Transmural Late Gadolinium Enhancement Research Articles

First report of the clinical characteristics and outcomes of cardiac amyloidosis in Saudi Arabia.

Cardiac amyloidosis (CA) is a potentially fatal multisystemic disease that remains significantly underdiagnosed, particularly in the Middle East. This study aims to evaluate the prevalence and clinical characteristics of CA in a high-risk population at a tertiary centre in Saudi Arabia. This cross-sectional, retrospective, single-centre study was conducted at a tertiary hospital in Riyadh, Saudi Arabia. We reviewed the medical records of heart failure patients seen between August 2018 and July 2022 who exhibited red flags for CA and subsequently underwent CA screening. Red flags that prompted the workup included at least two of the following factors: the presence of unilateral or bilateral carpal tunnel syndrome, a family history of transthyretin amyloid (ATTR) amyloidosis and specific electrocardiographic features (relative/absolute low QRS voltage, pseudoinfarct pattern and atrioventricular/interventricular conduction abnormalities). Echocardiographic red flags included mainly increased wall thickness (≥12mm), significant diastolic dysfunction, reduced left ventricular (LV) longitudinal function, right ventricular (RV) dysfunction and elevated right atrial (RA)/pulmonary artery (PA) pressure. Cardiac magnetic resonance (CMR) red flags included aspects similar to those in an echocardiogram as well as a subendocardial or transmural late gadolinium enhancement (LGE) pattern. These patients were assessed for CA through technetium-99m pyrophosphate ([99mTc]Tc-PYP) bone scintigraphy, serum and urine protein electrophoresis with immunofixation and a serum-free light chain assay. A total of 177 patients were screened, of which 21.0 (11.9%) patients were diagnosed with transthyretin amyloid CA (ATTR-CA) and 13 (7.3%) patients were diagnosed with light chain CA (AL-CA). Compared with patients with negative/equivocal [99mTc]Tc-PYP scans (grades 0-1), patients with positive [99mTc]Tc-PYP scans (grades 2-3) were older (78.0 vs. 68.0years, P<0.001), had higher levels of troponin (P=0.003) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (P<0.001), had a higher LV mass index (P<0.001), displayed a more depressed global longitudinal strain (GLS) (P<0.001) with a greater prevalence of a relative apical sparing pattern (P<0.001) and demonstrated a higher incidence of first-degree atrioventricular block (P=0.008) and low voltage patterns on electrocardiography (P<0.001). Patients with ATTR-CA and AL-CA were more likely to have a subendocardial or transmural LGE pattern on CMR (P<0.001) and had a significantly lower overall survival (P<0.001) when compared with other heart failure aetiologies. This is the first study to describe the clinical characteristics and outcomes of CA in the Middle East and Saudi Arabia. The prevalence of CA among screened heart failure patients here aligns with major international studies, suggesting significant underdiagnosis in the region. Therefore, larger multicentric studies and regional screening programmes are urgently needed to accurately characterize the epidemiology and outcomes of CA in the Middle East.

Parametric mapping using cardiovascular magnetic resonance for the differentiation of light chain amyloidosis and transthyretin-related amyloidosis.

To evaluate different cardiovascular magnetic resonance (CMR) parameters for the differentiation of light chain amyloidosis (AL) and transthyretin-related amyloidosis (ATTR). In total, 75 patients, 53 with cardiac amyloidosis (20 patients with AL (66±12 years, 14 males [70%]) and 33 patients with ATTR (78±5 years, 28 males [88%])) were retrospectively analyzed regarding CMR parameters such as T1 and T2 mapping, extracellular volume (ECV), and late gadolinium enhancement (LGE) distribution patterns, and myocardial strain, and compared to a control cohort with other causes of left ventricular hypertrophy (LVH; 22 patients (53±16 years, 17 males [85%])). One way-ANOVA and receiver operating characteristic analysis were used for statistical analysis. ECV was the single best parameter to differentiate between cardiac amyloidosis and controls (area under the curve [AUC]: 0.97, 95% confidence intervals [CI]: 0.89-0.99, p<.0001, cutoff: >30%). T2 mapping was the best single parameter to differentiate between AL and ATTR amyloidosis (AL: 63±4 ms, ATTR: 58±2 ms, p<.001, AUC: 0.86, 95% CI: 0.74-0.94, cutoff: >61 ms). Subendocardial LGE was predominantly observed in AL patients (10/20 [50%] vs. 5/33 [15%]; p=.002). Transmural LGE was predominantly observed in ATTR patients (23/33 [70%] vs. 2/20 [10%]; p<.001). The diagnostic performance of T2 mapping to differentiate between AL and ATTR amyloidosis was further increased with the inclusion of LGE patterns (AUC: 0.96, 95% CI: 0.86-0.99]; p=.05). ECV differentiates cardiac amyloidosis from other causes of LVH. T2 mapping combined with LGE differentiates AL from ATTR amyloidosis with high accuracy on a patient level.

ANOTHER BRICK IN THE WALL: A STRANGE CASE OF A BIG HUG

Abstract Background Left ventricular pseudoaneurysm (LVP) is a rare complication of myocardial infarction MI (less than 0,1% of all patients with MI) and develops when cardiac rupture is contained by adherent pericardium or scar tissue, thus contains no endocardium or myocardium, unlike a true left ventricular aneurysm (LVA). Clinical Case A 41–year–old man without remote cardiac history was admitted to the Emergency Department with chest pain that had started 7 days before after a referred ‘big hug’ from a friend. Results of the physical examination were unremarkable. Electrocardiogram: T waves negative in the inferior and lateral leads. Blood exams: normal troponins, C–reactive protein and D–dimer values. Chest computed tomography: no sign of pulmonary embolism. Transthoracic echocardiography (TE): ejection fraction 45%, voluminous aneurismal chamber communicating with the infero–posterior wall of the LV, stratified thrombus and mild mitral valve regurgitation. Coronary angiography: three vessel coronary artery disease. The last diagnosis was established by cardiac magnetic resonance imaging (MRI) which revealed a voluminous pseudoaneurysm of the inferior wall (56 mm x 50 mm with a 51 mm neck) and transmural late gadolinium enhancement (LGE) of the wall adjacent to the pseudoaneurysm with fibroadipose replacement and calcific metaplasia. The patient was transferred to the Cardiac Surgery Department. Intraoperatively the LVP was resected and the defect of the LV was repaired with a patch in bovine pericardium. In addition, coronary artery bypass grafting and mitral valve repair were performed. Discussion LVP develops when pericardium, in combination with thrombus and inflammation, surrounds a cardiac rupture. Inferior and posterolateral myocardial infarction (MI), due to occlusion of the Circumflex artery, are responsible for 82% of the LVP. LVP can be also found in the apical region due to anterior MI. In conclusion symptoms, signs, electrocardiographic abnormalities and radiographic findings seen in patients with LVP can be indistinguishable from those in patients with coronary disease alone. TE is the first non–invasive method for early diagnosis of LVA, but MRI is the gold standard for differential diagnosis between true aneurysm vs pseudoaneurysm. LGE of the pericardium is a new specific marker of pseudoaneurysm as opposed to true aneurysm.

LMNA–RELATED DILATED CARDIOMYOPATHY PRESENTING WITH REGIONAL WALL AKINESIS AND TRANSMURAL LATE GADOLINIUM ENHANCEMENT

Abstract A 26–year–old girl was admitted at hospital in December 2022 for a syncopal episode. She referred fatigue and dyspnea in the last 2 months. EKG was markedly abnormal showing peripheral low voltages, poor R wave progression in prechordial leads, negative T waves V4–V6, DII, DIII and aVF, fragmented QRS (Fig.1). Echo showed moderately dilated left ventricle (LV) with apical akinesia and apical aneurysm (no thrombi) and hypo–akinesia and hyperechoic appearance of the middle segments of the infero–posterior and lateral wall (Fig.2a). EF was 38%. There was no family history for sudden cardiac death and cardiomyopathy. Creatine kinase and neurological examination were normal. The diagnostic work–up included: myocardial scintigraphy which showed fixed tracer uptake deficit at apical and posterolateral levels (Fig.2b); cardiac magnetic resonance (CMR): apical aneurysm with extended late gadolinium enhancement (LGE) due to fibrosis, focally transmural, on the left ventricle’s midapical and infero–lateral thinned–hypokinetic myocardial walls (Fig.3a, 3b); Coronary angiography showed no stenosis. Due to myocardial aneurysm in absence of CAD, Chagas disease was excluded. We performed LV endomyocardial biopsy which showed cardiomyopathic changes and replacement fibrosis. Due to fibrosis extension, complex ventricular extrasystoles detected on monitoring and syncope, ICD was implanted. Finally genetic testing showed c.1621C&amp;gt;Tp.Arg541Cys LMNA pathogenetic mutation leading to the diagnosis of LMNA–related LV cardiomyopathy, with extensive fibrosis in multiple areas of left ventricle including the apical segments at a very young age. Patients with LMNA mutation-related heart disease are characterized by conduction abnormalities, ventricular tachyarrhythmias (VA) and high risk of sudden cardiac death with mildly impaired systolic function, often without chamber dilation. About 88% LMNA– cardiomyopathy have typical myocardial fibrosis, predominantly in the mid-myocardium of the basal septum. However, our patient and previous reported cases with the same p.R541 LMNA mutation presents with a specific phenotype including regional LV akinesis, segmental transmural LGE, significant LV dilatation and systolic dysfunction and VA without conduction abnormality. Of note, EKG shows normal A–V conduction but low voltage and negative T waves in precordial and inferior leads. These features are not typical for LMNA–disease and underline the phenotypic variability of cardiomyopathies.

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY AND CARDIAC SARCOIDOSIS: THE GREY ZONE

Abstract Cardiac sarcoidosis (CS) is a rare multisystem disorder characterized by granulomatous infiltration of the myocardium, whose clinical manifestations can be extremely heterogeneus. We report the case of a 47–year–old man with a previous diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVD). In history he had a marked arrhythmic pattern with multiple episodes of sustained ventricular arrhythmias, biventricular disfunction (LVEF 37%, RVEF 32%) and extensive biventricular transmural late–gadolinium enhancement (greater than 50%) at cardiac RMN. At EKG epsilon wave mainly seen in precordial leads. In November 2022 he was implanted with bicameral defibrillator and in March 2023 he underwent ablation procedure for ventricular tachycardia with RF with endo–epicardial approach. In May 2023 he arrived at our Centre for acute decompensated heart failure. At restored hemodynamic stability, screening for the possible inclusion in transplant list was started. Right heart catheterization (RHC) showed low cardiac index with no pulmonary hypertension. Chest CT unexpectedly showed the presence of multiple micronodules with perilymphatic distribution with confluent appearance compatible with pulmonary sarcoidosis. In consideration of this result, the transplant program was temporarily postponed and investigations for possible cardiac involvement of an inflammatory nature were started. 18F–FDG PET–CT showed pulmonary, splenic, lymphonodal and especially cardiac uptake in the mid–distal segment of the lateral wall of the left ventricle and in the inferior–apical site suspicious for inflammatory pathology. Unfortunately, both lymphonodal and cardiac biopsies were inconclusive because of insufficient material. Nevertheless, the clinical scenario satisfied the Japanese criteria for possible CS; therefore, treatment with prednisone 1 mg/kg was started and a 18F–FDG PET–CT was planned after 3 months of steroid therapy. CS can disguise as a phenocopy of arrhythmogenic right ventricular cardiomyopathy because of several common characteristics, especially arrhythmic presentation. Due to these similarities, a careful overall evaluation of each patient with ARVD is mandatory as several transplant centers have reported cases of CS in explanted heart with a pretransplant misdiagnosis of ARVD or dilated cardiomiopathy. Performing a chest CT in all ARVD patients as part of transplant screening may be considered.

Association between subclinical atherosclerosis burden and unrecognized myocardial infarction detected by cardiac magnetic resonance in middle-aged low-risk adults.

Evidence on the association between subclinical atherosclerosis (SA) and cardiovascular (CV) events in low-risk populations is scant. To study the association between SA burden and an ischaemic scar (IS), identified by cardiac magnetic resonance (CMR), as a surrogate of CV endpoint, in a low-risk population. A cohort of 712 asymptomatic middle-aged individuals from the Progression of Early SA (PESA-CNIC-Santander) study (median age 51 years, 84% male, median SCORE2 3.37) were evaluated on enrolment and at 3-year follow-up with 2D/3D vascular ultrasound (VUS) and coronary artery calcification scoring (CACS). A cardiac magnetic study (CMR) was subsequently performed and IS defined as the presence of subendocardial or transmural late gadolinium enhancement (LGE). On CMR, 132 (19.1%) participants had positive LGE, and IS was identified in 20 (2.9%) participants. Individuals with IS had significantly higher SCORE2 at baseline and higher CACS and peripheral SA burden (number of plaques by 2DVUS and plaque volume by 3DVUS) at both SA evaluations. High CACS and peripheral SA (number of plaques) burden were independently associated with the presence of IS, after adjusting for SCORE2 [OR for 3rd tertile, 8.31; 95% confidence interval (CI) 2.85-24.2; P < 0.001; and 2.77; 95% CI, 1.02-7.51; P = 0.045, respectively] and provided significant incremental diagnostic value over SCORE2. In a low-risk middle-aged population, SA burden (CAC and peripheral plaques) was independently associated with a higher prevalence of IS identified by CMR. These findings reinforce the value of SA evaluation to early implement preventive measures. Progression of Early Subclinical Atherosclerosis (PESA) Study Identifier: NCT01410318.

Impact of Myocardial Viability on Long-term Outcomes after Surgical Revascularization.

This study was conducted to evaluate whether myocardial viability assessed with cardiac magnetic resonance (CMR) affected long-term clinical outcomes after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICMP). Preoperative CMR with late gadolinium enhancement (LGE) was performed in 103 patients (64.9 ± 10.1 years, male:female = 82:21) with 3-vessel disease and left ventricular dysfunction (ejection fraction ≤ 0.35). Transmural extent of LGE was evaluated on a 16-segment model, and transmurality was graded on a 5-point scale: grades-0, absence; 1, 1 to 25%; 2, 26 to 50%; 3, 51 to 75%; 4, 76 to 100%. Median follow-up duration was 65.5 months (interquartile range = 27.5-95.3 months). Primary endpoint was the composite of all-cause mortality or hospitalization for congestive heart failure. Operative mortality was 1.9%. During the follow-up, all-cause mortality and readmission for congestive heart failure occurred in 29 and 8 patients, respectively. The cumulative incidence of the primary endpoint was 31.3 and 46.8% at 5 and 10 years, respectively. Multivariable analysis demonstrated that the number of segments with LGE grade 4 was a significant risk factor (hazard ratio 1.42, 95% confidence interval 1.10-1.83, p = 0.007) for the primary endpoint among the variables assessed by CMR. Other risk factors included age, dialysis, chronic obstructive pulmonary disease, and EuroSCORE II. The number of myocardial segments with transmurality of LGE >75% might be a prognostic factor associated with the composite of all-cause mortality or hospitalization for congestive heart failure after CABG in patients with 3-vessel disease and ICMP.

Cardiac MRI feature-tracking-derived torsion mechanics in systolic and diastolic dysfunction in systemic light-chain cardiac amyloidosis

To describe the myocardial torsion mechanics in cardiac amyloidosis (CA), and evaluate the correlations between left ventricle (LV) torsion mechanics and conventional parameters using cardiac magnetic resonance imaging feature tracking (CMR-FT). One hundred and thirty-nine patients with light-chain CA (AL-CA) were divided into three groups: group 1 with preserved systolic function (LV ejection fraction [LVEF] ≥50%, n=55), group 2 with mildly reduced systolic function (40%≤LVEF <50%, n=51), and group 3 with reduced systolic function (LVEF <40%, n=33), and compared with age- and gender-matched healthy controls (n=26). All patients underwent cine imaging and late gadolinium-enhancement (LGE). Cine images were analysed offline using CMR-FT to estimate torsion parameters. Global torsion, base-mid torsion, and peak diastolic torsion rate (diasTR) were significantly impaired in patients with preserved systolic function (p<0.05 for all), whereas mid-apex torsion and peak systolic torsion rate (sysTR) were preserved (p>0.05 for both) compared with healthy controls. In patients with mildly reduced systolic function, global torsion and base-mid torsion were lower compared to those with preserved systolic function (p<0.05 for both), while mid-apex torsion, sysTR, and diasTR were preserved (p>0.05 for all). In patients with reduced systolic function, only sysTR was significantly worse compared with mildly reduced systolic function (p<0.05). At multivariable analysis, right ventricle (RV) end-systolic volume RVESV index and NYHA class were independently related to global torsion, whereas LVEF was independently related to sysTR. RV ejection fraction (RVEF) was independently related to diasTR. LV global torsion performed well (AUC 0.71; 95% confidence interval [CI]: 0.61, 0.77) in discriminating transmural from non-transmural LGE in AL-CA patients. LV torsion mechanics derived by CMR-FT could help to monitor LV systolic and diastolic function in AL-CA patients and function as a new imaging marker for LV dysfunction and LGE transmurality.

Pulmonary Transit Time Derived from First-Pass Perfusion Cardiac MR Imaging: A Potential New Marker for Cardiac Involvement and Prognosis in Light-Chain Amyloidosis.

First-pass perfusion cardiac MR imaging could reflect pulmonary hemodynamics. However, the clinical value of pulmonary transit time (PTT) derived from first-pass perfusion MRI in light-chain (AL) amyloidosis requires further evaluation. To assess the clinical and prognostic value of PTT in patients with AL amyloidosis. Prospective observational study. 226 biopsy-proven systemic AL amyloidosis patients (age 58.62 ± 10.10 years, 135 males) and 43 healthy controls (age 42 ± 16.2 years, 20 males). SSFP cine and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences, and multislice first-pass myocardial perfusion imaging with a saturation recovery turbo fast low-angle shot (SR-TurboFLASH) pulse sequence at 3.0T. PTT was measured as the time interval between the peaks of right and left ventricular cavity arterial input function curves on first-pass perfusion MR images. Independent-sample t test, Mann-Whitney U test, Chi-square test, Fisher's exact test, analysis of variance, or Kruskal-Wallis test, as appropriate; univariable and multivariable Cox proportional hazards models and Kaplan-Meier curves, area under receiver operating characteristic curve were used to determine statistical significance. PTT could differentiate AL amyloidosis patients with (N = 188) and without (N = 38) cardiac involvement (area under the curve [AUC] = 0.839). During a median follow-up of 35 months, 160 patients (70.8%) demonstrated all-cause mortality. After adjustments for clinical (Hazard ratio [HR] 1.061, confidence interval [CI]: 1.021-1.102), biochemical (HR 1.055, CI: 1.014-1.097), cardiac MRI-derived (HR 1.077, CI: 1.034-1.123), and therapeutic (HR 1.063, CI: 1.024-1.103) factors, PTT predicted mortality independently in patients with AL amyloidosis. Finally, PTT could identify worse outcomes in patients demonstrating New York Heart Association class III, Mayo 2004 stage III, and transmural LGE pattern. PTT may serve as a new imaging predictor of cardiac involvement and prognosis in AL amyloidosis. 2 TECHNICAL EFFICACY: Stage 2.

Incremental prognostic value of late gadolinium enhancement extent, transmurality, and pattern in patients with ischaemic cardiomyopathy

Abstract Background Presence and extent of late gadolinium enhancement (LGE) using cardiac magnetic resonance (CMR) are strong prognosticators of outcomes in ischaemic cardiomyopathy (ICM), but the prognostic value of multiple location of LGE, LGE transmurality, and midwall LGE area in addition to ischaemic LGE is not well established. Purpose To assess the incremental prognostic value of presence, extent, transmurality, and pattern of LGE in patients with ICM and reduced left ventricular ejection fraction (LVEF)­­. Methods Between 2008 and 2022, all consecutive patients referred for myocardial viability assessment using CMR and a history of ICM (≥70% stenosis in ≥1 epicardial coronary vessel on angiography and/or history of myocardial infarction and/or coronary revascularization) and LVEF value &amp;lt;50% were prospectively recruited. The outcome was all-cause death using the electronic French National Registry of Death. Nested Cox proportional hazard models were used to assess the prognostic value of the following LGE features: the extent, the transmurality of subendocardial ischaemic LGE (&amp;lt;50%, ≥50%, or transmural), the presence of LGE in multiple areas, and the presence of midwall LGE. The additional predictive value of the LGE features was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 6,082 included patients (mean age 65±12 years, 73% male, mean LVEF 43.8±5.7%), 3,591 (59%) had ischaemic LGE; 652 (10.7%) patients died during a median follow up of 9 [6.6-11.5] years. After adjustment for risk factors in the overall population, the presence of ischaemic LGE was associated with a higher risk of death (adjusted HR=3.57; 95%CI: 2.89-4.40, p&amp;lt;0.001). Figure 1 shows survival according to the different LGE features. Patients with both multiple localisations of ischaemic LGE area and additional LGE midwall exhibited the highest risk of death (p&amp;lt;0.001). After adjustment in the subgroup of patients with ischaemic LGE (n=3,591), LGE extent (HR=1.55; 95%CI: 1.47-1.63), multiple localisations of ischaemic LGE (HR 1.61 95%CI: 1.32-1.97), LGE transmurality (HR=4.48; 95%CI: 3.39-5.93), and presence of additional midwall LGE (HR=1.77; 95%CI: 1.44-2.17, all p&amp;lt;0.001) were independently associated with a higher risk of death. A model combining all LGE features showed the best improvement in model discrimination and reclassification above traditional factors (C-statistic improvement: 0.17; NRI=54.1%; IDI=12.6%, Chi-2 global=1133, all p&amp;lt;0.001; LR-test p&amp;lt;0.001, Figure 2). Conclusion In a large cohort of ICM patients with reduced LVEF, ischaemic LGE extent, transmurality, multiple ischaemic LGE localisations, and additional presence of midwall LGE were independent prognosticators of death. A model combining all these LGE features had an incremental prognostic value over traditional prognostic factors to predict all-cause death.Kaplan-Meier survival curvesIncremental prognostic value

A high-risk late gadolinium enhancement pattern is associated with arrhythmic events in patients with dilated cardiomyopathy

Abstract Introduction Myocardial fibrosis constitutes a substrate for the development of ventricular arrhythmias in patients with non-ischaemic dilated cardiomyopathy (DCM). Late gadolinium enhancement (LGE)-cardiac magnetic resonance (CMR) imaging represents a powerful tool for arrhythmic risk stratification. Moreover, arrhythmic risk is determined by the extent and localization of LGE. A high-risk LGE pattern, defined as the presence of epicardial, transmural or septal plus free-wall LGE, has been recently associated with a higher incidence of arrhythmic events comparing with other LGE patterns. Purpose To evaluate the prevalence of a high-risk LGE pattern in patients with DCM and its association with arrhythmic events. Methods From 2014 to 2021, all patients (N = 229) with DCM were prospectively evaluated in our tertiary care hospital. 174 patients underwent a 1.5 Tesla scanner CMR as part of the diagnostic workup and were included in the present study. The primary endpoint was a composite of sudden cardiac death or sustained monomorphic ventricular tachycardia. Results Mean age of our cohort was 61 years (standard deviation 14.5), and 64.2% were male. Median follow-up was 41 (interquartile range 26-62) months. LGE was present in 96 (55.2%) patients of our cohort (LGE+), and a high risk LGE pattern was found in 41 (42.7% of all LGE+ patients). LGE was more frequently located in the basal segments (78.6%). Mid-wall septal LGE was found in 46.9% of LGE+ patients, and it was the most common pattern. 21.4% of LGE+ patients had combined septal and free-wall LGE, 23.5% had epicardial LGE and 13.3% had transmural LGE. Baseline characteristics of LGE+ patients with and without a high-risk LGE pattern are shown at the Table. The incidence of ventricular arrhythmic events during follow-up was 31.7% in patients with a high-risk LGE pattern, and 9.1% in LGE+ patients but without a high-risk pattern (p=0.005). In patients without a high-risk LGE, including LGE- patients and LGE+ patients with other LGE patterns, incidence of ventricular arrhythmic events was 8.3% (p&amp;lt;0.001). The survival free curves for the combined arrhythmic endpoint comparing LGE+ patients with and without a high-risk pattern are shown in the Figure. Conclusion The presence of a high-risk LGE pattern in patients with DCM its associated with a higher incidence of ventricular arrhythmic events, comparing with LGE+ patients without a high-risk pattern. We suggest that this high-risk pattern should be taken into account when performing arrhythmic risk stratification in patients with DCM.TableFigure

Incidence and predictors of heart failure in a cohort of MINOCA patients

Abstract Background/Introduction A higher risk of death and major cardiovascular events, including Heart Failure (HF), after a Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) has been described. In particular, HF has a negative impact not only on survival but also on quality of life. In this context, strategies to identify subjects with a greater risk of developing HF are needed. Purpose. Assess incidence and predictors of HF developing subsequently a MINOCA. Methods 461 subjects with suspected MINOCA from 2016 to 2021 were assessed. Acute myocarditis, Takotsubo syndromes, cardiomyopathies and patients with incomplete data were excluded. The final cohort consisted of 188 patients with a confirmed MINOCA diagnosis. After a mean follow-up of 36±14.8 months, 20 patients (10.6%) had hospital readmission for HF. Demographic, clinical, laboratory, and instrumental data were collected and analyzed. Results None among demographic characteristics, cardiovascular risk factors or comorbidities showed correlation with HF occurrences. Paroxysmal or permanent atrial fibrillation was more frequent among patients who developed HF (p .005), such as ST-elevation at onset (p .001). Higher glycemia at admission correlated with HF (p .012). In this regard, hyperglycemia could act as a direct toxic agent or as an indirect marker of a greater stress response. Cardiac troponin I (cTnI) at peak, but not first cTnI measurement, was significantly higher in patients who developed HF (p&amp;lt;.001), confirming the prognostic value of troponin, even in this context. Concerning echocardiography, HF incidence was higher in patients with any wall motion abnormalities (p .037), lower ejection fraction (EF; p .046), especially if EF≤40% (p&amp;lt;.001), higher atrial maximum diameter (p .005), end-diastolic diameter (p. 001) or normalized end-diastolic volume (p&amp;lt;.001). HF occurred more often (p&amp;lt;.001) in patients with a transmural pattern of late gadolinium enhancement (LGE), which resulted as an independent risk factor for HF developing in multivariate analysis (HR 15.32, 95% CI 5.13-45.75, p&amp;lt;.001). 32 patients (17%) were affected by non-obstructive coronary arteries stenosis (i.e., &amp;lt;50%). This finding, but not re-infarction, was also associated with HF development (p .004). Only 2 out of the 68 patients dismissed with DAPT developed HF (p .010). In our study beta-blockers, RAS inhibitors and statins at dismission had not reduced the risk of HF. Nevertheless, the low sample size forbids inferring conclusions about the therapy. Conclusion In our cohort of patients with MINOCA, several clinical, laboratory and echocardiographic characteristics correlated with a higher frequency of HF occurrences. Moreover, a broader extent of cardiac damage, as testified by cTnI, wall motion abnormalities, reduced EF and transmural LGE, could predict HF development. Further studies to establish adequate follow-up programs and therapy to prevent HF progression in these patients are needed.Figure 1

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.

The Diagnostic Value of the 12-Lead ECG in Arrhythmogenic Left Ventricular Cardiomyopathy: Novel ECG Signs

BackgroundElectrocardiographic (ECG) findings in arrhythmogenic left ventricular cardiomyopathy (ALVC) are limited to small case series. ObjectivesThis study aimed to analyze the ECG characteristics of ALVC patients and to correlate ECG with cardiac magnetic resonance and genotype data. MethodsWe reviewed data of 54 consecutive ALVC patients (32 men, age 39 ± 15 years) and compared them with 84 healthy controls with normal cardiac magnetic resonance. ResultsT-wave inversion was often noted (57.4%), particularly in the inferior and lateral leads. Low QRS voltages in limb leads were observed in 22.2% of patients. The following novel ECG findings were identified: left posterior fascicular block (LPFB) (20.4%), pathological Q waves (33.3%), and a prominent R-wave in V1 with a R/S ratio ≥0.5 (24.1%). The QRS voltages were lower in ALVC compared with controls, particularly in lead I and II. At receiver-operating characteristic analysis, the sum of the R-wave in I to II ≤8 mm (AUC: 0.909; P < 0.0001) and S-wave in V1 plus R-wave in V6 ≤12 mm (AUC: 0.784; P < 0.0001) effectively discriminated ALVC patients from controls. It is noteworthy that 4 of the 8 patients with an apparently normal ECG were recognized by these new signs. Transmural late gadolinium enhancement was associated to LPFB, a R/S ratio ≥0.5 in V1, and inferolateral T-wave inversion, and a ringlike pattern correlated to fragmented QRS, SV1+RV6 ≤12 mm, low QRS voltage, and desmoplakin alterations. ConclusionsPathological Q waves, LPFB, and a prominent R-wave in V1 were common ECG signs in ALVC. An R-wave sum in I to II ≤8 mm and SV1+RV6 ≤12 mm were specific findings for ALVC phenotypes compared with controls.

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.

Myocardial Scar and Revascularization on Mortality in Ischemic Cardiomyopathy (from the Late Gadolinium Enhancement Cardiac Magnetic Resonance Study)

Myocardial viability test to guide revascularization remains uncertain in patients with ischemic cardiomyopathy. We evaluated the different impacts of revascularization on cardiac mortality according to the extent of myocardial scar assessed by cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) in patients with ischemic cardiomyopathy. A total of 404 consecutive patients with significant coronary artery disease and an ejection fraction ≤35% were assessed by LGE-CMR before revascularization. Of them, 306 patients underwent revascularization and 98 patients received medical treatment alone. The primary outcome was cardiac death. During a median follow-up of 6.3years, cardiac death occurred in 158 patients (39.1%). Revascularization was associated with a significantly lower risk of cardiac death than medical treatment alone in the overall population (adjusted hazard ratio [aHR] 0.29, 95% confidence interval (CI) 0.19 to 0.45, p <0.001). There was a significant interaction between the number of segments with >75% transmural LGE and revascularization on the risk of cardiac death (p=0.037 for interaction). In patients with limited myocardial scar (<6 segments with >75% transmural LGE, n=354), revascularization had a significantly lower risk of cardiac death than medical treatment alone (aHR 0.24, 95% CI 0.15 to 0.37, p <0.001); in patients with extensive myocardial scar (≥6 segments with >75% transmural LGE, n=50), there was no significant difference between revascularization and medical treatment alone regarding the risk of cardiac death (aHR 1.33, 95% CI 0.46 to 3.80, p=0.60). In conclusion, the assessment of myocardial scar by LGE-CMR may be helpful in the decision-making process for revascularization in patients with ischemic cardiomyopathy.

855 PREDICTORS OF LATE GADOLINIUM ENHANCEMENT DEVELOPMENT AND EXTENSION IN MYOCARDIAL INFARCTION WITH NON-OBSTRUCTIVE CORONARY ARTERIES

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous clinical entity and in its complex diagnostic approach cardiovascular magnetic resonance (CMR) plays a pivotal role. Purpose To characterize the differences of MINOCA patients with and without late gadolinium enhancement (LGE) at CMR and to identify the predictors for ischemic LGE development and extension. Methods We assessed 461 MINOCA cases from January 2016 to June 2021. MINOCA were defined according to the current European guidelines criteria. We excluded acute myocarditis, Tako-tsubo syndromes, cardiomyopathies, or non-pathological CMR. According to CMR imaging findings, our cohort was divided into two CMR phenotypes based on regional myocardial necrosis detected throughout LGE (“LGE-positive MINOCA”) or regional ischemic injury without LGE (“LGE-negative MINOCA”). Extended LGE was considered as the presence of &amp;gt;2 segments with transmural LGE. Multivariate logistic regression analysis was used to determine the predictors of LGE and extended LGE. Results The final cohort included 175 MINOCA: 121 (69.1%) constituted the LGE-positive group. The mean time delay between acute clinical presentation and CMR was 6 ± 2.9 days. At admission, MINOCA LGE-patients more frequently presented angina and ST segment elevation (24% vs 7.4%, p = 0.01), compared to the LGE negative ones. Furthermore, the LGE positive group had a significantly greater infarct size, measured by peak hs-Troponin I values and left ventricular function. The only predictor of LGE was the peak troponin value (OR 1.64, 95% CI 1.18–2.28, p = 0.003), while predictors of extended LGE were ST-segment elevation at admission (OR 7.44, 95% CI 1.57–35.22, p = 0.01), peak troponin values (OR 1.07, 95% CI 1.02–1.13, p = 0.01) and the presence of non-obstructive coronary artery disease at coronary angiography (OR 5.49, 95% CI 1.20–25.09, p = 0.028). Conclusion The presence and extension of LGE at early CMR evaluation is an important feature in the setting of MINOCA. In addition, simple baseline characteristics (such as ST elevation, peak troponin value and LVEF) may aid the identification of a greater ischemic necrosis burden at CMR and therefore these high-risk MINOCA subjects could be benefit from a stricter management effort.

225 PROGNOSTIC ROLE OF EARLY CARDIAC MAGNETIC RESONANCE IN MYOCARDIAL INFARCTION WITH NON-OBSTRUCTIVE CORONARY ARTERIES (MINOCA)

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a significant proportion of acute myocardial infarction (AMI) population. MINOCA is a working diagnosis and an accurate investigation of the underlying causes should always be performed. In this setting, cardiac magnetic resonance (CMR) imaging plays a pivotal diagnostic role. However, a prognostic stratification based on the CMR findings in ischemic MINOCA is still unavailable. Purpose To evaluate the potential prognostic impact of specific CMR findings - especially ischemic late gadolinium enhancement (LGE) patterns - in order to look for measurable parameters that may guide the management of this still troubled clinical entity. Methods We assessed 461 MINOCA from January 2016 to June 2021. We excluded acute myocarditis, Tako-tsubo syndromes, cardiomyopathies, or non-pathological CMR. According to CMR findings, MINOCA were classified in two phenotypes: LGE-positive (an ischemic subendocardial or transmural LGE pattern) or LGE-negative (cases without LGE but exhibiting regional myocardial injury defined by myocardial edema in a coronary territory with a typically ischemic "wave-front" and/or regional wall motion abnormality consistent with coronary distribution). All-cause mortality, re-infarction, stroke, heart failure (HF) and the composite endpoint (MACE) were evaluated. Extended LGE was considered as the presence of &amp;gt;2 segments with transmural LGE. The mean follow-up was 36.1 ± 15.2 months and CMR was performed at a mean of 6 ± 2.9 days from the acute presentation. Results The final cohort included 175 MINOCA with a likely-ischemic etiology: 121 (69.1%) constituted the LGE-positive group. The mean age of the study population was 62.3 ± 12.9 years and more than 61% were females. During follow-up, HF (15.7% vs 1.9%, p=0.008) and MACE (20.7% vs 7.4%, p=0.029) occurred more frequently in MINOCA "LGE-positive" compared to the "LGE-negative" ones. Extended LGE was significantly more prevalent in patients with versus without subsequent HF. On multivariable Cox regression, extended LGE was an independent predictor of HF occurrence (HR 18.49, 95%CI 4.65–73.61, p &amp;lt; 0.001) and MACE (HR 14.64, 95%CI 3.91–54.86, p &amp;lt; 0.001). Conclusions Our data suggest that in MINOCA patients the detection of LGE is correlated with the incidence of major cardiovascular events and heart failure during long-term follow-up. In fact, LGE extension was identified as the strongest predictor of cardiac adverse events. The early execution of CMR is useful in the prognostic stratification of MINOCA and this could guide the subsequent clinical and therapeutic management.

996 INCIDENCE AND PREDICTORS OF HEART FAILURE DEVELOPMENT IN A COHORT OF PATIENTS WITH MYOCARDIAL INFARCTION WITH NON-OBSTRUCTIVE CORONARY ARTERIES

Abstract Background A higher risk of death and major cardiovascular events, including Heart Failure (HF), after a Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) has been described. In particular, HF has a negative impact not only on survival but also on quality of life. In this context, strategies to identify subjects with a greater risk of developing HF are needed. Aims To assess the incidence and predictors of HF developing subsequently a MINOCA. Methods 461 subjects with suspected MINOCA from 2016 to 2021 were assessed. Acute myocarditis, Takotsubo syndromes, cardiomyopathies and patients with incomplete data were excluded. The final cohort consisted of 188 patients with a confirmed MINOCA diagnosis. After a mean follow-up of 36±14.8 months, 20 patients (10.6%) had hospital readmission for HF. Demographic, clinical, laboratory, and instrumental data were collected and analyzed. Results None among demographic characteristics, cardiovascular risk factors or comorbidities showed correlation with HF occurrences. Paroxysmal or permanent atrial fibrillation was more frequent among patients who developed HF (p .005), such as ST-elevation at onset (p .001). Higher glycemia at admission correlated with HF (p .012). In this regard, hyperglycemia could act as a direct toxic agent or as an indirect marker of a greater stress response. Cardiac troponin I (cTnI) at peak, but not first cTnI measurement, was significantly higher in patients who developed HF (p&amp;lt;.001), confirming the prognostic value of troponin, even in this context. Concerning echocardiography, HF incidence was higher in patients with any wall motion abnormalities (p .037), lower ejection fraction (EF; p .046), especially if EF≤40% (p&amp;lt;.001), higher atrial maximum diameter (p .005), end-diastolic diameter (p. 001) or normalized end-diastolic volume (p&amp;lt;.001). Among cardiac magnetic resonance findings, HF occurred more often (p&amp;lt;.001) in patients with a transmural pattern of late gadolinium enhancement (LGE), which resulted as an independent risk factor for HF developing at the multivariate analysis (HR 15.32, 95% CI 5.13-45.75, p&amp;lt;.001). Finally, 32 patients (17%) were affected by non-obstructive coronary arteries stenosis (i.e., &amp;lt;50%). This finding, but not re-infarction, was also associated with HF development (p .004). Notably, only 2 out of the 68 patients dismissed with DAPT developed HF (p .010). In our study beta-blockers, RAS inhibitors and statins at dismission had not reduced the risk of HF. Nevertheless, the low sample size forbids inferring conclusions about the therapy. Conclusion In our cohort of patients with MINOCA, several clinical, laboratory and echocardiographic characteristics correlated with a higher frequency of HF occurrences. Moreover, a broader extent of cardiac damage, as testified by cTnI, wall motion abnormalities, reduced EF and transmural LGE, could predict HF development. Further studies to establish adequate follow-up programs and therapy to prevent HF progression in these patients are needed.

240 A PEDIATRIC CASE OF BIVENTRICULAR END-STAGE ARRHYTHMOGENIC CARDIOMYOPATHY

Abstract Background Arrhythmogenic cardiomyopathy (ACM) is a rare heart muscle disease characterized by cardiomyocyte necrosis and fibro-adipose substitution which contribute both to the genesis of malignant ventricular arrhythmias and the morpho-functional alterations of the ventricles. ACM has always been considered a right ventricular disease with secondary involvement of the left ventricle, but recently a left dominant phenotype has been also described. Case report A 14-year-old patient was admitted to our hospital after out-of-hospital cardiac arrest due to ventricular fibrillation, which occurred when she was at rest. A family history of sudden death and dilated cardiomyopathy was retrieved (her brother died at the age of 18 with a dilated heart), but other family members had never been screened to date. Cardiac magnetic resonance imaging (cMRI) appearance was consistent with biventricular dilatation along with severe systolic dysfunction (left ventricular ejection fraction 20%; right ventricular ejection fraction 25%). It showed also thinning and bulging of the basal free wall of the right ventricle proximal to the outflow tract (up to 4 mm) and multiple foci of subepicardial, mid-wall and transmural late gadolinium enhancement (LGE) in both ventricles. Signs of acute decompensated heart failure and a high arrhythmic burden were present. After cardiopulmonary stabilization, she underwent the implantation of a cardioverter-defibrillator (ICD). Conclusion We herein report an uncommon case of biventricular AC (‘definite diagnosis’ according to both Task force criteria 2010 and Padua criteria) with advanced morpho-functional dysfunction occurring already in pediatric age, without any alerting symptom until the cardiac arrest (the typical onset of the ACM in children). It shows how severe biventricular involvement may affect young patients with a rapid progression of the disease. It also stresses the need for a strict follow-up of the family members of a proband since his first diagnosis, highlighting the pivotal role of cMRI in the diagnosis of pediatric disease. This has not been thoroughly studied and lacks sensitive and specific diagnostic criteria.