Randomised trial of stable chest pain investigation: 3-year clinical and quality of life results from CE-MARC 2.

AIMS: Guidelines for suspected cardiac chest pain have used historical risk stratification tools, advocating invasive coronary angiography (ICA) first-line in those at highest risk. We aimed to determine whether different strategies to manage suspected stable angina affected medium-term cardiovascular event rates and patient-reported quality of life (QoL) measures. METHODS: CE-MARC 2, a three-arm parallel group trial, randomised patients with suspected stable cardiac chest pain and a Duke Clinical pretest likelihood of coronary artery disease between 10% and 90%. Patients were randomised to either first-line cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT) or the UK National Institute for Health and Care Excellence (NICE) CG95 (2010) guidelines-directed care. For the three arms, 1-year and 3-year first major adverse cardiovascular event (MACE) rates and QoL assessed by the Seattle Angina Questionnaire, Short Form 12 (V.12) Questionnaire and EuroQol-5 Dimension Questionnaire were recorded. RESULTS: 1202 patients were randomised to CMR (n=481), SPECT (n=481) and NICE (n=240). Forty-two patients (18 CMR, 18 SPECT, 6 NICE) experienced one or more MACEs. The percentage rates (95% CIs) of MACE in the CMR, SPECT and NICE groups at 3 years were 3.7% (2.4%, 5.8%), 3.7% (2.4%, 5.8%) and 2.1% (0.9%, 4.8%), respectively. QoL scores did not significantly differ across domains. CONCLUSION: Despite a fourfold increase in referrals for ICA, the NICE CG95 (2010) guidelines risk-stratified care strategy did not significantly reduce 3-year MACE or improve QoL, as compared with functional imaging with CMR or SPECT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01664858).

Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement: The British Society of Cardiovascular Magnetic Resonance AS700 Study.

Importance: Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived. Objective: To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement. Design, Setting, and Participants: This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021. Exposures: SAVR or TAVR. Main Outcomes and Measures: All-cause and cardiovascular (CV) mortality after aortic valve intervention. Results: Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume). Conclusions and Relevance: In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.

Feasibility and reproducibility of a cardiovascular magnetic resonance free-breathing, multi-shot, navigated image acquisition technique for ventricular volume quantification during continuous exercise.

BACKGROUND: Cardiovascular magnetic resonance (CMR) image acquisition techniques during exercise typically requires either transient cessation of exercise or complex post-processing, potentially compromising clinical utility. We evaluated the feasibility and reproducibility of a navigated image acquisition method for ventricular volumes assessment during continuous physical exercise. METHODS: Ten healthy volunteers underwent supine cycle ergometer (Lode) exercise CMR on two separate occasions using a free-breathing, multi-shot, navigated, balanced steady-state free precession cine pulse sequence. Images were acquired at 3-stages, baseline and during steady-state exercise at 55% and 75% maximal heart rate (HRmax), based on a prior supine cardiopulmonary exercise test. Intra-and inter-observer variability and inter-scan reproducibility were derived. Clinical feasibility was tested in a separate cohort of patients with severe mitral regurgitation (n=6). RESULTS: End-diastolic volume (EDV) of both LV and RV decreased during exercise at 55% and 75% HRmax, although a reduction in RVEDV index was only observed at 75% HRmax. Ejection fractions (EF) for both ventricles were significantly higher at 75% HRmax compared to their respective baselines (LVEF 68%±3% vs. 58%±5%, P=0.001; RVEF 66%±4% vs. 58%±7%, P=0.02). Intra-observer and inter-observer reproducibility of LV parameters was excellent at all 3-stages. Although measurements of RVESV were more variable during exercise, the reproducibility of both RVEF and RV cardiac index was excellent (CV <10%). Inter-scan LV and RV ejection fraction were highly reproducible at all 3 stages, although inter-scan reproducibility of indexed RVESV was only moderate. The protocol was well tolerated by all patients. CONCLUSIONS: Exercise CMR using a free-breathing, multi-shot, navigated cine imaging method allows simultaneous assessment of left and right ventricular volumes during continuous exercise. Intra- and inter-observer reproducibility were excellent. Inter-scan LV and RV ejection fraction were also highly reproducible.

Myocardial Effects of Aldosterone Antagonism in Heart Failure With Preserved Ejection Fraction.

Background Spironolactone may have prognostic benefit in selected patients with heart failure with preserved ejection fraction. This study assessed the myocardial tissue effects of spironolactone in heart failure with preserved ejection fraction. Methods and Results A 1:1 randomized controlled study of 6 months of spironolactone versus control in heart failure with preserved ejection fraction. The primary outcome was change in myocardial extracellular volume fraction by cardiovascular magnetic resonance as a surrogate of diffuse fibrosis. Of 55 randomized patients, 40 (20 women; age, 75.2±5.9 years) completed follow-up (19 treatment, 21 control). A significant change in extracellular volume over the study period was not seen (treatment, 28.7±3.7% versus 27.7±3.4% [P=0.14]; controls, 27.6±3.4% versus 28.3±4.4% [P=0.14]); however, the rate of extracellular volume expansion was decreased by spironolactone (-1.0±2.4% versus 0.8±2.2%). Indexed left ventricular mass decreased with treatment (104.4±26.6 versus 94.0±20.6 g/m2; P=0.001) but not in controls (101.4±29.4 versus 104.0±32.8 g/m2; P=0.111). Extracellular mass decreased by 13.8% (15.1±4.8 versus 13.0±3.4 g/m2; P=0.003), and cellular mass decreased by 8.3% (37.6±10.0 versus 34.3±7.9 g/m2; P=0.001) with spironolactone, but was static in controls. Conclusions Spironolactone did not lead to significant change in extracellular volume. However, spironolactone did decrease rate of extracellular expansion, with a decrease in the mass of both cellular and extracellular myocardial compartments. These data point to the mechanism of action of spironolactone in heart failure with preserved ejection fraction, including a direct tissue effect with a reduction in rate of myocardial fibrosis.

Silent cerebral infarction and cognitive function following TAVI: an observational two-centre UK comparison of the first-generation CoreValve and second-generation Lotus valve.

OBJECTIVE: To compare the incidence of silent cerebral infarction and impact on cognitive function following transcatheter aortic valve implantation (TAVI) with the first-generation CoreValve (Medtronic, Minneapolis, Minnesota, USA) and second-generation Lotus valve (Boston Scientific, Natick Massachusetts, USA). DESIGN: A prospective observational study comprising a 1.5 T cerebral MRI scan, performed preoperatively and immediately following TAVI, and neurocognitive assessments performed at baseline, 30 days and 1 year follow-up. SETTING: University hospitals of Leeds and Leicester, UK. PATIENTS: 66 (80.6±8.0 years, 47% male) patients with high-risk severe symptomatic aortic stenosis recruited between April 2012 and May 2015. MAIN OUTCOME MEASURES: Incidence of new cerebral microinfarction and objective decline in neurocognitive performance. RESULTS: All underwent cerebral MRI at baseline and immediately following TAVI, and 49 (25 Lotus, 24 CoreValve) completed neurocognitive assessments at baseline, 30 days and 1 year. There was a significantly greater incidence of new cerebral microinfarction observed following the Lotus TAVI (23 (79%) vs 22 (59%), p=0.025) with a greater number of new infarcts per patient (median 3.5 (IQR 7.0) vs 2.0 (IQR 3.0), p=0.002). The mean volume of infarcted cerebral tissue per patient was equivalent following the two prostheses (p=0.166). More patients suffered new anterior (14 (48%) vs 2 (5%), p=0.001) and vertebrobasilar (15 (52%) vs 7 (19%), p=0.005) lesions following Lotus. Lotus was associated with a decline in verbal memory and psychomotor speed at 30 days. However, performance longitudinally at 1 year was preserved in all neurocognitive domains. CONCLUSIONS: There was a higher incidence of silent cerebral microinfarction and a greater number of lesions per patient following Lotus compared with CoreValve. However, there was no objective decline in neurocognitive function discernible at 1 year following TAVI with either prosthesis.

Clinical evaluation of two dark blood methods of late gadolinium quantification of ischemic scar.

BACKGROUND: Late gadolinium enhancement (LGE) imaging was validated for diagnosis and quantification of myocardial infarction (MI). Despite good contrast between scar and normal myocardium, contrast between blood pool and myocardial scar can be limited. Dark blood LGE sequences attempt to overcome this issue. PURPOSE: To evaluate T1 rho (T1 ρ)-prepared dark blood sequence and compare to blood nulled (BN) phase sensitive inversion recovery (PSIR) and standard myocardium nulled (MN) PSIR for detection and quantification of scar. STUDY TYPE: Prospective. POPULATION: Thirty patients with prior MI. FIELD STRENGTH/SEQUENCE: Patients underwent identical 1.5 T MRI protocols. Following routine LGE imaging, a slice with scar, remote myocardium, and blood pool was selected. PSIR LGE was repeated with inversion time set to MN, to BN, and T1 ρ FIDDLE (flow-independent dark-blood delayed enhancement) in random order. ASSESSMENT: Three observers. Qualitative assessment of confidence scores in scar detection and degree of transmurality. Quantitative assessment of myocardial scar mass (grams), and contrast-to-noise ratio (CNR) measurements between scar, blood pool, and myocardium. STATISTICAL TESTS: Repeated-measures analysis of variance (ANOVA) with Bonferroni correction, coefficient of variation, and the Cohen κ statistic. RESULTS: CNRscar-blood was significantly increased for both BN (27.1 ± 10.4) and T1 ρ (30.2 ± 15.1) compared with MN (15.3 ± 8.4 P < 0.001 for both sequences). There was no significant difference in CNRscar-myo between BN (55.9 ± 17.3) and MN (51.1 ± 17.8 P = 0.512); both had significantly higher CNRscar-myo compared with the T1 ρ (42.6 ± 16.9 P = 0.007 and P = 0.014, respectively). No significant difference in scar size between LGE methods: MN (2.28 ± 1.58 g) BN (2.16 ± 1.57 g) and T1 ρ (2.29 ± 2.5 g). Confidence scores were significantly higher for BN (3.87 ± 0.346) compared with MN (3.1 ± 0.76 P < 0.001) and T1 ρ (3.20 ± 0.71 P < 0.001). DATA CONCLUSION: PSIR with inversion time (TI) set for blood nulling and the T1 ρ LGE sequence demonstrated significantly higher scar to blood CNR compared with routine MN. PSIR with TI set for blood nulling demonstrated significantly higher reader confidence scores compared with routine MN and T1 ρ LGE, suggesting routine adoption of a BN PSIR approach might be appropriate for LGE imaging. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:146-152.

Feasibility study of a single breath-hold, 3D mDIXON pulse sequence for late gadolinium enhancement imaging of ischemic scar.

BACKGROUND: Late gadolinium enhancement (LGE) imaging is well validated for the diagnosis and quantification of myocardial infarction (MI). 2D LGE imaging involves multiple breath-holds for acquisition of short-axis slices to cover the left ventricle (LV). 3D LGE methods cover the LV in a single breath-hold; however, breath-hold duration is typically long with images susceptible to motion artifacts. PURPOSE/HYPOTHESIS: To assess a single breath-hold 3D mDIXON LGE pulse sequence for image quality and quantitation of MI. STUDY TYPE: Prospective. POPULATION: Ninety- two patients with prior MI. FIELD STRENGTH/SEQUENCE: 1.5T cardiac MRI protocol using both conventional 2D phase sensitive inversion recovery and 3D mDIXON LGE imaging 10 minutes following contrast administration in random order to avoid bias. ASSESSMENT: Data were analyzed qualitatively for image quality (three observers). Quantitative assessment of myocardial scar mass (full-width half-maximum), scar transmurality, and contrast-to-noise ratio measurements were performed. Time for 2D and 3D LGE imaging was recorded. STATISTICAL TESTS: Paired Student's t-test, Wilcoxon rank test, Cohen κ statistic, Pearson correlation, linear regression, and Bland-Altman analysis. RESULTS: Image quality scores were comparable between 3D and 2D LGE (1.4 ± 0.6 vs. 1.3 ± 0.5; P = 0.162). 3D LGE was associated with greater scar tissue mass (3D: 18.9 ± 17.5 g vs. 2D: 17.8 ± 16.2 g P = 0.03), although this difference was less pronounced when scar tissue was expressed as %LV mass (3D: 13.4 ± 9.9% vs. 2D: 12.7 ± 9.5% P = 0.07). For 3D vs. 2D scar mass there was a strong and significant positive correlation; Bland-Altman analysis showed mean mass bias of 1.1 g (95% confidence interval [CI]: -5.7 to 7.9). Segmental level agreement of scar transmurality between 3D and 2D LGE at the clinical viability threshold of 50% transmurality was excellent (κ = 0.870). 3D image acquisition (15.6 ± 1.4 sec) was just 5% of time required for 2D images (311.6 ± 43.2 sec) P < 0.0001. DATA CONCLUSION: Single breath-hold 3D mDIXON LGE imaging allows quantitative assessment of MI mass and transmurality, with comparable image quality, in vastly shorter overall acquisition time compared with standard 2D LGE imaging. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1437-1445.

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

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.

CMR quantitation of change in mitral regurgitation following transcatheter aortic valve replacement (TAVR): impact on left ventricular reverse remodeling and outcome.

Current echocardiographic data reporting the impact of concomitant mitral regurgitation (MR) on outcome in patients who undergo transcatheter aortic valve replacement (TAVR) are conflicting. Using cardiovascular magnetic resonance (CMR) imaging, this study aimed to assess the impact of MR severity on cardiac reverse remodeling and patient outcome. 85 patients undergoing TAVR with CMR pre- and 6 m post-TAVR were evaluated. The CMR protocol included cines for left (LV) and right ventricular (RV) volumes, flow assessment, and myocardial scar assessment by late gadolinium enhancement (LGE). Patients were dichotomised according to CMR severity of MR fraction at baseline ('non-significant' vs 'significant') and followed up for a median duration of 3 years. Forty-two (49%) patients had 'significant MR' at baseline; they had similar LV and RV size and function compared to the 'non-significant MR' group but had greater LV mass at baseline. In those with significant MR at baseline, 77% (n = 32) had a reduction in MR post-TAVR, moving them into the 'non-significant' category at 6-months, with an overall reduction in MR fraction from 34 to 17% (p < 0.001). Improvement in MR was not associated with more favourable cardiac reverse remodeling when compared with the 'non-improvers'. Significant MR at baseline was not associated with increased mortality at follow-up. Significant MR is common in patients undergoing TAVR and improves in the majority post-procedure. Improvement in MR was not associated with more favourable LV reverse remodeling and baseline MR severity was not associated with mortality.

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.

Left ventricular blood flow kinetic energy after myocardial infarction - insights from 4D flow cardiovascular magnetic resonance.

BACKGROUND: Myocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics that are linked to clinical outcomes. We hypothesize that LV blood flow kinetic energy (KE) is altered in MI and is associated with LV function and infarct characteristics. This study aimed to investigate the intra-cavity LV blood flow KE in controls and MI patients, using cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow assessment. METHODS: Forty-eight patients with MI (acute-22; chronic-26) and 20 age/gender-matched healthy controls underwent CMR which included cines and whole-heart 4D flow. Patients also received late gadolinium enhancement imaging for infarct assessment. LV blood flow KE parameters were indexed to LV end-diastolic volume and include: averaged LV, minimal, systolic, diastolic, peak E-wave and peak A-wave KEiEDV. In addition, we investigated the in-plane proportion of LV KE (%) and the time difference (TD) to peak E-wave KE propagation from base to mid-ventricle was computed. Association of LV blood flow KE parameters to LV function and infarct size were investigated in all groups. RESULTS: LV KEiEDV was higher in controls than in MI patients (8.5 ± 3 µJ/ml versus 6.5 ± 3 µJ/ml, P = 0.02). Additionally, systolic, minimal and diastolic peak E-wave KEiEDV were lower in MI (P < 0.05). In logistic-regression analysis, systolic KEiEDV (Beta = - 0.24, P < 0.01) demonstrated the strongest association with the presence of MI. In multiple-regression analysis, infarct size was most strongly associated with in-plane KE (r = 0.5, Beta = 1.1, P < 0.01). In patients with preserved LV ejection fraction (EF), minimal and in-plane KEiEDV were reduced (P < 0.05) and time difference to peak E-wave KE propagation during diastole increased (P < 0.05) when compared to controls with normal EF. CONCLUSIONS: Reduction in LV systolic function results in reduction in systolic flow KEiEDV. Infarct size is independently associated with the proportion of in-plane LV KE. Degree of LV impairment is associated with TD of peak E-wave KE. In patient with preserved EF post MI, LV blood flow KE mapping demonstrated significant changes in the in-plane KE, the minimal KEiEDV and the TD. These three blood flow KE parameters may offer novel methods to identify and describe this patient population.

Fully automated, inline quantification of myocardial blood flow with cardiovascular magnetic resonance: repeatability of measurements in healthy subjects.

BACKGROUND: Non-invasive assessment of myocardial ischaemia is a cornerstone of the diagnosis of coronary artery disease. Measurement of myocardial blood flow (MBF) using positron emission tomography (PET) is the current reference standard for non-invasive quantification of myocardial ischaemia. Dynamic myocardial perfusion cardiovascular magnetic resonance (CMR) offers an alternative to PET and a recently developed method with automated inline perfusion mapping has shown good correlation of MBF values between CMR and PET. This study assessed the repeatability of myocardial perfusion mapping by CMR in healthy subjects. METHODS: Forty-two healthy subjects were recruited and underwent adenosine stress and rest perfusion CMR on two visits. Scans were repeated with a minimum interval of 7 days. Intrastudy rest and stress MBF repeatability were assessed with a 15-min interval between acquisitions. Interstudy rest and stress MBF and myocardial perfusion reserve (MPR) were measured for global myocardium and regionally for coronary territories and slices. RESULTS: There was no significant difference in intrastudy repeated global rest MBF (0.65 ± 0.13 ml/g/min vs 0.62 ± 0.12 ml/g/min, p = 0.24, repeatability coefficient (RC) =24%) or stress (2.89 ± 0.56 ml/g/min vs 2.83 ± 0.64 ml/g/min, p = 0.41, RC = 29%) MBF. No significant difference was seen in interstudy repeatability for global rest MBF (0.64 ± 0.13 ml/g/min vs 0.64 ± 0.15 ml/g/min, p = 0.80, RC = 32%), stress MBF (2.71 ± 0.61 ml/g/min vs 2.55 ± 0.57 ml/g/min, p = 0.12, RC = 33%) or MPR (4.24 ± 0.69 vs 3.73 ± 0.76, p = 0.25, RC = 36%). Regional repeatability was good for stress (RC = 30-37%) and rest MBF (RC = 32-36%) but poorer for MPR (RC = 35-43%). Within subject coefficient of variation was 8% for rest and 11% for stress within the same study, and 11% for rest and 12% for stress between studies. CONCLUSIONS: Fully automated, inline, myocardial perfusion mapping by CMR shows good repeatability that is similar to the published PET literature. Both rest and stress MBF show better repeatability than MPR, particularly in regional analysis.

Myocardial Scar and Mortality in Severe Aortic Stenosis.

BACKGROUND: Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. METHODS: In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. RESULTS: Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm2/m2; mean gradient, 46±18 mm Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11-2.04; P=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03-1.22; P=0.007), and scar presence (HR, 2.39; 95% CI, 1.40-4.05; P=0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P<0.001) and cardiovascular (15.0% versus 4.8%; P<0.001) mortality, regardless of intervention (transcatheter AVR, P=0.002; surgical AVR, P=0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05-1.17; P<0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01-1.17; P<0.001). CONCLUSIONS: In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.

Cardiovascular magnetic resonance assessment of 1st generation CoreValve and 2nd generation Lotus valves.

OBJECTIVES: We sought to compare using serial CMR, the quantity of AR and associated valve hemodynamics, following the first-generation CoreValve (Medtronic, Minneapolis, MN) and the second-generation Lotus valve (Boston Scientific, Natick, MA). BACKGROUND: Aortic regurgitation (AR) following Transcatheter Aortic Valve Replacement (TAVR) confers a worse prognosis and can be accurately quantified using cardiovascular magnetic resonance (CMR). Second generation valves have been specifically designed to reduce paravalvular AR and improve clinical outcomes. METHODS: Fifty-one patients (79.0 ± 7.7 years, 57% male) were recruited and imaged at three time points: immediately pre- and post-TAVR, and at 6 months. RESULTS: CMR-derived AR fraction immediately post-TAVR was greater in the CoreValve compared to Lotus group (11.7 ± 8.4 vs. 4.3 ± 3.4%, P = 0.001), as was the frequency of ≥moderate AR (9/24 (37.5%) versus 0/27, P < 0.001). However, at 6 months AR fraction had improved significantly in the CoreValve group such that the two valve designs were comparable (6.4 ± 5.0 vs 5.6 ± 5.3%, P = 0.623), with no patient in either group having ≥moderate AR. The residual peak pressure gradient immediately following TAVR was significantly lower with CoreValve compared to Lotus (14.1 ± 5.6 vs 25.4 ± 11.6 mmHg, P = 0.001), but again by 6 months the two valve designs were comparable (16.5 ± 9.4 vs 19.7 ± 10.5 mmHg, P = 0.332). There was no difference in the degree of LV reverse remodeling between the two valves at 6 months. CONCLUSION: Immediately post-TAVR, there was significantly less AR but a higher residual peak pressure gradient with the Lotus valve compared to CoreValve. However, at 6 months both devices had comparable valve hemodynamics and LV reverse remodeling.

Lobomycosis-like disease in common bottlenose dolphins Tursiops truncatus from Belize and Mexico: bridging the gap between the Americas.

Lobomycosis and lobomycosis-like diseases (LLD) (also: paracoccidioidomycosis) are chronic cutaneous infections that affect Delphinidae in tropical and subtropical regions worldwide. In the Americas, these diseases have been relatively well-described, but gaps still exist in our understanding of their distribution across the continent. Here we report on LLD affecting inshore bottlenose dolphins Tursiops truncatus from the Caribbean waters of Belize and from the eastern tropical Pacific Ocean off the southwestern coast of Mexico. Photo-identification and catalog data gathered between 1992 and 2017 for 371 and 41 individuals, respectively from Belize and Mexico, were examined for the presence of LLD. In Belize, 5 free-ranging and 1 stranded dolphin were found positive in at least 3 communities with the highest prevalence in the south. In Guerrero, Mexico, 4 inshore bottlenose dolphins sighted in 2014-2017 were affected by LLD. These data highlight the need for histological and molecular studies to confirm the etiological agent. Additionally, we document a single case of LLD in an adult Atlantic spotted dolphin Stenella frontalis in southern Belize, the first report in this species. The role of environmental and anthropogenic factors in the occurrence, severity, and epidemiology of LLD in South and Central America requires further investigation.

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

PURPOSE: 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). MATERIALS AND METHODS: Acceleration methods were investigated in static/pulsatile phantoms and 25 volunteers on 1.5 Tesla MR systems. In phantoms, flow was quantified by 2D phase-contrast (PC), the three 4D flow methods and the time-beaker flow measurements. The later was used as the reference method. Peak velocity and flow assessment was done by means of all sequences. For peak velocity assessment 2D PC was used as the reference method. For flow assessment, consistency between mitral inflow and aortic outflow was investigated for all pulse-sequences. Visual grading of image quality/artifacts was performed on a four-point-scale (0 = no artifacts; 3 = nonevaluable). RESULTS: For the pulsatile phantom experiments, the mean error for 2D PC = 1.0 ± 1.1%, 4D-SPGR = 4.9 ± 1.3%, 4D-EPI = 7.6 ± 1.3% and 4D-k-t BLAST = 4.4 ± 1.9%. In vivo, acquisition time was shortest for 4D-EPI (4D-EPI = 8 ± 2 min versus 4D-SPGR = 9 ± 3 min, P < 0.05 and 4D-k-t BLAST = 9 ± 3 min, P = 0.29). 4D-EPI and 4D-k-t BLAST had minimal artifacts, while for 4D-SPGR, 40% of aortic valve/mitral valve (AV/MV) assessments scored 3 (nonevaluable). Peak velocity assessment using 4D-EPI demonstrated best correlation to 2D PC (AV:r = 0.78, P < 0.001; MV:r = 0.71, P < 0.001). Coefficient of variability (CV) for net forward flow (NFF) volume was least for 4D-EPI (7%) (2D PC:11%, 4D-SPGR: 29%, 4D-k-t BLAST: 30%, respectively). CONCLUSION: In phantom, all 4D flow techniques demonstrated mean error of less than 8%. 4D-EPI demonstrated the least susceptibility to artifacts, good image quality, modest agreement with the current reference standard for peak intra-cardiac velocities and the highest consistency of intra-cardiac flow quantifications. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:272-281.

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.

A comparison of cardiovascular magnetic resonance and single photon emission computed tomography (SPECT) perfusion imaging in left main stem or equivalent coronary artery disease: a CE-MARC substudy.

BACKGROUND: Assessment of left main stem (LMS) stenosis has prognostic and therapeutic implications. Data on assessment of LMS disease by cardiovascular magnetic resonance (CMR) and single photon emission computed tomography (SPECT) are limited. CE-MARC is the largest prospective comparison of CMR and SPECT against quantitative invasive coronary angiography (QCA) for detection of coronary artery disease (CAD), and provided the framework for this evaluation. The aims of this study were to compare diagnostic accuracy of visual and quantitative perfusion CMR to SPECT in patients with LMS stable CAD. METHODS: Fifty-four patients from the CE-MARC study were included: 27 (4%) with significant LMS or LMS-equivalent disease on QCA, and 27 age/sex-matched patients with no flow-limiting CAD. All patients underwent multi-parametric CMR, SPECT and QCA. Performance of visual and quantitative perfusion CMR by Fermi-constrained deconvolution to detect LMS disease was compared with SPECT. RESULTS: Of 27 patients in the LMS group, 22 (81%) had abnormal CMR and 16 (59%) had abnormal SPECT. All patients with abnormal CMR had abnormal perfusion by visual analysis. CMR demonstrated significantly higher area under the curve (AUC) for detection of disease (0.95; 0.85-0.99) over SPECT (0.63; 0.49-0.76) (p = 0.0001). Global mean stress myocardial blood flow (MBF) by CMR in LMS patients was significantly lower than controls (1.77 ± 0.72 ml/g/min vs. 3.28 ± 1.20 ml/g/min, p < 0.001). MBF of <2.08 ml/g/min had sensitivity of 78% and specificity of 85% for diagnosis of LMS disease, with an AUC (0.87; 0.75-0.94) not significantly different to visual CMR analysis (p = 0.18), and more accurate than SPECT (p = 0.003). CONCLUSION: Visual stress perfusion CMR had higher diagnostic accuracy than SPECT to detect LMS disease. Quantitative perfusion CMR had similar performance to visual CMR perfusion analysis.

Extra-cellular expansion in the normal, non-infarcted myocardium is associated with worsening of regional myocardial function after acute myocardial infarction.

BACKGROUND: Expansion of the myocardial extracellular volume (ECV) is a surrogate measure of focal/diffuse fibrosis and is an independent marker of prognosis in chronic heart disease. Changes in ECV may also occur after myocardial infarction, acutely because of oedema and in convalescence as part of ventricular remodelling. The objective of this study was to investigate changes in the pattern of distribution of regional (normal, infarcted and oedematous segments) and global left ventricular (LV) ECV using semi-automated methods early and late after reperfused ST-elevation myocardial infarction (STEMI). METHODS: Fifty patients underwent cardiovascular magnetic resonance (CMR) imaging acutely (24 h-72 h) and at convalescence (3 months). The CMR protocol included: cines, T2-weighted (T2 W) imaging, pre-/post-contrast T1-maps and LGE-imaging. Using T2 W and LGE imaging on acute scans, 16-segments of the LV were categorised as normal, oedema and infarct. 800 segments (16 per-patient) were analysed for changes in ECV and wall thickening (WT). RESULTS: From the acute studies, 325 (40.6%) segments were classified as normal, 246 (30.8%) segments as oedema and 229 (28.6%) segments as infarct. Segmental change in ECV between acute and follow-up studies (Δ ECV) was significantly different for normal, oedema and infarct segments (0.8 ± 6.5%, -1.78 ± 9%, -2.9 ± 10.9%, respectively; P < 0.001). Normal segments which demonstrated deterioration in wall thickening at follow-up showed significantly increased Δ ECV compared with normal segments with preserved wall thickening at follow up (1.82 ± 6.05% versus -0.10 ± 6.88%, P < 0.05). CONCLUSION: Following reperfused STEMI, normal myocardium demonstrates subtle expansion of the extracellular volume at 3-month follow up. Segmental ECV expansion of normal myocardium is associated with worsening of contractile function.