Unravelling the mechanisms of CE-SSFP in imaging myocardium at risk: The effect of relaxation times on myocardial contrast.

PURPOSE: The aim of this study was to investigate the contrast mechanisms of Contrast-enhanced steady-state free-precession (CE-SSFP) through the utilization of Bloch simulations in an experimental porcine model and in patients with acute myocardial infarction. METHODS: Six pigs and ten patients with myocardial infarction underwent CMR and tissue characterization at 1.5 T whereas a Bloch simulation framework was utilized to simulate the CE-SSFP signal formation and compare it against the actual CE-SSFP signal acquired from the experimental porcine model and the patient population. The relaxation times of remote, salvaged, and infarcted myocardium were calculated after the injection of gadolinium, at the time of CE-SSFP acquisition. Simulations were performed using the same CE-SSFP pulse sequence as used on the scanner on a set of spins with the calculated relaxation times from the CMR scans. RESULTS: The normalized signal intensities of salvaged and infarcted myocardium obtained with simulations were lower than the corresponding normalized signal intensities obtained in vivo in pigs (p < 0.05, 134% vs 153%) and in patients (p < 0.05, 126% vs 145%). The results from simulations showed a linear relationship to the results obtained in the experimental porcine model (r2 = 0.61) and in patients (r2 = 0.69). CONCLUSION: The T1 and T2 values of remote, salvaged, and infarcted myocardium only partly explain the signal intensities in CE-SSFP images. Bloch simulations suggest that there may be more elements that contribute to the CE-SSFP contrast. Integration of other aspects of the MR experiment into the simulation model could further help to fully unravel the mechanisms of CE-SSFP.

Contractility, ventriculoarterial coupling, and stroke work after acute myocardial infarction using CMR-derived pressure-volume loop data.

BACKGROUND: Noninvasive left ventricular (LV) pressure-volume (PV) loops derived by cardiac magnetic resonance (CMR) have recently been shown to enable characterization of cardiac hemodynamics. Thus, such PV loops could potentially provide additional diagnostic information such as contractility, arterial elastance (Ea ) and stroke work (SW) currently not available in clinical routine. This study sought to investigate to what extent PV-loop variables derived with a novel noninvasive method can provide incremental physiological information over cardiac dimensions and blood pressure in patients with acute myocardial infarction (MI). METHODS: A total of 100 patients with acute MI and 75 controls were included in the study. All patients underwent CMR 2-6 days after MI including assessment of myocardium at risk (MaR) and infarct size (IS). Noninvasive PV loops were generated from CMR derived LV volumes and brachial blood pressure measurements. The following variables were quantified: Maximal elastance (Emax ) reflecting contractility, Ea , ventriculoarterial coupling (Ea /Emax ), SW, potential energy, external power, energy per ejected volume, and efficiency. RESULTS: All PV-loop variables were significantly different in MI patients compared to healthy volunteers, including contractility (Emax : 1.34 ± 0.48 versus 1.50 ± 0.41 mmHg/mL, p = .024), ventriculoarterial coupling (Ea /Emax : 1.27 ± 0.61 versus 0.73 ± 0.17, p < .001) and SW (0.96 ± 0.32 versus 1.38 ± 0.32 J, p < .001). These variables correlated to both MaR and IS (Emax : r2 = 0.25 and r2 = 0.29; Ea /Emax : r2 = 0.36 and r2 = 0.41; SW: r2 = 0.21 and r2 = 0.25). CONCLUSIONS: Noninvasive PV-loops provide physiological information beyond conventional diagnostic variables, such as ejection fraction, early after MI, including measures of contractility, ventriculoarterial coupling, and SW.

Mild hypothermia attenuates ischaemia/reperfusion injury: insights from serial non-invasive pressure-volume loops.

AIMS: Mild hypothermia, 32-35°C, reduces infarct size in experimental studies, potentially mediating reperfusion injuries, but human trials have been ambiguous. To elucidate the cardioprotective mechanisms of mild hypothermia, we analysed cardiac performance in a porcine model of ischaemia/reperfusion, with serial cardiovascular magnetic resonance (CMR) imaging throughout 1 week using non-invasive pressure-volume (PV) loops. METHODS AND RESULTS: Normothermia and Hypothermia group sessions (n = 7 + 7 pigs, non-random allocation) were imaged with Cardiovascular magnetic resonance (CMR) at baseline and subjected to 40 min of normothermic ischaemia by catheter intervention. Thereafter, the Hypothermia group was rapidly cooled (mean 34.5°C) for 5 min before reperfusion. Additional CMR sessions at 2 h, 24 h, and 7 days acquired ventricular volumes and ischaemic injuries (unblinded analysis). Stroke volume (SV: -24%; P = 0.029; Friedmans test) and ejection fraction (EF: -20%; P = 0.068) were notably reduced at 24 h in the Normothermia group compared with baseline. In contrast, the decreases were ameliorated in the Hypothermia group (SV: -6%; P = 0.77; EF: -6%; P = 0.13). Mean arterial pressure remained stable in Normothermic animals (-3%, P = 0.77) but dropped 2 h post-reperfusion in hypothermic animals (-18%, P = 0.007). Both groups experienced a decrease and partial recovery pattern for PV loop-derived variables over 1 week, but the adverse effects tended to attenuate in the Hypothermia group. Infarct sizes were 10 ± 8% in Hypothermic and 15 ± 8% in Normothermic animals (P = 0.32). Analysis of covariance at 24 h indicated that hypothermia has cardioprotective properties incremental to reducing infarct size, such as higher external power (P = 0.061) and lower arterial elastance (P = 0.015). CONCLUSION: Using non-invasive PV loops by CMR, we observed that mild hypothermia at reperfusion alleviates the heart's work after ischaemia/reperfusion injuries during the first week and preserves short-term cardiac performance. This hypothesis-generating study suggests hypothermia to have cardioprotective properties, incremental to reducing infarct size. The primary cardioprotective mechanism was likely an afterload reduction acutely unloading the left ventricle.

Quantitative myocardial perfusion during stress using CMR is impaired in healthy Middle Eastern immigrants without CV risk factors.

Middle Eastern immigrants constitute a growing proportion of the European population and compared to native Swedes are more insulin resistant, which can contribute to atherosclerosis. Quantitative first pass perfusion (qFPP) using cardiovascular magnetic resonance (CMR) can detect early signs of cardiovascular disease (CVD). The aim was to study if myocardial perfusion differs between healthy male Middle Eastern immigrants and native male Swedes. Eighteen Iraqi- and twelve Swedish born controls, all males, never smokers with no CVD risk factors were included. Global myocardial perfusion at rest and stress was assessed using qFPP and by phase-contrast CMR imaging of coronary sinus flow. Quantitative first pass perfusion analysis (mean ± SD) demonstrated no difference at rest between Iraqi and Swedish males (0.8 ± 0.2 vs 1.0 ± 0.4 ml/min/g, P = 0.38) but lower perfusion during adenosine in Iraqi males (2.9 ± 0.7 vs 3.5 ± 0.7 ml/min/g, P = 0.02). Myocardial perfusion assessed by coronary sinus flow demonstrated similar results with no difference in resting perfusion between groups (0.7 ± 0.2 vs 0.8 ± 0.2 ml/min/g, P = 0.21) but a lower perfusion during adenosine in the Iraqi group (3.0 ± 0.2 vs 3.7 ± 0.6 ml/min/g, P = 0.01. Myocardial perfusion during adenosine stress was lower in healthy Iraqi immigrants compared to Swedish controls suggesting impaired microvascular function and risk of underestimating CVD risk in healthy individuals of Middle Eastern origin.

Ventricular longitudinal function by cardiovascular magnetic resonance predicts cardiovascular morbidity in HFrEF patients.

AIMS: Ventricular longitudinal function measured as basal-apical atrioventricular plane displacement (AVPD) or global longitudinal strain (GLS) is a potent predictor of mortality and could potentially be a predictor of heart failure-associated morbidity. We hypothesized that low AVPD and GLS are associated with the combined endpoint of cardiovascular mortality and heart failure-associated morbidity. METHODS AND RESULTS: Two hundred eighty-seven patients (age 62 ± 12 years, 78% male) with heart failure with reduced (≤40%) ejection fraction (HFrEF) referred to a cardiovascular magnetic resonance exam were included. Ventricular longitudinal function, ventricular volume, and myocardial fibrosis or infarction were analysed from cine and late gadolinium enhancement images. National registries provided data on causes of cardiovascular hospitalizations and cardiovascular mortality for the combined endpoint. Time-to-event analysis capable of including reoccurring events was employed with a 5-year follow-up. HFrEF patients had EF 26.5 ± 8.0%, AVPD 7.8 ± 2.4 mm, and GLS -7.5 ± 3.0%. In contrast, ventricular longitudinal function was approximately twice as large in an age-matched control group (AVPD 15.3 ± 1.6 mm; GLS -20.6 ± 2.0%; P < 0.001 for both). There were 578 events in total, and the majority were HF hospitalizations (n = 418). Other major events were revascularizations (n = 64), cardiovascular deaths (n = 40), and myocardial infarctions (n = 21). One hundred fifty-five (54%) patients experienced at least one event (mean 2.0, range 0-64). Of these patients, 119 (71%) had three events or fewer, and the first three events comprised 51% of all events (295 events). Patients in the bottom AVPD or GLS tertile (<6.8 mm or >-6.1%) overall experienced more than 3 times as many events as the top tertile (>8.8 mm or <-8.4%; P < 0.001). Patients in this tertile also faced more cardiovascular deaths (P < 0.05), HF hospitalizations (P = 0.001), myocardial infarctions (only GLS: P = 0.032), and accumulated longer in-hospital length-of-stay overall (AVPD 20.9 vs. 9.1 days; GLS 22.4 vs. 6.5 days; P = 0.001 for both), and from HF hospitalizations (AVPD 19.3 vs. 8.3 days; GLS 19.3 vs. 5.4 days; P = 0.001 for both). In multivariate analysis adjusted for significant covariates, AVPD and GLS remained independent predictors of events (hazard ratio 1.12 per-mm-decrease and 1.13 per-%-increase) alongside hyponatremia (<135 mmol/L), aetiology of HF, and LV end-diastolic volume index. CONCLUSIONS: Low ventricular longitudinal function is associated with an increase in number of events as well as longer in-hospital stay from cardiovascular causes. In addition, AVPD and GLS have independent prognostic value for cardiovascular mortality and morbidity in HFrEF patients.

High ECG Risk-Scores Predict Late Gadolinium Enhancement on Magnetic Resonance Imaging in HCM in the Young.

An ECG risk-score has been described that predicts high risk of subsequent cardiac arrest in young patients with hypertrophic cardiomyopathy (HCM). Myocardial fibrosis measured by cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) also affects prognosis. We assessed whether an ECG risk-score could be used as an indicator of myocardial fibrosis or perfusion deficit on CMR in HCM. In total 42 individuals (7-31 years); 26 HCM patients, seven genotype-positive, phenotype-negative individuals at risk of HCM (first-degree relatives) and nine healthy volunteers, underwent CMR to identify, and grade extent of, myocardial fibrosis and perfusion defect. 12-lead ECG was used for calculating the ECG risk-score (grading 0-14p). High-risk ECG (risk-score > 5p) occurred only in the HCM group (9/26), and the proportion was significantly higher vs mutation carriers combined with healthy volunteers (0/16, p = 0.008). Extent of LGE correlated to the ECG-score (R2 = 0.47, p = 0.001) in sarcomeric mutations. In low-risk ECG-score patients (0-2p), median percent of myocardium showing LGE (LGE%LVM) were: 0% [interquartile range, IQR, 0-0%], in intermediate-risk (3-5p): 5.4% [IQR 0-13.5%] and in high-risk (6-14p): 10.9% [IQR 4.2-12.3%]. ECG-score > 2p had a sensitivity and specificity of 79% and 84% to detect positive LGE on CMR and 77% vs. 75% to detect perfusion defects in sarcomeric mutations carriers. In patients with myocardial fibrosis as identified by LGE, median ECG risk-score was 8p [range 3-10p]. In conclusions, ECG risk-score > 2 p could be used as a cut-off for screening of myocardial fibrosis. Thus ECG risk-score is an inexpensive complementary tool in risk stratification of HCM in the young.

Quantification of left ventricular contribution to stroke work by longitudinal and radial force-length loops.

Left ventricular (LV) stroke work (SW) is calculated from the pressure-volume (PV) loop. PV loops do not contain information on longitudinal and radial pumping, leaving their contributions to SW unknown. A conceptual framework is proposed to derive the longitudinal and radial contributions to SW, using ventricular force-length loops reflecting longitudinal and radial pumping. The aim of this study was to develop and validate this framework experimentally and to explore these contributions in healthy controls and heart failure patients. Thirteen swine underwent cardiovascular magnetic resonance (CMR) and LV pressure catheterization at baseline (n = 7) or 1 wk after myocardial infarction (n = 6). CMR and noninvasive PV loop quantification were performed on 26 human controls and 14 patients. Longitudinal and radial forces were calculated as LV pressure multiplied by the myocardial surface areas in the respective directions. Length components were defined as the atrioventricular plane and epicardial displacements, respectively. Contributions to SW were calculated as the area within the respective force-length loop. Summation of longitudinal and radial SW had excellent agreement with PV loop-derived SW (ICC = 0.95, R = 0.96, bias ± SD = -4.5 ± 5.4%) in swine. Longitudinal and radial contributions to SW were ~50/50% in swine and human controls, and 44/56% in patients. Longitudinal pumping required less work than radial to deliver stroke volume in swine (6.8 ± 0.8 vs. 8.7 ± 1.2 mJ/mL, P = 0.0002) and in humans (11 ± 2.1 vs. 17 ± 4.7 mJ/mL, P < 0.0001). In conclusion, longitudinal and radial pumping contribute ~50/50% to SW in swine and human controls and 44/56% in heart failure patients. Longitudinal pumping is more energy efficient than radial pumping in delivering stroke volume.NEW & NOTEWORTHY A novel method for quantifying the contributions of longitudinal and radial pumping to stroke work using global left ventricular force-length loops was proposed and validated, which can be quantified noninvasively using cardiovascular magnetic resonance and brachial cuff pressure. We found that longitudinal and radial pumping contributes equally to stroke work in controls and 44/56% in heart failure patients, and that the longitudinal pumping is more energy efficient in delivering stroke volume than radial pumping.

S100A9 Links Inflammation and Repair in Myocardial Infarction.

RATIONALE: The alarmin S100A9 has been identified as a potential therapeutic target in myocardial infarction. Short-term S100A9 blockade during the inflammatory phase post-myocardial infarction inhibits systemic and cardiac inflammation and improves cardiac function long term. OBJECTIVE: To evaluate the impact of S100A9 blockade on postischemic cardiac repair. METHODS AND RESULTS: We assessed cardiac function, hematopoietic response, and myeloid phagocyte dynamics in WT (wild type) C57BL/6 mice with permanent coronary artery ligation, treated with the specific S100A9 blocker ABR-238901 for 7 or 21 days. In contrast to the beneficial effects of short-term therapy, extended S100A9 blockade led to progressive deterioration of cardiac function and left ventricle dilation. The treatment reduced the proliferation of Lin-Sca-1+c-Kit+ hematopoietic stem and progenitor cells in the bone marrow and the production of proreparatory CD150+CD48-CCR2+ hematopoietic stem cells. Monocyte trafficking from the spleen to the myocardium and subsequent phenotype switching to reparatory Ly6CloMerTKhi macrophages was also impaired, leading to inefficient efferocytosis, accumulation of apoptotic cardiomyocytes, and a larger myocardial scar. The transcription factor Nur77 (Nr4a1 [nuclear receptor subfamily 4 group A member 1]) mediates the transition from inflammatory Ly6Chi monocytes to reparatory Ly6Clo macrophages. S100A9 upregulated the levels and activity of Nur77 in monocytes and macrophages in vitro and in Ly6Chi/int monocytes in vivo, and S100A9 blockade antagonized these effects. Finally, the presence of reparatory macrophages in the myocardium was also impaired in S100A9-/- mice with permanent myocardial ischemia, leading to depressed cardiac function long term. CONCLUSIONS: We show that S100A9 plays an important role in both the inflammatory and the reparatory immune responses to myocardial infarction. Long-term S100A9 blockade negatively impacts cardiac recovery and counterbalances the beneficial effects of short-term therapy. These results define a therapeutic window targeting the inflammatory phase for optimal effects of S100A9 blockade as potential immunomodulatory treatment in acute myocardial infarction.

Measuring extracellular volume fraction by MRI: First verification of values given by clinical sequences.

PURPOSE: To verify MR measurements of myocardial extracellular volume fraction (ECV) based on clinically applicable T1-mapping sequences against ECV measurements by radioisotope tracer in pigs and to relate the results to those obtained in volunteers. METHODS: Between May 2016 and March 2017, 8 volunteers (25 ± 4 years, 3 female) and 8 pigs (4 female) underwent ECV assessment with SASHA, MOLLI5(3b)3, MOLLI5(3s)3, and MOLLI5s(3s)3s. Myocardial ECV was measured independently in pigs using a radioisotope tracer method. RESULTS: In pigs, ECV in normal myocardium was not different between radioisotope (average ± standard deviation; 19 ± 2%) and SASHA (21 ± 2%; P = 0.086). ECV was higher by MOLLI5(3b)3 (26 ± 2%), MOLLI5(3s)3 (25 ± 2%), and MOLLI5s(3s)3s (25 ± 2%) compared with SASHA or radioisotope (P ≤ 0.001 for all). ECV in volunteers was higher by MOLLI5(3b)3 (26 ± 3%) and MOLLI5(3s)3 (26 ± 3%) than by SASHA (22 ± 3%; P = 0.022 and P = 0.033). No difference was found between MOLLI5s(3s)3s (25 ± 3%) and SASHA (P = 0.225). Native T1 of blood and myocardium as well as postcontrast T1 of myocardium was consistently lower using MOLLI compared with SASHA. ECV increased over time as measured by MOLLI5(3b)3 and MOLLI5(3s)3 for pigs (0.08% and 0.07%/min; P = 0.004 and P = 0.013) and by MOLLI5s(3s)3s for volunteers (0.07%/min; P = 0.032) but did not increase as measured by SASHA. CONCLUSION: Clinically available MOLLI and SASHA techniques can be used to accurately estimate ECV in normal myocardium where MOLLI-sequences show minor overestimation driven by underestimation of postcontrast T1 when compared with SASHA. The timing of imaging after contrast administration affected the measurement of ECV using some variants of the MOLLI sequence.

Comparison of short axis and long axis acquisitions of T1 and extracellular volume mapping using MOLLI and SASHA in patients with myocardial infarction and healthy volunteers.

BACKGROUND: Although previous studies have examined the impact of slice position in volumetric measurements in Cardiovascular Magnetic Resonance (CMR) imaging, very limited data are available today comparing T1 and Extra-Cellular Volume (ECV) measurements from short and long axis acquisitions. The purpose of this study was to investigate the impact of slice position and orientation on T1 and ECV measurements using the MOdified Look-Locker Inversion recovery (MOLLI) and Saturation recovery single-shot acquisition (SASHA) sequence in patients with myocardial infarction and in healthy volunteers. METHODS: Eight (8) healthy volunteers with no medical history and eight (8) patients with myocardial infarction were included in this study. MOLLI and SASHA were utilized and short-axis and long-axis images were acquired. T1 and ECV measurements were performed by drawing same size regions of interest on the myocardium as well in the blood pool at the intersections of the short axis and long axis images. RESULTS: In healthy volunteers, there were no statistically significant differences in native T1 and ECV values between short axis and long axis acquisitions using MOLLI (two-chamber, three-chamber and four-chamber) and SASHA (three-chamber). In patients, there were no statistically significant differences in native T1 and ECV values between short axis and 3-chamber long axis acquisitions in both remote and affected myocardium using MOLLI and SASHA. CONCLUSIONS: Long axis measurements of myocardial T1 and ECV using MOLLI and SASHA exhibit good agreement with the corresponding short axis measurements allowing for fast and reliable myocardial tissue characterization in cases where shortening of the overall imaging acquisition is required.

Ejection fraction in left bundle branch block is disproportionately reduced in relation to amount of myocardial scar.

INTRODUCTION: The relationship between left ventricular (LV) ejection fraction (EF) and LV myocardial scar can identify potentially reversible causes of LV dysfunction. Left bundle branch block (LBBB) alters the electrical and mechanical activation of the LV. We hypothesized that the relationship between LVEF and scar extent is different in LBBB compared to controls. METHODS: We compared the relationship between LVEF and scar burden between patients with LBBB and scar (n = 83), and patients with chronic ischemic heart disease and scar but no electrocardiographic conduction abnormality (controls, n = 90), who had undergone cardiovascular magnetic resonance (CMR) imaging at one of three centers. LVEF (%) was measured in CMR cine images. Scar burden was quantified by CMR late gadolinium enhancement (LGE) and expressed as % of LV mass (%LVM). Maximum possible LVEF (LVEFmax) was defined as the function describing the hypotenuse in the LVEF versus myocardial scar extent scatter plot. Dysfunction index was defined as LVEFmax derived from the control cohort minus the measured LVEF. RESULTS: Compared to controls with scar, LBBB with scar had a lower LVEF (median [interquartile range] 27 [19-38] vs 36 [25-50] %, p < 0.001), smaller scar (4 [1-9] vs 11 [6-20] %LVM, p < 0.001), and greater dysfunction index (39 [30-52] vs 21 [12-35] % points, p < 0.001). CONCLUSIONS: Among LBBB patients referred for CMR, LVEF is disproportionately reduced in relation to the amount of scar. Dyssynchrony in LBBB may thus impair compensation for loss of contractile myocardium.

The ability of the electrocardiogram in left bundle branch block to detect myocardial scar determined by cardiovascular magnetic resonance.

AIMS: We aimed to improve the electrocardiographic 2009 left bundle branch block (LBBB) Selvester QRS score (2009 LBSS) for scar assessment. METHODS: We retrospectively identified 325 LBBB patients with available ECG and cardiovascular magnetic resonance imaging (CMR) with late gadolinium enhancement from four centers (142 [44%] with CMR scar). Forty-four semi-automatically measured ECG variables pre-selected based on the 2009 LBSS yielded one multivariable model for scar detection and another for scar quantification. RESULTS: The 2009 LBSS achieved an area under the curve (AUC) of 0.60 (95% confidence interval 0.54-0.66) for scar detection, and R2 = 0.04, p < 0.001, for scar quantification. Multivariable modeling improved scar detection to AUC 0.72 (0.66-0.77) and scar quantification to R2 = 0.21, p < 0.001. CONCLUSIONS: The 2009 LBSS detects and quantifies myocardial scar with poor accuracy. Improved models with extensive comparison of ECG and CMR had modest performance, indicating limited room for improvement of the 2009 LBSS.

Importance of standardizing timing of hematocrit measurement when using cardiovascular magnetic resonance to calculate myocardial extracellular volume (ECV) based on pre- and post-contrast T1 mapping.

BACKGROUND: Cardiovascular magnetic resonance (CMR) can be used to calculate myocardial extracellular volume fraction (ECV) by relating the longitudinal relaxation rate in blood and myocardium before and after contrast-injection to hematocrit (Hct) in blood. Hematocrit is known to vary with body posture, which could affect the calculations of ECV. The aim of this study was to test the hypothesis that there is a significant increase in calculated ECV values if the Hct is sampled after the CMR examination in supine position compared to when the patient arrives at the MR department. METHODS: Forty-three consecutive patients including various pathologies as well as normal findings were included in the study. Venous blood samples were drawn upon arrival to the MR department and directly after the examination with the patient remaining in supine position. A Modified Look-Locker Inversion recovery (MOLLI) protocol was used to acquire mid-ventricular short-axis images before and after contrast injection from which motion-corrected T1 maps were derived and ECV was calculated. RESULTS: Hematocrit decreased from 44.0 ± 3.7% before to 40.6 ± 4.0% after the CMR examination (p < 0.001). This resulted in a change in calculated ECV from 24.7 ± 3.8% before to 26.2 ± 4.2% after the CMR examination (p < 0.001). All patients decreased in Hct after the CMR examination compared to before except for two patients whose Hct remained the same. CONCLUSION: Variability in CMR-derived myocardial ECV can be reduced by standardizing the timing of Hct measurement relative to the CMR examination. Thus, a standardized acquisition of blood sample for Hct after the CMR examination, when the patient is still in supine position, would increase the precision of ECV measurements.

Cardiovascular Magnetic Resonance to Predict Appropriate Implantable Cardioverter Defibrillator Therapy in Ischemic and Nonischemic Cardiomyopathy Patients Using Late Gadolinium Enhancement Border Zone: Comparison of Four Analysis Methods.

BACKGROUND: Late gadolinium enhancement (LGE) border zone on cardiac magnetic resonance imaging has been proposed as an independent predictor of ventricular arrhythmias. The purpose was to determine whether size and heterogeneity of LGE predict appropriate implantable cardioverter defibrillator (ICD) therapy in ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM) patients and to evaluate 4 LGE border-zone algorithms. METHODS AND RESULTS: ICM and NICM patients who underwent LGE cardiac magnetic resonance imaging prior to ICD implantation were retrospectively included. Two semiautomatic algorithms, expectation maximization, weighted intensity, a priori information and a weighted border zone algorithm, were compared with a modified full-width half-maximum and a 2-3SD threshold-based algorithm (2-3SD). Hazard ratios were calculated per 1% increase in LGE. A total of 74 ICM and 34 NICM were followed for 63 months (1-140) and 52 months (0-133), respectively. ICM patients had 27 appropriate ICD events, and NICM patients had 7 ICD events. In ICM patients with primary prophylactic ICD, LGE border zone predicted ICD therapy in univariable and multivariable analysis measured by the expectation maximization, weighted intensity, a priori information, weighted border zone, and modified full-width half-maximum algorithms (hazard ratios 1.23, 1.22, and 1.05, respectively; P<0.05; negative predictive value 92%). For NICM, total LGE by all 4 methods was the strongest predictor (hazard ratios, 1.03-1.04; P<0.05), though the number of events was small. CONCLUSIONS: Appropriate ICD therapy can be predicted in ICM patients with primary prevention ICD by quantifying the LGE border zone. In NICM patients, total LGE but not LGE border zone had predictive value for ICD therapy. However, the algorithms used affects the predictive value of these measures.

Evaluation of the ECG based Selvester scoring method to estimate myocardial scar burden and predict clinical outcome in patients with left bundle branch block, with comparison to late gadolinium enhancement CMR imaging.

BACKGROUND: Myocardial scar burden quantification is an emerging clinical parameter for risk stratification of sudden cardiac death and prediction of ventricular arrhythmias in patients with left ventricular dysfunction. We investigated the relationships among semiautomated Selvester score burden and late gadolinium enhancement-cardiovascular magnetic resonance (LGE-CMR) assessed scar burden and clinical outcome in patients with underlying heart failure, left bundle branch block (LBBB) and implantable cardioverter-defibrillator (ICD) treatment. METHODS: Selvester QRS scoring was performed on all subjects with ischemic and nonischemic dilated cardiomyopathy at Skåne University Hospital Lund (2002-2013) who had undergone LGE-CMR and 12-lead ECG with strict LBBB pre-ICD implantation. RESULTS: Sixty patients were included; 57% nonischemic dilated cardiomyopathy and 43% ischemic cardiomyopathy with mean left ventricular ejection fraction of 27.6% ± 11.7. All patients had scar by Selvester scoring. Sixty-two percent had scar by LGE-CMR (n = 37). The Spearman correlation coefficient for LGE-CMR and Selvester score derived scar was r = .35 (p = .007). In scar negative LGE-CMR, there was evidence of scar by Selvester scoring in all patients (range 3%-33%, median 15%). Fourteen patients (23%) had an event during the follow-up period; 11 (18%) deaths and six adequate therapies (10%). There was a moderate trend indicating that presence of scar increased the risk of clinical endpoints in the LGE-CMR analysis (p = .045). CONCLUSION: There is a modest correlation between LGE-CMR and Selvester scoring verified myocardial scar. CMR based scar burden is correlated to clinical outcome, but Selvester scoring is not. The Selvester scoring algorithm needs to be further refined in order to be clinically relevant and reliable for detailed scar evaluation in patients with LBBB.

Experimental validation of contrast-enhanced SSFP cine CMR for quantification of myocardium at risk in acute myocardial infarction.

BACKGROUND: Accurate assessment of myocardium at risk (MaR) after acute myocardial infarction (AMI) is necessary when assessing myocardial salvage. Contrast-enhanced steady-state free precession (CE-SSFP) is a recently developed cardiovascular magnetic resonance (CMR) method for assessment of MaR up to 1 week after AMI. Our aim was to validate CE-SSFP for determination of MaR in an experimental porcine model using myocardial perfusion single-photon emission computed tomography (MPS) as a reference standard and to test the stability of MaR-quantification over time after injecting gadolinium-based contrast. METHODS: Eleven pigs were subjected to either 35 or 40 min occlusion of the left anterior descending artery followed by six hours of reperfusion. A technetium-based perfusion tracer was administered intravenously ten minutes before reperfusion. In-vivo and ex-vivo CE-SSFP CMR was performed followed by ex-vivo MPS imaging. MaR was expressed as % of left ventricular mass (LVM). RESULTS: There was good agreement between MaR by ex-vivo CMR and MaR by MPS (bias: 1 ± 3% LVM, r 2 = 0.92, p < 0.001), between ex-vivo and in-vivo CMR (bias 0 ± 2% LVM, r 2 = 0.94, p < 0.001) and between in-vivo CMR and MPS (bias -2 ± 3% LVM, r 2 = 0.87, p < 0.001. No change in MaR was seen over the first 30 min after contrast injection (p = 0.95). CONCLUSIONS: Contrast-enhanced SSFP cine CMR can be used to measure MaR, both in vivo and ex vivo, in a porcine model with good accuracy and precision over the first 30 min after contrast injection. This offers the option to use the less complex ex-vivo imaging when determining myocardial salvage in experimental studies.

A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance: experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) using magnitude inversion recovery (IR) or phase sensitive inversion recovery (PSIR) has become clinical standard for assessment of myocardial infarction (MI). However, there is no clinical standard for quantification of MI even though multiple methods have been proposed. Simple thresholds have yielded varying results and advanced algorithms have only been validated in single center studies. Therefore, the aim of this study was to develop an automatic algorithm for MI quantification in IR and PSIR LGE images and to validate the new algorithm experimentally and compare it to expert delineations in multi-center, multi-vendor patient data. METHODS: The new automatic algorithm, EWA (Expectation Maximization, weighted intensity, a priori information), was implemented using an intensity threshold by Expectation Maximization (EM) and a weighted summation to account for partial volume effects. The EWA algorithm was validated in-vivo against triphenyltetrazolium-chloride (TTC) staining (n = 7 pigs with paired IR and PSIR images) and against ex-vivo high resolution T1-weighted images (n = 23 IR and n = 13 PSIR images). The EWA algorithm was also compared to expert delineation in 124 patients from multi-center, multi-vendor clinical trials 2-6 days following first time ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) (n = 124 IR and n = 49 PSIR images). RESULTS: Infarct size by the EWA algorithm in vivo in pigs showed a bias to ex-vivo TTC of -1 ± 4%LVM (R = 0.84) in IR and -2 ± 3%LVM (R = 0.92) in PSIR images and a bias to ex-vivo T1-weighted images of 0 ± 4%LVM (R = 0.94) in IR and 0 ± 5%LVM (R = 0.79) in PSIR images. In multi-center patient studies, infarct size by the EWA algorithm showed a bias to expert delineation of -2 ± 6 %LVM (R = 0.81) in IR images (n = 124) and 0 ± 5%LVM (R = 0.89) in PSIR images (n = 49). CONCLUSIONS: The EWA algorithm was validated experimentally and in patient data with a low bias in both IR and PSIR LGE images. Thus, the use of EM and a weighted intensity as in the EWA algorithm, may serve as a clinical standard for the quantification of myocardial infarction in LGE CMR images. CLINICAL TRIAL REGISTRATION: CHILL-MI: NCT01379261 . MITOCARE: NCT01374321 .