Ventricular Hypertrabeculation Research Articles

What can a cryptogenic stroke hide in a young patient?

Abstract Introduction Left ventricular hypertrabeculation is a recently described ventricular phenotype characterized by the alternation of excessive trabeculations with deep intertrabecular recesses that communicate with the left ventricular cavity but not with the coronary circulation. Case presentation We report the case of a young patient, recently diagnosed with ischemic stroke, in whom the cardiological assessment revealed the coexistence of left ventricular hypertrabeculation and dilated cardiomyopathy, which pathologies associated with a high risk of embolic events. The treatment administered followed the therapy for chronic heart failure, control of rhythm disorders that might occur, and the prevention of embolic accidents. Conclusions The particularity of the case is represented by atypical onset through a complication of the disease in a cardiovascular paucisymptomatic patient. Multimodal imaging corroborated with clinical and anamnestic elements had an essential role in the diagnosis.

198 ROLE OF CARDIAC MAGNETIC RESONANCE IMAGING IN ARRHYTMICH RISK STRATIFICATION

Abstract Introduction Danon disease (DD) is a rare multi-systemic disorder firstly described by Danon et al. in 1981 and characterized by a triad consisting with hypertrophic cardiomyopathy, skeletal myopathy, and intellectual disability. It is an inherited dominant X-linked condition, due to mutations in the lysosome-associated membrane protein 2 (LAMP2) gene. Typically, males present a more severe phenotype with earlier onset and rapid heart failure progression with extracardiac manifestations; female patients manifest a milder phenotype with later onset and isolated cardiac involvement. Female carriers may develop dilated cardiomyopathy (DCM). In recent years, it has been described a severe arrhythmogenic phenotype, particularly in women, with a high risk of sudden cardiac death (SCD). Case presentation Case 1 is a 16 y.o. woman referred to our outpatient cardiomyopathies clinic, diagnosed with left ventricle (LV) hypertrophy on the basis of ECG and echocardiography, performed in 2016, in view of cutaneous nevus surgical exeresis. At echocardiographic evaluation we found an asymmetric LV hypertrophy with preserved LV ejection fraction (LVEF 65%). A cMRI was performed, showing mild LV thickening and left ventricular hypertrabeculation morphology, mainly in the LV lateral wall, but not all criteria for LV noncompaction (NC) were satisfied. There was no late gadolinium enhancement (LGE) accumulation. She underwent a genetic screening with inconclusive results, so we started a clinical outpatient follow-up showing no significant arrhythmias at ECG Holter and no limitation of physical activities. In 2021, when she was 21 yo, her father died suddenly and no autoptic examination was performed. A genetic exam was repeated, highlighting a LAMP2 gene mutation. In 2016 her 3 years older sister, Case 2, underwent a familiar screening. She had a long history of mild dyspnea occurring during exertion. Echocardiography showed asymmetric hypertrophy with marked thickening of infero-lateral wall (25 mm,) with normal systolic function (EF 70%). She underwent a cMRI, highlighting diffuse asymmetric hypertrophy (max 24 mm) with LGE in lateral wall and lower septum. First genetic test was nonconclusive but after her father's death another test was performed, demonstrating LAMP2 gene mutation. In 2021 a follow-up cMRI showed markedly reduced myocardial thickness of the apex, with a pattern of noncompaction myocardial. We found a LVEF at lower limits, depressed longitudinal function (MAPSE 8 mm) and manly severe progression of fibrotic degeneration. ECG Holter revealed premature ventricular complex, in absence of nonsustained ventricular tachycardia. Following the evolution of fibrosis, cardioverter defibrillator (ICD) implantation was performed. Case 1 was clinically stable during strict follow-up. Conclusion Cardiac magnetic resonance imaging (cMRI) may be useful in arrhythmic risk stratification, accurate systolic dysfunction evaluation, and proper timing and indication for ICD implantation.

Abstract 10980: Echocardiographic Evaluation of the Left Ventricular Function in Patients With Noncompaction Cardiomyopathy: Biplane Method, Wall Motion Score or Global Longitudinal Strain?

Introduction: Noncompaction cardiomyopathy (NCCM) is characterized by left ventricular (LV) hypertrabeculation. Therefore, endocardial tracing / quantification of LV function could be cumbersome. Hypothesis: Accurate assessment of the (subclinical) LV dysfunction in NCCM patients could improve non-invasive monitoring of disease progression, risk stratification, and treatment. Method: We reviewed the echocardiographic images of 67 patients (54% male, median age 48 year [22-73]. LV function was assessed by conventional biplane disk summation, wall motion score (WMS), and global longitudinal strain (GLS). LV function was considered abnormal if LV ejection fraction (LVEF) <50% and GLS >-18,9%. Results: LV function measured by biplane vs WMS showed significantly lower LV EF with WMS (p-value: 0,0016; Figure ), while the average GLS in all patients was -11,0%, SD ±3,8 (normal values: -18,9%; p-value: p<0,001). By dichotomizing the group into LVEF <50% vs. ≥50%, biplane EF was abnormal in 68,7%, while this was with WMS 88,1% en GLS in 100% patients. In patient with EF <50% compared to ≥ 50% GLS in low biplane EF group was: -9.3% vs -14.5% (p<0.001). In the WMS EF was this respectively -10,3±3,6% versus -15.5± 1.5 (p<0.001). Conclusion: The systolic LV dysfunction in patients with NCCM noncompaction cardiomyopathy found by WMS and GLS was significantly lower compared to routine biplane EF measurement suggesting that WMS and GLS measurement are much more potential prognostic tool. Given the correct execution of WMS is limited by the assessor's experience, estimation of the LV function with GLS are probably most reliable. Future research should expel whether these results are representative in a larger group of patients and correlates with the clinically relevant endpoints.

Las mutaciones missense en el dominio ROD2 de la filamina C muestran un fenotipo con miocardiopatía restrictiva/hipertrófica y miocardio en dientes de sierra

Introduction and objectivesMissense mutations in the filamin C (FLNC) gene have been reported as cause of inherited cardiomyopathy. Knowledge of the pathogenicity and genotype-phenotype correlation remains scarce. Our aim was to describe a distinctive cardiac phenotype related to rare missense FLNC variants in the ROD2 domain. MethodsWe recruited 21 unrelated families genetically evaluated because of hypertrophic cardiomyopathy (HCM)/restrictive cardiomyopathy (RCM) phenotype carrying rare missense variants in the ROD2 domain of FLNC (FLNC-mRod2). Carriers underwent advanced cardiac imaging and genetic cascade screening. Myocardial tissue from 3 explanted hearts of a missense FLNC carrier was histologically analyzed and compared with an FLNC-truncating variant heart sample and a healthy control. Plasmids independently containing 3 FLNC missense variants were transfected and analyzed using confocal microscopy. ResultsEleven families (52%) with 20 assessed individuals (37 [23.7-52.7]) years showed 15 cases with a cardiac phenotype consisting of an overlap of HCM-RCM and left ventricular hypertrabeculation (saw-tooth appearance). During a median follow-up of 6.49 years, they presented with advanced heart failure: 16 (80%) diastolic dysfunction, 3 heart transplants, 3 heart failure deaths) and absence of cardiac conduction disturbances or skeletal myopathy. A total of 6 families had moderate genotype-phenotype segregation, and the remaining were de novo variants. Differential extracellular matrix remodeling and FLNC distribution among cardiomyocytes were confirmed on histology. HT1080 and H9c2 cells did not reveal cytoplasmic aggregation of mutant FLNC. ConclusionsFLNC-mRod2 variants show a high prevalence of an overlapped phenotype comprising RCM, HCM and deep hypertrabeculation with saw-tooth appearance and distinctive cardiac histopathological remodeling.Full English text available from:www.revespcardiol.org/en

The use of 2-D speckle tracking echocardiography in assessing adolescent athletes with left ventricular hypertrabeculation meeting the criteria for left ventricular non-compaction cardiomyopathy

BackgroundCurrent echocardiographic criteria cannot accurately differentiate exercise induced left ventricular (LV) hypertrabeculation in athletes from LV non-compaction cardiomyopathy (LVNC). This study aims to evaluate the role of speckle tracking echocardiography (STE) in characterising LV myocardial mechanics in healthy adolescent athletes with and without LVNC echocardiographic criteria. MethodsAdolescent athletes evaluated at three sports academies between 2014 and 2019 were considered for this observational study. Those meeting the Jenni criteria for LVNC (end-systolic non-compacted/compacted myocardium ratio > 2 in any short axis segment) were considered LVNC+ and the rest LVNC-. Peak systolic LV longitudinal strain (Sl), circumferential strain (Sc), rotation (Rot), corresponding strain rates (SRl/c) and segmental values were calculated and compared using a non-inferiority approach. ResultsA total of 417 participants were included, mean age 14.5 ± 1.7 years, of which 6.5% were LVNC+ (n = 27). None of the athletes showed any additional LVNC clinical criteria. All average Sl, SRl Sc, SRc and Rot values were no worse in the LVNC+ group compared to LVNC- (p values range 0.0003–0.06), apart from apical SRc (p = 0.2). All 54 segmental measurements (Sl/Sc SRl/SRc and Rot) had numerically comparable means in both LVNC+ and LVNC-, of which 69% were also statistically non-inferior. ConclusionsAmong healthy adolescent athletes, 6.5% met the echocardiographic criteria for LVNC, but showed normal LV STE parameters, in contrast to available data on paediatric LVNC describing abnormal myocardial function. STE could better characterise the myocardial mechanics of athletes with LV hypertrabeculation, thus allowing the transition from structural to functional LVNC diagnosis, especially in suspected physiological remodelling.

ROD2 domain filamin C missense mutations exhibit a distinctive cardiac phenotype with restrictive/hypertrophic cardiomyopathy and saw-tooth myocardium

Introduction and objectivesMissense mutations in the filamin C (FLNC) gene have been reported as cause of inherited cardiomyopathy. Knowledge of the pathogenicity and genotype-phenotype correlation remains scarce. Our aim was to describe a distinctive cardiac phenotype related to rare missense FLNC variants in the ROD2 domain. MethodsWe recruited 21 unrelated families genetically evaluated because of hypertrophic cardiomyopathy (HCM)/restrictive cardiomyopathy (RCM) phenotype carrying rare missense variants in the ROD2 domain of FLNC (FLNC-mRod2). Carriers underwent advanced cardiac imaging and genetic cascade screening. Myocardial tissue from 3 explanted hearts of a missense FLNC carrier was histologically analyzed and compared with an FLNC-truncating variant heart sample and a healthy control. Plasmids independently containing 3 FLNC missense variants were transfected and analyzed using confocal microscopy. ResultsEleven families (52%) with 20 assessed individuals (37 [23.7-52.7]) years showed 15 cases with a cardiac phenotype consisting of an overlap of HCM-RCM and left ventricular hypertrabeculation (saw-tooth appearance). During a median follow-up of 6.49 years, they presented with advanced heart failure: 16 (80%) diastolic dysfunction, 3 heart transplants, 3 heart failure deaths) and absence of cardiac conduction disturbances or skeletal myopathy. A total of 6 families had moderate genotype-phenotype segregation, and the remaining were de novo variants. Differential extracellular matrix remodeling and FLNC distribution among cardiomyocytes were confirmed on histology. HT1080 and H9c2 cells did not reveal cytoplasmic aggregation of mutant FLNC. ConclusionsFLNC-mRod2 variants show a high prevalence of an overlapped phenotype comprising RCM, HCM and deep hypertrabeculation with saw-tooth appearance and distinctive cardiac histopathological remodeling.

A Rare Case of Left Ventricular Non-Compaction with Coronary Artery Anomaly Complicated by ST-Elevation Myocardial Infarction and Subcutaneous Defibrillator Implantation

Left ventricular non-compaction (LVNC) is a rare congenital cardiomyopathy caused by arrest of normal endomyocardial embryogenesis and characterized by the persistence of ventricular hypertrabeculation, isolated or associated to other congenital defects. A 33-year-old male, with family history of sudden cardiac death (SCD), presented to our ER with typical chest pain and was diagnosed with anterior STEMI. Coronary angiography showed an anomalous origin of the circumflex artery from the right coronary artery and a critical stenosis on the proximal left anterior descending artery, treated with primary percutaneous coronary intervention. The echocardiogram documented left ventricular severe dysfunction with lateral wall hypertrabeculation, strongly suggestive for non-compaction, confirmed by cardiac MRI. At 3 months follow up, for the persistence of the severely depressed EF (30%) and the family history for SCD, the patient underwent subcutaneous ICD (sICD) implantation for primary prevention. To the best of our knowledge, this is the first case of LVNC associated with anomalous coronary artery origin and STEMI reported in the literature. Arrhythmias are common in LVNC due to endocardial hypoperfusion and fibrosis. sICD overcomes the risks of transvenous ICD, and it is a valuable option when there is no need for pacing therapy for bradycardia, cardiac resynchronization therapy and anti-tachycardia pacing.

8p23.1 deletion: Look out for left ventricular hypertrabeculation and not only congenital heart diseases. Single-center experience and literature revision.

Deletions involving the distal portion of the short arm of chromosome 8(8p23.1) show a high phenotypic variability. Congenital heart diseases (CHD) are often described. GATA4 when mutated or deleted is reported to be involved in cardiac morphogenesis. Only twice, left ventricular non compaction (LVNC) was reported in literature in association with 8p23.1 deletion. The present cohort includes five new patients with 8p23.1 deletions including GATA4. The spectrum of CHD is variable. Moreover, in four patients, LV hypertrabeculation was detected and in the fifth LVNC was recognized. Literature revision identified 45 patients with 8p23.1 deletions (encompassing GATA4) and heart involvement. It included wide spectrum of CHD including: heterotaxy spectrum 7/45 (15, 6%), atrioventricular canal 14/45 (balanced 3/45 including two of them with hypoplastic aortic arch; unbalanced 4/45, Fallot-AVC 1/45, partial AVC 3/45, unspecified 3/45), predominant major left heart lesions included 2/45 (4, 4%): interrupted aortic arch and hypoplastic left heart syndrome. Left ventricular hypertrabeculation might be potentially underestimated in patients with 8p23.1 deletion. These might suggest the importance of including microarray analysis in this group of patients. Moreover, 8p23.1 microdeletion or GATA4 variants can be considered in heterotaxy genetic panels.

Left ventricular non-compaction cardiomyopathy automatic diagnosis using a deep learning approach

Background and Objective: Left ventricular non-compaction (LVNC) is an uncommon cardiomyopathy characterised by a thick and spongy left ventricle wall caused by the high presence of trabeculae (hyper-trabeculation). Recently, the percentage of the trabecular volume to the total volume of the external wall of the left ventricle (VT%) has been proposed to diagnose this illness.Methods: This paper presents the use of a deep learning-based method to measure the (VT%) value and diagnose this rare cardiomyopathy.The population used in this research was composed of 277 patients suffering from hypertrophic cardiomyopathy. 134 patients only suffered hypertrophic cardiomyopathy, and 143 also suffered left ventricular non-compaction.Our deep learning solution is based on a 2D U-Net. This artificial neural network (ANN) was trained on short-axis magnetic resonance imaging to segment the left ventricle’s internal cavity, external wall, and trabecular tissue. 5-fold cross-validation was performed to ensure the robustness of the results. The Dice coefficient of the three classes was computed as a measure of the precision of the segmentation.Based on this segmentation, the percentage of the trabecular volume (VT%) was computed. Two specialist cardiologists rated the segmentation produced by the neural network for 25 patients to evaluate the clinical validity of the outputs. The computed VT% was used to automatically diagnose the 277 patients depending on whether or not a given threshold was exceeded. A receiver operating characteristic analysis was also performed.Results: According to the cross-validation results, the average and standard deviation of the Dice coefficient for the internal cavity, external wall, and trabeculae were 0.96±0.00, 0.89±0.00, and 0.84±0.00, respectively. The cardiologists rated 99.5% of the evaluated segmentations as clinically valid for diagnosis, outperforming existing automatic traditional tools. The area under the ROC curve was 0.94 (95% confidence interval, 0.91–0.96). The accuracy, sensitivity, and specificity values of diagnosis using a threshold of 25% were 0.87, 0.93, and 0.80, respectively.Conclusions: The U-Net neural network can achieve excellent results in the delineation of different cardiac structures of short-axis cardiac MRI. The high-quality segmentation allows for the correct measurement of left ventricular hyper-trabeculation and a definitive diagnosis of LVNC illness. Using this kind of solution could lead to more objective and faster analysis, reducing human error and time spent by cardiologists.

Left ventricular hypertrabeculation in Ebstein anomaly – a clinically significant or irrelevant problem?

Abstract Background Ebstein anomaly (EA) is characterized by anomalous tricuspid valve resulting in the whole right heart's distorted anatomy. Heart failure is the most frequent complication in adults with EA. Recently more attention is also paid to the left ventricle. Some limited echocardiographic data suggest a markedly increased occurrence of the left ventricular hypertrabeculation, by some authors called a non-compacted myocardium. Currently, cardiac magnetic resonance (CMR) is a gold standard in the evaluation of hypertrabeculation. However, different diagnostic criteria and discrepancies in the study outcomes make the clinical interpretation of this phenomenon questionable and challenging. Purpose To determine the frequency of the left ventricular hypertrabeculation among adults with EA; to assess its association with the ventricular size and function and the markers of heart failure. Methods Study group consisted of 35 unoperated adults (mean age 41.9±14.8 years) with Ebstein anomaly. The study protocol included: a) cardiac magnetic resonance (CMR) with the assessment of the left ventricle (LV) and functional right ventricle (fRV), including ejection fraction (EF), end-diastolic, end-systolic, and stroke volumes indexed by body surface area (respectively: EDVind, ESVind, SVind), and presence of hypertrabeculation defined according to Jacquier (1) as trabeculation mass >20% of the LV mass; b) cardiopulmonary tests with the assessment of peak oxygen consumption (peak VO2, % of predicted peak VO2), ventilation/carbon dioxide slope (VE/VCO2 slope) c) brain natriuretic peptide (BNP). Results Left ventricular hypertrabeculation was present in 13 (37.1%) patients. We demonstrated no difference between patients with and without LV hypertrabeculation regarding: s Conclusions Left ventricular hypertrabeculation demonstrated by cardiac magnetic resonance is a phenomenon frequently occurring among adults with Ebstein anomaly. However, its presence is not associated with both ventricles' worse function nor with reduced exercise capacity. Therefore, the clinical relevance of left ventricular hypertrabeculation in this population remains questionable and requires further prospective studies. Funding Acknowledgement Type of funding sources: None.

Left ventricular noncompaction: the importance of identifying high-risk patients within the scope of left ventricular hypertrabeculation

Abstract Introduction Prominent left ventricular (LV) trabeculation is frequently encountered, however LV noncompaction (LVNC) criteria are not always fulfilled. The clinical and prognostic significance of these findings remains unclear. Objectives To characterize the patients (P) with echocardiographic suspicion of LVNC and to assess clinical outcomes. Methods Retrospective single-centre study that included all echocardiograms between January 2018 and June 2020 perceiving LV hypertrabeculation. The cohort underwent diagnostic assessment for LVNC by Chin and Jenni criteria. Baseline characteristics were evaluated. Composite endpoint of cardiovascular death, heart failure (HF) hospitalization, ventricular arrythmias (VA) and nonfatal stroke was considered. Results 51P, 75% male, mean age 50±18 years. 35P (69%) had associated heart conditions, of which 57% had other known cardiomyopathy (mainly dilated cardiomyopathy), 14% congenital, 26% ischemic and 3% valvular heart disease. 2P were in postpartum period and 1P was an athlete. Family history of cardiomyopathy was present in 8P (16%). 12P underwent genetic testing, with TTN and MYH7 mutations being the most frequently detected. Prior clinical HF was reported in 53%, previous stroke in 14%, and non-sustained and sustained VA in 24% and 4%, respectively. Mean NYHA classification was 1.8±0.7, with 31% being asymptomatic. The prevalence of LVNC by Chin criteria was 31% and by Jenni criteria was 55%. 32P (63%) met at least one LVNC criteria. This group was younger (45±18 vs 59±15, p=0.004), had higher NT-proBNP levels (3644±2819 vs 389±640, p=0.048) and QRS fragmentation (59% vs 21%, p=0.027). Significantly higher LV end-diastolic volume (84 (41) vs 64 (28)ml/m2, p=0.008) and end-systolic volume (51 (37) vs 35 (20)ml/m2, p=0.004), along with lower LV ejection fraction (39±12 vs 49±13%, p=0.009) and global longitudinal strain (−11±5 vs −17±4%, p=0.003) were noticed. P who met LVNC criteria also had higher number of affected LV segments (6.4±1.8 vs 4.2±1.6, p<0.001). Over a mean follow-up of 18±9 months, the incidence of composite endpoint was 35%. Univariate Cox analysis showed a significant association between the presence of LVNC criteria and adverse outcomes (HR: 5.108, 95% CI: 1.682–11.236, p=0.030) (Fig. 1). Conclusion LV hypertrabeculation can be encountered in a variety of clinical scenarios and often overlaps with other heart diseases. P satisfying criteria for LVNC had more impairment in LV performance and worse clinical outcomes. Funding Acknowledgement Type of funding sources: None. Figure 1

Deletion of Sphingosine 1-Phosphate receptor 1 in cardiomyocytes during development leads to abnormal ventricular conduction and fibrosis.

Sphingosine 1‐Phosphate receptor 1 (S1P1, encoded by S1pr1) is a G protein‐coupled receptor that signals in multiple cell types including endothelial cells and cardiomyocytes. Cardiomyocyte‐specific deletion of S1pr1 during mouse development leads to ventricular noncompaction, with 44% of mutant mice surviving to adulthood. Adult survivors of embryonic cardiomyocyte S1pr1 deletion showed cardiac hypertrabeculation consistent with ventricular noncompaction. Surprisingly, systolic function in mutant mice was preserved through at least 1 year of age. Cardiac conduction was abnormal in cardiomyocyte S1pr1 mutant mice, with prolonged QRS intervals in mutants as compared with littermate control mice. Immunostaining of hearts from S1pr1 mutant embryos displayed a zone of intermediate Connexin 40 (Cx40) expression in the trabecular myocardium. However, we observed no significant differences in Cx40 and Connexin 43 immunostaining in hearts from adult survivors of embryonic cardiomyocyte S1pr1 deletion, which suggests normalized development of the ventricular conduction system in mutant mice. By contrast, the adult survivors of embryonic cardiomyocyte S1pr1 deletion showed increased cardiac fibrosis as compared with littermate controls. These results demonstrate that ventricular hypertrabeculation caused by embryonic deletion of cardiomyocyte S1pr1 correlates with cardiac fibrosis, which contributes to abnormal ventricular conduction. These results also reveal conduction abnormalities in the setting of hypertrabeculation with normal systolic function, which may be of clinical relevance in humans with ventricular hypertrabeculation.

Left ventricular hypertrabeculation - an unanswered question

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Supported by the ÚNKP-19-3-II New National Excellence Program of the Ministry for Innovation and Technology Left ventricular (LV) hypertrabeculation (H-TRAB) is a morphological description when the LV is highly trabeculated, but it remains below the diagnostic criterion of noncompaction cardiomyopathy (NCMP). Although, it is a frequent finding on cardiac MRI scans its diagnostic and prognostic relevance remains controversial. In this cardiac MRI study, we aimed to describe the LV functional and feature-tracking strain values of healthy subjects with LV H-TRAB to decide whether it is a normal variant or an NCMP-like pattern. We included 189 adult participants with good LV ejection fraction (EF), and without co-morbidities. 63 of them had a morphology of LV H-TRAB (H-TRAB, age: 37.1 ± 14.4 years; EF: 66.4 ± 5.1%), 63 patients were diagnosed with NCMP (age: 36.3 ± 14.0 years, EF: 65.8 ± 5.5%) and the remaining 63 people were healthy controls (38.3 ± 14.0 years, EF: 69.0 ± 4.9%). MR examinations were performed with 1,5T Philips Achieva and Siemens Aera devices. The Medis Suite software was used for post-processing analysis, the MedCalc software for statistics, p < 0.05 was considered statistically significant. No significant differences were found between the functional parameters of the H-TRAB and NCMP groups. However, the EF was decreased, the end-diastolic (EDVi), and end-systolic volume (ESVi), the myocardial mass (LV-massi), and trabeculated muscle mass (LV-trabi) values were increased in both groups compared to controls (H-TRAB vs. control: EF: 6.4 ± 5.4 vs. 69.0 ± 5.0%, EDVi: 74.4 ± 14.3 vs. 69.7 ± 12.8 ml/m2, ESVi: 25.1 ± 6.7 vs. 21.7 ± 5.8 ml/m2, LV-massi: 77.0 ± 15.1 vs. 71.2 ± 12.3 g/m2, LV-trabi: 25.0 ± 5.1 vs. 20.1 ± 4.0 g/m2; NCMP vs. control: EF: 65.8 ± 5.5 vs. 69.0 ± 5.0%, EDVi: 77.8 ± 15.0 vs. 69.7 ± 12.8 ml/m2, ESVi: 26.7 ± 7.9 vs. 21.7 ± 5.8 ml/m2, LV-massi: 76.8 ± 18.0 vs. 71.2 ± 12.3 g/m2, LV-trabi: 25.9 ± 7.5 vs. 20.1 ± 4.0 g/m2; p ≤ 0.05). The global circumferential strain (GCS) differed significantly between these groups: its absolute value was the lowest in the NCMP and the highest in the control group (NCMP vs. H-TRAB vs. control: -30.2% vs. -34.3% vs. -35.9%; p < 0.05). Similar results were found in the comparison of the mean segmental circumferential strain values of the apical-, mid- and basal-parts between the three groups. The absolute values of these parameters were the lowest in the NCMP patients, followed by the H-TRAB, and were the highest in the control group. These results suggest that the LV functional and strain values of the H-TRAB population are more similar to NCMP patients than healthy controls. Further studies are necessary to determine the pathological implications and consequences of this morphology.

The role of circumferential strain in the differential diagnosis of cardiomyopathies with left ventricular hypertrabeculation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by the ÚNKP-19-3-II New National Excellence Program of the Ministry for Innovation and Technology Dilated (DCM), hypertrophic (HCM) and noncompaction cardiomyopathy (NCMP) are genetically and morphologically overlapping diseases, however they differ in clinical manifestation, treatment and prognosis. Cardiac MRI feature-tracking might help to differentiate between these cardiomyopathies with left ventricular (LV) hypertrabeculation. We aimed to describe the differences in the functional and strain parameters of NCMP patients with good LV ejection fraction (EF, NCMP-G) compared with patients with HCM, and NCMP patients with reduced EF (NCMP-R) compared with patients with DCM . We included 62 NCMP patients from which 31 had good LV function and 31 had decreased LV-EF. The NCMP-G group was compared with an HCM population (n = 31) and the NCMP-R group was compared with a DCM group (n = 31) matching in age and sex (age, EF; NCMP-G 46.0 ± 13.0 years, 65.5 ± 5.3% vs. HCM 47.2 ± 14.4 years, 74.8 ± 6.3%; NCMP-R 54.5 ± 12.1 years, 32.8 ± 10.1% vs. DCM 50.8 ± 16.7 years, 34.0 ± 8.2%). 1.5 T Philips Achieva and Siemens Aera MRI machines were used for the scans, Medis Suite program was used for analysis and MedCalc software for statistics, p < 0.05 was considered statistically significant. Significant differences were found between the functional parameters of HCM and NCMP-G patients, while the DCM and NCMP-R groups differed only in the trabecular mass values (LV-trab, NCMP-G vs. HCM: 26.2 ± 7.5 vs. 30.7 ± 7.0 g/m2, NCMP-R vs. DCM: 48.2 ± 13.2 vs. 42.1 ± 10.1 g/m2, p < 0.05). The global longitudinal strain values of the studied populations were not significantly different, however the global circumferential strain (GCS) values were significantly better in patients with HCM and DCM compared with the NCMP groups (GCS, NCMP-G vs. HCM: -31.2 ± 4.9 vs. -43.0 ± 8.4%, NCMP-R vs. DCM: -11.7 ± 7.3 vs. -16.9 ± 6.1%). The average circumferential strain values of the LV basal, mid and apical parts were significantly better in the HCM and DCM groups compared with the NCMP groups (NCMP-G vs. HCM: -35.7 ± 9.5 vs. -50.5 ± 14.1%, NCMP-R vs. DCM: -29.5 ± 13.2 vs. -15.6 ± 6,7%). We assessed the cut-off point of the average LV apical circumferential strain to differentiate the studied populations (HCM vs. NCMP-G cut-off: -47.3% sens.: 83.9%, spec.: 67.7%, AUC: 0.81; DCM vs. NCMP-R cut-off: -19.3% sens.: 83.9%, spec.: 83.9%, AUC: 0.86). The diverse circumferential strain values of the hypertrabeculated LV apical third could help the differential diagnosis of NCMP, DCM and HCM.

Ebstein anomaly, left ventricular hypertrabeculation and ventricular septal defect associated with a myh7 mutation

Abstract Funding Acknowledgements Type of funding sources: None. Ebstein anomaly is an extremely rare anomaly of <1% among all congenital heart diseases. Pathologically, the septal and / or posterior leaflet of the tricuspid valve has abnormal locations towards the right ventricular apex. Ebstein anomaly is especially accompanied by atrial septal defect, patent ductus arteriosus, wolf parkinson white syndrome and pulmonary atresia. Defects located in the interventricular septum are called the ventricular septal defect (VSD). They can be single or multiple and congenital or acquired. Isolated VSDs are the most common congenital anomaly in childhood and constitute 20-30% of all congenital heart diseases. VSD can be a part of major congenital malformations ,such as, fallot tetralogy, transposition of the major arteries, double ventricular right ventricle. Left ventricular noncompaction (LVNC) is a relatively common genetic cardiomyopathy, characterized by prominent trabeculations with deep intertrabecular recesses in mainly the left ventricle. Although LVNC often occurs in an isolated entity, it may also be present in various types of congenital heart disease . A combination of Ebstein anomaly, hypertrabeculation and ventricular septal defect is a rare condition. Case Report A 49-year-old male patient presented to the emergency room with shortness of breath and swelling of the legs. The patient had diagnosed an Ebstein anomaly while the military examination in 1988. Already it ‘s known that he has gout disease and uses colchicine but no family history of any disease. On examination of the patient, bilateral ral in respiratory sounds and +++ / +++ pretibial edema in the lower extremity were detected. On his electrocardiogram, the sinus rhythm with first-degree atrioventricular block was observed. The findings on his echocardiographic examination are ejection fraction 30-35% with global left ventricular hypokinesia, Ebstein anomaly (Figure ), perimembranous type VSD, atrial septal aneurysm type 2 and left ventricular hypertrabeculation. His blood table was normal. Medical treatment of heart failure was started for the patient who was interneed to the service. After getting clinical relief, the patient was discharged under medical treatment. Genetic tests were studied while following up at the heart failure outpatient clinic. In the MYH7 gene, splice-acceptor-2 (PVS1) variation heterozygous was detected. This variant has not been seen in national data banks of genetics. Conclusion The MYH7 gene, localized on chromosome 14p12, is composed of 41 exons and encodes the b-myosin heavy chain, expressed in cardiac muscle. Mutations in the MYH7 gene have been identified in association with left ventricular hypertrabeculation and Ebstein anomaly. In conclusion, this is the first known report of Ebstein anomaly associated with the splice-acceptor-2 variation heterozygous of the MYH7 gene. Abstract Figure

Circumferential deformation in diagnosis and risk assessment of patients with left ventricular non-compaction

Abstract Introduction Echocardiography-based deformation analysis is used for studying left ventricular (LV) mechanics and have an emerging role in the diagnosis of cardiomyopathies. Left ventricular non-compaction (LVNC) is a rare cardiomyopathy characterised by a two-layered LV myocardium with prominent trabeculae separated by deep recesses perfused from the LV cavity. Left ventricular hypertrabeculation (LVHT) may be difficult to differentiate from LVNC. In this study, we aim to develop a diagnostic algorithm based on the circumferential deformation (CD) of LVNC, LVHT and controls; and find their associations with LVNC outcomes. Methods We compared 45 LVNC patients, 45 LVHT individuals, and 45 matched healthy controls. LVNC was diagnosed according to current echocardiographic criteria. LVHT was defined as presence of three or more trabeculae in the LV apex visualised in both parasternal short axis and apical views. Controls had a normal echocardiographic examination and no evidence of cardiovascular disease. Strain analysis was performed using TomTec Image-Arena (version 4.6). Results Receiver observer characteristics curve (ROC) analyses revealed that GCS <22.3% differentiated LVNC from control or LVHT. In individuals with global circumferential strain (GCS) below 22.3%, an apical peak circumferential strain (PCS) cut-off value of 18.4% differentiated LVNC [<18.4%] and LVHT [≥18.4%] (fig. 1). An independent echocardiographer (Table 1) performed blind validation of diagnosis on 32 subjects from each group. Combined endpoint of cardiovascular events in LVNC (CVE) is described in figure 2. Multi-variate regression analyses have shown that GCS was associated with 11-fold increased risk of CVE independent of LVEF and NC:C ratio, while global longitudinal strain (GLS) displayed only 2-fold increased risk. Regional basal and apical peak circumferential or longitudinal strain, left ventricular twist, basal-apical rotation ratio have shown significant associations (Fig. 3). Conclusions A diagnostic algorithm with GCS and aPCS (threshold value 18.4%) differentiates LVNC from LVHT and control with very high sensitivity and specificity independent of additional echocardiographic or clinical information. Circumferential strain derived parameters exhibit a very strong association with outcomes independent of LVEF and NC:C ratio. Absence of CVE in LVHT provides further evidence on the distinct nature of LVNC and LVHT. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): 2018 research grant from the Swiss Heart Foundation

Association Between Left Ventricular Noncompaction and Vigorous Physical Activity

BackgroundLeft ventricular (LV) hypertrabeculation fulfilling noncompaction cardiomyopathy criteria has been detected in athletes. However, the association between LV noncompaction (LVNC) phenotype and vigorous physical activity (VPA) in the general population is disputed. ObjectivesThe aim of this study was to assess the relationship between LVNC phenotype on cardiac magnetic resonance (CMR) imaging and accelerometer-measured physical activity (PA) in a cohort of middle-aged nonathlete participants in the PESA (Progression of Early Subclinical Atherosclerosis) study. MethodsIn PESA participants (n = 4,184 subjects free of cardiovascular disease), PA was measured by waist-secured accelerometers. CMR was performed in 705 subjects (mean age 48 ± 4 years, 16% women). VPA was recorded as total minutes per week. The study population was divided into 6 groups: no VPA and 5 sex-specific quintiles of VPA rate (Q1 to Q5). The Petersen criterion for LVNC was evaluated in all subjects undergoing CMR. For participants meeting this criterion (noncompacted-to-compacted ratio ≥2.3), 3 more restrictive LVNC criteria were also evaluated (Jacquier, Grothoff, and Stacey). ResultsLVNC phenotype prevalence according to the Petersen criterion was significantly higher among participants in the highest VPA quintile (Q5 = 30.5%) than in participants with no VPA (14.2%). The Jacquier and Grothoff criteria were also more frequently fulfilled in participants in the highest VPA quintile (Jacquier Q5 = 27.4% vs. no VPA = 12.8% and Grothoff Q5 = 15.8% vs. no VPA = 7.1%). The prevalence of the systolic Stacey LVNC criterion was low (3.6%) and did not differ significantly between no VPA and Q5. ConclusionsIn a community-based study, VPA was associated with a higher prevalence of CMR-detected LVNC phenotype according to diverse established criteria. The association between VPA and LVNC phenotype was independent of LV volumes. According to these data, vigorous recreational PA should be considered as a possible but not uncommon determinant of LV hypertrabeculation in asymptomatic subjects.

A clinical case of takotsubo syndrome in combination with left ventricular hypertrabeculation

The article describes the clinical case of takotsubo syndrome in female, who has also echocardiographic picture of a left ventricular noncompaction cardiomyopathy. According to the result of magnetic resonance imaging, the diagnosis of noncompaction cardiomyopathy was not confirmed, left ventricular hypertrabeculation was revealed. There are single descriptions of the combination of takotsubo syndrome and left ventricular hypertrabeculation, the pathogenetic relationship of these conditions has not yet been established.

Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation

BackgroundMarathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation. MethodsSixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study. ResultsAfter 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy. ConclusionTraining for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis.

Influence of observer-dependency on left ventricular hypertrabeculation mass measurement and its relationship with left ventricular volume and ejection fraction - comparison between manual and semiautomatic CMR image analysis methods.

Recent studies concerning left ventricular noncompaction (LVNC) suggest that the extent of left ventricular (LV) hypertrabeculation has no impact on prognosis. The variety of methods of LV noncompacted myocardial mass (NCM) assessment may influence the results. Hence, we compared two methods of NCM estimation: largely observer-independent Hautvast's(H) computed algorithm-based approach and commonly used Jacquier's(J) method, and their associations with LV end-diastolic volume (EDV) and ejection fraction (EF). Cardiac magnetic resonance images of 77 persons (45±17yo) - 42 LVNC, 15 non-ischemic dilative cardiomyopathy, 20 control group were analyzed. LVNC patients were divided into the subgroup with normal (LVNCN) and high EDV (LVNCDCM). NCM and total left ventricular mass (LVM) were estimated by Hautvast's [excluding intertrabecular blood (ITB) and including papillary muscles (PMs) into NCM] and Jacquier's approach (including ITB and PMs, if unclearly distinguished, into NCM). The cut-off value of NCM for LVNC diagnosis was 22% (AUC 0.933) for NCMH/LVMH and 26% (AUC 0.883) for NCMJ/LVMJ. Inter- and intra-observer variability (estimated by coefficient of variation [CoV] and intraclass correlation coefficient [ICC]) of NCMH/LVMH appeared better than of NCMJ/LVMJ (CoV 4.3%, ICC 0.981 and CoV 4.9%, ICC 0.978; respectively for NCMH/LVMH, while for NCMJ/LVMJ: CoV 19.7%, ICC 0.15 and CoV 12.9%, ICC 0.504). In LVNCN subgroup, the correlation between EDV and NCMH was stronger than NCMJ (r = 0.677, p<0.001 vs. r = 0.480, p = 0.038; respectively). In LVNC the EDV correlated with NCMH/LVMH (r = 0.391, p<0.01), but not with NCMJ/LVMJ. In the overall group a relationship was present between EF and NCMH/LVMH (r = -0.449, p<0.001), but not NCMJ/LVMJ. Only NCMH/LVMH explained the variability of EDV (b 0.434, p<0.001). Choosing a method of NCM assessment that is less observer-dependent might increase the reliability of results. The impact of method selection on the LV parameters and cut-off values for hypertrabeculation should be further investigated.