Non-ischemic Late Gadolinium Enhancement Research Articles

The influence of endurance exercise training on myocardial fibrosis and arrhythmogenesis in a coxsackievirus B3 myocarditis mouse model.

Nonischaemic myocardial fibrosis is associated with cardiac dysfunction, malignant arrhythmias and sudden cardiac death. In the absence of a specific aetiology, its finding as late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging is often attributed to preceding viral myocarditis. Athletes presenting with ventricular arrhythmias often have nonischaemic LGE. Previous studies have demonstrated an adverse effect of exercise on the course of acute viral myocarditis. In this study, we have investigated, for the first time, the impact of endurance training on longer-term outcomes such as myocardial fibrosis and arrhythmogenicity in a murine coxsackievirus B3 (CVB)-induced myocarditis model. Male C57BL/6J mice (n = 72) were randomly assigned to 8weeks of forced treadmill running (EEX) or no exercise (SED). Myocarditis was induced 2weeks later by a single intraperitoneal injection with CVB, versus vehicle in the controls (PBS). In a separate study, mice (n = 30) were subjected to pretraining for 13weeks (preEEX), without continuation of exercise during myocarditis. Overall, continuation of exercise resulted in a milder clinical course of viral disease, with less weight loss and better preserved running capacity. CVB-EEX and preEEX-CVB mice tended to have a lower mortality rate. At sacrifice (i.e. 6weeks after inoculation), the majority of virus was cleared from the heart. Histological assessment demonstrated prominent myocardial inflammatory infiltration and cardiomyocyte loss in both CVB groups. Inflammatory lesions in the CVB-EEX group contained higher numbers of pro-inflammatory cells (iNOS-reactive macrophages and CD8+ T lymphocytes) compared to these in CVB-SED. Treadmill running during myocarditis increased interstitial fibrosis [82.4% (CVB-EEX) vs. 56.3% (CVB-SED); P = 0.049]. Additionally, perivascular and/or interstitial fibrosis with extensive distribution was more likely to occur with exercise [64.7% and 64.7% (CVB-EEX) vs. 50% and 31.3% (CVB-SED); P = 0.048]. There was a numerical, but not significant, increase in the number of scars per cross-section (1.9 vs. 1.2; P = 0.195), with similar scar distribution and histological appearance in CVB-EEX and CVB-SED. In vivo electrophysiology studies did not induce sustained monomorphic ventricular tachycardia, only nonsustained (usually polymorphic) runs. Their cumulative beat count and duration paralleled the increased fibrosis between CVB-EEX and CVB-SED, but the difference was not significant (P = 0.084 for each). Interestingly, in mice that were subjected to pretraining only without continuation of exercise during myocarditis, no differences between pretrained and sedentary mice were observed at sacrifice (i.e. 6weeks after inoculation and training cessation) with regard to myocardial inflammation, fibrosis, and ventricular arrhythmogenicity. In conclusion, endurance exercise during viral myocarditis modulates the inflammatory process with more pro-inflammatory cells and enhances perivascular and interstitial fibrosis development. The impact on ventricular arrhythmogenesis requires further exploration.

European Association of Cardiovascular Imaging (EACVI) survey on Cardiovascular Multimodality Imaging in Acute Myocarditis.

To assess the current role of cardiac imaging in the diagnosis, management, and follow-up of patients with acute myocarditis (AM) through an European Association of Cardiovascular Imaging survey. A total of 412 volunteers from 74 countries responded to the survey. Most participants worked in tertiary centres(56%). All participants had access to echocardiography, while 79% and 75% had access to cardiac computed tomography (CCTA) and cardiac magnetic resonance (CMR), respectively. Less than half(47%) had access to myocardial biopsy and only 5% used this test routinely. CMR was performed within 7 days of presentation in 73% of cases. Non-ischemic late gadolinium enhancement (LGE,88%) and high-signal intensity in T2-weighted images(74%) were the most used diagnostic criteria for AM. CCTA was preferred to coronary angiography by 47% of participants to exclude coronary artery disease. Systematic prescription of beta-blockers and ACEi was reported by 38% and 32% of participants. Around a quarter of participants declared considering LGE burden as a reason to treat. Most participants (90%) reported performing a follow-up echocardiogram, while 63% scheduled a follow-up CMR. The main reason for treatment discontinuation was improvement of left ventricular ejection fraction(89%), followed by LGE regression(60%). In two-thirds of participants the decision to resume high-intensity sport was influenced by residual LGE. This survey confirms the high utilization of cardiac imaging in AM, but reveals major differences in how cardiac imaging is used and how the condition is managed between centres, underlining the need for recommendation statements in this topic.

Low rates of myocardial fibrosis and ventricular arrhythmias in recreational athletes after SARS-CoV-2 infection.

High rates of cardiac involvement were reported in the beginning of the coronavirus disease 2019 (COVID-19) pandemic. This led to anxiety in the athletic population. The current study was set up to assess the prevalence of myocardial fibrosis and ventricular arrhythmias in recreational athletes with the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consecutive adult recreational athletes (≥18 years old, ≥4 h of mixed type or endurance sports/week) underwent systematic cardiac evaluation after a prior confirmed COVID-19 infection. Evaluation included clinical history, electrocardiogram (ECG), 5-day Holter monitoring, and cardiac magnetic resonance (CMR) imaging with simultaneous measurement of high-sensitive cardiac Troponin I. Data from asymptomatic or mildly symptomatic athletes (Group 1) were compared with those with moderate to severe symptoms (Groups 2-3). Furthermore, a comparison with a historical control group of athletes without COVID-19 (Master@Heart) was made. In total, 35 athletes (18 Group 1, 10 female, 36.9 ± 2.2 years, mean 143 ± 20 days following diagnosis) were evaluated. The baseline characteristics for the Group 1 and Groups 2-3 athletes were similar. None of the athletes showed overt myocarditis on CMR based on the updated Lake Louise criteria for diagnosis of myocarditis. The prevalence of non-ischemic late gadolinium enhancement [1 (6%) Group 1 vs. 2 (12%) Groups 2-3; p = 0.603] or ventricular arrhythmias [1 Group 1 athlete showed non-sustained ventricular tachycardia (vs. 0 in Groups 2-3: p = 1.000)] were not statistically different between the groups. When the male athletes were compared with the Master@Heart athletes, again no differences regarding these criteria were found. In our series of recreational athletes with prior confirmed COVID-19, we found no evidence of ongoing myocarditis, and no more detection of fibrosis or ventricular arrhythmias than in a comparable athletic pre-COVID cohort. This points to a much lower cardiac involvement of COVID-19 in athletes than originally suggested.

Histopathological myocardial changes in patients with severe aortic stenosis referred for surgical valve replacement: a cardiac magnetic resonance correlation study.

Myocardial fibrosis (MF) takes part in left ventricular (LV) remodelling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural changes that occur in this transition are not fully enlightened. The aim of this study was to describe histopathological changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR) and to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR). One-hundred fifty-eight patients [73 (68-77) years, 50% women] were referred for surgical AVR because of severe symptomatic AS, with pre-operative CMR (n = 143) with late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction (ECV) quantification. Intra-operative septal EMB was obtained in 129 patients. MF was assessed through Masson's Trichrome histochemistry. Immunohistochemistry was performed for both inflammatory cells and extracellular matrix (ECM) characterization (Type I Collagen, Fibronectin, Tenascin C). Non-ischaemic LGE was present in 106 patients (67.1%) [median fraction: 5.0% (2.0-9.7)]. Native T1 was above normal [1053 ms (1024-1071)] and T2 within the normal range [39.3 ms (37.3-42.0)]. Median MF was 11.9% (6.54-19.97), with predominant type I collagen perivascular distribution (95.3%). Sub-endocardial cardiomyocyte ischaemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodelling expression. MF quantification at EMB was correlated with LGE mass (P = 0.008) but not with global ECV (P = 0.125). Patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischaemic insult. ECM remodelling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR protocols. However, no single CMR parameter captures the burden of MF and histological myocardial changes in this setting.

Risk stratification in patients with structurally normal hearts: Does fibrosis type matter?

The study sought to assess the prognostic significance of nonischemic myocardial fibrosis (MF) on cardiovascular magnetic resonance (CMR)-both macroscopic MF assessed by late gadolinium enhancement (LGE) and diffuse microscopic MF quantified by extracellular volume fraction (ECV)-in patients with structurally normal hearts. The clinical relevance of tissue abnormalities identified by CMR in patients with structurally normal hearts remains unclear. Consecutive patients undergoing CMR were screened for inclusion to identify those with LGE imaging and structurally normal hearts. ECV was calculated in patients with available T1 mapping. The associations between myocardial fibrosis and the outcomes of all-cause mortality, new-onset heart failure [HF], and an arrhythmic outcome were evaluated. In total 525 patients (mean age 43.1±14.2 years; 30.5% males) were included. Over a median follow-up of 5.8 years, 13 (2.5%) patients died and 18 (3.4%) developed new-onset HF. Nonischemic midwall /subepicardial LGE was present in 278 (52.9%) patients; isolated RV insertion fibrosis was present in 80 (15.2%) patients. In 276 patients with available T1 mapping, the mean ECV was 25.5 ± 4.4%. There was no significant association between LGE and all-cause mortality (HR: 1.36, CI: 0.42-4.42, p = 0.61), or new-onset HF (HR: 0.64, CI: 0.25-1.61, p = 0.34). ECV (per 1% increase) correlated with all-cause mortality (HR: 1.19, CI: 1.04-1.36, p = 0.009), but not with new-onset HF (HR: 0.97, CI: 0.86-1.10, p = 0.66). There was no significant association between arrhythmic outcomes and LGE (p = 0.60) or ECV (p = 0.49). In a multivariable model after adjusting for covariates, ECV remained significantly associated with all-cause mortality (HR per 1% increase in ECV: 1.26, CI: 1.06-1.50, p = 0.009). Nonischemic LGE in patients with structurally normal hearts is common and does not appear to be associated with adverse outcomes, whereas elevated ECV is associated with all-cause mortality and may be an important risk stratification tool.

Long-term cardiotoxicity in germ cell cancer survivors after platinum-based chemotherapy: cardiac MR shows impaired systolic function and tissue alterations

ObjectivesLong-term toxicities of germ cell cancer (GCC) treatment are of particular importance in young men with a life expectancy of several decades after curative treatment. This study aimed to investigate the long-term effects of platinum-based chemotherapy on cardiac function and myocardial tissue in GCC survivors by cardiac magnetic resonance (CMR) imaging.MethodsAsymptomatic GCC survivors ≥ 3 years after platinum-based chemotherapy and age-matched healthy controls underwent CMR assessment, including left ventricular (LV) and right ventricular (RV) ejection fraction (EF), strain analysis, late gadolinium enhancement (LGE) imaging, and T1/T2 mapping.ResultsForty-four survivors (age 44 [interquartile range, IQR 37–52] years; follow-up time 10 [IQR 5–15] years after chemotherapy) and 21 controls were evaluated. LV- and RVEF were lower in GCC survivors compared to controls (LVEF 56 ± 5% vs. 59 ± 5%, p = 0.017; RVEF 50 ± 7% vs. 55 ± 7%, p = 0.008). Seven percent (3/44) of survivors showed reduced LVEF (< 50%), and 41% (18/44) showed borderline LVEF (50–54%). The strain analysis revealed significantly reduced deformation compared to controls (LV global longitudinal strain [GLS] -13 ± 2% vs. -15 ± 1%, p < 0.001; RV GLS -15 ± 4% vs. -19 ± 4%, p = 0.005). Tissue characterization revealed focal myocardial fibrosis in 9 survivors (20%) and lower myocardial native T1 times in survivors compared to controls (1202 ± 25 ms vs. 1226 ± 37 ms, p = 0.016). Attenuated LVEF was observed after two cycles of platinum-based chemotherapy (54 ± 5% vs. 62 ± 5%, p < 0.001).ConclusionBased on CMR evaluation, combination chemotherapy with cumulative cisplatin ≥ 200 mg/m2 is associated with attenuated biventricular systolic function and myocardial tissue alterations in asymptomatic long-term GCC survivors.Clinical relevance statementPlatinum-based chemotherapy is associated with decreased systolic function, non-ischemic focal myocardial scar, and decreased T1 times in asymptomatic long-term germ cell cancer survivors. Clinicians should be particularly aware of the risk of cardiac toxicity after platinum-based chemotherapy.Key Points• Platinum-based chemotherapy is associated with attenuation of biventricular systolic function, lower myocardial T1 relaxation times, and non-ischemic late gadolinium enhancement.• Decreased systolic function and non-ischemic late gadolinium enhancement are associated with a cumulative cisplatin dose of ≥ 200 mg/m2.• Cardiac MRI can help to identify chemotherapy-associated changes in cardiac function and tissue in asymptomatic long-term germ cell cancer survivors.Graphical

Myocardial T1 dispersion in fabry disease: comprehensive evaluation of a novel measurement of cardiovascular disease severity

Abstract Background The cardiovascular manifestations of Fabry disease are common and represent the leading cause of death. Myocardial T1 dispersion has recently emerged as a robust predictor of adverse cardiac outcome in Fabry disease but the relationship between T1 dispersion and other cardiovascular manifestations has not been studied. Objective To evaluate the relationship between myocardial T1 dispersion and other cardiovascular manifestations of Fabry disease, and identify its determinants. Methods Prospective longitudinal cohort study including 181 participants with Fabry disease and 30 controls undergoing clinical cardiovascular magnetic resonance. T1 dispersion was assessed in relation to other structural and functional cardiovascular biomarkers and examined in Pre-hypertrophic, Hypertrophic and Fibrotic phenotypic sub-groups. Determinates of T1 dispersion were investigated using multivariable linear regression. Results T1 dispersion was similar in the Control, Pre-hypertrophic and Hypertrophic sub-groups, but was significantly elevated in the Fibrotic sub-group. Independent determinates of T1 dispersion were age, body surface area-indexed left ventricular mass, indexed left ventricular end diastolic volume, global longitudinal strain, native myocardial T1, non-ischaemic late gadolinium enhancement, and extracellular volume fraction (R2 0.414). T1 dispersion was consistently higher in females than males. Conclusions Myocardial T1 dispersion appears sensitive to both the T1 shortening effect of globotriaosylceramide accumulation and T1 lengthening effect of fibrosis, and accordingly increases as Fabry disease progresses. In conjunction with recent data showing it to be a robust predictor of adverse cardiac outcome, myocardial T1 dispersion is advocated as a key cardiovascular biomarker in Fabry disease.Figure 1Figure 2

Abstract 17881: A Predictive Algorithm to Identify Late Gadolinium Enhancement Using Echocardiography

Background: Late gadolinium enhancement (LGE) on cardiac MRI (CMR) correlates with fibrosis and arrhythmic risk, but cannot be used in several clinical settings compared the availability of echocardiography (TTE). Aim: To develop and evaluate a machine learning (ML) model that uses standard clinical and echocardiography (TTE) variables to identify LGE on paired CMR. Methods: Amongst 725 patients (mean age 56.9 ± 16.5 years, 40.3% female) with TTE and CMR within 3 months at our institution, 2018-2023, we derived and tested several ML models (recursive partitioning, random forest, boosted tree, neural networks, LASSO/Elastic Net) to identify LGE on CMR using age and 24 TTE features. Ten-fold cross validation was used for internal validation. Results: A total of 165 (23%) had the presence of LGE (40% ischemic, 60% nonischemic pattern). Of tested models, a boosted neural network performed best (validation area under the curve [AUC] = 0.98; Figure ). In the validation cohort, the algorithm had a sensitivity and specificity of 93.8% and 94.6% for identifying presence of LGE. Accuracy remained high regardless of gender (M vs. F, AUC, 0.987 vs. 0.988) or race (blacks vs. whites, AUC, 0.987 vs. 0.984) and was not related to time between studies (r = -0.06, p = 0.09). Accuracy was better for ischemic LGE (AUC = 0.94) than nonischemic LGE (AUC = 0.90). Left ventricular size, age, fractional shortening, and wall thickness, were amongst the top predictors of LGE presence in the model. Conclusions: In this single center study, a boosted neural network using TTE features identified LGE on paired CMR with high sensitivity and specificity. If confirmed in external data, this suggests possible utility of ML for improving the diagnostic value of TTE for LGE assessment.

Abstract 17726: Nonischemic Cardiomyopathy in Patients With Coronary Artery Disease

Introduction: Randomized trials in obstructive coronary artery disease (CAD) have largely shown no prognostic benefit from revascularization. While there are several potential reasons for the lack of benefit from coronary revascularization, an underexplored possibility is the presence of coexisting nonischemic myocardial pathology. Aim: We aimed to investigate the prevalence and prognostic significance of nonischemic cardiomyopathy (NICM) in CAD. Methods: We studied a large cohort of consecutive patients with obstructive CAD on coronary angiography who had cardiovascular magnetic resonance imaging (CMR) from 2004 to 2020 for clinical indications. CMRs were analyzed for this study for the presence and type of cardiomyopathy. Patients with normal left ventricular ejection fraction and no late gadolinium enhancement (LGE) were classified as having no cardiomyopathy. Ischemic cardiomyopathy (ICM) was defined by ischemic LGE or extensive hibernating myocardium in the absence of LGE. NICM was defined by nonischemic LGE, absence of LGE without hibernating myocardium, or morphological abnormalities of NICM such as left ventricular hypertrophy. The study endpoint was a composite of all-cause death or hospitalization for heart failure. Results: Among 3,027 patients (mean age 65 years, 24% women), 18% had no cardiomyopathy, 65% had only ICM, and 17% had NICM. Of those with NICM, 38% also had ICM (dual cardiomyopathy). At a median follow-up of 4.7 years, 1,112 patients experienced the study endpoint. On Kaplan-Meier analysis, patients with NICM had a higher cumulative incidence of the study endpoint compared with no cardiomyopathy and ICM (log-rank P&lt;0.001 for both comparisons). On multivariable regression analyses, NICM was associated with a greater risk for the study endpoint-hazard ratio (HR) 1.77; 95% confidence interval (CI) 1.43-2.19; P&lt;0.001 compared with no cardiomyopathy and HR 1.27; 95% CI 1.09-1.47; P=0.003 compared with ICM, after adjustment for potential confounders. Conclusions: NICM was identified in 1 in 6 patients with CAD and was associated with worse long-term outcomes compared with no cardiomyopathy and ICM. In patients with obstructive CAD, coexisting NICM may contribute to the lack of prognostic benefit from revascularization.

Myocardial Tissue Characterization in Patients with Hypertensive Crisis, Positive Troponin, and Unobstructed Coronary Arteries: A Cardiovascular Magnetic Resonance-Based Study.

Hypertensive crisis can present with cardiac troponin elevation and unobstructed coronary arteries. We used cardiac magnetic resonance (CMR) imaging to characterize the myocardial tissue in patients with hypertensive crisis, elevated cardiac troponin, and unobstructed coronary arteries. Patients with hypertensive crisis and elevated cardiac troponin with coronary artery stenosis <50% were enrolled. Patients with troponin-negative hypertensive crisis served as controls. All participants underwent CMR imaging at 1.5 Tesla. Imaging biomarkers and tissue characteristics were compared between the groups. There were 19 patients (63% male) with elevated troponin and 24 (33% male) troponin-negative controls. The troponin-positive group was older (57 ± 11 years vs. 47 ± 14 years, p = 0.015). The groups had similar T2-weighted signal intensity ratios and native T1 times. T2 relaxation times were longer in the troponin-positive group, and the difference remained significant after excluding infarct-pattern late gadolinium enhancement (LGE) from the analysis. Extracellular volume (ECV) was higher in the troponin-positive group (25 ± 4 ms vs. 22 ± 3 ms, p = 0.008) and correlated strongly with T2 relaxation time (rs = 0.701, p = 0.022). Late gadolinium enhancement was 32% more prevalent in the troponin-positive group (82% vs. 50%, p = 0.050), with 29% having infarct-pattern LGE. T2 relaxation time was independently associated with troponin positivity (OR 2.1, p = 0.043), and both T2 relaxation time and ECV predicted troponin positivity (C-statistics: 0.71, p = 0.009; and 0.77, p = 0.006). Left ventricular end-diastolic and left atrial volumes were the strongest predictors of troponin positivity (C-statistics: 0.80, p = 0.001; and 0.82, p < 0.001). The increased T2 relaxation time and ECV and their significant correlation in the troponin-positive group suggest myocardial injury with oedema, while the non-ischaemic LGE could be due to myocardial fibrosis or acute necrosis. These CMR imaging biomarkers provide important clinical indices for risk stratification and prognostication in patients with hypertensive crisis.

Cardiac Morphology, Function, and Left Ventricular Geometric Pattern in Patients with Hypertensive Crisis: A Cardiovascular Magnetic Resonance-Based Study.

(1) Background: Altered cardiac morphology and function are associated with increased risks of adverse cardiac events in hypertension. Our study aimed to assess left ventricular (LV) morphology, geometry, and function using cardiovascular magnetic resonance (CMR) imaging in patients with hypertensive crisis. (2) Methods: Patients with hypertensive crisis underwent CMR imaging at 1.5 Tesla to assess cardiac volume, mass, function, and contrasted study. Left ventricular (LV) function and geometry were defined according to the guideline recommendations. Late gadolinium enhancement (LGE) was qualitatively assessed and classified into ischemic and nonischemic patterns. Predictors of LGE was determined using regression analysis. (3) Results: Eighty-two patients with hypertensive crisis (aged 48.5 ± 13.4 years, and 57% males) underwent CMR imaging. Of these patients, seventy-eight percent were hypertensive emergency and twenty-two percent were urgency. Diastolic blood pressure was higher under hypertensive emergency (p = 0.032). Seventy-nine percent (92% of emergency vs. 59% of urgency, respectively; p = 0.003) had left ventricular hypertrophy (LVH). The most prevalent LV geometry was concentric hypertrophy (52%). Asymmetric LVH occurred in 13 (22%) of the participants after excluding ischemic LGE. Impaired systolic function occurred in 46% of patients, and predominantly involved hypertensive emergency. Nonischemic LGE occurred in 75% of contrasted studies (67.2% in emergency versus 44.4% in urgency, respectively; p < 0.001). Creatinine and LV mass were independently associated with nonischemic LGE. (5) Conclusion: LVH, altered geometry, asymmetric LVH, impaired LV systolic function, and LGE are common under hypertensive crisis. LVH and LGE more commonly occurred under hypertensive emergency. Longitudinal studies are required to determine the prognostic implications of asymmetric LVH and LGE in hypertensive crisis.

Impact of Diabetes on Myocardial Fibrosis in Patients With Hypertension: The REMODEL Study.

Compared with patients with hypertension only, those with hypertension and diabetes (HTN/DM) have worse prognosis. We aimed to characterize morphological differences between hypertension and HTN/DM using cardiovascular magnetic resonance; and compare differentially expressed proteins associated with myocardial fibrosis using high throughput multiplex assays. Asymptomatic patients underwent cardiovascular magnetic resonance: 438 patients with hypertension (60±8 years; 59% males) and 167 age- and sex-matched patients with HTN/DM (60±10 years; 64% males). Replacement myocardial fibrosis was defined as nonischemic late gadolinium enhancement on cardiovascular magnetic resonance. Extracellular volume fraction was used as a marker of diffuse myocardial fibrosis. A total of 184 serum proteins (Olink Target Cardiovascular Disease II and III panels) were measured to identify unique signatures associated with myocardial fibrosis in all patients. Despite similar left ventricular mass (P=0.344) and systolic blood pressure (P=0.086), patients with HTN/DM had increased concentricity and worse multidirectional strain (P<0.001 for comparison of all strain measures) compared to hypertension only. Replacement myocardial fibrosis was present in 28% of patients with HTN/DM compared to 16% of those with hypertension (P<0.001). NT-proBNP (N-terminal pro-B-type natriuretic peptide) was the only protein differentially upregulated in hypertension patients with replacement myocardial fibrosis and independently associated with extracellular volume. In patients with HTN/DM, GDF-15 (growth differentiation factor 15) was independently associated with replacement myocardial fibrosis and extracellular volume. Ingenuity Pathway Analysis demonstrated a strong association between increased inflammatory response/immune cell trafficking and myocardial fibrosis in patients with HTN/DM. Adverse cardiac remodeling was observed in patients with HTN/DM. The novel proteomic signatures and associated biological activities of increased immune and inflammatory response may partly explain these observations.

Development of cardiac amyloidosis: potential early indicators from a retrospective longitudinal CMR pilot study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction While early diagnosis and treatment initiation is crucial in cardiac amyloidosis (CA), the diagnosis is currently mostly established in advanced stages of the disease. Cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE) provides excellent sensitivity for the diagnosis of CA. A diffuse subendocardial or transmural LGE pattern independent from coronary perfusion areas is considered characteristic of CA. Purpose While there is a distinct LGE pattern in later stages of CA, CMR characteristics during early stages are not established. In this retrospective study, we sought to identify potential early CMR indicators of CA. Methods Patients undergoing CMR at our center between 2012 and 2022 were retrospectively screened. Those with at least two CMR studies, of which only the latter demonstrated LGE characteristic for CA, were included. All patients underwent CINE and LGE imaging. Results Fifteen patient (80% male; median age 76 [73–79] at first CMR) were included in this analysis. Median time interval between the two CMR studies was 4 years. We observed differences in left ventricular morphology between the initial and follow-up CMR (IVS 15±3 vs. 17±3 mm, p = 0.003; EDV 128±40 vs. 139±39, p = 0.02). LV function was preserved and did not differ between the two CMR (EF 65±10 vs. 62±9 %, p = 0.14). While an LGE pattern characteristic for CA was present in all patients on follow-up CMR, severe left ventricular hypertrophy (IVS &amp;gt;14 mm in 60%), atrial LGE (67%) and focal non-ischemic LGE of the posterolateral basal LV wall (87%) were identified as highly prevalent findings during the initial CMR already. Conclusions Based on these observations, we hypothesize that the combination of certain CMR characteristics (severe septal hypertrophy, atrial LGE and LGE of the basal posterolateral LV) may help to identify CA at an early stage. Prospective studies are needed to further investigate this hypothesis.

The role of T1 mapping and Extracellular Volume (ECV) in predicting cardiac reverse remodelling and response to Heart Failure with reduced Ejection Fraction (HFrEF) therapy

Abstract Funding Acknowledgements Type of funding sources: None. Background Adverse cardiac remodelling results from an insult such as myocardial infarction, or as seen in Heart Failure (HF), maladaptive neurohormonal activation. Reverse remodelling describes improvement in cardiac geometry; the left ventricle (LV) recovers more normal structure with improved function and prognosis. Cardiovascular Magnetic Resonance imaging (CMR) allows gold standard assessment of LV volumes and function, diffuse and focal fibrosis and estimation of extracellular volume (ECV) by T1 mapping. Purpose Elevated T1 and ECV values are associated with worse outcome in many cardiac conditions. We conducted the first prospective study to investigate whether T1 mapping and ECV can predict cardiac reverse remodelling in response to treatment, in a cohort of patients hospitalised with a new HF diagnosis. Methods This was a single centre observational study. Inclusion criteria were admission with new HF, LVEF ≤50% or elevated NTproBNP and being treated with intravenous furosemide. Only patients with Heart Failure with reduced Ejection Fraction (HFrEF) and EF &amp;lt;40% on baseline echocardiography were included in this analysis. 36 consecutive eligible participants were included and had both echocardiogram and CMR studies to establish anatomy, function, and myocardial tissue characteristics at baseline. Participants were treated according to international HF guidelines and underwent reviews and repeat echocardiography at 6, 12–18 and 24–30 months. "Responders" to guideline directed HFrEF therapy were defined as those who had an increase in LVEF of ≥10% to a value of ≥40% between their baseline and latest follow-up echocardiogram. Baseline CMR volumes, function, presence of Late Gadolinium Enhancement (LGE), septal and whole heart T1 and ECV values were compared between responder and non-responder groups. Results Median follow-up was 26 months. 27 (75%) participants were responders to therapy. There were no differences in baseline characteristics between groups. There was high uptake of HFrEF medical therapy in both groups. (Table 1) There was no significant difference found between septal or whole heart T1 or ECV values between responder and non-responder groups. There was a trend towards lower whole heart ECV values (29% vs. 35%; p = 0.06) in the responder group but this did not reach statistical significance. (Figure 1) Overall, there was no difference in rates of LGE presence between groups but there was a significantly higher proportion of participants with non-ischaemic LGE pattern in the responder group compared to non-responder group (48% vs 11%; p = 0.05). Conclusions In this cohort of patients hospitalised with a new HFrEF diagnosis, the majority demonstrated reverse remodelling in response to therapy by 26 months. Whole heart ECV (%) as a surrogate marker for fibrosis calculated by whole heart T1 mapping may play a role in understanding which patients are likely to respond to HF therapy but further larger studies are required.

Cardiac remodeling after tricuspid transcatheter edge-to-edge repair: From the right to the left ventricle

The management of isolated functional tricuspid regurgitation (TR) is under ongoing investigations as recent interventional breakthrough, such as transcatheter edge-to-edge repair (TEER). We aimed to assess whether and how such device would affect right and left reverse remodeling over time. This is a monocentric, prospective cohort of 10 consecutive patients treated by TEER between 2019 and 2022 who underwent successive cardiac magnetic resonance. Clinical and echocardiographic follow-up was performed up to 12 months after intervention. Overall patients were 81 [IQR: 77.5; 84.0] years old and 6 (60%) were women. TTE derived TR was reduced to stage moderate or less in 80% patients (n = 8) at discharge (P < 0.001) and in 77% (n = 7) at 1 year (P < 0.001) compared with 0% at baseline. CMR-derived Left ventricular ejection fraction (LVEF) and left cardiac output improved from 45 [IQR: 40; 56]% to 57 [IQR: 47; 57]% (P = 0.019) and from 2.6 [IQR: 2.1; 2.9] L/min/m2 to 3.1 [IQR: 2.6; 3.7] L/min/m2 (P = 0.020). The interobserver reliability of LVEF before and after TEER was r2 = 0.95 (P < 0.001) versus 0.95 (P < 0.001). Right ventricle end-diastolic volume (RVEDV) decreased from 107 mL/m2 [IQR: 75; 138] to 87 [IQR: 67; 115.0] mL/m2 (P = 0.039). There was no change in native T1 mapping. We found no non-ischemic late gadolinium enhancement. At 12 months, 67% of CMR patients presented with NYHA class I/II and KCCQ overall summery score increased from baseline 46 [IQR: 30.0; 49.1] to 66 [IQR: 57.4; 73.9] (P = 0.001). TR TEER led to encouraging reverse remodeling of the left ventricle, combining a large increase in LVEF, cardiac output and LV stroke volumes. As we found no changes in myocardial fibrosis, our results suggest a tight interdependence between both ventricles and question the role played by the RV on left ventricular efficiency. Outcomes were consistent with clinical amelioration.

PO-03-086 USING THE 3D ARCHITECTURE OF SCAR TO PREDICT LIFE-THREATENING VENTRICULAR ARRHYTHMIAS – STILL A LONG WAY TO GO

Late gadolinium enhancement (LGE) has been proposed as an independent predictor of ventricular arrhythmias. The purpose of this study was to assess if myocardial scar characterization could enhance the risk stratification for life-threatening arrhythmias and sudden cardiac death (SCD). We included patients with an indication for ICD or CRT-D implantation who underwent cardiac magnetic resonance for clinical proposes since February/2018 and in whom a 3D-LGE dataset was obtained. Patients with channelopathies (n=2) or inappropriate imaging quality (imaging artifacts; n=7) were excluded. Scar characterization using ADAS software was performed in 3D-LGE datasets in all but 16 patients, where 2D datasets were used. The primary endpoint was the composite of appropriate ICD therapy (classified as ATP or shock), sustained ventricular tachycardia or SCD. A total of 116 patients were analysed (mean age 66 ± 14 years; 81% male; mean LVEF 34 ± 14%; 74 patients with ischemic and 42 with non-ischemic cardiomyopathy; 40 patients received a device in the setting of secondary prevention). During a median follow-up of 2.3 years (IQR 1.3 – 3.3 years) there were 23 events (18 appropriate ICD therapies [9 shocks and 9 ATP], 3 episodes of VT under the threshold for ICD therapy and 2 SCD). No statistically significant differences were found between patients with or without events in terms of scar mass, border zone (BZ) mass, BZ channels (BZC), BZC mass, number of channels detected, and scar heterogeneity (BZ mass / scar mass ratio) - all p values > 0.2 – Figure. Restricting the analysis to only primary prevention cases yielded similar results. Overall, 26 patients did not show any channel. Four of these (all with non-ischemic LGE) experienced an arrhythmic event, yielding a negative predictive value of 83% (95% CI 64-93%) for the absence of channels. In this cohort with still relatively limited follow-up duration, no single parameter reflecting scar tissue characterization was able to predict appropriate device therapies or sudden cardiac death.

Characteristics and Prognosis of a Contemporary Cohort with Myocardial Infarction with Non-Obstructed Coronary Arteries (MINOCA) Presenting Different Patterns of Late Gadolinium Enhancements in Cardiac Magnetic Resonance Imaging.

To analyze the characteristics and prognosis of a contemporary cohort of patients with myocardial infarction with non-obstructed coronaries (MINOCA) were referred for cardiac magnetic resonance (CMR) imaging, focusing on late gadolinium enhancement (LGE) patterns. We retrospectively examined and prospectively followed up with 135 patients (49 ± 21 years old, 48% female) undergoing CMR imaging due to a MINOCA diagnosis from 2014 to 2016. We grouped and analyzed the sample according to ischemic (focal or transmural) and non-ischemic LGE patterns. The primary outcome was cardiac-related death; the secondary outcome was a composite of cardiac-related rehospitalizations, the new occurrence of acute myocardial infarction (AMI), heart failure (HF), or arrhythmias. CMR exams were performed after a median of 28 days from the acute event. One-third of the ischemic MINOCA were first managed as myocarditis, while CMR helped to adopt a different therapy regimen in 22% of patients (30/135). After a median follow-up of 2.3 years, more cardiac-related deaths occurred in the ischemic than non-ischemic group (2 vs. 1, p = 0.36), but it was not statistically significant. The ischemic group also experienced more cardiac-related-rehospitalizations (42%, p < 0.001). In a multivariable Cox regression model, dyslipidemia, reduced left ventricular ejection fraction, ST-elevation at the hospitalization, and the LGE transmural pattern were the independent predictors of cardiac-related rehospitalizations. In a contemporary cohort of MINOCA patients who underwent CMR, ischemic and non-ischemic patterns had distinct features and outcomes. Among the MINOCA patients, CMR can identify patients at higher risk who require more aggressive therapeutic approached and strict follow-up.

CMR tissue characterization and course of acute SARS-CoV-2 type B.1.1.529-associated myocarditis in a professional soccer player

We report the case of a young professional soccer player who underwent cardiac MRI (CMR) for work-up of discrete intermittent chest pain and subtle ST segment elevations in the ECG after having been tested positive for SARS-CoV-2 type B.1.1.529 despite full vaccination including recent mRNA booster. Troponin levels were significantly increased and myocarditis was suspected. Comprehensive CMR including CINE and late gadolinium enhancement as well as multi-parametric T1/T2 mapping techniques revealed local hypokinesia and swelling of the posterolateral wall with non-ischemic late gadolinium enhancement and increased T2 relaxation time compatible with acute viral myocarditis. The patient was admitted to a cardiology ward for rhythm and troponin monitoring and was discharged after two days of uneventful rhythm monitoring and with decreased troponin levels. Adhering to current recommendations the patient was advised to abstain from moderate- to high-intensity sports and exercise for 3-6 months. After 6 months of exercise avoidance, follow-up ECG showed regression of prior ST segment elevations, and Holter ECG as well as a treadmill exercise stress test did not reveal any abnormalities. Follow-up CMR was performed before return-to-sports which revealed persisting myocardial fibrosis but complete regression of myocardial edemam and excluded ongoing inflammation. This example underscores the value of multi-parametric CMR tissue characterization for the work-up of suspected SARS-CoV-2 associated myocarditis, as well as for follow-up before return-to-sports.

LGE prevalence and patterns in severe aortic stenosis: When “junctional” means the same

BackgroundLeft ventricular (LV) remodeling in severe aortic valve stenosis (AS) is a complex process that goes beyond hypertrophic response. Reparative/replacement fibrosis is considered irreversible and has recognized value in both risk stratification and prognosis. Currently, cardiac magnetic resonance (CMR) is the gold-standard imaging technique for fibrosis identification through late gadolinium enhancement (LGE) assessment. However, its prevalence and distribution are quite variable among series. Our goal was to assess LGE prevalence and patterns in severe AS. MethodologySingle-center prospective cohort of 140 patients with severe symptomatic high-gradient AS (mean age 72 ± 8 years; mean valvular transaortic gradient 61 ± 18 mmHg; mean LV ejection fraction by echocardiogram 58 ± 9%) undergoing surgical aortic valve replacement. Those with previous myocardial infarction and/or non-ischemic cardiomyopathy were excluded. All patients performed 1.5 T LGE-CMR prior to surgery. ResultsOverall, 103 patients (74%) had non-ischemic LGE (median LGE mass 2.8 g [IQR 0.0–7.8] g), many of them with combined mid-wall and junctional enhancement pattern (36%). LGE was most frequently observed in the mid-basal segments of the interventricular septum. Seventy-four patients (53%) had non-exclusively junctional LGE. Contrary to those with junctional enhancement, patients with non-exclusively junctional LGE had higher LV volumes/mass, worse LV ejection fraction and worse global longitudinal strain. ConclusionAmong patients with severe, symptomatic, high-gradient AS, LGE is frequent, primarily affecting the mid-basal interventricular septum. Contrary to junctional LGE, the presence of non-junctional LGE seems to correlate with adverse markers of LV remodeling.

CMR findings in patients referred for suspected myocarditis following mRNA-based COVID vaccination compared with pre-COVID myocarditis referrals: A single-centre observational study.

Vaccination is considered the key to overcome the COVID pandemic. For the first time mRNA-based vaccinations are used in humans. Case series suggested an increased risk of myocarditis after vaccination. This study sought to describe CMR findings in patients with suspected mRNA-vaccine associated myocarditis. A total of 33 consecutive patients referred for CMR work-up of suspected myocarditis associated with mRNA-based vaccination were included. A historical cohort of 135 consecutive patients referred for suspected myocarditis in the pre-COVID era served as control group. All patients underwent multi-parametric CMR including CINE and late gadolinium enhancement (LGE) imaging as well as parametric T1/T2 mapping of the left ventricular myocardium. Patients referred for suspected vaccination-related myocarditis were more often female (55% vs 32%, p=0.015) and demonstrated smaller LV dimensions as well as a better LV function compared to patients of the control group. CMR revealed a lower prevalence of non-ischemic LGE in patients with suspected vaccination-myocarditis (6% vs 22%, p=0.04). However, among patients without LGE we observed a higher prevalence of an abnormal T1/T2 mapping result in patients with suspected vaccination-myocarditis compared to the control group (45% vs 18%, p=0.010). In this small single-centre study, compared to myocarditis referrals in the pre-COVID era, patients currently referred for CMR work-up of suspected mRNA-vaccination-associated myocarditis demonstrated lower prevalence of LGE but higher prevalence of abnormal T1/T2 mapping. These hypothesis-generating observations may point towards a rather subtle myocardial damage and support the routine use of T1/T2 mapping in this indication.