813 The added value of transthoracic three dimensional echocardiography in apical hypertrophic cardiomyopathy

We present the case of a 73-year-old patient with a recent diagnosis of hypertrophic cardiomyopathy (HCM). He was asymptomatic and has no family history of sudden cardiac death (SCD), syncope or ventricular arrhythmias. An echocardiogram performed at the moment of diagnosis (2020), showed left ventricular (LV) asymmetric apical hypertrophy with maximal wall thickness of 21 mm. Cardiac magnetic resonance (CMR) confirmed LV apical hypertrophy with mid-ventricular obliteration, and late gadolinium enhancement in the apical segments, without wall motion abnormalities present at rest. According to 2014 ESC guidelines, his calculated risk score for sudden cardiac death was low (1.23% at 5 years). On 2021, a comprehensive transthoracic echocardiographic examination including advanced techniques (three-dimensional echo-3DE-, and two-dimensional speckle-tracking-2DSTE) was done as part of his routine follow-up in our cardiomyopathy outpatient clinic. The echo study showed an asymmetric pattern of LV hypertrophy with a maximal wall thickness of 21 mm at the level of the anterolateral apical segment, normal LV volumes (end-diastolic volume 55 mL/m2) and ejection fraction (69%) by 3DE. LV longitudinal strain analysis by 2DSTE showed impaired LV myocardial deformation mainly at the apical LV segments (GLS = −13.6%). There was evidence of dynamic intracavitary obstruction (maximal gradient 32 mmHg at rest and raised to 52 mmHg during Valsalva manoeuvre). 3DE views of the LV (both multi-slice display and 3D rendered image) allowed to avoid foreshortening of the LV apical views, and to appreciate the actual wall motion at the real LV apex. They revealed a LV apical aneurysm which was not detected in the conventional LV-focused apical 2D views (Figure 1A and B). Apical hypertrophic cardiomyopathy (ApHCM) is a variant of HCM that is characteristic of focal thickening of the LV apical myocardium and was reported to have a more benign course than other non-apical forms. However, the presence of LV aneurysm in ApHCM patients is associated with an increased risk for ventricular arrhythmias, sudden cardiac death and thromboembolism. Accordingly, the detection of apical LV aneurysms has significant impact on patient management. Guidelines recommend the use of contrast echocardiography or CMR when the apical region of the LV is suboptimally visualized by conventional 2D echocardiography. However, contrast echocardiography may still be affected by apical foreshortening resulting in suboptimal accuracy, as it is a 2D technique. On the other end, CMR may be contraindicated or not widely available for routine yearly follow-up for all HCM patients requiring regular imaging follow-up. Our clinical case emphasizes the added value of 3DE to increase the sensitivity of transthoracic echocardiography in detecting apical LV aneurysms in patients with apical HCM with important clinical implications for the management of the patient. 813 Figure 1(A) 2D 4chamber-view showing maximal wall thickness in the apical segments (21 mm) with apical obliteration. At a first evaluation, apical aneurism is not easily detected. (B) 4D rendering of the apex showing the apical aneurism.

Relationships between left ventricular mass and QRS duration in diverse types of left ventricular hypertrophy

Aims Hypertrophic cardiomyopathy (HCM) may be associated with very narrow QRS, while left ventricular hypertrophy (LVH) may increase QRS duration. We investigated the relationships between QRS duration and LV mass (LVM) in subtypes of abnormal LV wall thickness. Methods and results Automated measurement of LVM on MRI was correlated to automated measurement of QRS duration on ECG in HCM, left ventricular non compaction (LVNC), left ventricular hypertrophy (LVH), and controls with healthy hearts. Uni and multivariate analyses were performed between groups including explanatory variables expected to influence LVM and QRS duration. The relationships between QRS duration and LVM were further studied within each group. Two hundred and twenty-one HCM, 28 LVNC, 16 LVH, and 40 controls were retrospectively included. Mean QRS duration was 92 ms for HCM, 104 for LVNC, 110 for LVH, and 92 for controls (P < 0.01). Mean LVM was 100, 90, 108, and 68 g/m2 (P < 0.01). QRS duration, LVM, hypertension, maximal wall thickness, and late gadolinium enhancement were significantly linked to HCM in multivariate analysis (w/wo bundle branch block). An independent negative correlation was found between LVM and QRS duration in the HCM group, while the relationship was reverse in LVNC, LVH, and controls. Conclusion QRS duration increases with LVM in LVNC, LVH, or in healthy hearts, while reverse relationship is present in HCM. These relationships were independent from other parameters. These results warrant additional investigations for refining diagnosis criteria for HCM in the future.

Hypertrophy of unaffected cardiomyocytes correlates with severity of cardiomyopathy in female patients with Fabry disease

Aim To investigate the contribution of unaffected cardiomyocytes in Fabry disease cardiomyopathy. Findings Left ventricular (LV) endomyocardial biopsies from twenty-four females (mean age 53 ± 11 ys) with Fabry disease cardiomyopathy were studied. Diagnosis of FD was based on the presence of pathogenic GLA mutation, Patients were divided in four groups according with LV maximal wall thickness (MWT): group 1 MWT ≤ 10.5 mm, group 2 MWT 10.5–15 mm, group 3 MWT 16–20 mm, group 4 MWT > 20 mm. At histology mosaic of affected and unaffected cardiomyocytes was documented. Unaffected myocytes’ size ranged from normal to severe hypertrophy. Hypertrophy of unaffected cardiomyocytes correlated with severity of MWT (p < 0.0001, Sperman r 0,95). Hypertrophy of unaffected myocytes appear to concur to progression and severity of FDCM. It is likely a paracrine role from neighboring affected myocytes.

Sudden cardiac death risk in hypertrophic cardiomyopathy: comparison between echocardiography and magnetic resonance imaging

In hypertrophic cardiomyopathy (HCM) patients, left ventricular (LV) maximal wall thickness (MWT) is one of the most important factors determining sudden cardiac death (SCD) risk. In a large unselected sample of HCM patients, we aimed to simulate what changes would occur in the calculated SCD risk according to the European HCM Risk-SCD calculator when MWT measured using echocardiography was changed to MWT measured using MRI. All consecutive patients with HCM who underwent cardiac MRI were included. MWT measured with echocardiography and MRI were compared, and 5-year SCD risk according to the HCM Risk-SCD calculator was computed using four different models. The final population included 673 patients [389 (57.8%) males, median age 50 years, interquartile range (36–60)]. The median MWT was lower measured by echocardiography than by MRI [20 (17–24) mm vs 21 (18–24) mm; p < 0.0001]. There was agreement between echocardiography and MRI in the measurement of maximal LV wall thickness in 96 patients (14.3%). The largest differences between echo and MRI were − 13 mm and + 9 mm. The differences in MWT by echocardiography and MRI translated to a maximal difference of 8.33% in the absolute 5-year risk of SCD, i.e., the echocardiography-based risk was 8.33% lower than the MRI-based estimates. Interestingly, 13.7% of patients would have been reclassified into different SCD risk categories if MRI had been used to measure MWT instead of echocardiography. In conclusion, although there was high general intermodality agreement between echocardiography and MRI in the MWT measurements, the differences in MWT translated to significant differences in the 5-year risk of SCD.

447 Pathology of conduction tissue in cardiac amyloid: correlation with arrhythmic manifestations

Aims Pathology of conduction tissue (CT) and relative arrhythmic manifestations in living subjects with cardiac amyloid (CA) have never been reported. Methods and results In 17 out of 45 consecutive patients with CA, a left ventricular (LV) endomyocardial biopsy included CT sections. Extensive clinical examination, non-invasive (resting ECG, Holter monitoring, echocardiography), and invasive cardiac studies (selective coronary angiography, LV angiography, and LV endomyocardial biopsy) were performed in all patients. Cardiac magnetic resonance (CMR) was performed in 12 of the 17 patients (70%). CT was identified by Aschoff-Monckeberg histologic criteria associated to positive immunostaining for HCN4. Degree of CT infiltration was defined as mild when ≤ 30% of CT area was replaced by fibrous tissue and Congo red+ material, moderate in 30–70% CT area involvement and severe in &gt; 70% CT cell area replacement. CT infiltration was correlated with ventricular arrhythmias, echocardiographic LV maximal wall thickness (MWT) and type of amyloid protein identified by myocardial immunohistochemistry. CMR confirmed the presence of cardiac hypertrophy with preserved systolic function in all but one patient. LGE was present in all patients, predominantly with diffuse (5/11) or subendocardial (4/11) pattern compared to focal (2/11). In 7/11 patients T1 mapping sequences have been acquired; nT1 and ECV were increase in all patients (nT1: 1171 ± 61 ms; ECV: 59.9 ± 7.5%). Mild CT involvement was observed in 5 cases; moderate in 3; severe compromise in 9. CT involvement was associated with a parallel infiltration of CT artery. CT infiltration correlated with severity of arrhythmias (Spearman rho = 0.8, P &lt; 0.001) but not with age, MWT or type of amyloid protein. In particular, major ventricular tachyarrhythmias requiring pharmacologic treatment or ICD implantation occurred in 7 patients with severe, 1 patient with moderate and none with mild CT infiltration. Pacemaker implantation was required in 3 patients with complete CT area replacement. Conclusion CA associated arrhythmias correlate with severity of CT infiltration. CT involvement is independent from type and severity of CA suggesting a variable affinity of amyloid protein to CT.

Abstract 16702: Myocardial Deformation Analysis in Hypertrophic Cardiomyopathy With Sarcomere Mutations: Insights From 2,221 Patients Within the NHLBI-HCM Registry

Introduction: Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere genes that alter myocardial contractility and relaxation. Three-dimensional myocardial deformation analysis (3D-MDA) may elucidate left ventricular (LV) abnormalities associated with sarcomere genotype status. Hypothesis: We hypothesize that HCM patients with sarcomere mutations have changes in myocardial contractility profiles that are associated with adverse LV architectural changes. Methods: 3D-MDA was measured using validated feature-tracking software applied to 2D cine cardiac MRI studies in 2,221 genotyped patients within the NHLBI HCM Registry. Results: Baseline, cardiac MRI, and 3D MDA-derived strain characteristics stratified by sarcomere status are shown in Table 1. Sarcomere positive patients were younger, had less LV outflow tract obstruction and lower indexed LV mass, but similar LVEF and trend towards higher serum NT-proBNP levels. Maximal wall thickness, measures of diffuse myocardial fibrosis (native T1, extracellular volume fraction) were elevated with corresponding reduction in global radial strain. Global minimum principal and epicardial layer conventional strain values were higher in sarcomere positive patients. Epicardial minimum principal strain was highly correlated with indexed LV mass (r=0.42, P<0.0001), maximal wall thickness (r=0.29, P<0.0001), LVEF (r=-0.33, P<0.0001), late gadolinium enhancement (r=0.22, P<0.0001) and NT-proBNP (r=0.21, P<0.0001) levels in those with sarcomere mutations. Conclusions: Sarcomere positive HCM patients had differences in myocardial deformation strain profiles that were correlated to LV architectural changes and NT-proBNP levels despite lower indexed LV mass. More sensitive measures of contractile dysfunction may help elucidate pathophysiological mechanisms by which sarcomere mutations cause disease progression and adverse clinical outcomes in HCM.

Abstract 15270: Coronary Plaque Natural History Displays Marked Longitudinal Heterogeneity Along the Length of Individual Coronary Plaques

Introduction: Plaque natural history is related to local shear stress, and shear stress has been shown to be heterogeneously distributed along the length of individual plaques. We investigated the longitudinal spatial heterogeneity of plaque progression/regression/quiescence in human coronary arteries. Methods: 591 coronary arteries from 302 patients with coronary disease who presented with an acute coronary syndrome from the PREDICTION study were investigated for local plaque progression/regression/quiescence patterns in non-culprit plaques after 6-10 month FU. Arterial geometry was derived from angiography/IVUS-based vascular profiling and reported in 3 mm segments. Plaques were defined as >3 consecutive segments with maximal wall thickness>0.5 mm. Plaque progression was defined as >5% increase, regression as <-5% decrease, and quiescence as no change in plaque burden (plaque area/ total vessel area * 100%). Results: 5658 3mm-segments of 661 plaques were analyzed. Plaque burden changes ranged from -22% to +20%. Among all plaques, 56% showed segments with plaque progression, 60% with regression and 96% with quiescence. On average, 17% of the plaque length displayed plaque progression, 20% regression and 63% quiescence. The presence and number of natural history features (progression, regression, quiescence) within the individual plaques were significantly related to plaque length using logistic mixed model regression analysis (figure). Conclusions: Coronary plaque natural history is extremely heterogeneous along the length of an individual plaque. These observations may explain why revascularization of a focal severe obstruction in the ISCHEMIA trial did not affect clinical outcomes, since remaining high-risk plaque up- or down-stream from the revascularization may have led to future cardiac events.

Electrocardiographic differences between Anderson-Fabry and sarcomeric hypertrophic cardiomyopathy and correlation with cardiac magnetic resonance

Background Differential diagnosis between Anderson-Fabry (AF) and sarcomeric hypertrophic cardiomyopathy (HCM) is often very challenging particularly in AF patients with late onset cardiac involvement. Purpose To gain new insights from standard electrocardiogram (ECG) in AF disease for differential diagnosis from sarcomeric HCM. Additionally, to better understand ECG features in AF patients, a correlation substudy ECG-cardiac magnetic resonance (CMR) has been performed. Methods From 162 patients with definite diagnosis of AF disease, 111 [65 males, median age 57 (51–67) years] with pathologic left ventricular hypertrophy (LVH) (Group A) were compared with 111 sarcomeric HCM patients (Group B) sex, age and maximal wall thickness matched by 1:1 propensity score. Results AF patients showed shorter PR interval [155 (140–180) vs 163 (149–184) msec; p=0.005) and wider QRS interval [110 (100–134) vs 100 (90–106) msec; p&lt;0.0001). Additionally AF patients had a higher prevalence of complete (22% vs 3%; p&lt;0.0001) and incomplete (13% vs 1%; p&lt;0.0001) right bundle branch block (RBBB) and a higher percentage of ST segment depression (12% vs 1%; p=0.001) and inferior negative T waves (34% vs 19%; p=0.01). No differences in terms of Sokolow-Lyon and Cornell scores were found whereas total QRS score was higher in Group A [20 (16–27) vs 18 [14–22] mV; p=0.0004). Low QRS voltages and inferior Q waves were not present in AF patients. Among the 69 AF patients who underwent MRI, the 44 with late gadolinium enhancement (LGE) were older [59 (52–66) vs 53 (40–59) years; p=0.017] and had more frequently negative T waves on ECG, particularly in the inferior leads (64% vs 8%; p&lt;0.0001), compared to the 25 without LGE. At multivariate analysis, age and negative T waves were independently associated to the presence of LGE on CMR. Conclusions Compared to matched sarcomeric HCM, AF patients had a shorter PR, wider QRS and a higher percentage of RBBB in relation to to the different aetiology (storage vs “pure” hypertrophy). The higher total QRS score and the absence of inferior Q waves could reflect the more frequent concentric distribution of LVH. Additionally negative T waves, especially in inferior leads, are related to the presence of LGE on CMR (often in the postero-lateral wall). Funding Acknowledgement Type of funding source: None