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PURPOSE: Response to cardiac resynchronization therapy (CRT) is reduced in patients with high left ventricular (LV) scar burden, in particular when scar is located in the LV lateral wall or septum. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can identity scar, but is not feasible in all patients. This study investigates if myocardial metabolism by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contractile function by echocardiographic strain are alternatives to LGE-CMR. METHODS: In a prospective multicenter study, 132 CRT candidates (91% with left bundle branch block) were studied by speckle tracking strain echocardiography, and 53 of these by FDG-PET. Regional myocardial FDG metabolism and peak systolic strain were compared to LGE-CMR as reference method. RESULTS: Reduced FDG metabolism (10% could rule out transmural scar with high sensitivity (80%) and high negative predictive value (96%). Neither FDG-PET nor strain identified septal scars (for both, AUC

Aim The current proof-of-concept study investigates the value of radiomic features from normal 13N-ammonia positron emission tomography (PET) myocardial retention images to identify patients with reduced global myocardial flow reserve (MFR). Methods Data from 100 patients with normal retention 13N-ammonia PET scans were divided into two groups, according to global MFR (i.e., Results A total of 475 radiomic features were extracted per patient. Outcome independent and dependent feature selection resulted in a remainder of 35 features. Discretization at 16 bins (GL16) yielded the highest number of significant predictors of reduced MFR and was chosen for the final analysis. GLRLM_GLNU was the most robust parameter and at a cut-off of 948 yielded an accuracy, sensitivity, specificity, negative and positive predictive value of 67%, 74%, 58%, 64%, and 69%, respectively, to detect diffusely impaired myocardial perfusion. Conclusion A single radiomic feature (GLRLM_GLNU) extracted from visually normal 13N-ammonia PET retention images independently predicts reduced global MFR with moderate accuracy. This concept could potentially be applied to other myocardial perfusion imaging modalities based purely on relative distribution patterns to allow for better detection of diffuse disease.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain. PURPOSE: We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT. METHODS: Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and 18F-fluorodeoxyglucose (FDG) PET within 1 week before CRT implantation. Echocardiography was additionally performed 12 months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent. RESULTS: We evaluated 88 patients (67 ± 10 years, 72% males). 18F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12 months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively. CONCLUSIONS: FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.

As prognosis in sarcoidosis is determined by cardiac involvement, the objective was to study the added value of cardiovascular magnetic resonance (CMR) in risk stratification. In 114 patients (48 ± 12 years/52% male) with biopsy-proven sarcoidosis, we studied the value of clinical and CMR-derived parameters to predict future events, using sustained ventricular tachycardia, ventricular fibrillation, aborted cardiac death, implantable cardioverter-defibrillator (ICD) placement with appropriate shocks, hospitalization for heart failure, and death as composite endpoint. Median follow-up after CMR was 3.1 years (1.1–5.7 years). The ejection fraction (EF) was 58.2 ± 9.1% and 54.7 ± 10.8% for left ventricle (LV) and right ventricle (RV), respectively. LV late gadolinium enhancement (LGE) was present in 40 patients (35%) involving 5.1% of the LV mass (IQR, 3.0–12.0%), with concomitant RV involvement in 12 patients (11%). T2-weighting imaging and/or T2 mapping showed active disease in 14 patients. The composite endpoint was reached in 34 patients, with 7 deaths in the LGE-positive group (17.5%), versus two deaths in the LGE-negative group (2.7%) (p = 0.015). At univariate analysis, RVEF (p = 0.009), pulmonary arterial pressure (p = 0.002), and presence of LGE (p

ObjectiveTo evaluate the impact of a motion-correction (MC) algorithm, applicable post-hoc and not dependent on extended padding, on the image quality and interpretability of coronary computed tomography angiography (CCTA).MethodsNinety consecutive patients undergoing CCTA on a latest-generation 256-slice CT device were prospectively included. CCTA was performed with prospective electrocardiogram-triggering and the shortest possible acquisition window (without padding) at 75% of the R-R-interval. All datasets were reconstructed without and with MC of the coronaries. The latter exploits the minimal padding inherent in cardiac CT scans with this device due to data acquisition also during the short time interval needed for the tube to reach target currents and voltage (“free” multiphase). Two blinded readers independently assessed image quality on a 4-point Likert scale for all segments.ResultsA total of 1,030 coronary segments were evaluated. Application of MC both with automatic and manual coronary centerline tracking resulted in a significant improvement in image quality as compared to the standard reconstruction without MC (mean Likert score 3.67 [3.50;3.81] vs 3.58 [3.40;3.73], P = 0.005, and 3.7 [3.55;3.82] vs 3.58 [3.40;3.73], P < 0.001, respectively). Furthermore, MC significantly reduced the proportion of non-evaluable segments and patients with at least one non-evaluable coronary segment from 2% to as low as 0.3%, and from 14% to as low as 3%. Reduction of motion artifacts was predominantly observed in the right coronary artery.ConclusionsA post-hoc device-specific MC algorithm improves image quality and interpretability of prospectively electrocardiogram-triggered CCTA and reduces the proportion of non-evaluable scans without any additional radiation dose exposure.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation - Flanders (FWO) Introduction Myocardial scar detection with echocardiography in patients with ischemic heart disease typically relies on semi-quantitative evaluation of regional systolic wall thickening. In patients scheduled for cardiac resynchronization therapy (CRT) however, such echo scar estimation is complicated by the presence of dyssynchronous contraction and differential regional remodelling. Visual assessment of myocardial shortening during systole may be an alternative approach. We tested this against cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) in patients without and with conduction delay. Methods 122 patients with ischemic heart disease were included (n = 58 without, and n = 64 with conduction delay). Scar burden of the LV was determined in all patients on a segmental level in both CMR and echo. Reading of echo was blinded for CMR data and vice versa. Myocardial scar was defined as LGE > 50% of transmural thickness. On echo, scar was assessed visually, and defined as thin, echogenic myocardium with no visible shortening during systole. Analysis was performed per segment (18 segment model), and per region (6 walls with basal and mid segment and the apex region consisting of all apical segments). An additional analysis was performed with a tolerance of one adjacent segment in order to account for potential image misalignment between modalities. Results 2196 segments were available for comparison between echo and CMR. On CMR, 548 of those segments were defined as having >50% transmural scar. In echo, 565 segments were detected as having scar. On a segmental level, no difference was found for the correct assignment of segments by echo as having scar or not between patients without or with conduction delay (AUC 0.79 vs. 0.79; p = 0.968) (Figure, top panels). See Figure for sensitivity and specificity. If one segment tolerance was allowed, segments were correctly assigned with equal accuracy in both patient groups (AUC 0.98 vs. 0.96; p = 0.999) (see Figure; w. tolerance). Agreement on the level of LV regions was comparable. 295 regions had a scar on CMR while 286 regions were identified by echo. Echo correctly identified a scar in the same LV wall or apex as compared to CMR similarly in patients without or with conduction delay (AUC 0.79 vs. 0.77; p = 0.698). If one segment tolerance was allowed, correct identification improved further and was not different between both groups (AUC 0.93 vs. 0.91; p = 0.999). The extent of a scar was slightly underestimated (9%) by echocardiography in comparison to CMR in patients without, and slightly overestimated (3%) in patients with conduction delays. Conclusions Scars can be localized on echocardiography with good agreement to CMR-LGE as gold standard. The match between echo and CMR was similar for patients with and without conduction delay. Our findings demonstrate that echo can provide a valid impression of localization and extent of myocardial scar, even in the presence of conduction delays. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Background Diffuse interstitial or myocardial replacement fibrosis are common features of a large variety of cardiomyopathies. These alterations contribute to functional changes, particularly to an increased myocardial stiffness (MS). Histological examination is the gold standard for myocardial fibrosis quantification, however, it requires endomyocardial biopsy which is invasive and not without risks. Cardiac magnetic resonance (CMR) can characterize the extent of both diffuse and replacement fibrosis and may have prognostic value in various cardiomyopathies. Echocardiographic shear wave (SW) elastography is an emerging approach for measuring MS in vivo. SWs occur after mechanical excitation of the myocardium, e.g. after mitral valve closure (MVC), and their propagation velocity is directly related to MS, thus providing an opportunity to assess stiffness at end-diastole. Purpose The aim was to investigate if velocities of natural SW can distinguish between interstitial and replacement fibrosis. Methods We prospectively enrolled 47 patients (22 patients after heart transplant [54.2 ± 15.8 years, 82.6% male] and 25 patients with established hypertrophic cardiomyopathy [54.0 ± 13.5 years, 80.0% male]) undergoing CMR during their check-up. We performed SW elastography in parasternal long axis views of the LV using a fully programmable experimental scanner (HD-PULSE) equipped with a clinical phased array transducer (Samsung Medison P2-5AC) at 1100 ± 250 frames per second. Tissue acceleration maps were extracted from an anatomical M-mode line along the midline of the LV septum. The SW propagation velocity at MVC was measured as the slope in the M-mode image. All patients underwent T1 mapping as well as late gadolinium enhancement (LGE) cardiac magnetic resonance at 1.5 T to assess the presence of diffuse or replacement fibrosis (Figure A). Therefore, patients were divided in three groups: no fibrosis, diffuse fibrosis and replacement fibrosis. Results Mechanical SW’s were observed in 46 subjects starting immediately after MVC and propagating from the LV base to the apex. SW propagation velocity at MVC correlated well with native myocardial T1 values (r = 0.65, p Conclusions Shear wave velocities after mitral valve closure can distinguish between normal and pathological myocardium and can detect differences between diffuse and replacement fibrosis. Abstract Figure.

Funding Acknowledgements The study was supported by Center for Cardiological Innovation Background Many patients referred for cardiac resynchronization therapy (CRT) do not respond to the treatment. Scar either in septum or the left ventricular (LV) lateral wall, as well as global scar burden, influence the outcome negatively. Preoperative scar assessment is therefore recommended in this patient group. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is considered reference standard for scar detection, but is not always available. Purpose To investigate the ability of advanced echocardiographic and nuclear imaging techniques to detect septal and left ventricular (LV) lateral wall scar in patients referred for CRT, compared to late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR). Methods Scar was quantified as percentage segmental LGE in 131 patients (age 66 ± 10, 66% male, QRS-width 164 ± 17ms) referred for CRT, 92% with left bundle branch block (LBBB). Longitudinal strain was assessed by speckle tracking echocardiography in 130 patients (641 septal and 630 LV lateral wall segments). Wall motion score index (WMSI) was assessed visually in all patients by an experienced operator, and graded from one to four. Glucose metabolism was assessed by 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) in 52 patients. Perfusion was assessed in 46 patients by either 13N-ammonia PET (n = 32) or Single Photon Emission Computed Tomography (SPECT) (n = 14). Metabolism and perfusion were reported as percentages of the segment with maximum tracer uptake. The ability of each parameter to identify scar was evaluated with receiver operating characteristic (ROC) curves with calculation of area under the curve (AUC) and 95% confidence interval (CI). AUC≥0.800 was considered reasonable agreement with LGE. Results Scar was present in 574 of total 2090 interpretable segments (79% ischemic etiology). Globally, perfusion (AUC = 0.845, 95% CI 0.777-0.914) and glucose metabolism (AUC = 0.807, 95% CI 0.758-0.855) adequately detected transmural scars, but not smaller scars (all AUC Conclusions Neither echocardiographic nor nuclear imaging techniques can replace LGE-CMR in scar assessment prior to CRT. Septum is especially challenging, explained by LBBB-induced reduction in strain, metabolism and perfusion in this region. Abstract P975 Figure. Detection of transmural septal scar

Background In order to better understand the concept of mechanical dyssynchrony, a promising hallmark of cardiac resynchronization therapy (CRT) response, we investigated its effect on regional myocardial metabolism and myocardial blood flow (MBF) in non-ischemic CRT candidates. Results Thirty consecutive non-ischemic CRT eligible patients underwent static 18F-FDG and resting dynamic 13N-NH3 PET/CT. 18F-FDG uptake and MBF for septal and lateral wall were analysed and septal-to-lateral wall ratios (SLR) were calculated. Based on the presence of mechanical dyssynchrony (septal flash and/or apical rocking) on echocardiography, patients were divided into 2 groups, with (n = 23) and without (n = 7) mechanical dyssynchrony. Patients with mechanical dyssynchrony had significantly lower 18F-FDG SUVmean in the septum compared with the lateral wall (5.58 ± 2.65 vs 11.19 ± 4.10, p 18F-FDG distribution (7.33 ± 2.88 vs 8.31 ± 2.50, respectively, p = 0.30). Similarly, MBF was significantly different between the septal and lateral wall in the dyssynchrony group (0.57 ± 0.11 ml/g/min vs 0.92 ± 0.23 ml/g/min, respectively, p p = 0.16). 18F-FDG SLR, but not MBF SLR, was associated with the presence of mechanical dyssynchrony and showed a significant inverse correlation with volumetric reverse remodeling after CRT (r = − 0.62, p = 0.001). Conclusions Non-ischemic heart failure patients with mechanical dyssynchrony demonstrate heterogeneous regional metabolism and MBF compared with patients without dyssynchrony. However, only 18F-FDG SLR appeared to be highly associated with the presence of mechanical dyssynchrony. Trial registration Clinicaltrials, NCT02537782. Registered 2 September 2015.

Background Myocardial scar is frequently present in patients with heart failure and left bundle branch block (LBBB), and associated with reduced response to cardiac resynchronization therapy (CRT). Furthermore, LBBB may be associated with markedly reduced strain, work, metabolism and perfusion in septum, even without septal ischemia. Therefore, it may be challenging to identify scar by functional imaging methods. Purpose To investigate the ability of advanced echocardiographic and nuclear imaging techniques to detect septal and left ventricular (LV) lateral wall scar in patients referred for CRT, compared to late gadolinium enhancement (LGE) cardiac magnetic resonance. Methods Scar was quantified as percentage LGE in five septal and five LV lateral wall segments of 131 patients (age 66±10, 66% male, QRS-width 164±17ms) referred for CRT, 92% with LBBB. Longitudinal strain was assessed by speckle tracking echocardiography in 130 patients (652 septal and 631 LV lateral wall segments). Myocardial work was calculated by LV pressure-strain analysis. Systolic shortening defined positive work, while systolic lengthening defined negative work. Glucose metabolism was assessed by 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) in 52 patients (260 septal and 260 LV lateral wall segments). Perfusion was assessed in 46 patients (230 septal and 230 LV lateral wall segments) by either 13N-ammonia PET (n=32) or Single Photon Emission Computed Tomography (SPECT) (n=14). Metabolism and perfusion were reported as percentages of the segment with maximum tracer uptake. We evaluated parameter relationship to scar with Spearman correlation (rs) and regression analysis. Results LGE was present in 198 septal (30%) and 136 LV lateral wall (21%) segments. In a multivariate regression model with negative work, metabolism, perfusion and peak strain, only the first three parameters showed a significant association with LGE percent in septum (p In the LV lateral wall, however, negative work did not shown a significant association with percentage LGE in univariate regression analysis (p=0.109). In a multivariate regression model positive work, metabolism and perfusion correlated with percentage LGE (p=0.049, p=0.008 and p Two representative patients Conclusions Septal negative work correlates inversely with septal scar in patients referred for CRT. This finding is probably linked to LBBB, and may be explained by increased stiffness of scar tissue. Myocardial work, but not peak strain, reflects scar in the LV lateral wall. Future studies should explore the assessment of scar in the complete LV and how this relates to CRT response.

Background Sarcoidosis is a multi-organ granulomatous disease of unknown aetiology. Adverse outcome related with cardiac involvement, makes early diagnosis of cardiac sarcoidosis crucial. Case summary In a 55-year-old man presenting with recurrent pulmonary infections, computed tomography (CT) showed several enlarged mediastinal lymph nodes and no lung pathology. Subsequent mediastinoscopy revealed the diagnosis of sarcoidosis. Further screening for organ involvement showed multifocal cardiac involvement both on cardiac magnetic resonance (CMR) and 18-F-fluorodeoxyglucose-positron emission tomography-computed tomography (18F-FDG PET-CT). Because of the lack of functional deterioration and clinical symptoms, no steroid treatment was initiated and regular follow-up of cardiac abnormalities was performed by CMR. Unremarkable progression of cardiac involvement during the first 2 years of follow-up turned into a dramatic involvement after 4 years, with the increase in the number and size of lesions at late gadolinium enhancement (LGE) CMR. Late gadolinium enhancement areas matched the regions of strongly increased 18F-FDG uptake. For the first time, the patient started complaining on shortness of breath, electrocardiography showed an atrioventricular block Grade 1. Cardiac biomarkers and cardiac function were still preserved. Steroid treatment was started. Although an electrophysiology study was negative, Holter monitoring showed ventricular arrhythmia. Cardioverter-defibrillator was implanted. Discussion This case shows the progression of cardiac sarcoidosis on CMR in an asymptomatic untreated patient over a 4-year period, and rises the awareness of possible severe cardiac damage even in the absence of clinical signs of cardiac involvement. Combination of PET and CMR is appealing to better understand the evolution of cardiac sarcoidosis and may help in the management of such patients.

BACKGROUND: Better understanding of pathophysiological changes, induced by left bundle branch block (LBBB), may improve patient selection for cardiac resynchronization therapy (CRT). Therefore, we assessed the effect of LBBB on regional glucose metabolism, 13N-NH3-derived absolute and semiquantitative myocardial blood flow (MBF), and their relation in non-ischemic CRT candidates. METHODS: Twenty-five consecutive non-ischemic patients with LBBB underwent 18F-FDG and resting dynamic 13N-NH3 PET/CT prior to CRT implantation. Regional 18F-FDG uptake, absolute MBF, and late 13N-NH3 uptake were analyzed and corresponding septal-to-lateral wall ratios (SLR) were calculated. Segmental analysis was performed to evaluate "reverse mismatch," "mismatch," and "match" patterns, based on late 13N-NH3/18F-FDG uptake ratios. RESULTS: A significantly lower 18F-FDG uptake was observed in the septum compared to the lateral wall (SLR 0.53 ± 0.17). A similar pattern was observed for MBF (SLR 0.68 ± 0.18), whereas late 13N-NH3 uptake showed a homogeneous distribution (SLR 0.96 ± 0.13). 13N-NH3/18F-FDG "mismatch" and "reverse mismatch" segments were predominantly present in the lateral (52%) and septal wall (61%), respectively. CONCLUSIONS: Non-ischemic CRT candidates with LBBB demonstrate lower glucose uptake and absolute MBF in the septum compared to the lateral wall. However, late static 13N-NH3 uptake showed a homogenous distribution, reflecting a composite measure of altered regional MBF and metabolism, induced by LBBB.

Aims Regional myocardial work may be assessed by pressure–strain analysis using a non-invasive estimate of left ventricular pressure (LVP). Strain by speckle tracking echocardiography (STE) is not always accessible due to poor image quality. This study investigated the estimation of regional myocardial work from strain by feature tracking (FT) cardiac magnetic resonance (CMR) and non-invasive LVP. Methods and results Thirty-seven heart failure patients with reduced ejection fraction, left bundle branch block (LBBB), and no myocardial scar were compared to nine controls without LBBB. Circumferential strain was measured by FT-CMR in a mid-ventricular short-axis cine view, and longitudinal strain by STE. Segmental work was calculated by pressure–strain analysis. Twenty-five patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography. Segmental values were reported as percentages of the segment with maximum myocardial FDG uptake. In LBBB patients, net CMR-derived work was 51 ± 537 (mean ± standard deviation) in septum vs. 1978 ± 1084 mmHg·% in the left ventricular (LV) lateral wall (P Conclusion FT-CMR in combination with non-invasive LVP demonstrated markedly reduced work in septum compared to the LV lateral wall in patients with LBBB. Work distribution correlated with STE-derived work and energy demand as reflected in FDG uptake. These results suggest that FT-CMR in combination with non-invasive LVP is a relevant clinical tool to measure regional myocardial work.

Aims Left ventricular (LV) dilatation results in increased sphericity and affects position and orientation of papillary muscles (PMs), which may influence their performed work. The aim of this study was to assess the contribution of PM to LV function and its changes with dilatation. Methods and results Fifteen sheep were investigated. Ten animals were subjected to 8 weeks of rapid (180 bpm) pacing, inducing LV dilatation. Five animals served as controls. High-resolution gated computed tomography was performed to assess LV volumes, left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), sphericity index, and PM angle, width and fractional shortening. 18F-fluorodeoxyglucose positron emission tomography (PET) was used to measure glucose metabolism as surrogate of regional myocardial work. Spatial resolution of PET images was maximized by electrocardiogram- and respiratory-gating. 18F-fluorodeoxyglucose uptake was measured in PM and compared with remaining left ventricular myocardium (MYO) to obtain a PM/MYO ratio. Animals with dilated heart had a more spherical left ventricle, with reduced LVEF (P

Regional contribution to left ventricular (LV) ejection is of much clinical importance but its assessment is notably challenging. While deformation imaging is often used, this does not take into account loading conditions. Recently, a method for intraventricular pressure estimation was proposed, thus allowing for loading conditions to be taken into account in a non-invasive way. In this work, a method for 3D automatic myocardial performance mapping in echocardiography is proposed by performing 3D myocardial segmentation and tracking, thus giving access to local geometry and strain. This is then used to assess local LV stress-strain relationships which can be seen as a measure of local myocardial work. The proposed method was validated against 18F-fluorodeoxyglucose positron emission tomography, the reference method to clinically assess local metabolism. Averaged over all patients, the mean correlation between FDG-PET and the proposed method was [Formula: see text]. In conclusion, stress-strain loops were, for the first time, estimated from 3D echocardiography and correlated to the clinical gold standard for local metabolism, showing the future potential of real-time 3D echocardiography (RT3DE) for the assessment of local metabolic activity of the heart., European Research Council under the European Union's Seventh Framework Program (HeartMAPAS; FP7/2007–2013/ERC Grant Agreement No. 281748)