Presence Of Myocardial Scar Research Articles

Interplay between strain pattern-based classification of dyssynchrony and myocardial scar in CRT patients

Abstract Introduction Echocardiography-derived septal strain patterns are valuable for predicting volumetric reverse remodelling and survival in patients undergoing cardiac resynchronization therapy (CRT). Nevertheless, presence of myocardial scarring in the left ventricle (LV) is known to attenuate CRT treatment response. Purpose This study aims to investigate the interplay between septal strain patterns and myocardial scarring in CRT candidates, and how they link to outcome after CRT. Methods In this prospective multicentre study, CRT candidates from five European institutions underwent pre-implantation assessments using speckle-tracking strain analysis on echocardiography and cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). Dyssynchrony was graded through analysis of septal strain curves, categorizing patients into five distinct patterns, denoted as strain Stage-0 through strain Stage-4 (Fig. A). LGE of the LV wall was quantitatively assessed using CMR (as a percentage). The study endpoints were volumetric reverse remodelling (volume responder = more than 15% decrease LV end-systolic volume) after one year, and all-time all-cause mortality. Results A total of 267 patients, with a mean age of 66±11 years (69% males, 90% left bundle branch block [LBBB]) presented with an average LV ejection fraction (EF) of 30±7%. With each stepwise increase in strain stage, global LV scarring decreased (p<0.01; Fig. B) and the proportion of volume responders increased (all p<0.0001; Fig. C). ROC curves demonstrated that the predictive power of strain stages for CRT volumetric response was not significantly improved when scarring percentage was added (AUC 0.78 [95% CI: 0.69-0.83] vs. 0.81 [95% CI: 0.71-0.90]; p>0.05; Fig. D). In a multivariate cox regression model – including clinical characteristics that were significantly related to survival in univariate analysis – a patients’ strain stage was the only significant predictor of survival, also outperforming scar burden as determinant of outcome (HR 0.68; p=0.041; Fig. E). Conclusions Septal strain patterns show a strong association with the extent of reverse remodelling and outcome in CRT-treated patients. An inverse relationship is observed between pre-implant strain stages and the extent of myocardial scarring. However, scar burden did not provide incremental predictive value over the strain stages. Strain-pattern-based dyssynchrony assessment is a meaningful predictive marker which integrates information on myocardial dysfunction due to dyssynchrony as well as scar burden.

ECGWiz: a unified and generalizable AI model for comprehensive ECG diagnosis

Abstract Background Deep learning has demonstrated diagnostic performance in electrocardiogram (ECG) analysis comparable to that of clinicians. However, existing models primarily excel in diagnosing common conditions such as arrhythmias and heart blocks, which are easily identifiable using standard predictor variables. Conversely, models aiming to uncover novel insights, such as detecting structural changes or the presence of myocardial scar, often lack generalizability due to insufficient data, model architecture limitations, and other factors. Moreover, these models frequently encounter challenges, such as a decline in performance when applied to external datasets. To address these issues comprehensively, we propose the ECGWiz — a unified model capable of tackling diverse ECG-related problems with consistently high performance. Objective To develop a generalizable Foundation AI model for ECG diagnosis capable of detecting diverse cardiac abnormalities and diseases using few training samples. Methods We utilized publicly available datasets like PTB-XL, CPSC, etc. To build our model, totaling approximately 80,000 ECGs. These 12 lead ECGs are scaled and filtered before using them for training. The AI model is pretrained using Self Supervised Learning and Contrastive Learning strategies. Further, the model undergoes supervised training using a hierarchy of labels that increase in granularity, encompassing arrhythmias, heart blocks, other cardiac abnormalities, heart failure, sudden cardiac death and more. Lastly, the model is prepared for Few-Shot Learning — where the model learns from a minimal set of samples (5 to 10 ECGs) of the target disease. For testing the model, we are using unique datasets like PROSE which consists of non-ischemic cardiomyopathy patients with and without myocardial scaring detected using cardiac MRI imaging at the Johns Hopkins University. Results Our model, trained on a dataset of only 5 ECG recordings, demonstrated a 74% accuracy in identifying myocardial scarring as detected by LGE MRI, utilizing a standard 12-lead ECG. This performance is comparable to that of conventional deep learning methods, which necessitate datasets containing upwards of 120 ECG recordings. Conclusion Our model represents a promising stride in creating a unified and adaptable foundation AI model for comprehensive ECG-based diagnosis. Its capacity to learn from a minimal set of examples signifies a robust framework that can evolve and adapt to new challenges in ECG diagnosis. Ongoing improvements, particularly through dataset expansion, underscore its potential to enhance cardiovascular diagnostics, offering precise and efficient patient care.

Histological evaluation of cardiac remodelling in equine athletes

Approximately 1–2 per 100,000 young athletes die from sudden cardiac death (SCD) and extreme exercise may be associated with myocardial scar and arrhythmias. Racehorses have a high prevalence of atrial fibrillation (AF) and SCD but the presence of myocardial scar and inflammation has not been evaluated. Cardiac tissues from the left (LAA) and right (RAA) atrial appendages, left ventricular anterior (LVAPM) and posterior (LVPPM) papillary muscles, and right side of the interventricular septum (IVS-R) were harvested from racehorses with sudden cardiac death (SCD, n = 16) or other fatal injuries (OFI, n = 17), constituting the athletic group (ATH, n = 33), and compared to sedentary horses (SED, n = 10). Horses in the ATH group had myocyte hypertrophy at all sites; increased fibrosis at all sites other than the LAA; increased fibroblast infiltration but a reduction in the overall extracellular matrix (ECM) volume in the RAA, LVAPM, and IVS-R compared to SED horses. In this horse model, athletic conditioning was associated with myocyte hypertrophy and a reduction in ECM. There was an excess of fibrocyte infiltration and focal fibrosis that was not present in non-athletic horses, raising the possibility of an exercise-induced pro-fibrotic substrate.

Diagnostic values of inferior Q-waves for myocardial scar identification detected by 3.0 T cardiac MRI

While Q-waves in inferior leads, particularly lead III, can be regarded as a minor abnormality, it can also indicate the presence of myocardial scar. This study assessed the diagnostic value of pathologic inferior Q-waves (lead II, III, aVF) for detecting ischemic scars using a high-resolution 3.0 T cardiac magnetic resonance (CMR). We retrospectively analyzed 1692 patients with suspected or known coronary artery disease who underwent stress CMR perfusion or viability assessment. Pathologic Q-waves were defined as duration of ≥ 30 ms and depth of ≥ 1 mm or QS-complex. Eleven models were created to evaluate the presence of Q-waves in different combinations of inferior leads. Of the 1692 patients, 436 (25.8%) had pathologic Q-waves. Models with Q-waves in leads II + aVF (model 7) and II + III + aVF (model 9) showed high specificity (100% and 99.6%), positive predictive value (PPV) (80.0% and 86.7%), and negative predictive value (NPV) (82.6% and 84.3%) but low sensitivity (1.3% and 13.1%). Other models also maintained high specificity and NPV but poor sensitivity and PPV. Notably, 21% of patients with an isolated pathologic Q-wave in lead III (model 4) exhibited scars. These findings highlight the need for careful clinical assessment when pathologic Q-waves are present.

Unrecognized myocardial scar by late-gadolinium-enhancement cardiovascular magnetic resonance: Insights from the population-based Hamburg City Health Study

The presence of myocardial scar is associated with poor prognosis in several underlying diseases. Late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging reveals clinically silent "unrecognized myocardial scar" (UMS), but the etiology of UMS often remains unclear. This population-based CMR study evaluated prevalence, localization, patterns, and risk factors of UMS. The study population consisted of 1064 consecutive Hamburg City Health Study participants without a history of coronary heart disease or myocarditis. UMS was assessed by standard-phase-sensitive-inversion-recovery LGE CMR. Median age was 66 [quartiles 59, 71] years and 37% (388/1064) were females. UMS was detected in 244 (23%) participants. Twenty-five participants (10%) had ischemic, and 217 participants (89%) had non-ischemic scar patterns, predominantly involving the basal inferolateral left-ventricular (LV) myocardium (75%). Two participants (1%) had coincident ischemic and non-ischemic scar. The presence of any UMS was independently associated with LV ejection fraction (odds ratios (OR) per standard deviation (SD) 0.77 (confidence interval (CI) 0.65-0.90), p=0.002) and LV mass (OR per SD 1.54 (CI 1.31-1.82), p<0.001). Ischemic UMS was independently associated with LV ejection fraction (OR per SD 0.58 (CI 0.39-0.86), p=0.007), LV mass (OR per SD 1.74 (CI 1.25-2.45), p=0.001), and diabetes (OR 4.91 (CI 1.66-13.03), p=0.002). Non-ischemic UMS was only independently associated with LV mass (OR per SD 1.44 (CI 1.24-1.69), p<0.001). UMS, in particular with a non-ischemic pattern, is frequent in individuals without known cardiac disease and predominantly involves the basal inferolateral LV myocardium. Presence of UMS is independently associated with a lower LVEF, a higher LV mass, and a history of diabetes.

Reproductive Factors Linked With Myocardial Fibrosis: MESA (Multi-Ethnic Study of Atherosclerosis)

BackgroundRecent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the pathogenic pathways underlying this relationship are unclear. Subclinical myocardial fibrosis has been found to be a common pathway in a large proportion of patients with heart failure with preserved ejection fraction. ObjectivesThis study examined the relationship between vital reproductive factors (parity, pregnancy, age at menopause, and use of hormone replacement therapy [HRT]) with interstitial myocardial fibrosis (IMF) and myocardial scar measured by cardiac magnetic resonance imaging (CMR) T1 mapping and late gadolinium enhancement, respectively. MethodsThere were 596 female participants (mean age 67 ± 8 years) enrolled in MESA (Multi-Ethnic Study of Atherosclerosis) who had complete parity data and underwent CMR. Parity was categorized as 0 live births, 1 to 2, 3 to 4, and ≥5 live births. Multivariable regression models were constructed to assess the associations of parity status, history of null gravidity, age at menopause and HRT with CMR obtained measures of IMF (extracellular volume [ECV], native-T1 time) and myocardial scar. ResultsWomen with a history of nulliparity had greater ECV% (β = 0.95 ± 0.28, P = 0.001) and native-T1 ms (β = 10.6 ± 4.9, P = 0.03) than those who had 1 to 2 live births. These associations were independent of age, traditional cardiovascular risk factors, and interim cardiovascular events. Similar associations were found for women with a history of null gravidity compared to those with a history of pregnancy (ECV% [β = 0.7 ± 0.3, P = 0.02] and native-T1 ms [β = 10.6 ± 5.2, P = 0.04]). There was no association between age at menopause and HRT with markers of IMF. There were no associations between parity status, null gravidity, and age of menopause with the presence of myocardial scar; however, those who used HRT were independently associated with a lesser risk of myocardial scar (OR: 0.20; 95% CI: 0.05-0.82). ConclusionsIn a multiethnic cohort, women with a history of nulliparity or null gravidity had greater IMF defined by CMR, while those who used HRT were less likely to have myocardial scar.

Abstract 12857: Electrocardiographic Findings in Women With Ischemic Sudden Cardiac Death and Anatomic Left Ventricular Hypertrophy

Background: Sudden cardiac death (SCD) is a major mode of death worldwide. Previous SCD studies have shown that left ventricular hypertrophy (LVH) is a risk factor for SCD, especially in the presence of myocardial scarring or ischemia. Due to the lower incidence, women are often underrepresented in SCD studies and therefore, most recognized SCD risk factors are biased towards men. Aim: The aim of this study was to investigate sex-specific ECG findings in subjects with ischemic SCD and LVH. Methods: The study population was derived from the FinGesture study, which has collected all SCD cases from Northern Finland 1998-2017. All SCD cases underwent medicolegal autopsy to determine the cause of death. In the present study, we selected SCD cases with coronary artery disease (CAD) and anatomic LVH at autopsy, of whom antemortem electrocardiogram (ECG) was available for 483 subjects (24.4 % women; 75.6 % men). Antemortem recorded ECGs were obtained from medical records and independently analyzed by two investigators. Results: The prevalence of pathological Q-waves (11.9 % vs. 22.1 %, p = 0.016) and fragmented QRS (fQRS) (43.9 % vs. 56.4 %, p = 0.033) was lower in women compared to men. In addition, women were less likely to have prolonged QTc duration (17.8 % in women vs. 32.3 % in men, p = 0.003). The only ECG finding that appeared as more prevalent in women with anatomic LVH was ECG-LVH by Cornell’s criteria (26.4 % vs. 12.4 %, p = 0.002). The prevalence of having abnormal ECG was slightly lower in women (82.2 %) compared to men (89.2 %), p = 0.054. There were no significant differences between sexes when comparing the prevalence of anatomic LVH in subjects with ECG-LVH and ischemic SCD (90.6 % in women vs. 84.9 % in men, p = 0.524). Conclusions: Except for ECG-LVH by Cornell’s criteria, women with ischemic SCD and anatomic LVH were less likely than men to have ECG findings that are often associated with an increased risk of SCD.

Impact of Cardiac Magnetic Resonance to Arrhythmic Risk Stratification in Nonischemic Cardiomyopathy.

Left ventricular ejection fraction-based arrhythmic risk stratification in nonischemic cardiomyopathy (NICM) is insufficient and has led to the failure of primary prevention implantable cardioverter defibrillator trials, mainly due to the inability of selecting patients at high risk for sudden cardiac death (SCD). Cardiac magnetic resonance offers unique opportunities for tissue characterization and has gained a central role in arrhythmic risk stratification in NICM. The presence of myocardial scar, denoted by late gadolinium enhancement, is a significant, independent, and strong predictor of ventricular arrhythmias and SCD with high negative predictive value. T1 maps and extracellular volume fraction, which are able to quantify diffuse fibrosis, hold promise as complementary tools but need confirmatory results from large studies.

Mechanical dyssynchrony combined with septal scarring reliably identifies responders to cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Research Foundation Flanders (FWO). Background The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodeling after cardiac resynchronization therapy (CRT). In contrast, recent studies suggest that presence of myocardial scarring – particularly in the septal wall – reduces the effect of CRT. Recently, a combined assessment of mechanical dyssynchrony and septal wall scarring has demonstrated high predictive power for CRT response. However, a direct comparison of different markers of mechanical dyssynchrony has not yet been performed. Aim This study: (I) investigated how well a combined assessment of different markers of mechanical dyssynchrony and septal scarring identifies responders to CRT, and (II) evaluated potential differences in predictive power. Methods In a prospective multicentre study in 170 CRT recipients, septal flash (SF) or apical rocking (ApRock), systolic stretch index (SSI) and lateral-to-septal (LW-S) work difference were assessed on echocardiography. SSI was calculated from longitudinal strain traces of the four-chamber view as the sum of the septal systolic stretch and lateral systolic pre-stretch before aortic valve closure. The LW-S work difference was calculated from the regional work of the lateral wall and septal wall - considering the averaged work from the basal- and mid-ventricular segments in the apical four-chamber view. Myocardial scarring of the septum was quantified on cardiac magnetic resonance imaging (CMR) late gadolinium enhancement (LGE) images (n=125 patients), or excluded based on a coronary angiogram and clinical history (n=45 patients). Myocardial scarring was reported regionally as percentage of total amount of scarred tissue per wall. The study’s endpoint was CRT response, defined as ≥15% reduction in LV end-systolic volume 12 months after CRT implantation. AUC’s from ROC curves were used to investigate the predictive power of the different markers for CRT response. Results The AUC’s for the combined assessment of the markers of mechanical dyssynchrony and septal scarring as predictor of CRT-response were 0.86 (95% CI: 0.79–0.91) for presence of SF or ApRock, 0.81 (95% CI: 0.74–0.88) for SSI, and 0.84 (95% CI: 0.76–0.90) for LW-S work difference (all p&amp;lt;0.0001). No significant difference was observed between the different markers of mechanical dyssynchrony (p&amp;gt;0.05 between all). Conclusions The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers demonstrated similar results. Our data demonstrates the importance of assessing LV mechanics and scarring in CRT-candidates, which can easily be achieved in clinical routine.

Machine learning outcome prediction using stress perfusion cardiac magnetic resonance and electronic health records

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Wellcome Trust. Background Stress perfusion cardiac magnetic resonance (SP-CMR) is a well validated and guidelines backed diagnostic test for non-invasive assessment of patients with known or suspected coronary artery disease (CAD)(1). The prognostic value of SP-CMR is enhanced by adding clinical information, however, most electronic health record (EHR) is stored in an unstructured format, therefore limiting access to the information stored when large datasets are concerned. Furthermore, current outcome prediction models rely on linear models, but recent literature has shown stronger prediction using non-linear models (2). Purpose We aimed to address these challenges by using artificial intelligence (AI) tools to extract unstructured data from SP-CMR database and improve outcome prediction. Methods SP-CMR cases from 2011 to 2021 were screened. Data extraction was performed using Cogstack (3), an information retrieval and extraction platform for unstructured data based on natural language processing (NLP). Data were analysed for survival using Log Normal curves. Multivariate analysis was performed using survival Cox model. Different machine learning models were trained to predict survival, and compared using area under the receiver operating characteristic curve (AUC) and the DeLong test. 80% of dataset was used for training and 20% for testing. P value of &amp;lt;0.05 was considered statistically significant. Results 4,188 cases were included in the analysis. Total number of events (deaths) was 252 (6%). Ischaemia on stress perfusion imaging or the presence of myocardial scar on late gadolinium enhancement were significantly associated with events (Logrank p&amp;lt;0.001). Independent predictors from Cox survival analysis used to train machine learning models were: age, chronic kidney disease, hypertension, male gender, smoking, heart failure, positive ischaemic myocardial scar, positive stress perfusion, and ventricular ejection fraction. Considering clinical parameters only, support vector machine survival prediction performed best (AUC 0.76, F1 score 0.24), followed by XGBoost, random forest and ensemble classifier. After adding CMR predictors (stress perfusion, ischaemic myocardial scar, and left ventricular ejection fraction), prediction power improved for all machine learning models, with support vector machine having the best performance (AUC 0.82, F1 score 0.30). After comparing AUCs, non-linear models were better than multilinear regression (p&amp;lt;0.001, Z score −19). Conclusion NLP-based data extraction enables immediate access to unstructured EHR and reveals plausible results, which can be used within an integrated pipeline for data analysis and prediction, and has advantages over structured data due to access to large datasets. Machine learning-based prediction is superior to conventional linear models due to the added ability to model non-linear relationships. CMR predictors improve the survival prediction, compared to clinical variables alone.

QRS Fragmentation in Preserved Ejection Fraction Heart Failure: Functional Insights, Pathological Correlates, and Prognosis.

Background Fragmented QRS (fQRS) morphology as a surrogate marker of the possible presence of myocardial scarring has been shown to confer a higher risk in patients with reduced ejection fraction heart failure. We aimed to investigate the pathophysiological correlates and prognostic implications of fQRS in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We consecutively studied 960 patients with HFpEF (76.4±12.7 years, men: 37.2%). fQRS was assessed using a body surface ECG during hospitalization. QRS morphology was available and classified into 3 categories among 960 subjects with HFpEF as non-fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the 3 fQRS categories, anterior/lateral fQRS showed significantly higher B-type natriuretic peptide/troponin levels (both P<0.001), with both the inferior and anterior/lateral fQRS HFpEF groups demonstrating a higher degree of unfavorable cardiac remodeling, greater extent of myocardial perfusion defect, and slower coronary flow phenomenon (all P<0.05). Patients with anterior/lateral fQRS HFpEF exhibited significantly altered cardiac structure/function and more impaired diastolic indices (all P<0.05). During a median of 657 days follow-up, the presence of anterior/lateral fQRS conferred a doubled HF re-admission risk (adjusted hazard ratio 1.90, P<0.001), with both inferior and anterior/lateral fQRS having a higher risk of cardiovascular and all-cause death (all P<0.05) by using Cox regression models. Conclusions The presence of fQRS in HFpEF was associated with more extensive myocardial perfusion defects and worsened mechanics, which possibly denotes a more severe involvement of cardiac damage. Early recognition in such patients with HFpEF likely benefits from targeted therapeutic interventions.

P26 “FUNCTION FOLLOWS FORM”: THE ROLE OF THE CARDIAC MAGNETIC RESONANCE IN THE ARRHYTHMIC RISK STRATIFICATION IN PATIENTS WITH CARDIAC SARCOIDOSIS

Abstract Background Sarcoidosis is an inflammatory disorder characterized by non–caseating granulomatous infiltration in multiple organs, including the heart. The presence of granulomas within the myocardium can cause heart failure, atrio–ventricular block, ventricular arrhythmias (VA) and sudden cardiac death (SCD). Due to the patchy pattern of sarcoid infiltration, endomyocardial biopsy has a poor sensitivity and cardiac magnetic resonance (CMR) is becoming the gold standard imaging, detecting small area of myocardial fibrosis and scar using late gadolinium enhancement (LGE). The identification of LGE in patients with dilated cardiomyopathy is strongly associated with VA and SCD and similar findings were reported in cardiac sarcoidosis (CS) patients. Methods In order to assess the risk of VA and SCD related to LGE in the CS, we performed a meta–analysis including all the studies enrolling patients with suspected or confirmed CS undergoing CMR. We conducted a digital search in PubMed, Embase, Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Google Scholar from inception through October 2021. Clinical outcomes of interest were arrhythmogenic events defined as VA (ventricular tachycardia or ventricular fibrillation), SCD or aborted SCD (appropriate ICD discharge) during follow–up. Results Eleven studies with a total of 1.123 CS patients (left ventricular ejection function [LVEF]: 59 ± 23%) with an appropriate follow–up were included in the final analysis. Overall, as depicted in the Figure 1, the identification of LGE at CMR was associated with a 13–fold increase risk in potentially lethal VA (R = 12.76, 95% CI [6.30–25.87]) than patients without LGE. Conclusions Our findings suggest that the presence of myocardial scarring as evidenced by the identification of LGE in CMR provides meaningful information about the arrhythmic risk stratification of CS patients.

Myocardial Viability, Functional Status, and Collaterals of Patients With Chronically Occluded Coronary Arteries.

Objective: Viability and functional assessments are recommended for indication and intervention for chronic coronary total occlusion (CTO). We aimed to evaluate myocardial viability and left ventricular (LV) functional status by using cardiovascular magnetic resonance (CMR) and to investigate the relationship between them and collaterals in patients with CTO.Materials and Methods: We enrolled 194 patients with one CTO artery as detected by coronary angiography. Patients were scheduled for CMR within 1 week after coronary angiography.Results: A total of 128 CTO territories (66%) showed scar based on late gadolinium enhancement (LGE) imaging. There were 1,112 segments in CTO territory, while only 198 segments (18%) subtended by the CTO artery showed transmural scar (i.e., >50% extent on LGE). Patients with viable myocardium had higher LV ejection fraction (LVEF) (56.7 ± 13.5% vs. 48.3 ± 15.4%, p < 0.001) than those with transmural scar. Angiographically, well-developed collaterals were found in 164 patients (85%). There was no significant correlation between collaterals and the presence of myocardial scar (p = 0.680) or between collaterals and LVEF (p = 0.191). Nevertheless, more segments with transmural scar were observed in patients with poorly-developed collaterals than in those with well-developed collaterals (25 vs. 17%, p = 0.010).Conclusion: Myocardial infarction detected by CMR is widespread among patients with CTO, yet only a bit of transmural myocardial scar was observed within CTO territory. Limited number of segments with transmural scar is associated with preserved LV function. Well-developed collaterals are not related to the prevalence of myocardial scar or systolic functioning, but could be related to reduce number of non-viable segments subtended by the CTO artery.

Cardiac shear wave elastography can distinguish healthy and scarred myocardium in patients with conduction delays

Abstract Background Cardiac resynchronization therapy (CRT) is an established therapy for patients suffering from heart failure and left bundle branch block (LBBB) conduction delays. Despite its proven beneficial effects, CRT is associated with a high percentage of non-response. Since CRT has shown to be less effective in patients with ischemic cardiomyopathy, determining the presence of myocardial scar before implantation could help to improve the response-rate. However, the gold standard to assess myocardial scar, magnetic resonance imaging (MRI), cannot be used in every patient, due to already implanted devices and/or reduced renal function. Recently introduced shear wave elastography (SWE) allows the non-invasive assessment of myocardial stiffness. Natural shear waves are excited by mitral valve closure (MVC) and travel through the heart with a speed directly related to tissue stiffness. SWE has previously been proven to be able to detect myocardial scar, however this has never been shown in the presence LBBB. Purpose The aim of this study was to evaluate the capability of SWE as a novel method to determine myocardial scar in patients with conduction delays. Methods We included 24 heart failure patients (age: 68±10; 50% males) with ischemic (n=8) and non-ischemic (n=16) cardiomyopathy. The CRT device was set to AAI mode in order to obtain native ventricular conduction. For patients with ischemic cardiomyopathy, the presence and location of scar was determined by MRI or scintigraphy. All ischemic patients had septal scar only. For SWE, left ventricular parasternal long-axis views were acquired with an experimental high frame rate ultrasound scanner (average frame rate: ±1200 Hz). Shear waves were visualized in M-modes of the septum, colour coded for tissue acceleration. The slope of the shear waves in the M-mode represents their propagation speed (Figure A). Results There was no significant difference between the ischemic and non-ischemic patients in QRS width after CRT (149±31 ms vs 144±26 ms), systolic blood pressure blood pressure (135±11 mmHg vs 135±23 mmHg), diastolic blood pressure (74±9 mmHg vs 70±11 mmHg) and heart rate (58±4 bpm vs 63±9 bpm) (all p&amp;gt;0.05). Ejection fraction (33±8% vs 45±10%), end-diastolic volume (196±34 ml vs 129±64 ml) and global longitudinal strain (−9.8±3.1% vs −14.1±4.1%) differed significantly between the groups (all p&amp;lt;0.05). Shear wave speed after MVC was significantly higher in patients with septal scar compared to non-ischemic patients (8.2±1.9 m/s vs 5.5±1.2 m/s; p&amp;lt;0.01) (Figure B). Conclusion In the presence of scar, we found markedly elevated shear wave propagation speed compared to non-ischemic patients. These results indicate that SWE is able to identify scarred myocardium even in patients with LBBB. We therefore believe that SWE could be a novel easy and non-invasive method to evaluate septal myocardial scarring in patients before CRT implantation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWO - Research Foundation Flanders

B-AB03-03 PULSED FIELD ABLATION OF LEFT VENTRICULAR MYOCARDIUM IN A SWINE INFARCT MODEL

Pulsed field ablation (PFA) leads to cell death by irreversible electroporation. However, there is limited data about lesion characteristics in ventricular myocardium in the presence of myocardial scar. To evaluate the lesion characteristics of PFA in healthy and infarcted left ventricular (LV) myocardium. Swine (n=6) underwent 120min LAD balloon occlusion myocardial infarction (MI) and were survived 6-8 weeks. PFA was delivered to the LV endocardium of 1) healthy myocardium or 2) MI identified with electroanatomic mapping. Bipolar, biphasic PFA was delivered for 2.5secs x 4 applications/site (10secs total) using 2 different catheters: a linear quadripolar (FOCAL, 2000-2100V) or multi-spline 8-pole catheter (BASKET, 1800V) (FARAPULSE, Menlo Park, CA) (Figure). After sectioning, gross lesions were identified, measured using calipers and tissue stained for histology. 21 lesions were delivered to healthy LV and 20 to areas with MI, all without complications. Overall, there was no significant difference in lesion depth between groups (FOCAL vs. BASKET; depth: 5.6 ±1.1 mm vs. 5.5 ± 1.1 mm, P=0.740), while lesion width was greater for BASKET (10.6 ± 2.4 mm vs. 13.3 ± 3.3 mm, P=0.007). In regions of MI, histology showed ablation of surviving myocardium both within and epicardial to scar; lesion depth in MI was not significantly different between catheters (5.6 ± 1.5 mm vs. 4.6 ± 0.9 mm; P=0.235). PFA allows rapid, safe, and effective ablation of surviving islands of myocardium within and around infarcted LV substrate. This technology holds promise for treating infarct-related ventricular tachycardia in humans.

Magnetic resonance imaging of dilated cardiomyopathy: prognostic benefit of identifying late gadolinium enhancement in Asian patients.

Risk stratification in dilated cardiomyopathy (DCM) is imprecise, relying largely on echocardiographic left ventricular ejection fraction (LVEF) and severity of heart failure symptoms. Adverse cardiovascular events are increased by the presence of myocardial scarring. Late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging is the gold standard for identifying myocardial scars. We examined the association between LGE on CMR imaging and adverse clinical outcomes during long-term follow-up of Asian patients with DCM. Consecutive patients with DCM undergoing CMR imaging at a single Asian academic medical centre between 2005 and 2015 were recruited. Clinical outcomes were tracked using comprehensive electronic medical records and mortality was determined by cross-linkages with national registries. Presence and distribution of LGE on CMR imaging were determined by investigators blinded to patient outcomes. Primary endpoint was a composite of heart failure hospitalisations, appropriate implantable cardioverter-defibrillator shocks and cardiovascular mortality. Of 86 patients, 64.0% had LGE (80.2% male; mean LVEF 30.1% ± 12.7%). Mid-wall fibrosis (71.7%) was the most common pattern of LGE distribution. Over a mean follow-up period of 4.9 ± 3.2 years, 19 (34.5%) patients with LGE reached the composite endpoint compared to 4 (12.9%) patients without LGE (p = 0.01). Presence of LGE, but not echocardiographic LVEF, independently predicted the primary endpoint (hazard ratio 4.15 [95% confidence interval 1.28-13.50]; p = 0.02). LGE presence independently predicted adverse clinical events in Asian patients with DCM. Routine use of CMR imaging to characterise the myocardial substrate is recommended for enhanced risk stratification and should strongly influence clinical management.

Additional prognostic value of vasodilator stress CMR in patients with inconclusive stress test to detect coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Guidelines recommend performing a non-invasive testing for ischemia to diagnose coronary artery disease (CAD). However, these tests are frequently inconclusive (25%). This population has been poorly studied because of its heterogeneity. In such cases, stress cardiac magnetic resonance (CMR) may be useful to improve diagnostic certainty. To date, no study has evaluated the prognostic value of stress CMR in these patients presenting with prior inconclusive test. PURPOSE To assess the additional prognostic value of vasodilator stress perfusion CMR in patients with a first inconclusive stress test to detect CAD. METHODS Between 2008 and 2018, consecutive patients with inconclusive stress test prospectively referred for vasodilator stress perfusion CMR with dipyridamole were followed for major adverse cardiovascular events (MACE) defined as cardiac death or myocardial infarction. Inconclusive stress test was defined by echocardiography or nuclear stress testing with uncertain conclusion about the diagnosis of CAD. To characterize this population, an unsupervised clustering analysis was performed using 18 variables. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia by stress CMR in each cluster. RESULTS Of 1502 patients with inconclusive stress test (62 ± 12 years, 59% men), 1441 (96%) completed the CMR protocol and 1397(93%) completed the follow-up (median 5.5 ± 2.3 years). Stress CMR was well tolerated without occurrence of death or severe adverse event. The clustering analysis identified 3 clusters: Cluster 1 (n = 524, 35%) had the highest prevalence of previous percutaneous coronary intervention (PCI), the highest presence of myocardial scar on CMR, the lowest LVEF(35 ± 7%) and the highest degree of LV dilatation. Cluster 2 (n = 406, 27%) had the highest prevalence of previous coronary artery bypass grafting (CABG), preserved LVEF(54 ± 10%), absence of LV dilatation and rate of male(89%). Cluster 3 (n = 572, 38%) had the lowest rate of previous PCI/CABG and of myocardial scar. This cluster gathered the oldest patients (73 ± 11 years), predominantly female (60%), with the highest rate of atrial fibrillation and body mass index. Survival analysis found significant differences across clusters for the occurrence of MACE (p = 0.02). Moreover, inducible ischemia was significantly associated with the occurrence of MACE in each cluster (cluster 1, HR 2.28; [95%CI: 1.31-3.99]; p = 0.0028; cluster 2, HR 3.37; [95%CI, 1.97-5.75]; p &amp;lt; 0.0001; cluster 3, HR 2.73; [95%CI, 1.67-4.46]; p &amp;lt; 0.0001). In multivariable Cox regression, inducible ischemia was an independent predictor of a higher incidence of MACE in each cluster (p &amp;lt; 0.001). CONCLUSIONS Cluster analysis identified 3 different phenotypes of patients with inconclusive stress test that were associated with distinct clinical and prognostic profiles. Within these clusters, CMR stress has an additional prognostic value to predict the occurrence of MACE. Abstract Figure. Kaplan-Meier for MACE in each cluster

Myocardial Scar and Mortality in Chronic Aortic Regurgitation.

BackgroundChronic aortic regurgitation (AR) can be associated with myocardial scarring. It is unknown if scarring in AR is linked to poor outcomes and whether aortic valve replacement impacts this association. We investigated the relationship of myocardial scarring to mortality in chronic AR using cardiac magnetic resonance.Methods and ResultsWe enrolled patients with moderate or greater AR between 2009 and 2019 and performed a blinded assessment of left ventricle remodeling, AR severity, and presence and extent of myocardial scarring by late gadolinium enhancement. The primary outcome was all‐cause mortality. We followed 392 patients (median age 62 [interquartile range, 51–71] years), and 78.1% were men, and 25.8% had bicuspid valves. Median aortic valve regurgitant volume was 39 mL (interquartile range, 30–60). Myocardial scar was present in 131 (33.4%) patients. Aortic valve replacement was performed in 165 (49.1%) patients. During follow‐up, up to 10.8 years (median 32.3 months [interquartile range, 9.8–69.5]), 51 patients (13%) died. Presence of myocardial scar (hazard ratio [HR], 3.62; 95% CI, 2.06–6.36; P<0.001), infarction scar (HR, 4.94; 95% CI, 2.58–9.48; P<0.001), and noninfarction scar (HR, 2.75; 95% CI, 1.39–5.44; P<0.004) were associated with mortality. In multivariable analysis, the presence of scar remained independently associated with death (HR, 2.53; 95% CI, 1.15–5.57; P=0.02). Among patients with myocardial scar, aortic valve replacement was independently associated with a lower risk of mortality (HR, 0.34; 95% CI, 0.12–0.97; P=0.03), even after adjustment for confounders.ConclusionsIn aortic regurgitation, myocardial scar is independently associated with a 2.5‐fold increase risk in mortality. Aortic valve replacement was associated with a reduction in risk of mortality in patients with scarring.

Abstract 13471: Additional Prognostic Value of Vasodilator Stress Cardiovascular Magnetic Resonance in Patients With Inconclusive Stress Test to Detect Coronary Artery Disease

Introduction: Non-invasive testing for ischemia to diagnose coronary artery disease(CAD) are frequently inconclusive(25%). Hypothesis: To assess the prognostic value of stress CMR in patients with a first inconclusive stress test. Methods: Between 2008 and 2018, consecutive patients with inconclusive stress test, defined by stress echocardiography or nuclear testing with uncertain conclusion, prospectively referred for stress CMR with dipyridamole were followed for major adverse cardiovascular events(MACE): cardiac death or myocardial infarction. An unsupervised clustering analysis was performed. Results: Of 1502 patients (62±12yrs, 59%men), 1397 completed the follow-up (median 5.5±2.3yrs). Three clusters were identified: Cluster 1 (n=524) had the highest prevalence of previous PCI, the highest presence of a myocardial scar defined, the lowest LVEF (35±7%) and the highest LV dilatation. Cluster 2 (n=406) had the highest previous CABG prevalence, preserved LVEF, absence of LV dilatation, and presence of myocardial scar. This cluster comprised predominantly male patients, with the highest rate of hypertension. Cluster 3 (n=572) had the lowest rate of previous PCI/CABG, the lowest rate of myocardial scar, predominantly female, the highest atrial fibrillation rate and body mass index. Survival analysis found significant differences across clusters for the occurrence of MACE (p=0.02). Inducible ischemia was associated with MACE occurrence in each cluster (C1, HR 2.28; 95%CI[1.31-3.99]; p=0.0028; C2, HR 3.37; 95%CI[1.97-5.75]; p&lt;0.0001; C3, HR 2.73; 95%CI[1.67-4.46]; p&lt;0.0001). In multivariable analysis, inducible ischemia predicted MACE in each cluster (p&lt;0.001 for all). Conclusions: Cluster analysis identified 3 different phenotypes with distinct clinical and prognostic profiles. Within these clusters, stress CMR has an additional prognostic value to predict MACE..

Fibroblast Growth Factor 23 and Long-Term Cardiac Function: The Multi-Ethnic Study of Atherosclerosis.

Although FGF23 (fibroblast growth factor 23) is associated with heart failure and atrial fibrillation, the mechanisms driving these associations are unclear. Sensitive measures of cardiovascular structure and function may provide mechanistic insight behind the associations of FGF23 with various cardiovascular diseases. In MESA (the Multi-Ethnic Study of Atherosclerosis), we evaluated the associations of baseline serum FGF23 (2000-2002) with measures of left ventricular (LV) and left atrial mechanical function on cardiac magnetic resonance at 10-year follow-up (2010-2012). Of 2276 participants with available FGF23 and cardiac magnetic resonance at 10-year follow-up, participants with higher FGF23 levels were more likely White race, taking antihypertensive medications, and had lower kidney function. After covariate adjustment, FGF23 was associated with higher LV mass (β coefficient per 1 SD higher, 1.14 [95% CI, 0.16-2.12], P=0.02), worse LV global circumferential strain (β coefficient per 1 SD higher, 0.15 [95% CI, 0.05-0.25], P=0.003), worse LV midwall circumferential strain (β coefficient per 1 SD higher, 0.20 [95% CI, 0.08-0.31], P=0.001), and lower left atrial total emptying fraction (β coefficient per 1 SD higher, -0.52 [95% CI, -1.02 to -0.02], P=0.04). These associations were consistent across racial/ethnic groups and the spectrum of glomerular filtration rates. FGF23 was not associated with the presence of myocardial scar (odds ratio per 1 SD higher, 1.12 [95% CI, 0.86-1.45], P=0.42). In a multiethnic, community-based cohort, baseline FGF23 levels were independently associated with higher LV mass, lower LV systolic function, and reduced left atrial function over long-term follow-up. These findings provide potential mechanistic insight into associations of FGF23 with incident heart failure and atrial fibrillation.