Diffuse Late Gadolinium Enhancement Research Articles

Coronary artery disease in cardiac amyloidosis

Abstract Background Cardiac amyloidosis is an important disease causing significant morbidity and mortality. Due to the ageing society as well as better diagnostic tools such as 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy (DPD scan), cardiac amyloidosis has increased in prevalence, however, the coexistence, as well as the differences in presentation with coronary artery disease (CAD), has not yet been discovered. Purpose The purpose of the study is to evaluate the prevalence of CAD in patients with cardiac amyloidosis, to assess differences in late gadolinium enhancement (LGE) in cardiac MRI, and to assess differences in symptoms such as dyspnea. Materials and Methods We retrospectively assessed all patients with cardiac amyloidosis at our center and screened for an evaluation of coronary artery disease with coronary angiography, coronary CT, or myocardial scintigraphy. In all patients, who underwent cardiac MRI we assessed the pattern of LGE using the cardiac left ventricular segmentation model published by the AHA [1]. Results 295 patients (27% female, 74 ± 11 years) with cardiac amyloidosis (26% AL-amyloidosis, 74% ATTR-amyloidosis) were retrospectively assessed. Of those, 205 (69%) had a CAD evaluation. In 69 patients (34%), significant CAD was present, 10 patients (5%) had undergone CABG and 48 patients (23%) had received a PCI in the past. In patients with CAD, 3 patients (4%) suffered from NYHA IV and 51 patients (74%) were symptomatic with NYHA II or NYHA III. There were no significant differences to patients without CAD (p=0.252). In 153 patients (75%), cardiac MRI was performed. In 7% of the patients, no LGE was obvious, in 84%, a diffuse circular subendocardial to transmural LGE with basoapical gradient, typical for cardiac amyloidosis, could be observed. In 6% of the cases, a subendocardial pattern typical for post-ischemic changes could be observed; in 56% of the patients, a previous myocardial infarction was known. In the remaining 3%, LGE in the insertion points could be observed. Conclusion With 34%, CAD is highly prevalent in patients with cardiac amyloidosis. In 28%, a coronary intervention (surgical or interventional) was performed, making coronary interventions in patients with cardiac amyloidosis a feasible option. Cardiac MRI in patients with concomitant CAD and cardiac amyloidosis often shows the typical diffuse LGE, therefore, visualization of postischemic changes in these patients is difficult. Furthermore, symptoms do not differ between patients with CAD and no CAD.

Abstract 14254: Myocarditis in Athletes and Non-Athletes: Evaluating the Persistence and Degree of Myocardial Fibrosis at Follow Up

Introduction: Myocarditis is a common acquired cardiac disorder that may lead to persistent scar. Current guidelines recommend follow up cardiac MRI (CMR) in 3-6 months for athletes. Data supporting this recommendation is unfortunately very limited. Aim: The aim of this study was to evaluate the demographic and clinical variables of patients diagnosed with myocarditis. Clinical data for those who had a follow up CMR was also evaluated separately. Methodology: Patients who had a cardiac MRI (CMR) organised between July 2019 till December 2022 because of a MINOCA/Myocarditis hospital admission were retrospectively reviewed. Those with a myocarditis diagnosis were included. An athlete was defined as an individual who engaged in >4 hours of physical activity weekly or underwent organized sport. Results: 105 patients were included (mean age 35.4±15.6 years, 83.8% male). 34.3% were athletes. 12.4% had possible acute myocarditis, 10.5% had likely myocarditis and 77.1% had confirmed myocarditis on cardiac MRI (median 4 days from presentation). ECG was abnormal in 60.0%. 8.6% had arrhythmias. Echocardiography was abnormal in 26.7%. CMR revealed 15.2% reduced LV EF, 57.1% regional wall motion abnormalities, 5.7% reduced RV EF, 25.7% pericardial effusion, 84.5% myocardial oedema. Most (88.5%) had late gadolinium enhancement (LGE). 56.2% were started on anti-heart failure medical therapy. 29.5% had a CMR repeated (interval between scans 14.7±14.2 months). 77.4% showed persistent LGE, less pronounced in most (71.0%). Diffuse LGE at baseline was the only predictor for persistent scar (p=0.004). Scar persisted equally in athletes and non-athletes (p=0.666). Clinical variables were similar in both. At follow-up (24.6±15.3 months), 8.6% had adverse outcomes. The event rate was similar in athletes and non-athletes. A low LV EF on CMR (p=0.011) and abnormal ECHO (p=0.027) were the only variables that could predict outcome. Conclusion: LGE after myocarditis persists in 77.4% of cases, albeit better. No variable could predict the persistence of LGE in this cohort. Athletes and non-athletes had a similar clinical course, suggesting that repeat CMR in non-athletes is reasonable. The diagnostic utility of repeat CMR after myocarditis remains questionable.

P423 RELAPSE OF ACUTE MYELOID LEUKEMIA WITH CARDIAC INFILTRATION: A CASE REPORT

Abstract We describe the case of a 42–year–old man who presented to the emergency department suffering from asthenia, dyspnea and tachycardia. The patient had been diagnosed, two years earlier, with acute myeloid leukemia (AML), treated with two lines of chemotherapy and allogeneic bone marrow transplantation from a family donor. Atrial fibrillation with rapid ventricular response was documented at the ECG. The echocardiogram showed moderate left ventricular dysfunction in the presence of dishomogeneous thickening of left and right ventricular wall and a severe circumferential pericardial effusion causing cardiac tamponade, with the need of urgent pericardiocentesis. AML relapse was documented at the laboratory tests. The suspected cardiac involvement was investigated with cardiac MRI which documented thickening and diffuse late gadolinium enhancement at the level of the left and right ventricular wall, the interatrial septum and the atria walls. The pericardium and the epicardial fat were also thickened and endowed with contrast enhancement. A lymphocyte assay was performed on pericardial fluid and showed the presence of a blast population (approximately 27% of white blood cells) with variable expression of myeloid antigens. The clinical, radiological and finally immunophenotypic picture therefore concluded with relapse of acute myeloid leukemia with myocardial and pericardial infiltration. Acute myeloid leukemia usually presents with symptoms related to bone marrow failure. Clinically significant cardiac involvement is rare but should be considered when cardiorespiratory symptoms occur. Cardiac manifestations include coronary artery disease, heart failure, conduction disturbances, myocarditis, pericarditis, and pericardial effusion. Understanding the underlying pathophysiology and recognizing potential cardiac manifestations could help in the early diagnosis, evaluation, and treatment of these patients. Echocardiography or cardiac MRI could reveal morphological, structural and signal abnormalities of the cardiac structures and therefore should raise the suspicion of a possible myocardial infiltration by leukemia cells, both in patients with a positive history of leukemia and in those in whom cardiac involvement could represent the first manifestation of a hematological pathology.

Right ventricular myocarditis and rapid fibrosis induced by pazopanib.

A 56-year-old woman with metastatic chondrosarcoma visited our emergency department because of chest discomfort. Treatment with oral pazopanib, a multi-targeted tyrosine kinase inhibitor that targets angiogenesis growth factor receptors, fibroblast growth factor receptors, platelet-derived growth factor receptors, and vascular endothelial growth factor receptors, was initiated 26 days previously. Electrocardiography showed new-onset significant ST elevation in the precordial leads V1–V3 and pathologic Q-waves in leads III and aVF (Panel A). The cardiac and inflammatory biomarker levels were elevated as follows: creatine kinase (CK), 705 (reference range, 32–135 IU/L); CK-myocardial band (MB) fraction, 12.5 (reference range, 0–5 ng/mL); troponin-T, 402 (reference range, 0–14 pg/mL); NT-proBNP, 11 230 (reference range, 0–287 pg/mL); and C-reactive protein, 77.3 (reference range, 0–8 mg/L). Echocardiography showed newly developed akinesia with thinning in the septum and throughout the right ventricle with markedly reduced biventricular systolic dysfunction compared with echocardiography performed 1 month ago (Panel B and Supplementary data online, Video). Luminal narrowing or thrombosis in the coronary arteries was not observed on emergency coronary angiography (Panel C). Cardiac magnetic resonance imaging performed on the second day of hospitalization showed diffuse late gadolinium enhancement in the right ventricular wall and the right side of the septum (Panel D). The nails of both hands showed hyperpigmentation and onycholysis induced by taking pazopanib (Panel E). Despite the discontinuation of pazopanib and heart failure management, she developed fatal ventricular tachycardia and cardiogenic shock (Panel F). Imaging findings show pazopanib-induced right ventricular myocarditis with subsequent rapid wall thinning and fibrosis.

Abstract 14106: Prevalence and Respective Predictive Value of Late Gadolinium Enhancement Phenotypes in Patients Referred for Suspected Infiltrative Cardiomyopathy

Introduction: The respective value of different late gadolinium enhancement (LGE) phenotypes in patients with suspected infiltrative cardiomyopathy remains uncertain. Methods: In a large cohort of patients referred for suspected infiltrative cardiomyopathy, we evaluated respective associations between the dominant LGE phenotype and the composite endpoint of heart failure hospitalization, survived cardiac arrest or death. Kaplan-Meier survival curves were executed for six pre-defined LGE phenotypes. Multivariable analysis was performed to assess their independent association with the composite outcome, adjusted for relevant confounders. Final diagnosis was adjudicated using standardized disease-specific criteria. Results: 588 patients (68% male, median age 70 years, mean LVEF 54.7±12.7%) were studied. Of these patients, 139 (24%) were confirmed to have cardiac amyloidosis (CA) (81 [58%] transthyretin, 54 [39%] light chain and 4 [3%] undifferentiated) by objective non-CMR diagnostic criteria. Any LGE was present in 394 patients (67%) with the dominant phenotype being diffuse in 137 (23%), mid-wall patchy in 118 (20%), ischemic in 55 (9.4%), subepicardial in 18 (3.1%), mid-wall striae in 8 (1.4%), and RV insertion site in 58 (9.9%). The sensitivity and specificity of diffuse LGE for CA was 86% and 96%, respectively. Over a median 855 (IQR 372, 1542) days, 239 (41%) experienced the primary outcome. Unadjusted survival curves for each LGE phenotype are shown in the Figure. Following adjustment, diffuse (HR 2.30, p<0.001), mid-wall patchy (HR 1.52, p=0.040) and ischemic LGE (HR 1.78, p=0.023) remained independently associated (Figure). Conclusions: In patients referred for suspected infiltrative cardiomyopathy, diffuse, mid-wall patchy and ischemic patterns all showed independent prognostic value. We confirm that diffuse LGE pattern reliably identifies CA patients with high sensitivity and specificity while delivering strong prognostic value.

Abstract 13860: Heart Failure With Preserved Ejection Fraction Induced by Amyloid Light Chain Amyloidosis: A Case Report

Introduction: Cardiac amyloidosis is a clinical disorder defined as an extracellular deposition of protein in the heart. Typically, signs and symptoms of heart failure develop in the advanced disease. High index of suspicion is required for the diagnosis of this disorder. Results: A 62 years old male came to the cardiology clinic due to lower extremity edema, fatigue, dyspnea on exertion. He had a 3 month history of progressive lower leg edema. On physical examination he had a positive S4; lung sounds were diminished and there was dullness to percussion over the lower two thirds; and bilateral lower extremity edema. Hospital admission was decided for management of decompensated heart failure. On admission, the surface ECG showed normal sinus rhythm with low QRS voltage in the limb leads, a RBBB and LPFB. Initial laboratory reported elevated NT-proBNP: 13,816 pg/mL. Chest x-ray demonstrated right interstitial infiltration and bilateral pleural effusion. The echocardiogram revealed severe concentric hypertrophy of the left ventricle, an apical sparing left ventricle longitudinal strain, and an ejection fraction of 68%. A cardiac MRI showed concentric biventricular hypertrophy associated with extensive diffuse late gadolinium enhancement, suggestive of cardiac amyloidosis. Screening resulted in a Perugini score of 1 on Tc-PYP scintigraphy, elevated Kappa and Lambda light chains on serum, and kidney biopsy positive for amyloidosis. Hematology-oncology consultation was done and a daratumumab-CyBorD protocol was started. Conclusions: This case elucidated a stepwise diagnostic approach of cardiac amyloidosis in a patient presenting with signs and symptoms of heart failure. Amyloid AL cardiac amyloidosis and its repercussions are severe because it not only compromises by being infiltrative but also by its toxic capacity. A high index of suspicion and a multidisciplinary approach is needed in order to improve quality of life and prolong survival.

Cardiovascular Magnetic Resonance Imaging Patterns in Rare Cardiovascular Diseases

Rare cardiovascular diseases (RCDs) have low incidence but major clinical impact. RCDs' classification includes Class I-systemic circulation, Class II-pulmonary circulation, Class III-cardiomyopathies, Class IV-congenital cardiovascular diseases (CVD), Class V-cardiac tumors and CVD in malignancy, Class VI-cardiac arrhythmogenic disorders, Class VII-CVD in pregnancy, Class VIII-unclassified rare CVD. Cardiovascular Magnetic Resonance (CMR) is useful in the diagnosis/management of RCDs, as it performs angiography, function, perfusion, and tissue characterization in the same examination. Edema expressed as a high signal in STIRT2 or increased T2 mapping is common in acute/active inflammatory states. Diffuse subendocardial fibrosis, expressed as diffuse late gadolinium enhancement (LGE), is characteristic of microvascular disease as in systemic sclerosis, small vessel vasculitis, cardiac amyloidosis, and metabolic disorders. Replacement fibrosis, expressed as LGE, in the inferolateral wall of the left ventricle (LV) is typical of neuromuscular disorders. Patchy LGE with concurrent edema is typical of myocarditis, irrespective of the cause. Cardiac hypertrophy is characteristic in hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA) and Anderson-Fabry Disease (AFD), but LGE is located in the IVS, subendocardium and lateral wall in HCM, CA and AFD, respectively. Native T1 mapping is increased in HCM and CA and reduced in AFD. Magnetic resonance angiography provides information on aortopathies, such as Marfan, Turner syndrome and Takayasu vasculitis. LGE in the right ventricle is the typical finding of ARVC, but it may involve LV, leading to the diagnosis of arrhythmogenic cardiomyopathy. Tissue changes in RCDs may be detected only through parametric imaging indices.

Accuracy of diagnostic score by echocardiography for the detection of cardiac amyloidosis in patients with proven extracardiac amyloidosis

Abstract Background In 2021, a position statement of the ESC Working Group on Myocardial and Pericardial Diseases suggested to use an echocardiographic score (i.e., ECHO score) to confirm cardiac amyloidosis (CA) thus to avoid heart biopsy in patients with left ventricular (LV) hypertrophy >12 mm and proven extracardiac amyloidosis. Purpose To test the accuracy of ECHO-score in a broad spectrum of patients with proven cardiac amyloidosis and anatomical LV hypertrophy measured by echocardiography. Methods One hundred and twenty patients with proven CA (both from ATTR and AL forms) underwent comprehensive echocardiography including parietal wall thickness (+3 points), Doppler E/e' ratio (+1 point), TAPSE (+2 points), LV global longitudinal strain (1 point) and systolic longitudinal strain apex to base ratio (+3 points) and compared to 13 controls. A score ≥8 points in the presence of LV wall >12 mm which predicts CA, was investigated in patients with LV hypertrophy from 12.1 to 15.0 mm, from 15.1 to 20 mm and over 20 mm. Cardiovascular magnetic resonance (CMR) imaging was available in 63 patients for extracellular volume measurement >0.40% and diffuse late gadolinium enhancement assessment, both present to confirmed amyloidosis. Results ATTR and AL amyloidosis accounted for 77% and 23%, respectively. Age averaged 76±7yo and 72% of patients were male. LV ejection fraction averaged 61±5%. The ECHO score averaged 6.4±2.5 in patients with LV hypertrophy from 12.1 to 15.0 mm (n=29), 7.9±2.6 in patients with LV hypertrophy from 15.1 to 20.0 mm (n=59) and 9.8±1.7 when LV hypertrophy was >20 mm (n=32). Figure 1 depicts the sensitivity of ECHO score alone and in addition to CMR as a function of LV hypertrophy range. In patients with LV hypertrophy >20 mm, ECHO score alone has a sensitivity near 100% and CMR is useless to confirm cardiac amyloidosis. Between 15.1 to 20.0 mm of hypertrophy, both ECHO and CMR are necessary to reach a sensitivity of 100%. Unfortunately, below 15 mm of LV hypertrophy, neither ECHO nor CMR altogether predict cardiac amyloidosis with good accuracy, meaning heart biopsy is still useful. Conclusion Upon the degree of LV hypertrophy in a patient with extrcardiac amyloidosis, ECHO score alone or in combination with MRI are efficient only if myocardial parietal thickness is above 15 mm. Funding Acknowledgement Type of funding sources: None.

Hypertrophic obstructive cardiomyopathy complicated with acute myocardial infarction and diffuse fibrosis: surgery or not?

BackgroundHypertrophic cardiomyopathy with extreme hypertrophy, biventricular obstruction and diffuse myocardial fibrosis complicated by myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is a rare phenotype. Evidence and guideline recommendations are still lacking for a treatment strategy.Case presentationEmergency coronary angiography was performed in a 38-year-old man with a 2-year history of nonobstructive hypertrophic cardiomyopathy (HCM) presenting with acute myocardial infarction. The coronary angiogram yielded no stenotic lesions but showed a diffusely dilated left descending artery with slow blood flow. All evidence from biomarker analysis, electrocardiography, echocardiography, and imaging supported the diagnosis of acute myocardial infarction in the left ventricular anterior wall. The echocardiogram demonstrated severe interventricular and apical hypertrophy, severe left ventricular outflow tract obstruction and mild right ventricular outflow tract obstruction. Cardiac magnetic resonance imaging showed a concentric morphological subtype of HCM with diffuse late gadolinium enhancement in the left ventricle. Extended septal myectomy was performed 1 month later, and the patient recovered well.ConclusionsHypertrophic obstructive cardiomyopathy with acute myocardial infarction is an indication for coronary angiography. Septal reduction surgery could be performed cautiously in HCM patients with extreme hypertrophy, biventricular obstruction and diffuse myocardial fibrosis complicated by MINOCA to improve the patient’s symptoms.

Abstract 12898: Eosinophilic Myocarditis Following Osimertinib Treatment for Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma

A 60-year-old man with oligometastatic adenocarcinoma of the lung presented with symptoms of heart failure 6 weeks after initiation of treatment with osimertinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. A transthoracic echocardiography (TTE) showed a moderately sized pericardial effusion, mildly increased left ventricular (LV) wall thickness, and mildly depressed LV ejection fraction (45-50%), without tamponade physiology. His TTE prior to treatment initiation was normal. He endorsed chest pain across the entire chest that had started on the second day after initiation of osimertinib and was worse when laying down. His serum troponin I concentration was elevated to 10.6 ng/mL upon admission and ECG showed sinus tachycardia. He was carefully diuresed with some improvement in symptoms. A peripheral eosinophilia was noted, which raised suspicion for eosinophilic myocarditis. A cardiac magnetic resonance imaging confirmed a mildly reduced LVEF of 51% and mildly increased LV wall thickness. There was diffuse late gadolinium enhancement throughout the entire myocardium, with increased T1 and T2 signals and the extracellular volume was increased to 40%, supporting a diagnosis of perimyocarditis. A left and a right heart catheterization were subsequently undertaken. His coronary arteries were normal and the right heart cathetherization showed unremarkable hemodynamics, including a right atrium pressure of 6 mm Hg, right ventricular pressure of 34/6 mm Hg, pulmonary artery pressure of 33/9 mm Hg, and a pulmonary capillary wedge pressure of 10 mm Hg. A right heart biopsy revealed a dense eosinophilic infiltration of the myocardium, consistent with an eosinophilic hypersensitivity reaction, manifesting as myocarditis. High dose prednisone was initiated and after 2 months of treatment, repeat TTE showed resolution of his pericardial effusion and normalization of the LV wall thickness and LVEF (65%). This case illustrates the value of multi-modality imaging and endomyocardial biopsy to diagnose rare complications of novel, targeted cancer therapeutics.

Massive necrotizing myocarditis in a young patient with idiopathic hypereosinophilic syndrome

Abstract A 27-years-old female with multiple autoimmune disorders presented to our cardiology unit for acute chest pain and worsening dyspnoea. Admission blood tests revealed increased serum levels of high-sensitive cardiac troponin, eosinophilic count and C-reactive protein. Laboratory findings, low QRS voltages by ECG, mildly reduced left ventricular systolic function in the context of pseudohypertrophy, mild and diffuse late gadolinium enhancement associated with markedly increased native T1 and T2 mapping levels assessed by echocardiography and cardiovascular magnetic resonance imaging, raised the suspicion of massive eosinophilic myocarditis, subsequently confirmed by histological examination of endomyocardial biopsy. Prompt initiation of immunosuppressive treatment allowed swift regression of myocardial inflammation and full recovery of left ventricular systolic function within one month. After ruling-out clonal myeloid disorder, lymphocyte-variant and reactive hypereosinophilia, the young lady was eventually diagnosed with idiopathic hypereosinophilic syndrome. This case report turns the spotlight on the role and importance of advanced multi-modality cardiovascular imaging for raising clinical suspicion of acute eosinophilic myocarditis, guiding diagnostic work-up and monitoring response to treatment.

Analysis of a large cohort of African/Afro-Caribbean patients by cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background Limited data is available in the literature on Cardiac Magnetic Resonance (CMR) features of African/Afro-Caribbeans, in particular exploring differences between hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM). Purpose To describe the cardiac morphology and pattern of late gadolinium enhancement (LGE) in patients of African/Afro-Caribbean origin. Methods We retrospectively analysed African/Afro-Caribbean patients who underwent clinical CMR at a tertiary centre. Three groups were specifically investigated: HHD, HCM and combination of HHD and HCM or ambiguous (HHD&HCM). Results Overall, 166 consecutive patients (58% male, mean age 55 ± 14yo) were analysed. One-hundred fifty-four (93%) had history of arterial hypertension (HTN), including 17 with uncontrolled/malignant HTN. Overall, 28(17%) had normal scans, 70(42%) HHD, 15(9%) apical HCM, 10(6%) classical septal HCM, 19(11%) dilated cardiomyopathy, 6(4%) cardiac amyloidosis, 3(2%) ischemic heart disease, 4(2%) myocarditis, 2 sarcoidosis and 1 valvular disease. In 7(4%) the diagnosis was ambiguous between HHD and HCM and 1 uncertain. Forty-four (27%) had dual pathology, most frequently HHD, bystander myocardial infarction (MI) and embolic MI. LGE was detected in 95(57%), 26 with ischemic pattern, 13 diffuse mid-wall, 29 focal non-ischemic and 28 diffuse/multifocal non-ischemic. CMR features and correlations between subgroups are reported in the Table. Patients with HHD had significantly higher left ventricular (LV) end-diastolic (ED) volume indexed (Vi) and LV end-systolic (ES) Vi, but lower LV ejection fraction (EF) and LV maximum wall thickness (MWT) compared to HCM patients. HHD&HCM had higher LVEF and MWT compared to HHD and higher LVEDVi compared to HCM. LGE was more frequently seen in HCM and HHD&HCM as focal non-ischemic (6vs5vs10,p = 0.049) and diffuse multifocal(5vs6vs9,p = 0.009). A history of uncontrolled/malignant HTN was more frequent in HHD and HHD&HCM (11vs1vs5,p = 0.025) and was associated with diffuse LGE with lateral wall involvement (p < 0.0001) (Figure). Conclusions: CMR findings in African/Afro-Caribbeans may overlap between aetiologies. A specific pattern of diffuse non-ischaemic LGE involving the lateral wall appears though to be more often associated with severe uncontrolled HTN. Table HHD(n = 70) HCM(n = 19) HHD&HCM or ambiguous (n = 13) p LVEDVi, ml/m2 88 ± 33 62 ± 11 77 ± 6 0.003 LVESVi, ml/m2 36 ± 26 16 ± 10 26 ± 19 0.002 LVEF, % 62 ± 16 79 ± 6 74 ± 12 0.567 LVMWT, mm 13 ± 2 15 ± 4 14 ± 3 <0.0001 CMR features and correlations between subgroups Abstract Figure

Prognostic impact of multiple fragmented QRS on cardiac events in idiopathic dilated cardiomyopathy.

To evaluate the prognostic impact of fragmented QRS (fQRS) on idiopathic dilated cardiomyopathy (DCM). We conducted a prospective observational study of 290 consecutive patients with DCM (left ventricular ejection fraction ≤ 40%) and narrow QRS who underwent cardiac magnetic resonance. We defined fQRS as the presence of various RSR' patterns in ≥2 contiguous leads representing the anterior (V1-V5), inferior (II, III, and aVF), or lateral (I, aVL, and V6) myocardial segments. Multiple fQRS was defined as the presence of fQRS in ≥2 myocardial segments. Patients were divided into three groups: no fQRS, single fQRS, or multiple fQRS. The primary endpoint was a composite of hard cardiac events consisting of heart failure death, sudden cardiac death (SCD), or aborted SCD. The secondary endpoints were all-cause death and arrhythmic event. During a median follow-up of 3.8 years (interquartile range, 1.8-6.2), 31 (11%) patients experienced hard cardiac events. Kaplan-Meier analysis showed that the rates of hard cardiac events and all-cause death were similar in the single-fQRS and no-fQRS groups and higher in the multiple-fQRS group (P = 0.004 and P = 0.017, respectively). Multivariable Cox regression identified that multiple fQRS is a significant predictor of hard cardiac events (hazard ratio, 2.23; 95% confidence interval, 1.07-4.62; P = 0.032). The multiple-fQRS group had the highest prevalence of a diffuse late gadolinium enhancement pattern (no fQRS, 21%; single fQRS, 22%; multiple fQRS, 39%; P < 0.001). Multiple fQRS, but not single fQRS, is associated with future hard cardiac events in patients with DCM.

Predictors of death, heart transplantation and relapse in clinically suspected and biopsy-proven myocarditis in the pre-immunosuppression era

Abstract Background Myocarditis is an infectious or autoimmune inflammatory disease of the myocardium; diagnosis relies on the exclusion of an acute coronary syndrome, and is confirmed by endomyocardial biopsy (EMB). Prognosis is highly variable, outcome predictors are not well defined. Purpose To identify clinical, imaging and immunological predictors of death, heart transplantation (HTx) and relapse in patients with myocarditis in the pre-immunosuppression era. Methods From 1993 to 2012 we consecutively enrolled 466 patients (68% male, mean age 37±17 years), 216 with clinically suspected and 250 with EMB-proven myocarditis. All patients underwent coronary angiogram and transthoracic echocardiogram, 44% of patients underwent cardiac magnetic resonance (CMR). Circulating auto-antibodies were measured in patients' sera by indirect immunofluorescence. All patients were prospectively followed-up at the local Cardio-immunology outpatient clinic. Results After a median follow-up of 50 months (IQR 25–75), 366 patients (79%) were alive, while 42 (9%) were dead or underwent HTx; 58 were lost to follow-up. Ten-year survival free from death or HTx was overall 83%, but was lower in patients with EMB-proven myocarditis (76% vs 94% in patients with clinically suspected myocarditis, p&amp;lt;0.001). On univariate analysis, predictors of death and HTx were female gender (p=0.003), previous myocarditis (p=0.03), heart failure on presentation and advanced NYHA class (p&amp;lt;0.001, respectively), histological diagnosis of giant-cell myocarditis (p=0.002), positivity for anti-heart antibodies (AHA, p=0.04), anti-cardiac endothelial cell (AECA, p=0.002) and anti-nucleus antibodies (ANA, p=0.003). On multivariate analysis, female gender (HR 2.69, p=0.02), lower left ventricular ejection fraction on echocardiogram (p&amp;lt;0.001), positivity for high-titre organ-specific AHA (HR 4.1, p=0.02) and for ANA (HR 5.1, p&amp;lt;0.001) were independent predictors of death and HTx. Seventy-seven patients had relapsing myocarditis; on univariate analysis, young age (p&amp;lt;0.001), previous myocarditis (p&amp;lt;0.001), symptoms preceding diagnosis (p=0.004), positivity for anti-intercalated disk autoantibody (AIDA, p=0.02), and presence of diffuse late gadolinium enhancement (LGE) on CMR (p&amp;lt;0.001) were predictors of relapse. On multivariate analysis young age (p=0.02) and previous myocarditis (HR 8.4, p&amp;lt;0.001) were independent predictors of relapse. Predictors of death, HTx and relapse, respectively, did not differ when considering separately patients with EMB-proven myocarditis and those with clinically suspected myocarditis. Conclusions In the pre-immunosuppressive era, young age and a previous episode of myocarditis were independent predictors of relapse, female gender, left ventricular dysfunction at presentation and high-titre organ-specific AHA and ANA were independent predictors of death and HTx, suggesting that autoimmune features in myocarditis predict worse prognosis. Funding Acknowledgement Type of funding source: None

Intracardiac Thrombus in Sinus Rhythm: A Case of Missed Cardiac Amyloidosis

Intracardiac thrombus in patients with amyloid cardiomyopathy in sinus rhythm is a rare phenomenon, and no guidelines currently exist regarding screening, diagnosis, or management. We describe a case of a 59 year-old female who presented to the hospital with dyspnea on exertion, orthopnea, pedal edema, and weight gain. She had a one year history of heart failure with preserved ejection fraction, treated with metoprolol, bumetanide, and metolazone, and three month history of AL amyloidosis, treated with Bortezomib and Dexamethasone. Upon admission, labs showed leukocytosis, thrombocytosis, and elevated troponin and BNP. Electrocardiogram revealed sinus rhythm with left atrial enlargement. CT chest angiography showed pulmonary edema and a hypodense mass in the right atrium/atrial appendage. Cardiac magnetic resonance imaging demonstrated moderate concentric hypertrophy, elevated native T1 (1126 ms), diffuse late gadolinium enhancement, and elevated ECV (52%) consistent with cardiac amyloidosis. A right atrial mass consistent with a thrombus was visualized. Intracardiac thrombus was treated with intravenous heparin, which was transitioned to warfarin. Volume overload secondary to AL-cardiac amyloidosis was managed with diuresis. She was discharged home with hospice and passed approximately one month later. This case illustrates a missed diagnosis of cardiac involvement of systemic AL amyloidosis, ultimately resulting in death within nearly one year from initial diagnosis of heart failure. It also explores the etiology, diagnosis, and treatment of an intracardiac thrombus in patients with cardiac amyloidosis in sinus rhythm. Therefore, this case demonstrates the need for evidence-based guidelines regarding stratification of thrombotic risk and serial monitoring in patients with cardiac amyloidosis without arrythmia. Furthermore, it exemplifies the importance of high suspicion for cardiac amyloidosis to guide early diagnosis and management of patients with cardiac involvement of systemic amyloidosis, in addition to screening and monitoring of associated comorbidities, to improve prognosis and overall survival.

From Hip to Heart: Cobalt-induced Cardiomyopathy Requiring Cardiac Transplantation

Cobalt toxicity is a rare cause of infiltrative cardiomyopathy. We describe a case of cobalt-induced cardiomyopathy that progressed to end stage heart failure requiring orthotopic heart transplantation. A 67 year old woman with history of bilateral cobalt-chromium hip replacements presented with dyspnea of 3 weeks duration. She was tachycardic and hypotensive, with elevated NT- proBNP. Electrocardiogram demonstrated sinus tachycardia, low voltage and right bundle branch block. Transthoracic echocardiogram revealed left ventricular ejection fraction of 20-25% with global hypokinesis and a moderate circumferential pericardial effusion. Left and right heart catheterization showed normal coronaries, elevated filling pressures and low cardiac index. Dobutamine infusion was initiated for management of cardiogenic shock. Cardiac magnetic resonance imaging (MRI) illustrated diffuse late gadolinium enhancement concerning for infiltrative cardiomyopathy. Extensive non-ischemic and rheumatologic workup was negative. Cobalt and chromium levels were significantly elevated at 121 mcg/L (Nl

Tissue Characterization by Mapping and Strain Cardiac MRI to Evaluate Myocardial Inflammation in Fulminant Myocarditis.

The clinical value of novel mapping techniques and strain measures to assess myocardial inflammation in fulminant myocarditis (FM) has not been fully explored. To evaluate the ability of mapping and strain cardiac MRI to assess myocardial inflammation in patients with FM, and to which degree the strain metrics correlate with myocardial edema. Prospective. Twenty-nine patients (37 ± 16 years, 48% male) with FM and 29 patients with nonfulminant acute myocarditis (NFAM) (29 ± 14 years, 69% male). 3.0T; Cine imaging, black blood T2 -weighted imaging, T1 mapping, T2 mapping, and late gadolinium enhancement. Native T1 , extracellular volume (ECV), and T2 were measured. Myocardial strain was evaluated by feature tracking. Student's t- or Mann-Whitney U-test. Spearman correlation analysis. The myocardial edema rate (2.6 ± 0.7 vs. 1.6 ± 0.2, P < 0.001) and late gadolinium enhancement (LGE) mass (16.5 [11.7, 41.7] vs. 6.9 [2.2, 15.8] g, P < 0.001) were significantly increased in FM patients when compared to the NFAM group. LGE in the FM group was predominantly located in the septal wall, and 38% of the patients showed a diffuse LGE pattern. Native T1 , ECV, and T2 values in the FM group were significantly more elevated than those with NFAM, while global peak radial, circumferential, and longitudinal strain values were significantly reduced (all P < 0.001). Circumferential strain showed the strongest correlations with ECV (r = 0.72, P < 0.001). Patients with FM showed significant differences in LGE patterns, increased edema, and decreased strain measurements compared to those with NFAM. Circumferential strain showed significant associations with quantitative cardiac MRI parameters of myocardial inflammation. 2 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:930-938.

P5274Characterization of cardiac involvement in patients with MELAS syndrome in comparison to HCM patients by conventional LGE imaging and novel T1-mapping

Abstract Background MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a rare clinical subtype of mitochondrial myopathy. Cardiovascular magnetic resonance (CMR) images of MELAS-patients at an advanced state of the disease often show characteristic patterns: septal pronounced left ventricular (LV) hypertrophy and distinct focal myocardial scars in late-gadolinium-enhancement (LGE) images. This specific pattern is different from those seen in patients with hypertrophic cardiomyopathy (HCM) due to sarcomere protein mutations. Besides LGE imaging another method for the assessment of myocardial integrity, T1-mapping, has been established recently. This is the first study comparing native and enhanced T1-mapping (T1-na/en) as well as extracellular volume (ECV) values in HCM and MELAS. Methods 12 patients with confirmed MELAS syndrome at different states of the disease, 13 HCM patients and 15 controls were included. All CMR studies were performed on a 1.5T MR scanner (Ingenia, Philips) using bSSFP cine sequences for the assessment of LV-function and MOLLI sequences for T1-na/en mapping. 15min after IV injection of 0.1mmol/kg BW Gadobutrol for LGE imaging, T1-en maps were acquired. For comparison of groups T1-na/en and ECV values in a basal short axis slice were used. Results Median and interquartile ranges of LV function, T1 and ECV are shown in the table. There was no difference in LV ejection fraction (LVEF) between the groups, but end-diastolic LV-mass was increased in HCM- and MELAS-patients vs. controls (p&lt;0.001, p=0.028). In MELAS-patients, myocardial fibrosis was detected in focal spots clearly defined in both septum and free lateral wall. In HCM patients there was a rather diffuse LGE pattern in the hypertrophic septum and the RV insertion points. Here T1-na/en and ECV significantly differed from those measured in healthy controls (p&lt;0.001, p&lt;0.001, p=0.002). In the MELAS group T1-na values were significantly higher compared to controls (p=0.004) and significantly lower compared to HCM patients (p=0.003). LV-function and mapping parameters of compared groups LV-EF, % LV-EDV, ml/m2 LV-mass, g/m2 T1-na, ms T1-en, ms ECV, % MELAS 57 (44–63) 86 (81–122) 80 (50–131) 969 (940–1033) 409 (381–465) 27 (24–35) HCM 60 (57–65) 50 (73–94) 94 (72–102) 1041 (1021–1074) 362 (346–430) 31 (28–36) Controls 61 (58–65) 72 (67–89) 53 (42–60) 937 (894–951) 464 (446–513) 26 (24–27) Conclusion Compared to healthy controls and HCM-patients, cardiac involvement in MELAS-patients is not only reliably visualized by conventional LGE imaging but also detected without the use of contrast agent by native T1-mapping. MELAS vs. HCM-patients show a different pattern of LGE and higher native T1 values, respectively.

A case report: X-linked dystrophin gene mutation causing severe isolated dilated cardiomyopathy

Background X-linked dilated cardiomyopathy (XLDCM) is a rare but rapidly progressive cardiomyopathy caused by dystrophin gene mutation. Mutations are more often associated with Duchenne and Becker Muscular Dystrophy, which are characterized by skeletal muscle weakness or limb girdle dystrophy. However, patients with isolated XLDCM have normal skeletal muscle but complete dystrophin loss in cardiac muscle resulting in isolated myocardial involvement without overt signs of skeletal myopathy.Case summary A previously well 16-year-old boy developed sudden onset dense left-sided weakness and facial droop. Computed tomography (CT) angiography and CT brain showed an occluded right internal carotid artery extending to the right middle cerebral artery. He underwent successful endovascular clot retrieval but developed frank pulmonary oedema and cardiogenic shock requiring inotropic support and intubation. Transthoracic echocardiography demonstrated severe left ventricular (LV) cardiomyopathy and an apical thrombus. Subsequent cardiac magnetic resonance (CMR) imaging confirmed the LV parameters and diffuse late gadolinium enhancement. Despite absence of skeletal manifestations, subsequent genetic testing revealed an X-linked dystrophin gene mutation [c.31+G>T (IVS1G>T)]. He was commenced on empirical heart failure therapy and underwent successful cardiac transplantation.Discussion X-linked dilated cardiomyopathy is a rare, rapidly progressing cardiomyopathy. Patients show normal skeletal muscle dystrophin but absent expression in cardiac muscle, resulting fibrosis, and atrophy. About 20% of affected young males have significantly reduced survival and thus the diagnosis must be considered in cases of idiopathic cardiomyopathy with CMR and genetic testing key to the diagnosis. Whilst evidence exists for empirical heart failure medications, cardiac transplantation remains the definitive treatment.

Abstract 16938: Late Gadolinium Enhancement on Cardiac Magnetic Resonance as Predictor of Overall Mortality in Patients With Non-Ischemic Cardiomyopathy

Background: Patients with heart failure due to non-ischemic cardiomyopathy (NICM) constitute a heterogenous group of patients with diverse prognosis. The presence of late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging represents a measure of myocardial damage and can provide prognostic information. Objective: This study aimed to evaluate the prognostic role of the presence and pattern of LGE in patients with NICM . Methods: Using the NICM registry, we conducted a retrospective cohort study of adult patients with NICM, undergoing CMRI between 1999–2016. Using multivariable Cox regression model and Fine and Gray’s competing risk regression model, we evaluated the association between LGE presence and patterns with all-cause mortality, heart transplant, and ventricular assist device (VAD). We adjusted the model for clinically important covariates. Results: Our cohort of 1842 patients showed a mean age of 56 ± 14, 73% male sex, 30% NYHA class III-IV, 15% diabetic and 89% had idiopathic dilated cardiomyopathy. During a median follow-up of 2.3 years, we observed 215 composite outcome of all-cause mortality, transplant, or VAD. LGE was present in 56% of our cohort: 18% subendocardial, 18% mid-wall, 17% diffuse pattern, and 3% subepicardial. LGE was significantly associated with a 2-fold increased risk of events (HR 2.0, 95%CI 1.4-3.0) (figure). Of all LGE patterns, subendocardial, midwall, and diffuse LGE patterns were associated with the worst prognosis. (table). Conclusions: In patients with NICM, LGE in significantly associated with increased risk of death or need for advanced heart failure therapies. The use of CMR in patients with NICM provides both diagnostic and prognostic information.