Function In Hypertrophic Cardiomyopathy Research Articles

The effect of atrial morphology on atrial function in hypertrophic cardiomyopathy

Abstract Background Atrial dysfunction is a relevant marker of disease progression in hypertrophic cardiomyopathy (HCM). Left atrial (LA) longitudinal functional parameters and volumes derived from cardiac magnetic resonance (CMR) are associated with new-onset atrial fibrillation (AF) and its complications. The asymmetrical shape of the LA and its morphological alterations may influence LA function and could provide new mechanistic insights into HCM. Objective To assess the association between CMR derived functional and morphological LA characteristics in HCM patients. Methods Patients with an established diagnosis of HCM were included. HCM patients with a history of AF or without available CMR were excluded. CMR acquisitions used for clinical indication of heart failure diagnosis and etiology were retrospectively analyzed to obtain LA reservoir (LAres), booster (LAboost), and conduit (LAcond) strain on 2-chamber views (Medis Suite v3.2). Strain measurements of the other cardiac chambers were also performed. Manual tracing of LA endocardial border at the LA orthogonal longitudinal and transverse diameters on 2-, 3-, and 4-chamber views was performed (Philips Portal v10.1). Univariable and multivariable forward linear regression was employed to assess associations between functional and morphological LA measures. Results A total of 81 HCM patients were included, mean age 52±16 years, 59 (73%) male, and left ventricular ejection fraction 72.0±8.3%. Mean LAres was 27.2±11.0%, LAboost -14.9%±6.4%, and LAcond -12.5%±7.5%. LA morphological parameters are summarized in Table 1. The strongest correlates in multivariable regression for LAres were longitudinal LA diameter on 2-chamber view (Figure 1) and transverse LA diameter ratio between 4- and 2-chamber view (R2 0.30, p<0.001). The strongest correlates in multivariable regression for LAboost were longitudinal LA diameter on 2- and 4-chamber view, antero-posterior LA diameter on 3-chamber view, and LA area on 4-chamber view (R2 0.29, p<0.001). Longitudinal 2-chamber LA diameter also correlated with LAcond, but the strongest correlates of LAcond in multivariable regression were longitudinal-transversal LA diameter ratio on 2-chamber view, LA area on 3-chamber view, and LA sphericity (R2 0.25, p<0.001). Conclusions CMR-derived LA functions in HCM patients differently correlated with LA morphology. LA longitudinal 2-chamber diameter had a strong influence on all LA functions.Left atrial measures in HCMLA function and diameter correlations

Evaluation of global and regional myocardial work in hypertrophic cardiomyopathy patients by left ventricular pressure-strain loop

ObjectiveThis study aimed to investigate the value of left ventricular (LV) press-strain loop (PSL) in evaluating global and regional myocardial work (MW) in hypertrophic cardiomyopathy (HCM) patients.MethodsA total of 30 HCM patients with interventricular septum hypertrophy (HCM group) and 35 healthy subjects (control group) were selected from First Hospital of Qinhuangdao. The general clinical data and conventional ultrasound parameters of two groups were acquired. The MW parameters were analyzed using LV PSL. The regional MW parameters in the HCM group were compared between ventricular septum and the free walls of left ventricle.ResultsThe epicardial adipose tissue thickness of the HCM group was significantly greater than that of the control group (P < 0.05). Global work efficiency was significantly reduced, while global wasted work was increased in patients with HCM compared with controls (all P < 0.05). The HCM group was compared in the group, to be specific, in the HCM group, the work index, the work efficiency, and the longitudinal strain on the interventricular septum were lower than those on the free wall (all P < 0.05).ConclusionPSL is more effective than LVEF in assessing left ventricular systolic function in HCM and is able to quantify regional myocardial work in the ventricular septum in HCM patients with preserved LVEF, suggesting a novel idea for clinical diagnosis and assessment.

Mavacamten, a precision medicine for hypertrophic cardiomyopathy: From a motor protein to patients.

Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder characterized by left ventricular hypertrophy, hyperdynamic contraction, and impaired relaxation of the heart. These functional derangements arise directly from altered sarcomeric function due to either mutations in genes encoding sarcomere proteins, or other defects such as abnormal energetics. Current treatment options do not directly address this causal biology but focus on surgical and extra-sarcomeric (sarcolemmal) pharmacological symptomatic relief. Mavacamten (formerly known as MYK-461), is a small molecule designed to regulate cardiac function at the sarcomere level by selectively but reversibly inhibiting the enzymatic activity of myosin, the fundamental motor of the sarcomere. This review summarizes the mechanism and translational progress of mavacamten from proteins to patients, describing how the mechanism of action and pharmacological characteristics, involving both systolic and diastolic effects, can directly target pathophysiological derangements within the cardiac sarcomere to improve cardiac structure and function in HCM. Mavacamten was approved by the Food and Drug Administration in April 2022 for the treatment of obstructive HCM and now goes by the commercial name of Camzyos. Full information about the risks, limitations, and side effects can be found at www.accessdata.fda.gov/drugsatfda_docs/label/2022/214998s000lbl.pdf.

DNA methylome and transcriptome profiling reveal key electrophysiology and immune dysregulation in hypertrophic cardiomyopathy

ABSTRACT Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. However, a detailed DNA methylation (DNAme) landscape has not yet been elucidated. Our study combined DNAme and transcriptome profiles for HCM myocardium and identify aberrant DNAme associated with altered myocardial function in HCM. The transcription of methylation-related genes did not significantly differ between HCM and normal myocardium. Nevertheless, the former had an altered DNAme profile compared with the latter. The hypermethylated and hypomethylated sites in HCM tissues had chromosomal distributions and functional enrichment of correlated genes differing from those of their normal tissue counterparts. The GO analysis of network underlying the genes correlated with DNAme alteration and differentially expressed genes (DEGs) shows functional clusters centred on immune cell function and muscle system processes. In KEGG analysis, only the calcium signalling pathway was enriched either by the genes correlated with changes in DNAme or DEGs. The protein-protein interactions (PPI) underlying the genes altered at both the DNAme and transcriptional highlighted two important functional clusters. One of these was related to the immune response and had the estrogen receptor-encoding ESR1 gene as its node. The other cluster comprised cardiac electrophysiology-related genes. Intelliectin-1 (ITLN1), a component of the innate immune system, was transcriptionally downregulated in HCM and had a hypermethylated site within 1500 bp upstream of the ITLN1 transcription start site. Estimates of immune infiltration demonstrated a relative decline in immune cell population diversity in HCM. A combination of DNAme and transcriptome profiles may help identify and develop new therapeutic targets for HCM.

Predictive value of cardiac magnetic resonance mechanical parameters for myocardial fibrosis in hypertrophic cardiomyopathy with preserved left ventricular ejection fraction.

Myocardial fibrosis leads to systolic dysfunction in hypertrophic cardiomyopathy (HCM) patients. This study aims to investigate the relationship between cardiac magnetic resonance mechanical parameters for evaluating the left ventricular function in HCM with preserved left ventricular ejection fraction (LVEF ≥50%) and the association between myocardial fibrosis defined by late gadolinium enhancement (LGE). This study was a retrospective analysis of CMR images of 93 patients with HCM with preserved ejection fraction (HCMpEF) and 96 controls diagnosed by cardiac magnetic resonance (CMR) at our hospital from July 2019 to January 2022. The myocardial contraction fraction (MCF) was calculated, and myocardial mechanical parameters, including global myocardial longitudinal strain (GLS), circumferential strain (GLS), and myocardial strain (GLS), were obtained by tissue tracking and LGE quantitative modules of dedicated software, respectively. The correlation between myocardial strain and LGE was analyzed, and a multivariate logistic regression model was developed to discuss the risk predictors of LGE. Compared to the control group, the left ventricular mechanical parameters GLS (-13.90 ± 3.80% versus -18.20 ± 2.10%, p < 0.001), GCS (-16.62 ± 3.50% versus -18.4 ± 2.69%, p < 0.001), GRS (28.99 ± 10.38% versus 33.02 ± 6.25%, p < 0.01), and MCF (64 ± 16% versus 99 ± 18%, p < 0.001) were found significantly lower in HCM group. Moreover, even in LGE-negative HCM patients, GLS (-16.3 ± 3.9%) and MCF (78 ± 19%) were significantly lower compared to the control group. Left ventricular GLS [OR = 1.61, (1.29, 2.02), p = 0.001] and MCF [OR = 0.90, (0.86, 0.94), p = 0.001] independently predicted myocardial late gadolinium enhancement (LGE). In participants of HCM with preserved ejection fraction, the early onset of reduced left ventricular GLS and MCF in patients with HCMpEF may provide new evidence for evaluating impaired myocardial systolic function. The reduction of myocardial mechanical indexes may reflect the presence and extent of myocardial fibrosis, and the more significant the reduction, the more severe the myocardial fibrosis; GLS and MCF may be ideal predictors for LGE.

Effects of left atrial function on pulmonary arterial pressure in acute myocardial infarction, hypertrophic and dilated cardiomyopathy

BackgroundTo investigate the differential contribution of the left atrial (LA) function and left ventricular (LV) fibrosis to pulmonary arterial systolic pressure (PASP) in hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and reperfused acute myocardial infarction (AMI).MethodsData of 370 patients with HCM (n = 133), DCM (n = 114) and reperfused AMI (n = 123) who underwent both echocardiography and cardiovascular magnetic resonance (CMR) were comprehensively reviewed. Phasic LA volumes, LA-global longitudinal strain (GLS), LA stiffness index, defined as E/e′/LA-GLS and extracellular volume fraction (ECV) of LV were measured using CMR.ResultsE/e′ was correlated with PASP in all groups; however, the predicted value was significantly attenuated after adjusting for LA volume and LA strain in HCM and DCM, but remained significant in AMI. The LA stiffness index was related to PASP in HCM (p = 0.01) and DCM (p = 0.03) independent of LA volume index and E/e′, but not in AMI. In DCM, ECV was significantly related to PASP (p < 0.001) independent of LA volume index and E/e′. When subdivided according to the linear regression between PASP and E/e′, patients in the discrepantly high PASP group had lower total emptying fraction and reservoir fraction of left atrium in HCM and DCM but not in AMI.ConclusionsThe LA function in HCM and DCM and LV fibrosis in DCM correlated with PASP independent of E/e′ and LA size, contrary to that in AMI. These results suggest the presence of LA dysfunction in non-ischemic cardiomyopathies and usefulness of ECV measurement in DCM for the comprehensive evaluation of LV diastolic function.

Analysis of Left Atrial Function after Percutaneous Intramyocardial Septal Radiofrequency Ablation in Hypertrophic Cardiomyopathy

Introduction: The main goal of our research was to explore the effect of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) on left atrial (LA) phasic function in hypertrophic cardiomyopathy (HCM). Methods: The study included 13 patients who underwent PIMSRA at our hospital. The function of LA including reservoir, conduit, and booster pump was analyzed and compared before and 6 months after PIMSRA in HCM patients. LA reservoir function parameters contain maximal LA volume, minimal LA volume (LAV min), LA ejection fraction (LAEF), LA expansion index (LAEI), and reservoir strain; LA conduit function includes LA volume before atrial systole, LA passive volume, LA passive ejection fraction, and conduit strain; LA booster function involves LA booster volume, LA active ejection fraction, and LA contraction strain. Additionally, 20 healthy controls were selected to compare the LA function of HCM patients. Results: The preoperative LA reservoir and conduit function in HCM patients were significantly impaired compared with the control group, while the change in booster pump function was not obvious. HCM patients at 6 months after PIMSRA had remarkably enhanced reservoir and conduit functions which were manifested by lower LAV min, higher LAEF, LAEI, reservoir, and conduit strain than before the operation, and the differences among these parameters between patients after PIMSRA and the healthy control group were not significant. However, with regard to LA contraction function, there was no significant improvement at 6 months after PIMSRA compared with before operation. Conclusion: PIMSRA is effective in the amelioration of LA reservoir and conduit function in patients with HCM but not in a marked improvement of LA contraction function in these individuals in short term.

Abstract 11880: Effects of Left Atrial Function on Pulmonary Arterial Pressure in Acute Myocardial Infarction, Hypertrophic and Dilated Cardiomyopathy

Introduction: We evaluated differential contribution of the left atrial (LA) function by cardiovascular magnetic resonance (CMR) and left ventricular (LV) fibrosis to pulmonary arterial systolic pressure in hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and reperfused acute myocardial infarction (AMI). Hypothesis: The differential role of the LA function and LV fibrosis indices for pulmonary pressure elevation would be different in various myocardial diseases and there would be a predictive value in addition to the conventional echocardiographic parameters. Methods: Data of 370 patients with HCM (n=133), DCM (n=114) and reperfused AMI (n=123) who underwent both echocardiography and CMR were comprehensively reviewed. Phasic LA volumes, LA-global longitudinal strain (GLS), LA stiffness index, defined as E/e’/LA-GLS and extracellular volume fraction (ECV) of LV were measured using CMR. Results: E/e’ was correlated with PASP in all groups; however, the predicted value was significantly attenuated after adjusting for LA volume and LA strain in HCM and DCM, but remained significant in AMI. The LA stiffness index was related to PASP in HCM (p=0.01) and DCM (p=0.03) independent of LA volume index and E/e', but not in AMI. In DCM, ECV was significantly related to PASP (p&lt;0.001) independent of LA volume index and E/e’. Conclusions: The LA function in HCM and DCM and LV fibrosis in DCM correlated with PASP independent of E/e’ and LA size, contrary to that in AMI. These results suggest the presence of left atrial dysfunction in non-ischemic cardiomyopathies and usefulness of ECV measurement in DCM for the comprehensive evaluation of LV diastolic function.

Left ventricular strain patterns and their relationships with cardiac biomarkers in hypertrophic cardiomyopathy patients with preserved left ventricular ejection fraction.

AimsThis study aims to assess left ventricular (LV) function in hypertrophic cardiomyopathy (HCM) patients with preserved left ventricular ejection fraction (LVEF) by LV strain patterns based on cardiac magnetic resonance feature tracking (CMR-FT) and to explore the relationships between LV strain patterns and cardiac biomarkers in these patients, such as cardiac troponin (cTnT) and N-terminal prohormone of the brain natriuretic peptide (NT-proBNP).MethodsA total of 64 HCM patients with preserved LVEF and 33 healthy people were included in this study. All subjects underwent contrast-enhanced CMR, and all patients took blood tests for cTnT and NT-proBNP during hospitalization.ResultsDespite the absence of a significant difference in LVEF between HCM patients and healthy controls, almost all global and segmental strains in radial, circumferential, and longitudinal directions in the HCM group deteriorated significantly as compared to controls (p < 0.05). Moreover, some global and segmental strains correlated significantly with NT-proBNP and cTnT in HCM patients, and the best correlations were global radial strain (GRS) (r = −0.553, p < 0.001) and mid-ventricular radial strain (MRS) (r = −0.582, p < 0.001), respectively, with a moderate correlation. The receiver operating characteristic (ROC) results showed that among the LV deformation parameters, GRS [area under the curve (AUC), 0.76; sensitivity, 0.49; specificity, 1.00], MRS (AUC, 0.81; sensitivity, 0.77; specificity, 0.79) demonstrated greater diagnostic accuracy to predict elevated NT-proBNP, and abnormal cTnT, respectively. Their cut-off values were 21.17 and 20.94%, respectively. Finally, all global strains demonstrated moderate, good, and excellent intra- and inter-observer reproducibility.ConclusionLV strain patterns can be used to assess the subclinical cardiac function of HCM patients on the merit of being more sensitive than LVEF. In addition, LV strain patterns can detect serious HCM patients and may be helpful to non-invasively predict elevated NT-proBNP and cTnT.

Exercise training during childhood and adolescence is associated with favorable diastolic function in hypertrophic cardiomyopathy

BackgroundDiastolic dysfunction is an important part of the clinical phenotype in hypertrophic cardiomyopathy (HCM). While exercise training is known to improve left ventricular (LV) diastolic function in normal hearts, the effects of exercise training during childhood and adolescence in carriers of HCM-associated genetic variants are unknown. MethodsIn a cross-sectional and retrospective study, we combined clinical and echocardiographic data with history of exercise training from childhood to time of examination in 187 participants with HCM or an HCM-causative genotype. Multiple linear regression was used to identify correlations between exercise training performed prior to 20 years of age and LV diastolic parameters from echocardiography. ResultsExercise training during childhood and adolescence was correlated with a favorable e’, E/e’, E deceleration time, and end-diastolic volume (EDV), when adjusting for the effects of age at examination, and presence of left ventricular hypertrophy (LVH). This correlation was evident both in patients with a HCM phenotype (HCM LVH+), and in individuals with an HCM-causative genotype without LV hypertrophy (G+ LVH-). None of the diastolic parameters correlated unfavorably with increasing exercise exposure. ConclusionMore exercise training during childhood and adolescence was associated with favorable LV diastolic function in both HCM LVH+ and G+ LVH- groups, regardless of presence of hypertrophy at the time of examination. These results indicate that exercise training initiated during childhood and adolescence has positive effects on cardiac function later in life for individuals with HCM or an HCM-causative genotype.

Strain-volume loops for assessment of diastolic function in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Diastolic function assessment in patients with hypertrophic hearts and preserved ejection fraction (EF) is a rather challenging task, necessitating the introduction of new parameters. Strain-volume loops (SVLs), based on simultaneous frame-by-frame strain and volume changes’ recordings acquired by means of three-dimensional (3D) speckle tracking imaging, is an innovative tool which has been applied in various substrates. The ability of SVLs to assess diastolic function in hypertrophic cardiomyopathy (HCM) has not been investigated until now. Purpose Aim of this study was to investigate potential correlations between SVLs, traditional diastolic function indices and phenotypic features of HCM (thickness, obstruction and fibrosis) that may also reflect myocardial "stiffness". Methods We included 40 HCM patients (54.1 ± 14.3 years, 82.5% male, maximum wall thickness 19.3 ± 4.8mm) who have consecutively undergone 3D-speckle tracking echocardiography (panel A) and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Values of 3D strain were plotted vs. volume for each frame to build an SVL. Peak of radial, longitudinal and circumferential systolic strain (Rsp, Lsp, and Csp, respectively), systolic slopes of the loops (RsSl, LsSl, CsSl), strain to end-diastolic volume (EDV) ratios (Rs/V, Ls/V, Cs/V) as well as the extent of systolic-diastolic uncoupling (difference between systolic and diastolic strain for the same volume) were computed for the analysis. Left atrial volume index (LAVI), E/E’ and tricuspid regurgitation velocity (TRvel) were measured to define diastolic dysfunction (DD) stage. Burden of fibrosis was evaluated by LGE extent in CMR slices. Results All HCM patients had preserved EF (60.5 ± 5,7%), while 16 (40%) had LV outflow tract obstruction (LVOTO &amp;gt; 30 mm Hg at rest). Mean LV mass index was 78.9 ± 14.5 g (evaluated by 3D echocardiography). LGE was observed in 23 patients (57.5%) occupying 5.2 ± 4.5% of LV mass. Concerning SVLs the following values were recorded for radial (Rsp 30.8 ± 9.8%, RsSl 0.4 ± 0.13 and Rs/V 0.25 ± 0.09), longitudinal (Lsp -9.4 ± 3.7%, LsSl 0.12 ± 0.06 and Ls/V 0.08 ± 0.04) and circumferential deformation (Csp -14.2 ± 3.5%, CsSl 0.18 ± 0.05 and Cs/V 0.11 ± 0.03). Traditional isolated diastolic indices (E/E’, LAVI, TRvel and DD stage) did not present significant correlations with SVL parameters or HCM phenotypic features. However, potentially "stiffer" hearts (combination of increased LVMI and fibrosis) presented a leftward transition of longitudinal SVLs, which also became wider (greater uncoupling) (panel B). Conclusions Traditional diastolic indices show modest only correlations with SVLs or HCM phenotypic characteristics, necessitating new approaches to DD of HCM patients. SVLs seem to be a promising-innovative tool for indirect assessment of myocardial "stiffness" and diastolic function. Abstract Figure.

Right ventricular function declines prior to left ventricular ejection fraction in hypertrophic cardiomyopathy

BackgroundThe right ventricle (RV) in hypertrophic cardiomyopathy (HCM) tends to be neglected, as previous efforts have predominantly focused on examining the prognostic value of left ventricular (LV) abnormalities. The objectives of this study were to assess RV function in HCM, changes over time, and association with clinical outcomes.MethodsTwo hundred and ninety HCM patients with preserved LV ejection fraction (LVEF ≥ 55%) and 30 age- and sex-matched controls underwent cardiovascular magnetic resonance (CMR). All patients were followed up for clinical events for a median duration of 4.4 years. Sixty-three patients had a follow-up CMR undertaken at a median interval of 5.4 years. Main study measures and outcomes were RV function (RV ejection fraction (RVEF) and RV strain) at baseline, temporal changes in RV function over time and prognostic value of RV dysfunction for predicting cardiovascular outcomes in HCM.ResultsWhen compared to controls, HCM patients exhibited lower RV and LV peak global longitudinal systolic strains on feature-tracking analysis of cine images, while RVEF and LVEF were within the normal range. On follow-up CMR, both RV and LV strain parameters decreased over time. RVEF decreased at follow-up (65 ± 7% to 62 ± 7%, P < 0.001) but the change in LVEF was not significant (68 ± 10% to 66 ± 8%, P = 0.30). On clinical follow up, reduced RVEF was an independent predictor of non-sustained ventricular tachycardia (NSVT) [HR 1.10 (95% CI 1.06–1.15), P < 0.001] and composite cardiovascular events (NSVT, stroke, heart failure hospitalisation and cardiovascular death) [HR 1.07 (95% CI 1.03–1.10), P < 0.001]. RV longitudinal strain was an independent predictor of NSVT [HR 1.05 (95% CI 1.01–1.09), P = 0.029]. Patients with RVEF < 55% showed an increased risk of NSVT and composite cardiovascular events. In contrast, LVEF and LV global longitudinal strain were not predictive of such events on multivariable analysis.ConclusionsIn HCM, RV function, including RV strain, and LV strain decrease over time despite preserved LVEF. Reduction in RV but not LV function is associated with adverse cardiovascular outcomes. Assessing RV function in early HCM disease might have a role in risk stratification to prevent future cardiovascular events.

Value of the left atrial size and function in hypertrophic cardiomyopathy for best understand who are the patients at risk for atrial arrhythmia and stroke

Patient with hypertrophic cardiomyopathy (HCM) are at high-risk for atrial arrhythmia (AA) and stroke. We sought to look at atrial remodeling and atrial function by echocardiography in a HCM-cohort to assess the association with the occurrence of AA and stroke. We retrospectively studied 216 patients diagnosed for HCM (mean age 52 ± 16 years) from 2015 to 2020. Complete echocardiography at baseline was performed including measurement of left atrial volume (LAV) and peak left atrial strain (PLAS). Patients were followed for development of the composite endpoint comprising history or occurrence of atrial arrhythmias and/or stroke during mean follow-up of 3 years. Seventy-eight patients had an event (24 stroke and 54 documented atrial arrhythmia). Univariable analysis showed that LAV (37.2 ± 15.7 mL/m 2 vs. 47 ± 20 mL/m 2 ; P = 0.0001), anteroposterior LA diameter (41.7 ±7.58 mm vs. 45.8 ± 8.9 mm; P = 0.0006) and PLAS (27.1 ± 9.77% vs. 20.4 ± 10.5%; P < 0.0001) were significantly associated with the occurrence of the endpoint. NTproBNP level (216 vs. 818 ng/L; P < 0.0001), history of hypertension (42.3% vs. 62.3%; P = 0.005) and age at diagnosis (50.3 ± 16.7 years vs. 57.1 ± 14.4 years; P = 0.0035) were the clinical parameters different between groups. In a multivariable analysis, PALS was the only independent maker associated with the occurrence of AA and stroke, particularly for stroke with an odd ratio of 0.51 ([0.36–0.69]; P ≤ 0,05). Interestingly, 19 of 28 stroke patients (67%) did not experience any documented atrial arrhythmias ( Table 1 , Fig. 1 ). The decrease of PLAS is strongly associated with the risk of stroke, even in patients without documented atrial arrhythmia. Its use to guide the indication for an implantable Holter monitoring and perhaps a prophylactic oral anticoagulation in HCM requires further investigation.

Association Between Heart Failure With Preserved Left Ventricular Ejection Fraction and Impaired Left Atrial Phasic Function in Hypertrophic Cardiomyopathy: Evaluation by Cardiac MRI Feature Tracking.

The majority of heart failure (HF) in hypertrophic cardiomyopathy (HCM) manifests as a phenotype with preserved left ventricular (LV) ejection fraction; however, the exact contribution of left atrial (LA) phasic function to HF with preserved ejection fraction (HFpEF) in HCM remains unresolved. To define the association between LA function and HFpEF in HCM patients using cardiac magnetic resonance imaging (MRI) feature tracking. Retrospective. One hundred and fifty-four HCM patients (HFpEF vs. non-HF: 55 [34 females] vs. 99 [43 females]). 3.0 T/balanced steady-state free precession. LA reservoir function (reservoir strain [εs ], total ejection fraction [EF]), conduit function (conduit strain [εe ], passive EF), booster-pump function (booster strain [εa ] and active EF), LA volume index, and LV global longitudinal strain (LV GLS) were evaluated in HCM patients. Chi-square test, Student's t-test, Mann-Whitney U test, multivariate linear regression, logistic regression, and net reclassification analysis were used. Two-sided P < 0.05 was considered statistically significant. No significant difference was found in LV GLS between the non-HF and HFpEF group (-10.67 ± 3.14% vs. -10.14 ± 4.01%, P=0.397), whereas the HFpEF group had more severely impaired LA phasic strain (εs : 27.40 [22.60, 35.80] vs. 18.15 [11.98, 25.90]; εe : 13.80 [9.20, 18.90] vs. 7.95 [4.30, 14.35]; εa : 13.50 [9.90, 17.10] vs. 7.90 [5.40, 14.15]). LA total EF (37.91 [29.54, 47.94] vs. 47.49 [39.18, 55.01]), passive EF (14.70 [7.41, 21.49] vs. 18.07 [9.32, 24.78]), and active EF (27.19 [17.79, 36.60] vs. 36.64 [26.63, 42.71]) were all significantly decreased in HFpEF patients compared with non-HF patients. LA reservoir (β=0.90 [0.85, 0.96]), conduit (β=0.93 [0.87, 0.99]), and booster (β=0.86 [0.78, 0.95]) strain were independently associated with HFpEF in HCM patients. The model including reservoir strain (Net Reclassification Index [NRI]: 0.260) or booster strain (NRI: 0.325) improved the reclassification of HFpEF based on LV GLS and minimum left atrial volume index (LAVImin ). LA phasic function was severely impaired in HCM patients with HFpEF, whereas LV function was not further impaired compared with non-HF patients. 4 TECHNICAL EFFICACY: Stage 3.

Abstract 10678: Butyrate Improves Energetics, Diastolic Function and Contractile Reserve in Hearts from Mice with Hypertrophic Cardiomyopathy Due to Myosin R403Q Mutation

Background: It is well established that hearts with hypertrophic cardiomyopathy (HCM) are energy starved as reflected by a decreased phosphocreatine to ATP ratio that corresponds to increased ADP and decreased free energy of ATP hydrolysis (ΔG ~ATP ). Notably, worsened energetics precedes hypertrophy in development of HCM and mitochondrial mutations impeding ATP synthesis frequently lead to a hypertrophic phenotype similar to HCM. It remains unclear whether targeted strategies to boost mitochondrial ATP synthesis may improve chronically depressed diastolic function and contractile reserve. Here we hypothesize that saturating mitochondria with an accessible substrate, butyrate, acutely improves energetics and function in HCM. Methods and Results: Isolated hearts from 6 months old mice with HCM due to R403Q myosin mutation (R403Q) vs. the wild type littermates (WT) were studied using 31 P NMR spectroscopy to measure ATP synthesis, ADP and ΔG ~ATP at low (LW) and high workload (HW) and HW plus 4 mM butyrate (HWB). As expected, compared to WT, R403Q hearts showed: ↑ATP synthesis associated with a trend for ↑rate pressure product (RPP, p=0.08) at LW but were unable to increase these parameters further at HW. Energetics (↑ADP and ↓ΔG ~ATP ) were depressed at LW and worsened further at HW. Diastolic dysfunction (↑EDP) developed at HW. Butyrate perfusion (HWB) significantly improved all energetic and contractile parameters in R403Q hearts. Conclusion: Here we show that mouse hearts with HCM due to myosin R403Q mutation have worsened energetics despite a higher ATP synthesis rate at baseline. With higher work demand R403Q hearts are unable to dynamically increase ATP synthesis or work. Acute saturation with butyrate enables a further increase in ATP synthesis, normalizing energetics and improving diastolic function and contractile reserve. Thus, our results suggest that targeting mitochondrial function may be a promising strategy in management of HCM.

ANALYSIS OF ECHOCARDIOGRAPHIC AND MRI ANATOMICAL CHARACTERISTICS AND HEMODYNAMIC CHARACTERISTICS OF LEFT VENTRICULAR OUTFLOW TRACT STENOSIS

Objective: To analyze the anatomical morphological and hemodynamic characteristics of left ventricular outflow tract stenosis (LVOTS) by echocardiography and MRI. Methods: The Echocardiography data of 112 patients with LVOTS were retrospectively analyzed by measuring the basal interventricular septal thickness (IVST-b), the left ventricle posterior wall thickness (LVPWT), and the peak pressure gradient of LVOTS, as well as by observing the characteristics of spectral pattern and the presence of systolic anterior motion of mitral valve leaflets. A Siemens 3.0T MRI scanner was used to scan the contrast-enhanced left ventricular (LV) volume of all cases. The obtained end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) of LV were compared with the Echocardiography results. Results: The 112 patients were divided into four groups: hypertrophic obstructive cardiomyopathy (Group I, 42 cases), hypertensive left ventricular hypertrophy (Group II, 40 cases), basal septal hypertrophy in the elderly (Group III, 21 cases), and the subaortic membrane (Group IV, 9 cases). The continuous wave (CW) Doppler characteristic of Groups I, II, and III was broadsword-shaped jet, and that of Group IV was equilateral triangle-like spectrum. The IVST-b, IVST-b/LVPWT ratio and peak pressure gradient of LVOTS of Group I was significantly higher than those in Groups II and III ([Formula: see text]). The LVPWT of the first three groups was slightly correlated with the LVOTS peak pressure gradient ([Formula: see text], respectively, [Formula: see text]). There were no statistically significant differences between Echocardiography and MRI results regarding the LV EDV, ESV, SV, and EF ([Formula: see text]), and no statistically significant differences were found between Echocardiography and MRI results regarding the myocardial thicknesses of septal, anterior, lateral, and inferior walls ([Formula: see text]). The Pearson’s correlation analysis demonstrated correlations between MRI and Echocardiography results for LV EDV, ESV, SV, and EF ([Formula: see text], 0.002, 0.009, and [Formula: see text], respectively). The MRI enhancement was shown as delayed enhancement in 52 cases, localized enhancement in 8 cases, diffuse enhancement in 6 cases, and transmural enhancement in 3 cases, with abnormal enhancement lesions distributed in the area of ventricular septum free wall junctions and ventricular septum. Conclusion: Using MRI to evaluate LV function of hypertrophic cardiomyopathy is reliable and accurate. MRI enhancement can be used for the quantitative measurement of myocardial fibrosis. Echocardiography can distinguish the stenosis types of LVOTS. The IVST-b and existence of SAM may be important anatomical characteristics determining the degree of dynamic stenosis, and MRI combined with Echocardiography can provide important detailed information.

Prognostic value of fast semi-automated left atrial long-axis strain analysis in hypertrophic cardiomyopathy

BackgroundThe prognostic value of left atrial (LA) size and function in hypertrophic cardiomyopathy (HCM) is well recognized, but LA function is difficult to routinely analyze. Fast LA long-axis strain (LA-LAS) analysis is a novel technique to assess LA function on cine cardiovascular magnetic resonance (CMR). We aimed to assess the association between fast LA-LAS and adverse clinical outcomes in patients with HCM.Methods359 HCM patients and 100 healthy controls underwent routine CMR imaging. Fast LA-LAS was analyzed by automatically tracking the length between the midpoint of posterior LA wall and the left atrioventricular junction based on standard 2- and 4-chamber balanced steady-state free precession cine-CMR. Three strain parameters including reservoir strain (εs), conduit strain (εe), and active strain (εa) were assessed. The endpoint was set as composite adverse events including cardiovascular death, resuscitated cardiac arrest, sudden cardiac death aborted by appropriate implantable cardioverter-defibrillator discharge, and hospital admission related to heart failure.ResultsDuring an average follow-up of 40.9 months, 59 patients (19.7%) reached endpoints. LA strains were correlated with LA diameter, LA volume index (LAVI) and LA empty fraction (LAEF) (all p < 0.05). In the stepwise multivariate Cox regression analysis, εs and εe (hazard ratio, 0.94 and 0.89; p = 0.019 and 0.006, respectively) emerged as independent predictors of the composite adverse events. Fast LA εs and LA εe are stronger prognostic factors than LA size, LAVI and the presence of left ventricular late gadolinium enhancement.ConclusionsFast LA reservoir and conduit strains are independently associated with adverse outcomes in HCM.

Assessment of atrial function by myocardial deformation techniques in hypertrophic cardiomyopathy.

Diastolic dysfunction in hypertrophic cardiomyopathy (HCM) is common, but its assessment is difficult using conventional echocardiography. To assess left atrial (LA) function in HCM by longitudinal strain and determine its role in understanding of symptoms. We studied 144 patients divided into 3 age- and sex-matched groups: 48 consecutive patients with HCM, 48 control subjects, and 48 athlete subjects. We assessed LA function by conventional echocardiographic parameters and by longitudinal atrial strain (early-diastolic left atrial strain during reservoir phase [LASr]; end-diastolic left atrial strain during conduit phase; end-systolic peak of the left atrial strain during contraction phase). NYHA classification was as follows in HCM group: I in 46%, II in 31%, III in 19%, and IV in 4%. Conventional echocardiographic parameters of diastolic function were depressed in the HCM group as compared to the control and athlete groups, but not related to symptoms. All longitudinal atrial strain parameters were significantly reduced in HCM group as compared to two groups (P<.0001). LASr was significantly correlated to peak VO2 (r=0.44, P=.01) and was the best parameter for detecting symptomatic patients presenting with HCM, with a cutoff value of 15%: Sensitivity was 71%, specificity was 79%, PPV was 77%, and NPV was 73%. Assessment of LA function in HCM is feasible using longitudinal strain, and this technique is more reliable than conventional echocardiographic parameters for the understanding of determinants of symptoms.

Left ventricular long-axis function in hypertrophic cardiomyopathy - Relationships between e`, early diastolic excursion and duration, and systolic excursion.

The peak velocity of early diastolic mitral annular motion (e`) is believed to provide sensitive detection of left ventricular (LV) diastolic dysfunction in hypertrophic cardiomyopathy (HCM), but other aspects of LV long-axis function in HCM have received less attention. Systolic mitral annular excursion (SExc) is also reduced in HCM and must be an intrinsic limitation to the extent of the subsequent motion during diastole. However, the effects of HCM on excursion during early diastole (EDExc) and atrial contraction (AExc), the duration of early diastolic motion (EDDur), and the relationships of EDExc with SExc, and of e`with EDExc and EDDur, are all unknown. The study group was 22 subjects with HCM and there were 22 age and sex matched control subjects. SExc, EDExc, e`, AExc and EDDur were measured from pulsed wave tissue Doppler signals acquired from the septal and lateral walls. In the combined group of HCM and control subjects, multivariate analyses were performed to identify independent predictors of EDExc and e`for both LV walls. SExc, EDExc and e`were all lower, and EDDur was longer in the HCM group compared to the control group for both LV walls (p<0.05 for all). In contrast, AExc was lower for the septal wall in the HCM group (p<0.05), but not different between the groups for the lateral wall. In regression analyses of the combined group, EDExc was positively correlated with SExc, and SExc explained 57-86% of the variances in septal and lateral EDExc, e`was positively correlated with EDExc, and EDExc explained 58-68% of the variances of e`, whereas the combination of EDExc with EDDur explained 87-92% of the variances in e`. A diagnosis of HCM was not an independent predictor of EDExc when in combination with SExc, but was a minor contributor to the prediction of e`in combination with EDExc and EDDur. In HCM, the decrease in LV longitudinal contraction is the major mechanism accounting for a lower EDExc, the lower e`is accounted for by contributions from the lower EDExc and prolongation of early diastolic motion, and there is no atrial compensation for the reduction of long-axis contraction.

UTILITY OF LEFT ATRIAL STRAIN MECHANICS FOR PREDICTING EXERCISE INTOLERANCE IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

Exercise intolerance (EI) is a negative prognostic factor in hypertrophic cardiomyopathy (HCM). Left atrium (LA) is often dilated with reduced mechanical function in HCM. We assessed the relationship between LA function and EI in HCM patients. A random cohort of HCM patients who underwent exercise