Scar Burden Research Articles

Pulse-Cancellation Echocardiography for Clinical Evaluation of Myocardial Scar Burden.

Echocardiography has been completely abandoned as far as myocardial tissue characterization is concerned, but recently, the possibility to detect scarred myocardial tissue has been revived. We review the most recent studies aiming to assess the presence of myocardial fibrosis or scar using echocardiography. The use of a simple and clinically available ultrasound, such as method pulse-cancellation, is a promising add-on to standard echocardiography for the detection of scarred myocardial tissue, mostly, but not only, in the setting of post-myocardial infarction patients. Pulse-cancellation technique, available since at least 20 years ago on commercial ultrasound machines, is reasonably accurate to detect myocardial scar tissue caused by recent or prior myocardial infarction, the accuracy varying depending on the spatial distribution of myocardial scars in the left ventricle. Severe myocardial fibers disarray, as found in hypertrophic cardiomyopathy, can also be detected by this ultrasound method.

Acute myocarditis: prognostic role of speckle tracking echocardiography and comparison with cardiac magnetic resonance features.

To evaluate longitudinal systolic function in patients with myocarditis, its correlation with cardiac magnetic resonance (CMR) features, and its predictive value in functional recovery and arrhythmias onset during follow-up (FU) on optimized medical therapy (OMT). Patients with acute myocarditis, confirmed through CMR criteria, and age- and sex-matched healthy controls were enrolled. Two-dimensional (2D) transthoracic echocardiography, including speckle tracking analysis, was performed at admission and after 6months of FU. Patients of myocarditis group also underwent 24h ECG Holter monitoring during FU. 115 patients with myocarditis (mean age 41 ± 17, 70% males) and 70 healthy subjects were enrolled. Global longitudinal strain (GLS) and sub-epicardial strain were markedly lower in the myocarditis group than in controls (mean GLS%: -14.1 ± 5.1 vs -23.1 ± 3.6, p < 0.001). A strong positive correlation between total scar burden (TSB) on CMR and baseline LV GLS was found (r = 0.67, p < 0.0001). GLS improved after 6months of FU in myocarditis on OMT (mean GLS%: -14.1 ± 5.1 vs -16.5 ± 4.8, p < 0.01). By bivariate correlation analysis, baseline LVEF, GLS, and TSB were all associated with LVEF at 6months of FU. Moreover, by multivariable linear regression analysis, these parameters confirmed to be independent predictors of functional recovery at 6months (LVEF β 0.38, p < 0.01; GLS β -0.35, p < 0.01; total scar burden β -0.52, p < 0.0001). Segmental peak systolic strain was significantly different between segments with and without late gadolinium enhancement on CMR (-13.2 ± 3.1% vs -18.1 ± 3.5%, p < 0.001). A segmental strain of - 12% identified scar with a sensitivity of 79% and a specificity of 84% (AUC = 0.91; 95% CI 0.73-0.97; p < 0.001). In addition, baseline LV GLS in myocarditis resulted predictive of non-sustained ventricular tachycardias (cut-off value > -12%; sensitivity84%; specificity74.4%; AUC = 0.75). Parameters of myocardial longitudinal deformation are importantly associated with the presence of a scar on CMR and are predictors of functional outcome and ventricular arrhythmias in patients with acute myocarditis. Their assessment during ultrasound examination should be considered to get more information about the prognosis and risk stratification of this subset of patients.

Classification of Left Atrial Diseased Tissue Burden Determined by Automated Voltage Analysis Predicts Outcomes after Ablation for Atrial Fibrillation.

Background The burden and persistence of atrial fibrillation (AF) have been associated with the presence and extent of left atrial (LA) fibrosis. Recent reports have implicated an association between the extent of LA fibrosis and the outcome of pulmonary vein isolation (PVI). We aimed to analyse the value of an automated scar quantification method in the prediction of success following PVI. Methods One hundred and nine consecutive patients undergoing PVI for paroxysmal or persistent AF were included in our observational study with a 2-year follow-up. Prior to PVI, patients underwent high-definition LA electroanatomical mapping, and scar burden was quantified by automated software (Voltage Histogram Analysis, CARTO 3, Biosense Webster), then classified into 4 subgroups (Dublin Classes I-IV). Recurrence rates were analysed on and off antiarrhythmic drug therapy (AAD), respectively. Results The overall success rate was 74% and 67% off AAD at 1- and 2-year follow-up, respectively. Patients with Dublin Class IV had significantly lower success rates (p = 0.008, off AAD). Dublin Class IV (OR = 2.27, p = 0.022, off AAD) and the presence of arrhythmia in the blanking period (OR = 3.28, p = 0.001, off AAD) were the only significant predictors of recurrence. The use of AAD did not affect these results. Conclusions We propose a classification of low voltage areas based on automated quantification by software during 3D mapping prior to PVI. Patients with high burden of low voltage areas (>31% of <0.5 mV, Dublin Class IV) have a higher risk of recurrence following PVI. Information gathered during electroanatomical mapping may have important prognostic value.

Left ventricular systolic and diastolic dyssynchrony to improve cardiac resynchronization therapy response in heart failure patients with dilated cardiomyopathy

BackgroundThe systolic and diastolic dyssynchrony is physiologically related, but measure different left ventricular mechanisms. Left ventricular systolic mechanical dyssynchrony (systolic LVMD) has shown significant clinical values in improving cardiac resynchronization therapy (CRT) response in the heart failure patients with dilated cardiomyopathy (DCM). Our recent study demonstrated that LV diastolic dyssynchrony (diastolic LVMD) parameters have important prognostic values for DCM patients. However, there are a limited number of studies about the clinical value of diastolic LVMD for CRT. This study aims to explore the predictive values of both systolic LVMD and diastolic LVMD for CRT in DCM patients. MethodsEighty-four consecutive CRT patients with both DCM and complete left bundle branch block (CLBBB) who received gated resting SPECT MPI at baseline were included in the present study. The phase analysis technique was applied on resting gated short-axis SPECT MPI images to measure systolic LVMD and diastolic LVMD, characterized by phase standard deviation (PSD) and phase histogram bandwidth (PBW). CRT response was defined as ≥ 5% improvement of LVEF at 6-month follow-up. Variables with P < 0.10 in the univariate analysis were included in the multivariate cox analysis. ResultsDuring the follow-up period, 59.5% (50 of 84) patients were CRT responders. The univariate cox regression analysis showed that at baseline QRS duration, non-sustained ventricular tachycardia (NS-VT), systolic PSD, systolic PBW, diastolic PSD, diastolic PBW, scar burden and LV lead in the scarred myocardium were statistically significantly associated with CRT response. The multivariate cox regression analysis showed that QRS duration, NS-VT, systolic PSD, systolic PBW, diastolic PSD, and diastolic PBW were independent predictive factors for CRT response. Furthermore, the rate of CRT response was 94.4% (17 of 18) in patients whose LV lead was in the segments with both the first three late contraction and the first three late relaxation; by contrast, the rate of CRT response was only 6.7% (1 of 15, P < 0.000) in patients whose LV lead was in the segments with neither the first three late contraction nor the first three late relaxation. ConclusionBoth systolic LVMD and diastolic LVMD from gated SPECT MPI have important predictive values for CRT response in DCM patients. Pacing at LV segments with both late contraction and late relaxation has potential to increase the CRT response.

Left atrial scar burden in sinus rhythm differs from atrial fibrillation using automated voltage analysis during radiofrequency ablation for atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Scar burden in atrial fibrillation (AF) can be overestimated due to many factors. Scar burden has prognostic value and substrates considered for ablation by some electrophysiologists. We compared left atrial (LA) scar voltage in AF to sinus rhythm (SR) using voltage histogram analysis (VHA) of those undergoing pulmonary vein isolation (PVI) for persistent AF (PeAF). We believe this is the first study analysing LA scar location in SR and AF using VHA. Methods We retrospectively analysed 120 anatomical segments (AS) and whole LA voltages (N= 10 patients, mean age 68 ± 7, 4 females) in SR and AF. Fast anatomical maps (FAM) were grouped into 6 AS in AF and SR: Anterior, Posterior, Roof, Floor, Septal and Lateral AS, which were analysed via VHA (Figure 1) in 10 voltage ranges between 0mV-0.5mV. Total LA area in each voltage aliquot was recorded in SR and AF, taking diseased LA as 0.2-0.5mV and dense LA scar as &amp;lt;0.2mV. The pulmonary veins, mitral annulus and trans-septal puncture sites were excluded from analyses. We included patients over age 18 with PeAF who had de novo PVI with no extra ablation lines, maps with &amp;gt;1000 voltage points in both rhythms and uniform procedure involving initial mapping in AF then remapping in SR after PVI. Statistical analyses conducted with IBM SPSS v.26. Results Total LA scar burden was greater in AF (Mean 142.76 mm², SD ± 138.78mm²) than SR (Mean 109mm², SD ± 107.8mm²), p= &amp;lt;0.0001, Table 1. Scar correlation in SR and AF had a good relationship, R = 0.416 (p= &amp;lt;0.001). Every 1mm² of scar identified during SR yielded a mean of 1.54mm² in AF, (p= &amp;lt;0.001). Conclusions AF was associated with higher scar burden in the Roof, Anterior, Lateral and Posterior AS. Dense LA scar (≤ 0.2mV) on the Posterior AS was significantly higher in AF, while in other AS was comparable to SR. Mapping substrate in AF, especially the posterior wall, may be misleading as scar burden may be overestimated when compared to SR. Table 1Voltage&amp;lt; 0.02 mV (mean area ± SD mm2)0.2-0.5mV (mean area mm2)RhythmSRAFp-valueSRAFp-valueEntire LA115.89 ± 113.61143.41 ± 144.230.02*105.78 ± 103.73144.00 ± 135.24&amp;lt;0.0001*Roof82.72 ± 117.3283.68 ± 113.560.95115 ± 77.14150.61 ± 93.170.01*Anterior131.8 ± 169.53126.5 ± 154.570.85158.53 ± 99.22220.87 ± 173.070.002*Lateral70.5 ± 80.0090.57 ± 117.990.3687.52 ± 66.82137.05 ± 104.990.0002*Septal80.99 ± 89.0380.99 ± 89.030.6899.123 ± 73.62115.37 ± 84.830.18Floor105.1 ± 134.91106.42 ± 148.670.96117.62 ± 85.41151.2 ± 110.070.052Posterior102.14 ± 157.47159.03 ± 194.650.02*138.27 ± 112.28234 ± 150.45&amp;lt;0.0001*LA scar distribution in SR and AF, *denotes significant results.Abstract Figure 1

Myocardial Work, an Echocardiographic Measure of Post Myocardial Infarct Scar on Contrast-Enhanced Cardiac Magnetic Resonance

This study investigates the relation of non-invasive myocardial work and myocardial viability following ST-segment elevation myocardial infarction (STEMI) assessed on late gadolinium contrast enhanced cardiac magnetic resonance (LGE CMR) and characterizes the remote zone using non-invasive myocardial work parameters. STEMI patients who underwent primary percutaneous coronary intervention (PCI) were included. Several non-invasive myocardial work parameters were derived from speckle tracking strain echocardiography and sphygmomanometric blood pressure, e.g.: myocardial work index (MWI), constructive work (CW), wasted work (WW) and myocardial work efficiency (MWE). LGE was quantified to determine infarct transmurality and scar burden. The core zone was defined as the segment with the largest extent of transmural LGE and the remote zone as the diametrically opposed segment without LGE. A total of 53 patients (89% male, mean age 58 ± 9 years) and 689 segments were analyzed. The mean scar burden was 14 ± 7% of the total LV mass, and 76 segments (11%) demonstrated transmural hyperenhancement, 280 (41%) non-transmural hyperenhancement and 333 (48%) no LGE. An inverse relation was observed between segmental MWI, CW and MWE and infarct transmurality (p < 0.05). MWI, CW and MWE were significantly lower in the core zone compared to the remote zone (p<0.05). In conclusion, non-invasive myocardial work parameters may serve as potential markers of segmental myocardial viability in post-STEMI patients who underwent primary PCI. Non-invasive myocardial work can also be utilized to characterize the remote zone, which is an emerging prognostic marker as well as a therapeutic target.

A Retrospective Comparative Functional and Aesthetic Outcome Study of Muscle versus Cutaneous Free Flaps for Distal Upper Extremity Reconstruction.

Function and cosmesis are crucial in upper extremity reconstruction. Yet, there persists a lack of outcome evaluations, particularly regarding differences between free flap types. In a single-center retrospective analysis, outcomes were compared between patients with cutaneous or muscle free flaps for distal upper extremity reconstruction between 2008 and 2018. The Disabilities of Arm, Shoulder and Hand -Score, Michigan-Hand (MHQ), and Short Form 36 Health Survey (SF-36) Questionnaires were assessed, motor function was quantified, and self-reported measures of cosmesis were compared, including the Vancouver Scar-Scale (VSS), MHQ aesthetics-subscale (MAS), and Moscona's cosmetic validation-score (CVS). One-hundred forty-one cases were identified, with a shift toward cutaneous flaps over the study period. Muscle flaps were used for larger defects (251 vs. 142 cm2, p = 0.008). Losses, thromboses, and donor-site complications were equally distributed. Partial necroses were more frequent in muscle flaps (11 vs. 1%, p = 0.015). Seventy patients with 53 cutaneous versus 17 muscle flaps were reexamined. There was no difference in the timing of flap coverage (after 16 vs. 15 days, p = 0.79), number of preceding (2 vs. 1.7, p = 0.95), or subsequent operations (19/53 vs. 5/17, p = 0.77). Patients with cutaneous flaps showed higher grip strength (25 vs. 17 kg, p = 0.046) and reported better hand function (MHQ: 58 vs. 47, p = 0.044) and general health (SF-36: 70 vs. 61, p = 0.040), as well as more favorable appearance (MAS: 71 vs. 57, p = 0.044, CVS: 77 vs. 72, p = 0.048), and scar burden (VSS: 0 vs. 3, p < 0.001). Cutaneous flaps yielded better motor function, self-perceived cosmesis, patient satisfaction, and quality of life in our cohort of distal upper extremity reconstructions.

Cardiac MRI structural and functional predictors of left ventricular ejection fraction recovery following PVC catheter ablation

Frequent premature ventricular contractions (PVCs) can induce cardiomyopathy (PVC CM). We sought to use cardiac magnetic resonance imaging (CMR) to quantify changes in cardiac structure and function of cardiomyopathy patients following catheter ablation for PVCs. Patients undergoing PVC ablation at the Johns Hopkins Hospital with pre-procedural CMR from 2010 to 2018 were included in this study. CMR Images were analyzed to collect information on cardiac structure and function as well as to quantify scar. Of the total 51 included patients, PVC CM (LVEF < 45%) was observed in 51% (n = 29). Of these, 19 had post-ablation ejection fractions quantified, with 78.9% (n = 15) recovering function. Global longitudinal strain was significantly correlated with LVEF (OR 1.831, p < 0.01) but did not predict recovery of function. RV origin of PVCs was more common in the preserved LVEF group but was also significantly correlated with persistently reduced EF post-ablation in the PVC CM group. Scar burden was not correlated with either cardiac function or post-ablation recovery of function. In this cohort, there were no significant CMR findings to predict subsequent recovery of EF after ablation among those with PVC CM. PVC origin in the RV was associated with persistently reduced LVEF after ablation.

Global and regional cardiac dysfunction quantified by 18F-FDG PET scans can predict ventricular arrhythmia in patients with implantable cardioverter defibrillator

BackgroundA low appropriate therapy rate indicates that a minority of patients will benefit from their implantable cardioverter defibrillator (ICD). Quantitative measurements from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) may predict ventricular arrhythmia (VA) occurrence after ICD placement. MethodsWe performed a prospective observational study and recruited patients who required ICD placement. Pre-procedure image scans were performed. Patients were followed up for VA occurrence. Associations between image results and VA were analyzed. ResultsIn 51 patients (33 males, 53.9 ± 17.2 years) analyzed, 17 (33.3%) developed VA. Compared with patients without VA, patients with VA had significantly larger values in scar area (17.7 ± 12.4% vs. 7.0 ± 7.9%), phase standard deviation (51.4° ± 14.0° vs. 34.0° ± 15.0°), bandwidth (172.9° ± 39.8° vs. 128.7° ± 49.9°), sum thickening score (STS, 29.5 ± 11.1 vs. 17.8 ± 13.2), and sum motion score (42.9 ± 11.5 vs. 33.0 ± 19.0). Cox regression analysis and receiver operating characteristic curve analysis showed that scar size, dyssynchrony, and STS were associated with VA occurrence (HR, 4.956, 95% CI 1.70-14.46). ConclusionLarger left ventricular scar burden, increased dyssynchrony, and higher STS quantified by 18F-FDG PET may indicate a higher VA incidence after ICD placement.

Predicting Significant Right Ventricular Failure Post-LVAD Implantation Using CMR Compared to Echocardiography and Right Heart Catheterisation

Purpose Right ventricular failure (RVF) complicates 10-40% of LVAD implants. Significant RVF is associated with increased mortality and reduced chance of being bridged to transplant. It is therefore crucial to identify patients at high risk of RVF using pre-operative investigations. We investigated markers of RV function on pre-LVAD echocardiography (echo), right heart catheterization (RHC) and cardiovascular magnetic resonance imaging (CMR) in predicting significant post-LVAD RVF. Methods We performed a single centre retrospective analysis of 220 patients who underwent LVAD implantation between 2011-18. 33 patients had CMR within 15 months pre-LVAD implantation. CMR was used to derive RV volumes, TAPSE, RV ejection fraction, strain and scar burden. RV function parameters were derived from echo and RHC just prior the LVAD implantation. INTERMACS criteria was used to categorize RVF based on duration of pharmaceutical support (post-implant IV inotropes/vasodilators/inhaled nitrous oxide) - mild ( 14 days). The latter also included the need for RVAD or death due to RVF. Moderate and severe RVF were considered as significant RVF. Results The median age was 49 (IQR 39-56). 31 were males. 18 patients had no/mild RVF; 14 had significant RVF (8 moderate RVF, 6 severe RVF); 1 patient was not categorised due to incomplete data. 29 survived to discharge. Dilated cardiomyopathy was the commonest aetiology of heart failure (17/33) followed by ischaemic heart disease (11/33). Echo derived pulmonary hypertension (42 vs 36mmHg) and proportion of those with tricuspid regurgitation (83.3% vs 92.8%) were not different in the two groups. PVR on RHC was not different between the groups (2.82 vs 3.68 WU). CMR derived volumes, TAPSE (12.2 vs 12.1mm), Global longitudinal strain (-9.1% vs -7.2%) and radial strain (-12.4% vs -10.0%) and the presence of scar were not different between the two groups. CMR-RVEF however was lower in the group significant RVF (23.5 ± 8.2%) when compared to the group with no/mild RVF (31.0 ± 10.7%) (p=0.03). Conclusion When compared to indices from RHC and echo, pre-operative RVEF on CMR is the only marker that differentiated the group who developed significant post-LVAD RVF from the group that did not. A larger study with CMR closer to the time of LVAD implant is needed to validate this.

Myocardial Scar Burden Correlates with NT-proBNP Levels and Changes in Left Ventricular Filling Pressures in Heart Transplant Recipients

Purpose Although myocardial scar burden represents an established prognostic marker in heart failure, its predictive value after heart transplantation (HTX) remains poorly defined. We sought to investigate clinical correlates and prognostic impact of myocardial scar burden in patients after HTX. Methods In a prospective single-center study we enrolled 112 consecutive HTX recipients transplanted between 2010 and 2018. At 1-year after HTX all patients underwent cardiac echo and cardiac magnetic resonance imaging (cMRI). Cardiac echo was repeated again at 2 years after HTX. Patients with a history of primary graft dysfunction, CAV or history of rejection >1R were excluded. Allograft myocardial fibrosis was quantified with late gadolinium enhancement (LGE). Results Extent of myocardial fibrosis was above mean value (2.5%) in 54 patients (48%; Group A) and below mean in 58 patients (52%; Group B). The two groups did not differ in age (56±8 years in Group A vs. 54±11 years in Group B,P=0.10), gender (male: 87% vs. 73%,P=0.25), creatinine (92±19 μmol/L vs. 92±22 μmol/L,P=0.96), troponin (0.01±0.02 μg/L vs. 0.01±0.04 μg/L,P=0.64), tacrolimus trough levels (7.1±1.8 μg/L vs. 7.3±1.6 μg/L,P=0.54), the presence of hypertension (48% vs. 63%,P=0.11) or diabetes (33% vs. 24%,P=0.11). The two groups also had similar rates of pre-transplant LVAD support (11% in Group A vs. 17% in Group B,P=0.33) and comparable allograft ischemic time (185±76 min vs. 199±69 min,P=0.30). On echocardiography we found no differences in LVEF (66.4±8.4% in Group A vs. 66.1±6.8% in Group B,P=0.79), TAPSE (1.57±0.34 cm vs. 1.58±0.38 cm,P=0.80) or E/e’ (10.6±3.9 vs. 11.2±4.1,P=0.42). However, we found significantly higher NT-proBNP levels in Group A than in Group B (median: 693 pg/mL (IQR 210-716) vs. 366 pg/mL (IQR 160-514),P=0.04). At 1 year after cMRI E/e’ increased in Group A, but not in Group B (+2.8±4.9 vs. 0.1±4.9,P=0.004); the same was observed when analyzing changes in NT-proBNP (+93.4±455.9 pg/mL in Group A vs. -12.1±158.2 pg/mL in Group B,P=0.03). Conclusion In HTX recipients myocardial scar burden appears to correlate with serum levels of NT-proBNP. High myocardial scar burden at 1 year post HTX may be associated with subsequent increases in left ventricular filling pressures and could thus serve as a predictor of adverse remodeling of the transplanted allograft.

Strain by speckle tracking echocardiography correlates with electroanatomic scar location and burden in ischaemic cardiomyopathy.

Ventricular tachycardia (VT) in ischaemic cardiomyopathy (ICM) originates from scar, identified as low-voltage areas with invasive high-density electroanatomic mapping (EAM). Abnormal myocardial deformation on speckle tracking strain echocardiography can non-invasively identify scar. We examined if regional and global longitudinal strain (GLS) can localize and quantify low-voltage scar identified with high-density EAM. We recruited 60 patients, 40 ICM patients undergoing VT ablation and 20 patients undergoing ablation for other arrhythmias as controls. All patients underwent an echocardiogram prior to high-density left ventricular (LV) EAM. Endocardial bipolar and unipolar scar location and percentage were correlated with regional and multilayer GLS. Controls had normal GLS and normal bipolar and unipolar voltages. There was a strong correlation between endocardial and mid-myocardial longitudinal strain and endocardial bipolar scar percentage for all 17 LV segments (r = 0.76-0.87, P < 0.001) in ICM patients. Additionally, indices of myocardial contraction heterogeneity, myocardial dispersion (MD), and delta contraction duration (DCD) correlated with bipolar scar percentage. Endocardial and mid-myocardial GLS correlated with total LV bipolar scar percentage (r = 0.83; 0.82, P < 0.001 respectively), whereas epicardial GLS correlated with epicardial bipolar scar percentage (r = 0.78, P < 0.001). Endocardial GLS -9.3% or worse had 93% sensitivity and 82% specificity for predicting endocardial bipolar scar >46% of LV surface area. Multilayer strain analysis demonstrated good linear correlations with low-voltage scar by invasive EAM. Validation studies are needed to establish the utility of strain as a non-invasive tool for quantifying scar location and burden, thereby facilitating mapping and ablation of VT.

Septal scar predicts non-response to cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority Norwegian Health Association Background Scar in the left ventricular (LV) posterolateral wall is associated with poor response to cardiac resynchronization therapy (CRT). The impact of septal scar, however, has been less thoroughly investigated. As recovery of septal function seems to be an important effect of CRT, we hypothesized that CRT response depends on septal viability. Aim The aim of the present study was to investigate the association between septal scar and volumetric response to CRT, and to compare the impact of scar located in septum to scar located in the posterolateral wall. Methods 128 patients with symptomatic heart failure undergoing CRT implantation based on current guidelines (ejection fraction 30 ± 8%, QRS-width 164 ± 17 ms) were included in the study. Volumes and ejection fraction were measured by echocardiography using the biplane Simpson’s method at baseline and six months follow up. Non-response was defined as less than 15% reduction in end-systolic volume. Scar was assessed by late gadolinium enhancement cardiac magnetic resonance, and reported as percentage scar per regional myocardial volume. Numbers are given in [median ;10-90% percentile]. Results Scar was present in 62 patients (48%). Scar burden was equal in septum [0% ;0-34%] and the posterolateral wall [0% ;0-36%], p = 0.10. 31 patients (24%) did not respond to CRT. The non-responders had higher scar burden than the responders in both septum [16% ;0-57% vs 0% ;0-23%, p &amp;lt; 0.001] and the posterolateral wall [6% ;0-74% vs 0% ;0-22%, p &amp;lt; 0.001]. In univariate regression analysis both septal and posterolateral scars correlated with non-response to CRT (r = 0.51 and r = 0.33, respectively). However, combined in a multivariate model only septal scar remained a significant marker of non-response (p &amp;lt; 0.001), while posterolateral scar did not (p = 0.23). Septal scar ≥ 7.1% predicted non-response with a specificity of 81% and a sensitivity of 70% by receiver operating characteristic curve analyses. The area under the curve was 0.79 (95% confidence interval 0.70 – 0.89) (Figure). Conclusions Septal scar is more closely associated with volumetric non-response to CRT than posterolateral scar. Future studies should explore the correlation between regional scar burden and different functional parameters, and how they relate to CRT response. Abstract Figure. Septal scar predicts non-response to CRT

Novel dark-blood versus conventional bright-blood late gadolinium enhancement CMR: A pilot study comparing impact on myocardial ischaemic burden

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background In patients with coronary artery disease (CAD), increasing myocardial ischaemic burden (MIB) is a strong predictor of adverse events. When measured by cardiovascular magnetic resonance (CMR), a MIB ≥12.5% is considered significant and often used as a threshold to guide revascularisation. Ischaemic scar can cause stress perfusion defects which do not represent ischaemia and should be excluded from the MIB calculation. Conventional bright-blood late gadolinium enhancement (LGE) is able to identify ischaemic scar but can suffer from poor scar-to-blood contrast, making accurate assessment of scar volume difficult. Dark-blood LGE methods increase scar-to-blood contrast and improve scar conspicuity which may impact the calculated scar burden and consequently the estimation of MIB when read in conjunction with perfusion images. Purpose To evaluate the impact of dark-blood LGE versus conventional bright-blood LGE on the estimation of MIB in patients with CAD. Methods 37 patients with suspected or known CAD who had evidence of CMR stress perfusion defects and ischaemic scar on LGE imaging were recruited. Patients underwent adenosine stress perfusion imaging followed by dark-blood LGE then conventional bright-blood LGE imaging at 3T. For dark-blood LGE, phase sensitive inversion recovery imaging with a shorter inversion time to null the LV blood-pool was used without any additional magnetization preparation. For each patient, three short-axis LGE slices were selected to match the three perfusion slice locations. Images were anonymised and analysed in random order. Ischaemic scar burden (ISB) was quantified for both LGE methods using a threshold &amp;gt;5 standard deviations above remote myocardium. Perfusion defect burden (PDB) was quantified by manual contouring of perfusion defects. MIB was calculated by subtracting the ISB from the PDB. Results MIB calculated using dark-blood LGE was 19% less compared to bright-blood LGE (15.7 ± 15.2% vs 19.4 ± 15.2%, p &amp;lt; 0.001). There was a strong positive correlation between the two LGE methods (rs = 0.960, p &amp;lt; 0.001, Figure 1A). Bland-Altman analysis revealed a significant fixed bias (mean bias = -3.6%, bias 95% CI: -2.6 to -4.7%, 95% limits of agreement: -9.8 to 2.5%) with no proportional bias (Figure 1B). MIB was calculated ≥12.5% and &amp;lt;12.5% by both LGE methods in 19 (51%) and 12 (32%) patients respectively. In 6 patients (16%), MIB was ≥12.5% using bright-blood LGE and &amp;lt;12.5% using dark-blood LGE (Figure 1A – orange data points). Overall, when used to classify MIB as &amp;lt;12.5% or ≥12.5%, there was only substantial agreement between the two LGE methods (κ=0.67, 95% CI: 0.45 to 0.90). Conclusions The use of dark-blood LGE in conjunction with perfusion imaging results in a lower estimate of MIB compared to conventional bright-blood LGE. This can cause disagreement around the threshold of clinically significant ischaemia which could impact clinical management in patients being considered for coronary revascularisation. Abstract Figure. Linear regression with corresponding B&amp;A

Localizing myocardial scar on echocardiography. How good does it work in the presence of conduction delays?

Abstract 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 &amp;gt; 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 &amp;gt;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.

Local electromechanical alterations determine the left ventricle rotational dynamics in CRT-eligible heart failure patients

Left ventricle, LV wringing wall motion relies on physiological muscle fiber orientation, fibrotic status, and electromechanics (EM). The loss of proper EM activation can lead to rigid-body-type (RBT) LV rotation, which is associated with advanced heart failure (HF) and challenges in resynchronization. To describe the EM coupling and scar tissue burden with respect to rotational patterns observed on the LV in patients with ischemic heart failure with reduced ejection fraction (HFrEF) left bundle branch block (LBBB). Thirty patients with HFrEF/LBBB underwent EM analysis of the left ventricle using an invasive electro-mechanical catheter mapping system (NOGA XP, Biosense Webster). The following parameters were evaluated: rotation angle; rotation velocity; unipolar/bipolar voltage; local activation time, LAT; local electro-mechanical delay, LEMD; total electro-mechanical delay, TEMD. Patients underwent late-gadolinium enhancement cMRI when possible. The different LV rotation pattern served as sole parameter for patients’ grouping into two categories: wringing rotation (Group A, n = 6) and RBT rotation (Group B, n = 24). All parameters were aggregated into a nine segment, three sector and whole LV models, and compared at multiple scales. Segmental statistical analysis in Group B revealed significant inhomogeneities, across the LV, regarding voltage level, scar burdening, and LEMD changes: correlation analysis showed correspondently a loss of synchronization between electrical (LAT) and mechanical activation (TEMD). On contrary, Group A (relatively low number of patients) did not present significant differences in LEMD across LV segments, therefore electrical (LAT) and mechanical (TEMD) activation were well synchronized. Fibrosis burden was in general associated with areas of low voltage. The rotational behavior of LV in HF/LBBB patients is determined by the local alteration of EM coupling. These findings serve as a strong basic groundwork for a hypothesis that EM analysis may predict CRT response.Clinical trial registration: SUM No. KNW/0022/KB1/17/15.

Does Left Ventricular Dyssynchrony by Positron Emission Tomography Predict Ventricular Tachyarrhythmia?

While left ventricular (LV) dyssynchrony and myocardial scar have been associated with ventricular tachyarrhythmia, the utility of these parameters measured by positron emission tomography (PET) is lacking. We investigated the relationship between LV dyssynchrony and myocardial scar burden assessed by PET and ventricular tachyarrhythmia.

Impact of Myocardial Scar on Prognostic Implication of Secondary Mitral Regurgitation in Heart Failure

ObjectivesThe objective of the present study was to use cardiovascular magnetic resonance (CMR) to examine the natural history of secondary MR severity and the implication of left ventricular (LV) scar on its prognostic significance. BackgroundThere is a need for further understanding of the prognostic implication of secondary mitral regurgitation (MR) given the heterogeneous findings of the 2 recent randomized trials on percutaneous mitral intervention in patients with secondary MR. MethodsPatients with heart failure were enrolled into a prospective observational registry between 2008 and 2019. Outcomes were a composite of all-cause death, heart transplantation, or LV assist device implantation at follow-up. CMR was used to quantify the mitral regurgitation volume and mitral regurgitation fraction (MRF) along with scar burden utilizing late gadolinium enhancement. Patients were categorized into 4 subgroups based on presence and tertiles of scar extent: no scar, limited scar (scar burden 1% to 4%), intermediate scar (scar burden 5% to 20%), and extensive scar (scar burden >20%). ResultsAmong patients (n = 441) included in the study (age 59 ± 14 years, 43% with ischemic etiology), 85 (19%) experienced an adverse event. MRF ≥30% was associated with increased risk of events among the study group (hazard ratio: 1.74; 95% confidence interval: 1.10 to 2.76; p = 0.02). When stratified by presence or absence of scar, MRF ≥30% was associated with events only among patients with scar (hazard ratio: 1.67; 95% confidence interval: 1.02 to 2.76; p = 0.04) but not among patients without scar. On further classification of patients with scar, the prognostic significance of secondary MR was observed primarily among patients with intermediate scar burden. ConclusionsThe natural history of secondary MR is complex, and outcomes are affected by severity of MR and vary depending upon the extent of scar. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823)

Association Between Myocardial Scar Burden and Left Ventricular Ejection Fraction in Ischemic Cardiomyopathy.

BackgroundThis study was conducted to assess the relationship between scar burden (extent and severity) and the follow-up left ventricular ejection fraction (LVEF).MethodsPatients were referred for viability assessment with late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging. To measure the transmural extent of LGE in each segment (scar score), we used a five-point scale system. Baseline ejection fraction (EF) and at follow-up were recorded. LVEF classified as non-severe and severely depressed.ResultsThe study included 178 patients (males: 88.8%; mean age: 57.1±10.02 years; mean baseline LVEF: 28.61±10.39). In patients with severe baseline LVEF, the mean scar percentage was higher than that in patients who had non-severe LVEF (38.8±19.41 vs. 24.61±21.21; p˂0.001). On linear regression analysis, aldosterone antagonist and total scar score significantly predicted follow-up ejection fraction (EF) (B=-7.083, p˂0.001 and B=-3.038, p=0.038, respectively). Left anterior descending artery (LAD) territory viability and baseline EF significantly predicted change in EF in patients with LVEF ≤ 35% (B=5.389, p=0.009 and B=-0.581, p˂0.001, respectively). On binary regression analysis for the prediction of at least 5% improvement in EF in patients with baseline EF ≤ 35%, baseline EF and LAD viability were significant (B=-0.15, p=0.014 and B=1.042 and p=0.054, respectively).ConclusionsThe extent of myocardial scar and viability of LAD territory are identified as the important and independent parameters for the predictions of improvement in EF even after adjustment for demographics and baseline EF and following the standards of care medication.

Short-term adverse remodeling progression in asymptomatic aortic stenosis

ObjectivesAortic stenosis (AS) is characterised by a long and variable asymptomatic course. Our objective was to use cardiovascular magnetic resonance imaging (MRI) to assess progression of adverse remodeling in asymptomatic AS.MethodsParticipants from the PRIMID-AS study, a prospective, multi-centre observational study of asymptomatic patients with moderate to severe AS, who remained asymptomatic at 12 months, were invited to undergo a repeat cardiac MRI.ResultsForty-three participants with moderate-severe AS (mean age 64.4 ± 14.8 years, 83.4% male, aortic valve area index 0.54 ± 0.15 cm2/m2) were included. There was small but significant increase in indexed left ventricular (LV) (90.7 ± 22.0 to 94.5 ± 23.1 ml/m2, p = 0.007) and left atrial volumes (52.9 ± 11.3 to 58.6 ± 13.6 ml/m2, p < 0.001), with a decrease in systolic (LV ejection fraction 57.9 ± 4.6 to 55.6 ± 4.1%, p = 0.001) and diastolic (longitudinal diastolic strain rate 1.06 ± 0.2 to 0.99 ± 0.2 1/s, p = 0.026) function, but no overall change in LV mass or mass/volume. Late gadolinium enhancement increased (2.02 to 4.26 g, p < 0.001) but markers of diffuse interstitial fibrosis did not change significantly (extracellular volume index 12.9 [11.4, 17.0] ml/m2 to 13.3 [11.1, 15.1] ml/m2, p = 0.689). There was also a significant increase in the levels of NT-proBNP (43.6 [13.45, 137.08] pg/ml to 53.4 [19.14, 202.20] pg/ml, p = 0.001).ConclusionsThere is progression in cardiac remodeling with increasing scar burden even in asymptomatic AS. Given the lack of reversibility of LGE post-AVR and its association with long-term mortality post-AVR, this suggests the potential need for earlier intervention, before the accumulation of LGE, to improve the long-term outcomes in AS.Key Points• Current guidelines recommend waiting until symptom onset before valve replacement in severe AS.• MRI showed clear progression in cardiac remodeling over 12 months in asymptomatic patients with AS, with near doubling in LGE.• This highlights the need for potentially earlier intervention or better risk stratification in AS.