Mechanics In Hypertrophic Cardiomyopathy Research Articles

Transcriptomic Analyses and Experimental Validation Identified Immune-Related lncRNA-mRNA Pair MIR210HG-BPIFC Regulating the Progression of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a disease in which the myocardium of the heart becomes asymmetrically thickened, malformed, disordered, and loses its normal structure and function. Recent studies have demonstrated the significant involvement of inflammatory responses in HCM. However, the precise role of immune-related long non-coding RNAs (lncRNAs) in the pathogenesis of HCM remains unclear. In this study, we performed a comprehensive analysis of immune-related lncRNAs in HCM. First, transcriptomic RNA-Seq data from both HCM patients and healthy individuals (GSE180313) were reanalyzed thoroughly. Key HCM-related modules were identified using weighted gene co-expression network analysis (WGCNA). A screening for immune-related lncRNAs was conducted within the key modules using immune-related mRNA co-expression analysis. Based on lncRNA-mRNA pairs that exhibit shared regulatory microRNAs (miRNAs), we constructed a competing endogenous RNA (ceRNA) network, comprising 9 lncRNAs and 17 mRNAs that were significantly correlated. Among the 26 lncRNA-mRNA pairs, only the MIR210HG-BPIFC pair was verified by another HCM dataset (GSE130036) and the isoprenaline (ISO)-induced HCM cell model. Furthermore, knockdown of MIR210HG increased the regulatory miRNAs and decreased the mRNA expression of BPIFC correspondingly in AC16 cells. Additionally, the analysis of immune cell infiltration indicated that the MIR210HG-BPIFC pair was potentially involved in the infiltration of naïve CD4+ T cells and CD8+ T cells. Together, our findings indicate that the decreased expression of the lncRNA-mRNA pair MIR210HG-BPIFC was significantly correlated with the pathogenesis of the disease and may be involved in the immune cell infiltration in the mechanism of HCM.

Genetics, patterns of hypertrophy and fibrosis on myocardial mechanics in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Asymmetrical hypertrophy, myocyte disarray and fibrosis due to genetic cause are underlying pathology of hypertrophic cardiomyopathy (HCM). However, their contribution to myocardial functional mechanics are not extensively evaluated yet. Purpose In this study, we sought to investigate effects of genetic mutation, patterns of ventricular hypertrophy and fibrosis on myocardial mechanics in HCM. Methods In 133 patients with HCM, chamber geometry, segmental late gadolinium enhancement (LGE), extracellular volume fraction (ECV) by cardiac magnetic resonance imaging (CMR), echo-derived diastolic function analyses and genetic test were performed. Left ventricular (LV) segmental and global longitudinal strain (LS), circumferential strain (CS), and rotation were measured by feature tracking analysis of CMR. Results Patients with sarcomere gene mutation (SM) had lower LV-CS (global and all three slices) along with higher prevalence of midwall type LGE, LGE amount and ECV. Despite global LS was not lower in SM, anteroseptal-LS was significantly impaired accompanying with higher septal wall thickness. To compensate impaired anteroseptal LS, basal endocardial rotation was paradoxically increased in SM. Augmented basal segmental was significantly related to obstructive HCM. In apical HCM, although apical segmental LS was significantly lower, higher apical rotation and preserved apical CS along with lower prevalence of SM. The E/e’ was significantly related to LV mass index, LGE extent but not with SM. Conclusion Circumferential myocardial function was significantly reduced in SM independent of fibrosis extent, suggesting primary phenotype. However, longitudinal fiber function was more related to hypertrophy regardless of SM. LV diastolic function was more related to LV mass, extent and degree of fibrosis including non-thickened myocardium regardless of SM.

Atrial Mechanics in Hypertrophic Cardiomyopathy: Discriminating between Ventricular Hypertrophy and Fibrosis.

ResumoFundamento A cardiomiopatia hipertrófica (CMH) e a hipertrofia ventricular esquerda (HVE) secundária à hipertensão arterial sistêmica (HAS) podem estar associadas a anormalidades funcionais do átrio esquerdo (AE).Objetivos Caracterizar a mecânica do AE na CMH e na HAS e avaliar qualquer correlação com a extensão da fibrose ventricular esquerda medida por ressonância magnética cardíaca (RMC) em pacientes com CMH.Métodos A função longitudinal do AE derivada do ecocardiograma bidimensional com speckle tracking foi adquirida a partir de cortes apicais de 60 pacientes com CMH e 34 indivíduos controles, pareados por idade. Pacientes com CMH também foram submetidos à RMC, com medida da extensão do realce tardio por gadolínio. A associação com parâmetros de strain do AE foi analisada. Valores p < 0,05 foram definidos como estatisticamente significativos.Resultados A média da fração de ejeção do ventrículo esquerdo não foi diferente entre os grupos. A razão E/e’ estava comprometida no grupo CMH e preservada no grupo controle. A mecânica do AE estava significativamente reduzida na CMH em comparação aos pacientes com HAS. O strain rate do AE nas fases de reservatório (SRrAE) e na fase contrátil (SRctAE) foram os melhores parâmetros de discriminação de CMH com uma área sob a curva (AUC) de 0,8, seguido do strain do AE na fase de reservatório (SrAE) (AUC 0,76). O SRrAE e o SRctAE apresentaram elevada especificidade (89% e 91%, respectivamente), e o SrAE apresentou sensibilidade de 80%. Um decréscimo de 2,79% no strain rate do AE na fase de condução (SRcdAE) foi preditor de um aumento de 1 cm na extensão do RT pelo gadolínio (r2=0,42, β 2,79, p=0,027).Conclusões O SRrAE e o SRctAE foram os melhores fatores de discriminação de HVE secundária à CMH. O SRcdAE foi preditor do grau de fibrose ventricular esquerda avaliada por RMC. Esses achados sugerem que a mecânica do AE pode ser um potencial preditor de gravidade de doença na CMH.

Hypertrophic Cardiomyopathy: From Phenotype and Pathogenesis to Treatment.

Hypertrophic cardiomyopathy (HCM) is a very common inherited cardiovascular disease (CAD) and the incidence is about 1/500 of the common population. It is caused by more than 1,400 mutations in 11 or more genes encoding the proteins of the cardiac sarcomere. HCM presents a heterogeneous clinical profile and complex pathophysiology and HCM is the most important cause of sudden cardiac death (SCD) in young people. HCM also contributes to functional disability from heart failure and stroke (caused by atrial fibrillation). Current treatments for HCM (medication, myectomy, and alcohol septal ablation) are geared toward slowing down the disease progression and symptom relief and implanted cardiac defibrillator (ICD) to prevent SCD. HCM is, however, entering a period of tight translational research that holds promise for the major advances in disease-specific therapy. Main insights into the genetic landscape of HCM have improved our understanding of molecular pathogenesis and pointed the potential targets for the development of therapeutic agents. We reviewed the critical discoveries about the treatments, mechanism of HCM, and their implications for future research.

Causes of altered ventricular mechanics in hypertrophic cardiomyopathy: an in-silico study

BackgroundHypertrophic cardiomyopathy (HCM) is typically caused by mutations in sarcomeric genes leading to cardiomyocyte disarray, replacement fibrosis, impaired contractility, and elevated filling pressures. These varying tissue properties are associated with certain strain patterns that may allow to establish a diagnosis by means of non-invasive imaging without the necessity of harmful myocardial biopsies or contrast agent application. With a numerical study, we aim to answer: how the variability in each of these mechanisms contributes to altered mechanics of the left ventricle (LV) and if the deformation obtained in in-silico experiments is comparable to values reported from clinical measurements.MethodsWe conducted an in-silico sensitivity study on physiological and pathological mechanisms potentially underlying the clinical HCM phenotype. The deformation of the four-chamber heart models was simulated using a finite-element mechanical solver with a sliding boundary condition to mimic the tissue surrounding the heart. Furthermore, a closed-loop circulatory model delivered the pressure values acting on the endocardium. Deformation measures and mechanical behavior of the heart models were evaluated globally and regionally.ResultsHypertrophy of the LV affected the course of strain, strain rate, and wall thickening—the root-mean-squared difference of the wall thickening between control (mean thickness 10 mm) and hypertrophic geometries (17 mm) was >10%. A reduction of active force development by 40% led to less overall deformation: maximal radial strain reduced from 26 to 21%. A fivefold increase in tissue stiffness caused a more homogeneous distribution of the strain values among 17 heart segments. Fiber disarray led to minor changes in the circumferential and radial strain. A combination of pathological mechanisms led to reduced and slower deformation of the LV and halved the longitudinal shortening of the LA.ConclusionsThis study uses a computer model to determine the changes in LV deformation caused by pathological mechanisms that are presumed to underlay HCM. This knowledge can complement imaging-derived information to obtain a more accurate diagnosis of HCM.

Systemic Bioinformatic Analyses of Nuclear-Encoded Mitochondrial Genes in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease and mitochondria plays a key role in the progression in HCM. Here, we analyzed the expression pattern of nuclear-encoded mitochondrial genes (NMGenes) in HCM and found that the expression of NMGenes was significantly changed. A total of 316 differentially expressed NMGenes (DE-NMGenes) were identified. Pathway enrichment analyses showed that energy metabolism-related pathways such as “pyruvate metabolism” and “fatty acid degradation” were dysregulated, which highlighted the importance of energy metabolism in HCM. Next, we constructed a protein-protein interaction network based on 316 DE-NMGenes and identified thirteen hubs. Then, a total of 17 TFs (transcription factors) were predicted to potentially regulate the expression of 316 DE-NMGenes according to iRegulon, among which 8 TFs were already found involved in pathological hypertrophy. The remaining TFs (like GATA1, GATA5, and NFYA) were good candidates for further experimental verification. Finally, a mouse model of transverse aortic constriction (TAC) was established to validate the genes and results showed that DDIT4, TKT, CLIC1, DDOST, and SNCA were all upregulated in TAC mice. The present study represents the first effort to evaluate the global expression pattern of NMGenes in HCM and provides innovative insight into the molecular mechanism of HCM.

Comparison of vector velocity imaging and three-dimensional speckle tracking echocardiography for assessment of left ventricular longitudinal strain in hypertrophic cardiomyopathy.

Background: Vector velocity imaging (VVI) is a two-dimensional wall motion tracking method that can measure cardiac mechanics in hypertrophic cardiomyopathy (HCM). 3D-speckle tracking echocardiography (3D-STE) has been proven to be superior to conventional measures in assessment of LV function. The aim of this study was to compare the two technologies in the assessment of LV longitudinal strain (LS) in HCM patients.Methods: A total of 50 patients with HCM were investigated using VVI and 3D-STE in same setting. 3D-STE allows obtaining longitudinal, circumferential, radial and area strains (AS). Values of longitudinal strain (LS) and AS by 3D-STE were compared to VVI- derived analyses. Thereafter, VVI-LS values were correlated with LV phenotype. Last, the variability of VVI versus 3DE strain measurements as well as recorded time of analysis was assessed.Results: The absolute value of 3D-STE LS and AS is significantly higher than VVI-LS (P < 0.0001). VVI provided complete longitudinal LV strain information, similar to 3D-STE. There is excellent agreement between the two technologies-derived values, however, a greater number of segments could be analyzed using VVI (94.7%), compared with 3DE (62.1%). Despite VVI being more time consuming, VVI-LS is more correlated to LV mass index, mitral regurgitation severity and functional class when compared with 3D-STE LS and AS.Conclusions: VVI is a feasible modality for assessing LV longitudinal strain. Although VVI agreed well with 3D-STE for most of regional and global LS, a better correlation was found between VVI-LS and HCM phenotype. It is hypothesized that this discrepancy originates from the inferior imaging quality using 3D tracking algorithms.

P1258Characterization of left atrial mechanics in hypertrophic cardiomyopathy and essential hypertension using vector velocity imaging

P1258Characterization of left atrial mechanics in hypertrophic cardiomyopathy and essential hypertension using vector velocity imaging

MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM

BackgroundMicroRNAs (miRNAs) are non-coding RNAs that function as regulators of gene expression and thereby contribute to the complex disease phenotypes. Hypertrophic cardiomyopathy (HCM) and Dilated cardiomyopathy (DCM) can cause sudden cardiac death and eventually develop into heart failure. However, they have different clinical and pathophysiological phenotype and the expressional spectrum of miRNAs in left ventricles of HCM and DCM has never been compared before.MethodsThis study selected 30 human left ventricular heart samples belonged to three diagnostic groups (Control, HCM, DCM). Each group has ten samples. Based on previous findings, the expression of 13 different microRNAs involving heart failure and hypertrophy (miR-1-3p, miR-10b, miR-21, miR-23a, miR-27a, miR-29a, miR-133a-3p, miR-142-3p, miR-155, miR-199a-3p, miR-199a-5p, miR-214, miR-497) was measured. 17 HCM patients were included as second group to validate the associations.ResultsWe found miR-155, miR-10b and miR-23a were highly expressed in both HCM and DCM compared with control. MiR-214 was downregulated and miR-21 was upregulated in DCM but not in HCM. We also identified miR-1-3p and miR-27a expressed significantly different between HCM and DCM and both miRNAs downregulated in HCM. And only miR-1-3p correlated with left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) that reflected the cardiac function in HCM. A second HCM group also confirmed this correlation. We then predicted Chloride voltage-gated channel 3 (Clcn3) as a direct target gene of miR-1-3p using bioinformatics tools and confirmed it by Luciferase reporter assay.ConclusionOur data demonstrated that different cardiomyopathies had unique miRNA expression pattern. And the expression levels of miR-1-3p and miR-27a had disease-specificity and sensitivity in HCM, whereas only miR-1-3p was significantly associated with left ventricular function in HCM identifying it as a potential target to improve the cardiac function in end-stage HCM. We also provide Clcn3 as a direct target of miR-1-3p which sheds light on the mechanism of HCM.

Prognostic implications of global myocardial mechanics in hypertrophic cardiomyopathy by cardiovascular magnetic resonance feature tracking. Relations to left ventricular hypertrophy and fibrosis

BackgroundInterstitial fibrosis, myocardial fiber disarray and non-uniform shortening are common histological features of hypertrophic cardiomyopathy (HCM). The degree of LV hypertrophy and fibrosis are postulated to contribute to the impairment of myocardial shortening. Cardiovascular magnetic resonance myocardial (CMR) feature tracking (CMR-FT) has emerged as a robust method that provides quantitative measurements of myocardial deformation. Our aim was first to evaluate LV strain parameters in HCM by CMR-FT and their dependence on both functional parameters and late gadolinium enhancement (LGE); and secondly we sought to determine their association with major cardiovascular outcomes. Methods and results74 patients with HCM and 75 controls subjects underwent a CMR study including LGE imaging. Global peak longitudinal, circumferential and radial systolic strain values (GLS, GCS, GRS) were measured by CMR-FT. A primary endpoint of all-cause mortality and secondary combined endpoint of hospital admission related to heart failure, lethal ventricular arrhythmias or cardiovascular death were defined. Patients with HCM showed attenuation of all LV strain values (p<0.001). Multivariate analysis showed that both LV hypertrophy and %of LGE were independent predictors of attenuated LV strains. All systolic LV strain parameters were impaired in patients with primary and secondary endpoints (follow up time: 25.6±9.9months, p<0.05 and p<0.01 respectively). Abnormal GLS, GCS and GRS were significantly associated with primary and secondary endpoints. ConclusionBoth LV hypertrophy and fibrosis contribute to the impairment of LV myocardial mechanics in HCM. In this population, reduced LV strain is associated with poor cardiac outcomes, particularly cardiovascular mortality and HF.

RNA‑seq profiling of mRNA associated with hypertrophic cardiomyopathy.

The mechanisms of hypertrophic cardiomyopathy (HCM) pathogenesis can be investigated by determining the differences between healthy and disease states at the molecular level. In the present study, large‑scale transcriptome sequencing was performed to compare mRNA expression in patients with HCM and control groups using an Illumina sequencing platform. Compared with the genome background, 257 differentially expressed genes (DEGs) were identified in which 62 genes were downregulated and 195genes were upregulated. Reverse transcription‑quantitative polymerase chain reaction was performed to validate the expression pattern of certain mRNAs. Gene ontology enrichment and KEGG analysis of mRNAs was conducted to identify the biological modules and pathological pathways associated with the DEGs. To the best of our knowledge, this is the first time study to investigate the differences in mRNA between patients with HCM and normal controls at the transcriptome level. The results of the study will contributed to the understanding of the important molecular mechanisms involved in HCM and aid the selection of key genes to investigate in the future.

Left Atrial Performance in the Course of Hypertrophic Cardiomyopathy: Relation to Left Ventricular Hypertrophy and Fibrosis.

Hypertrophic cardiomyopathy (HCM) is associated with left atrial (LA) functional abnormalities. The determinants and the degree of LA dysfunction in the course of HCM are not fully understood. We aimed to characterize LA mechanics in HCM, according to the extent of left ventricular (LV) hypertrophy and fibrosis. Seventy-three HCM patients and 23 age- and sex-matched controls underwent cardiovascular magnetic resonance imaging including late gadolinium enhancement (LGE). LA reservoir, conduit, and contractile functions were quantified by fractional volume changes and cardiovascular magnetic resonance feature-tracking-derived strain and strain rate. In multivariable regression, LA mechanics were associated with the extent of LV LGE (P = 0.033 to P < 0.001), but not with the LV mass extent or maximum wall thickness (P = 0.108 to P = 0.964). Left atrial function decreased according to the increase in extent of LV fibrosis (non-LGE; mild LGE ≤ 10%; intermediate LGE 11%-19%; severe LGE ≥ 20%). Compared with healthy controls, LA conduit function was impaired in HCM with no LGE already (LA emptying fraction conduit: 32% ± 7% vs 26 ± 14, P = 0.037). Conversely, LA contractile booster pump function was impaired in HCM with severe LGE only (LA emptying fraction booster: 40% ± 8% vs 20% ± 10%, P < 0.001; for controls vs LGE ≥ 20%, respectively). Left atrial functional abnormalities are associated with LV fibrosis, but not with LV hypertrophy. While LA conduit function is impaired in early HCM stages as represented by mild or absent LV fibrosis, LA contractile function is impaired later in the course of disease progression as demonstrated by the presence of severe LV fibrosis only. These novel markers of LA performance may potentially proof useful for disease staging and early detection of cardiac deterioration.

Systolic and Diastolic Myocardial Mechanics in Hypertrophic Cardiomyopathy and Their Link to the Extent of Hypertrophy, Replacement Fibrosis and Interstitial Fibrosis

Systolic and Diastolic Myocardial Mechanics in Hypertrophic Cardiomyopathy and Their Link to the Extent of Hypertrophy, Replacement Fibrosis and Interstitial Fibrosis

LEFT ATRIAL PERFORMANCE IN THE COURSE OF HYPERTROPHIC CARDIOMYOPATHY: RELATION TO LEFT VENTRICULAR HYPERTROPHY AND FIBROSIS

Hypertrophic cardiomyopathy (HCM) is associated with left atrial (LA) functional abnormalities. The determinants and the degree of LA dysfunction in the course of HCM are not fully understood. We aimed to characterize LA mechanics in HCM, according to the extent of left ventricular (LV) hypertrophy

Systolic and diastolic myocardial mechanics in hypertrophic cardiomyopathy and their link to the extent of hypertrophy, replacement fibrosis and interstitial fibrosis.

Aim of the present study was to investigate the relations between myocardial mechanics and the extent of hypertrophy and fibrosis in hypertrophic cardiomyopathy (HCM). Forty-five consecutive patients with HCM and 15 subjects without structural heart disease were included. Cardiac magnetic resonance with late gadolinium enhancement (LGE) imaging was performed to evaluate biventricular function, LV mass index and presence/extent of LGE, expression of replacement fibrosis. Myocardial T1 relaxation, a surrogate of interstitial fibrosis, was measured from Look-Locker sequence. Feature-tracking analysis was applied to LV basal, mid and apical short-axis images to assess systolic and diastolic global LV circumferential strain (CS) and strain rate (CSr). Peak systolic CS and CSr were significantly higher among HCM patients as compared to control subjects (p = 0.015 and p = 0.007, respectively). The ratio of peak CSr during early filling to peak systolic CSr was significantly lower among HCM patients (p = 0.002). At multivariate linear regression analysis, LV mass index (p < 0.001) and %LV LGE (p = 0.011) were significantly and independently related to peak systolic CS; LV mass index (p < 0.001) and %LV LGE (p = 0.023) were significantly and independently related to peak systolic CSr; %LV LGE (p = 0.021) and T1 ratio (p = 0.006) were significantly and independently related to the ratio of peak CSr during early filling to peak systolic CSr. LV systolic mechanics are enhanced and LV diastolic mechanics are impaired in HCM. Extent of hypertrophy and replacement fibrosis influence the LV systolic mechanics while extent of replacement fibrosis and interstitial fibrosis influence the LV diastolic mechanics.

Characterization of Left Atrial Mechanics in Hypertrophic Cardiomyopathy and Essential Hypertension Using Vector Velocity Imaging.

Systemic hypertension (HTN) and hypertrophic cardiomyopathy (HCM) may be associated with left atrial (LA) dilation, but whether LA functional abnormalities are characteristic to each disease or not, is unknown. The aim of this study was to characterize LA mechanical changes in patients with HTN and HCM using vector velocity imaging (VVI). VVI-derived longitudinal LA function was acquired from apical views in 76 CM patients, 33 hypertension patients and 30 age-matched controls. Peak atrial longitudinal strain (ɛsys ), atrial strain rate during systole (SRsys ), early diastole (SRe ), and late diastole (SRa ) were measured (corresponding to LA reservoir, conduit and contractile functions, respectively). Similar parameters were used to assess left ventricular (LV) function. LV mass and LA volume index were higher in HCM and HTN than in controls. Both LA Reservoir function (LA ɛsys SRsys ) and conduit function (SRe ) were more declined in HCM patients, in comparison to HTN patients and controls (P < 0.0001),whereas conduit function was the only function deteriorated in the HTN group. LA contractile function was preserved among patient groups. In HCM, LV ɛsys and SRa [P < 0.001] are independent predictors for LA ɛsys . While in hypertension, only LVMI is an independent predictor for LA dysfunction (P < 0.01). By receiver operating characteristic analyses, only atrial reservoir function was extrapolative and appeared to be accurate in discriminating HCM from both hypertension and controls, with LA ɛsys ≤ 33% being more sensitive (71.8%) and specific (75%). Response of LA mechanics to pathologic hypertrophy is entirely different. In HCM LA reservoir and conduit functions are more deteriorated and related to the severity of phenotype, while in hypertension the conduit function is chiefly affected and LA dysfunction is linked to a more advanced disease.

Effect of Left Ventricular Outflow Tract Obstruction on Left Atrial Mechanics in Hypertrophic Cardiomyopathy.

Left atrial (LA) volumes are known to be increased in hypertrophic cardiomyopathy (HCM) and are a predictor of adverse outcome. In addition, LA function is impaired and is presumed to be due to left ventricular (LV) diastolic dysfunction as a result of hypertrophy and myocardial fibrosis. In the current study, we assess the incremental effect of outflow tract obstruction (and concomitant mitral regurgitation) on LA function as assessed by LA strain. Patients with HCM (50 obstructive, 50 nonobstructive) were compared to 50 normal controls. A subset of obstructive patients who had undergone septal myectomy was also studied. Utilising feature-tracking software applied to cardiovascular magnetic resonance images, LA volumes and functional parameters were calculated. LA volumes were significantly elevated and LA ejection fraction and strain were significantly reduced in patients with HCM compared with controls and were significantly more affected in patients with obstruction. LA volumes and function were significantly improved after septal myectomy. LVOT obstruction and mitral regurgitation appear to further impair LA mechanics. Septal myectomy results in a significant reduction in LA volumes, paralleled by an improvement in function.

PM054 Myocardial Mechanics in Hypertrophic Cardiomyopathy: Is There a Difference between Subtypes?

Introduction: Myocardial Mechanics in Hypertrophic Cardiomyopathy: Is There a Difference between Subtypes? Objectives: We compared global longitudinal strain (GLS) derived by 2-dimensional speckle tracking echocardiography (STE) using the EchoPAC workstation (GE, Horton, Norway) in HCM patients categorised according to the distribution of hypertrophy. Methods: We prospectively assessed GLS in 86 HCM patients attending a quaternary cardiomyopathy clinic: 53 with asymmetrical septal hypertrophy (ASH), 21 with concentric hypertrophy (cHCM) and 12 with apical hypertrophy (ApHCM). Overall group differences were assessed with one-way ANOVA with the post-hoc Tukey test for three-way comparisons. To correct for the impact of afterload, the analysis was repeated for patients with no evidence of dynamic left ventricular obstruction either at rest or post Valsalva manoeuvre (n1⁄4 54). Results: Mean age was 49 15 years; 68 % were males. Mean age was similar in ASH, cHCM and ApHCM groups respectively (48 13 vs. 51 15 vs. 49 19 years). There was a significant difference between the 3 groups in the GLS: ApHCM (-12.8 2.6%) vs. ASH (-16.9 3.6%) vs. cHCM (-18.4 2.7%), one-way ANOVA P <0.001 (see figure). The post-hoc Tukey test showed that the differences were due to significantly reduced GLS in the ApHCM group compared to the ASH and cHCM groups, with no significant differences between the latter 2 groups. Similar findings were noted when the patients with dynamic obstruction were excluded.

PM055 Twisting Myocardial Mechanics are Impaired in Apparently Unaffected Hypertrophic Cardiomyopathy Mutation Carriers

Introduction: Myocardial Mechanics in Hypertrophic Cardiomyopathy: Is There a Difference between Subtypes? Objectives: We compared global longitudinal strain (GLS) derived by 2-dimensional speckle tracking echocardiography (STE) using the EchoPAC workstation (GE, Horton, Norway) in HCM patients categorised according to the distribution of hypertrophy. Methods: We prospectively assessed GLS in 86 HCM patients attending a quaternary cardiomyopathy clinic: 53 with asymmetrical septal hypertrophy (ASH), 21 with concentric hypertrophy (cHCM) and 12 with apical hypertrophy (ApHCM). Overall group differences were assessed with one-way ANOVA with the post-hoc Tukey test for three-way comparisons. To correct for the impact of afterload, the analysis was repeated for patients with no evidence of dynamic left ventricular obstruction either at rest or post Valsalva manoeuvre (n1⁄4 54). Results: Mean age was 49 15 years; 68 % were males. Mean age was similar in ASH, cHCM and ApHCM groups respectively (48 13 vs. 51 15 vs. 49 19 years). There was a significant difference between the 3 groups in the GLS: ApHCM (-12.8 2.6%) vs. ASH (-16.9 3.6%) vs. cHCM (-18.4 2.7%), one-way ANOVA P <0.001 (see figure). The post-hoc Tukey test showed that the differences were due to significantly reduced GLS in the ApHCM group compared to the ASH and cHCM groups, with no significant differences between the latter 2 groups. Similar findings were noted when the patients with dynamic obstruction were excluded.

Three-dimensional speckle tracking echocardiography for the preclinical diagnosis of hypertrophic cardiomyopathy

The aim is to detect early changes in myocardial mechanics in hypertrophic cardiomyopathy (HCM) mutation carriers, three-dimensional speckle tracking echocardiography (3DSTE) was used for screening of family members in the HCM population. Eighty subjects were divided as: HCM mutation carriers (n = 23), manifest HCM patients (n = 28), and normal controls (n = 29). They prospectively underwent 3DSTE for left atrial (LA) and left ventricle (LV) strain analysis. HCM mutation carriers showed significantly higher LA minimum volume (ml/m(2)) (17 ± 6 vs. 14 ± 4, respectively, P = 0.03) and a significantly lower peak atrial longitudinal strain (PALS) (%), (27 ± 5 vs. 31 ± 7, respectively, P = 0.02) when compared to controls. However, no differences were found in global or regional LV systolic myocardial deformation between both groups. Manifest HCM patients, compared to carriers showed significantly higher LA minimum (27 ± 10 vs. 17 ± 6, respectively, P < 0.001) and maximum volume (42 ± 14 vs. 32 ± 8, respectively, P = 0.007) as well as lower LA ejection fraction (%) (35 ± 8 vs. 47 ± 9, respectively, P < 0.001) and PALS (17 ± 5 vs. 27 ± 5, respectively, P < 0.001). Comparing LV strain, HCM patients showed reduced global longitudinal (-11 ± 4 vs. -16 ± 3, respectively, P < 0.001) and area strain (-35 ± 6 vs. -40 ± 5, respectively, P = 0.005). HCM mutation carriers may be distinguished from healthy subjects using 3DSTE through detection of LA dysfunction that may indicate LV diastolic dysfunction. Further research in a larger study population with gene-specific analysis is warranted for potential clinical usefulness of 3DSTE in family screening for HCM.