8 ± 4.7°, P = 0.017) compared to ICM. Conclusion Twist, torsion, and strain are reduced in HF patients compared to controls. Torsion and twist are significantly lower in patients with NICM compared to ICM, despite similar volumetric dimensions, circumferential and longitudinal strain parameters, and LVEF.