From Atrial Fibrillation Management to Atrial Myopathy Assessment: The Evolving Concept of Left Atrium Disease in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetically inherited cardiovascular disorder in adults and a significant cause of heart failure and sudden cardiac death. Historically, atrial fibrillation (AF) has been considered as a critical aspect in HCM patients as it is considered to be a marker of disease progression, escalates the frequency of heart failure hospitalisations, increases the risk of thromboembolic events, and worsens quality of life and outcome. Increasing evidence suggests that AF is the result of a subtle long-standing process that starts early in the history of HCM. The process of left atrial dilation accompanied by morphologic and functional remodelling is the quintessential prerequisite for the onset of AF. This review aims to describe the current understanding of AF pathophysiology in HCM, emphasising the role of left atrial myopathy in its development. In addition, we discuss risk factors and management strategies specific to AF in the context of HCM, providing insights into the complexities and challenges of treating this specific patient population.

Deep learning-based automated left ventricular ejection fraction assessment using 2-D echocardiography.

Deep learning (DL) has been applied for automatic left ventricle (LV) ejection fraction (EF) measurement, but the diagnostic performance was rarely evaluated for various phenotypes of heart disease. This study aims to evaluate a new DL algorithm for automated LVEF measurement using two-dimensional echocardiography (2DE) images collected from three centers. The impact of three ultrasound machines and three phenotypes of heart diseases on the automatic LVEF measurement was evaluated. Using 36890 frames of 2DE from 340 patients, we developed a DL algorithm based on U-Net (DPS-Net) and the biplane Simpson's method was applied for LVEF calculation. Results showed a high performance in LV segmentation and LVEF measurement across phenotypes and echo systems by using DPS-Net. Good performance was obtained for LV segmentation when DPS-Net was tested on the CAMUS data set (Dice coefficient of 0.932 and 0.928 for ED and ES). Better performance of LV segmentation in study-wise evaluation was observed by comparing the DPS-Net v2 to the EchoNet-dynamic algorithm (P = 0.008). DPS-Net was associated with high correlations and good agreements for the LVEF measurement. High diagnostic performance was obtained that the area under receiver operator characteristic curve was 0.974, 0.948, 0.968, and 0.972 for normal hearts and disease phenotypes including atrial fibrillation, hypertrophic cardiomyopathy, dilated cardiomyopathy, respectively. High performance was obtained by using DPS-Net in LV detection and LVEF measurement for heart failure with several phenotypes. High performance was observed in a large-scale dataset, suggesting that the DPS-Net was highly adaptive across different echocardiographic systems.NEW & NOTEWORTHY A new strategy of feature extraction and fusion could enhance the accuracy of automatic LVEF assessment based on multiview 2-D echocardiographic sequences. High diagnostic performance for the determination of heart failure was obtained by using DPS-Net in cases with different phenotypes of heart diseases. High performance for left ventricle segmentation was obtained by using DPS-Net, suggesting the potential for a wider range of application in the interpretation of 2DE images.

Assessment of dynamic cardiac repolarization and contractility in patients with hypertrophic cardiomyopathy.

AIMS: Arrhythmia mechanisms in hypertrophic cardiomyopathy remain uncertain. Preclinical models suggest hypertrophic cardiomyopathy-linked mutations perturb sarcomere length-dependent activation, alter cardiac repolarization in rate-dependent fashion and potentiate triggered electrical activity. This study was designed to assess rate-dependence of clinical surrogates of contractility and repolarization in humans with hypertrophic cardiomyopathy. METHODS: All participants had a cardiac implantable device capable of atrial pacing. Cases had clinical diagnosis of hypertrophic cardiomyopathy, controls were age-matched. Continuous electrocardiogram and blood pressure were recorded during and immediately after 30 second pacing trains delivered at increasing rates. RESULTS: Nine hypertrophic cardiomyopathy patients and 10 controls were enrolled (47% female, median 55 years), with similar baseline QRS duration, QT interval and blood pressure. Median septal thickness in hypertrophic cardiomyopathy patients was 18mm; 33% of hypertrophic cardiomyopathy patients had peak sub-aortic velocity >50mmHg. Ventricular ectopy occurred during or immediately after pacing trains in 4/9 hypertrophic cardiomyopathy patients and 0/10 controls (P = 0.03). During delivery of steady rate pacing across a range of cycle lengths, the QT-RR relationship was not statistically different between HCM and control groups; no differences were seen in subgroup analysis of patients with or without intact AV node conduction. Similarly, there was no difference between groups in the QT interval of the first post-pause recovery beat after pacing trains. No statistically significant differences were seen in surrogate measures for cardiac contractility. CONCLUSION: Rapid pacing trains triggered ventricular ectopy in hypertrophic cardiomyopathy patients, but not controls. This finding aligns with pre-clinical descriptions of excessive cardiomyocyte calcium loading during rapid pacing, increased post-pause sarcoplasmic reticulum calcium release, and subsequent calcium-triggered activity. Normal contractility at all diastolic intervals argues against clinical significance of altered length-dependent myofilament activation.

Diagnostic value of the novel CMR parameter "myocardial transit-time" (MyoTT) for the assessment of microvascular changes in cardiac amyloidosis and hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction (CMD) is present in various non-ischemic cardiomyopathies and in particular in those with left-ventricular hypertrophy. This study evaluated the diagnostic value of the novel cardiovascular magnetic resonance (CMR) parameter "myocardial transit-time" (MyoTT) in distinguishing cardiac amyloidosis from other hypertrophic cardiomyopathies. METHODS: N = 20 patients with biopsy-proven cardiac amyloidosis (CA), N = 20 patients with known hypertrophic cardiomyopathy (HCM), and N = 20 control patients without relevant cardiac disease underwent dedicated CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as first-pass perfusion acquisitions at rest for MyoTT measurement. MyoTT was defined as the blood circulation time from the orifice of the coronary arteries to the pooling in the coronary sinus (CS) reflecting the transit-time of gadolinium in the myocardial microvasculature. RESULTS: MyoTT was significantly prolonged in patients with CA compared to both groups: 14.8 ± 4.1 s in CA vs. 12.2 ± 2.5 s in HCM (p = 0.043) vs. 7.2 ± 2.6 s in controls (p < 0.001). Native T1 and extracellular volume (ECV) were significantly higher in CA compared to HCM and controls (p < 0.001). Both parameters were associated with a higher diagnostic accuracy in predicting the presence of CA compared to MyoTT: area under the curve (AUC) for native T1 = 0.93 (95% confidence interval (CI) = 0.83-1.00; p < 0.001) and AUC for ECV = 0.95 (95% CI = 0.88-1.00; p < 0.001)-compared to the AUC for MyoTT = 0.76 (95% CI = 0.60-0.92; p = 0.008). In contrast, MyoTT performed better than all other CMR parameters in differentiating HCM from controls (AUC for MyoTT = 0.93; 95% CI = 0.81-1.00; p = 0.003 vs. AUC for native T1 = 0.69; 95% CI = 0.44-0.93; p = 0.20 vs. AUC for ECV = 0.85; 95% CI = 0.66-1.00; p = 0.017). CONCLUSION: The relative severity of CMD (measured by MyoTT) in relationship to extracellular changes (measured by native T1 and/or ECV) is more pronounced in HCM compared to CA-in spite of a higher absolute MyoTT value in CA patients. Hence, MyoTT may improve our understanding of the interplay between extracellular/intracellular and intravasal changes that occur in the myocardium during the disease course of different cardiomyopathies.

Coronary microvascular dysfunction in hypertrophic cardiomyopathy: Pathophysiology, assessment, and clinical impact.

Myocardial ischemia constitutes one of the most important pathophysiological features in hypertrophic cardiomyopathy. Chronic and recurrent myocardial ischemia leads to fibrosis, which may culminate in myocardial dysfunction. Since the direct visualization of coronary microcirculation in vivo is not possible, its function must be studied indirectly. Invasive and noninvasive techniques allow microcirculatory dysfunction to be evaluated, including echocardiography, magnetic resonance, positron emission tomography, and cardiac catheterization. Blunted myocardial blood flow and coronary flow reserve have been suggested to associate with unfavorable prognosis. Microcirculatory dysfunction may be one additional important parameter to take into account for risk stratification beyond the conventional risk factors.

Micro-computed tomography (micro-CT) for the assessment of myocardial disarray, fibrosis and ventricular mass in a feline model of hypertrophic cardiomyopathy.

Micro-computed tomography (micro-CT) is a high-resolution imaging modality that provides accurate tissue characterization. Hypertrophic cardiomyopathy (HCM) occurs as a spontaneous disease in cats, and is characterized by myocardial hypertrophy, disarray and fibrosis, as in humans. While hypertrophy/mass (LVM) can be objectively measured, fibrosis and myocyte disarray are difficult to assess. We evaluated the accuracy of micro-CT for detection and quantification of myocardial disarray and fibrosis by direct comparison with histopathology. 29 cat hearts (12 normal and 17 HCM hearts) underwent micro-CT and pathologic examination. Myocyte orientation was assessed using structure tensor analysis by determination of helical angle (HA), fractional anisotropy (FA) and myocardial disarray index (MDI). Fibrosis was segmented and quantified based on comparison of gray-scale values in normal and fibrotic myocardium. LVM was obtained by determining myocardial volume. Myocardial segments with low FA, low MDI and disruption of normal HA transmural profile on micro-CT were associated with myocardial disarray on histopathology. FA was consistently lower in HCM than normal hearts. Assessment of fibrosis on micro-CT closely matched the histopathologic evaluation. LVM determined by micro-CT was higher in HCM than normal hearts. Micro-CT can be used to detect and quantify myocardial disarray and fibrosis and determine myocardial mass in HCM.

Assessment of left ventricular systolic function in hypertrophic cardiomyopathy patients with myocardial injury: a study based on layer-specific speckle tracking echocardiaography.

We conducted this study to investigate left ventricle (LV) systolic function in endocardial, mid-myocardial, and epicardial layers by two-dimensional (2D) speckle tracking echocardiography (STE) in hypertrophic cardiomyopathy (HCM) patients with myocardial injury indexed by elevated serum cardiac troponin I (cTnI). Twenty-nine HCM patients with myocardial injury, thirty-five HCM patients without myocardial injury, and ninty-one healthy controls were enrolled in this study. Serum cTnI > 0.026 ng/mL was defined as myocardial injury. LV longitudinal and circumferential strain (LS and CS) were assessed in endocardial, mid-myocardial and epicardial layers. Layer-specific LS and CS differed significantly (all P < 0.001) among all three groups in all three layers, in a descending order from healthy controls to HCM patients without myocardial injury to HCM patients with myocardial injury. Layer-specific LS and CS were decreased the most in HCM patients with myocardial injury indexed by elevated seum cTnI (all P < 0.05). In HCM patients with myocardial injury, layer-specific LS and CS were significantly lower in the segments with greater hypertrophy (segmental thickness ≥ 15 mm) (all P < 0.001) except for endocardial CS (P > 0.05). Layer-specific evaluation of LV strain may improve understanding of impaired LV systolic function in HCM patients with myocardial injury, thus preventing further damage.

Sex differences in cardiac magnetic resonance features in patients with hypertrophic cardiomyopathy.

Whether sex differences exist in cardiac magnetic resonance (CMR) findings in patients with hypertrophic cardiomyopathy (HCM) remain unknown. We sought to assess and compare CMR characteristics in male and female patients with HCM. From January-2006 to October-2017, 165 consecutive HCM patients evaluated with CMR were included. All clinical and complementary test information was prospectively collected. At the time of CMR evaluation women were older (70 [57-75] vs. 61 [47-72] years, p = 0.02) and more symptomatic in terms of dyspnea (New York Heart Association class II-IV 47.2 vs. 24.1%, p = 0.003) and palpitations (19.6 vs. 4.6%, p = 0.006) and received more frequently treatment with diuretics (49.1% vs. 23.4%, p = 0.001). On echocardiographic examination more women had obstructive physiology (45.1 vs. 20.6%, p = 0.002). On CMR evaluation, women showed smaller left ventricular end-systolic volume index (13 [10-15] vs. 16 [13-21] ml/m2, p < 0.001), higher left ventricular ejection fraction (77 [74-80] vs. 72 [66-78]%, p = 0.004), more marked left ventricular outflow tract acceleration (54.7 vs. 26.4%, p < 0.001) and mitral regurgitation (33.3 vs. 12.7%, p = 0.002). In multivariable analysis, female sex [OR 2.44 (1.04-5.73), p = 0.04] and left ventricular end-systolic volume index [OR 1.60 (1.08-2.38), p = 0.018] were independently associated with obstructive physiology. Women with HCM have more frequently obstructive physiology, a finding that could be related to the smaller left ventricular end-systolic volume.

Assessment of diastolic function using mitral flow propagation velocity in cats.

The objectives of this study were to investigate the usefulness of mitral flow propagation velocity (Vp) in cats by evaluating the effect of the flow pattern summation and evaluation of Vp variables in cats with hypertrophic cardiomyopathy (HCM). Healthy cats were categorized into summation (Sum) and separation (Sepa) groups to evaluate the effects of the flow pattern summation on Vp. Cats with HCM were categorized into HCM left atrial (LA) (-), LA (+), and LA (++) groups according to the degree of LA enlargement to investigate the feasibility of Vp. There were no significant differences noted in Vp between the Sum and Sepa groups and no significant correlation between Vp and heart rate. Decline of Vp was associated with the degree of LA enlargement. Mitral flow propagation velocity appeared to be clinically feasible in cats and could possibly be useful in the detection of diastolic dysfunctions in cats with HCM.

Les objectifs de la présente étude étaient d'examiner l'utilité de la vélocité du flux de propagation mitral (Vp) chez les chats en évaluant les effets du résumé du schéma de flux et l'évaluation de variables de Vp chez des chats avec cardiomyopathie hypertrophique (HCM). Des chats en santé ont été catégorisés dans les groupes résumé (Sum) et séparation (Sepa) afin d'évaluer les effets sur Vp du résumé du schéma de flux. Les chats avec HCM furent catégorisés en groupes HCM atrial gauche (LA) (−), LA (+) et LA (++) selon le degré d'hypertrophie de LA dans le but d'examiner la faisabilité de Vp. Il n'y avait pas de différence significative notée dans la Vp entre les groupes Sum et Sepa et aucune corrélation significative entre Vp et le rythme cardiaque. Une diminution de Vp était associée avec le degré d'hypertrophie de LA. La vélocité du flux de propagation mitral semble être cliniquement réalisable chez les chats et pourrait possiblement être utile dans la détection de dysfonction diastolique chez les chats avec HCM.(Traduit par Docteur Serge Messier).

Prevention of sudden cardiac death in hypertrophic cardiomyopathy: Risk assessment using left atrial diameter predicted from left atrial volume.

BACKGROUND: Left atrial diameter (LAd) is included in the European Society for Cardiology's (ESC) risk model for assessment of sudden cardiac death (SCD) risk in hypertrophic cardiomyopathy (HCM), but the recommended measure of LA size is left atrial volume (LAv). HYPOTHESIS: We hypothesized that LAv could be used instead of LAd in the HCM risk-SCD model. We aimed to determine the relation between LAd and LAv and to assess the impact of using LAv instead of LAd. METHODS: Echocardiographic measurements of anteroposterior LAd in the parasternal long-axis window and LAv from Simpson's biplane method of disks were used. The 5-year risk of SCD by measured LAd and by LAd predicted from LAv were estimated using the ESC risk-SCD model. RESULTS: In 205 HCM patients (age 56 ± 14 years, 62% male), the relation between LAd and LAv was linear. Median 5-year risk of SCD was 2.4% (interquartile range [IQR]: 1.6; 3.8) using measured LAd and 2.4% (IQR: 1.6; 3.7) using predicted LAd. The correlation between the SCD risk assessed by measured vs predicted LAd was excellent (r2 = 0.96). Use of predicted LAd resulted in four patients (2%) being recategorized between the moderate and high-risk categories. CONCLUSIONS: The relation between LAd and LAv was linear with good agreement. On a population level, the correlation between the risk of SCD using measured LAd or LAd predicted from LAv was excellent. On a patient level, using LAd predicted from LAv resulted in the vast majority remaining in the same risk category; however, for a minority of patients, it changed the recommendation.

Impact of gender on heart failure presentation in non-obstructive hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that represents a broad spectrum of morphologic features and clinical presentations. However, little is known about the impact of gender differences in heart failure (HF) development in non-obstructive HCM. We assessed clinical and echocardiographic parameters according to gender in patients with non-obstructive HCM and evaluated the impact of gender on HF presentation and cardiovascular (CV) outcomes in this population. We investigated 202 consecutive patients with non-obstructive HCM. Clinical parameters and conventional echocardiographic measurements including tissue Doppler measurements were evaluated and compared according to gender. Additionally, left ventricular (LV) deformation was assessed with global longitudinal strain (GLS) utilizing 2D speckle tracking software. Of the 202 patients (age = 63 ± 14 years, male: female = 141: 61), 51 patients (24.8%) presented with HF and female patients had HF more frequently (52.5% vs. 12.8%, P < 0.001). Females were older, had a higher prevalence of atrial fibrillation, had increased left atrial volume (LAV), and a higher ratio of early diastolic mitral inflow to early annular velocity (E/e') than males (70 ± 12 years vs. 59 ± 14 years, P < 0.001 for age; 51.4 ± 19.3 mL/m2 vs. 40.0 [Formula: see text] 13.4 mL/m2, P < 0.001 for indexed LAV; 17.2 [Formula: see text] 6.0 vs. 13.0 [Formula: see text] 4.3, P < 0.001 for E/e'). While LV maximal thickness and LV ejection fraction were comparable between men and women, GLS was decreased significantly in female patients (- 13.5 [Formula: see text] 3.4% vs. - 15.6 [Formula: see text] 4.0%, P = 0.001 for GLS). Even after adjusting for clinical factors, female was independently associated with HF presentation (Odd ratio 5.19, 95% CI 2.24-12.03, P < 0.001). During a median follow-up duration 34.0 months, 20 patients (9.9%) had HF hospitalization or CV death. In a multivariable analysis, female gender was associated with higher risk of the composite of HF hospitalization or CV death and HF hospitalization alone than male (Adjusted hazard ratio [HR] = 3.31, 95% CI 1.17-9.35, P = 0.024 for primary composite outcome of HF hospitalization or CV death; adjusted HR = 4.78, 95% CI 1.53-14.96, P = 0.007 for HF hospitalization). In patients with non-obstructive HCM, female patients presented with HF more frequently and showed a higher risk of CV events than male patients. LA volume, E/e' and LV mechanics were different between the genders, suggesting that these might contribute to greater susceptibility to HF in women with HCM.

Diastolic dysfunction evaluated by cardiac magnetic resonance: the value of the combined assessment of atrial and ventricular function.

OBJECTIVES: We sought to evaluate the role of cardiac magnetic resonance imaging (CMR) in the evaluation of diastolic function by a combined assessment of left ventricular (LV) and left atrial (LA) function in a cohort of subjects with various degrees of diastolic dysfunction (DD) detected by echocardiography. METHODS: Forty patients with different stages of DD and 18 healthy controls underwent CMR. Short-axis cine steady-state free precession images covering the entire LA and LV were acquired. Parameters of diastolic function were measured by the analysis of the LV and LA volume/time (V/t) curves and the respective derivative dV/dt curves. RESULTS: At receiver operating characteristic (ROC) curve analysis, the peak of emptying rate A indexed by the LV filling volume with a cut-off of 3.8 was able to detect patients with grade I DD from other groups (area under the curve [AUC] 0.975, 95% confidence interval [CI] 0.86-1). ROC analysis showed that LA ejection fraction with a cut-off of ≤36% was able to distinguish controls and grade I DD patients from those with grade II and grade III DD (AUC 0.996, 95% CI 0.92-1, p < 0.001). The isovolumetric pulmonary vein transit ratio with a cut-off of 2.4 allowed class III DD to be distinguished from other groups (AUC 1.0, 95%CI 0.93-1, p < 0.001). CONCLUSIONS: Analysis of LV and LA V/t curves by CMR may be useful for the evaluation of DD. KEY POINTS: • Combined atrial and ventricular volume/time curves allow evaluation of diastolic function. • Atrial emptying fraction allows distinction between impaired relaxation and restrictive/pseudo-normal filling. • Isovolumetric pulmonary vein transit ratio allows distinction between restrictive and pseudo-normal filling.

Assessment of left ventricular systolic and diastolic abnormalities in patients with hypertrophic cardiomyopathy using real-time three-dimensional echocardiography and two-dimensional speckle tracking imaging.

BACKGROUND: Conventional echocardiography is not sensitive enough to assess left ventricular (LV) dysfunction in hypertrophic cardiomyopathy (HCM) patients. This research attempts to find a new ultrasonic technology to better assess LV diastolic function, systolic function, and myocardial longitudinal and circumferential systolic strain of segments with different thicknesses in HCM patients. METHODS: This study included 50 patients with HCM and 40 healthy subjects as controls. The peak early and late mitral annulus diastolic velocities at six loci (Ea' and Aa', respectively) and the Ea'/Aa' ratio were measured using real-time tri-plane echocardiography and quantitative tissue velocity imaging (RT-3PE-QTVI). The mean value of Ea' at six loci (Em') was obtained for the calculation of E/Em' ratio. The LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), and LV ejection fraction (LVEF) were measured using real-time three-dimensional echocardiography (RT-3DE). LV myocardial longitudinal peak systolic strain (LPSS) and circumferential peak systolic strain (CPSS) in the apical-middle-basal segments (LPSS-api, LPSS-mid, LPSS-bas; CPSS-api, CPSS-mid, and CPSS-bas, respectively) were obtained using a software for two-dimensional speckle tracking imaging (2D-STI). According to the different segmental thicknesses (STs) in each HCM patient, the values (LPSS and CPSS) of all the myocardial segments were categorized into three groups and the respective averages were computed. RESULTS: The Ea', Aa', and, Ea'/Aa' ratio in HCM patients were lower than those in the controls (all p < 0.001), while the E/Em' ratio in HCM patients was higher than that in the controls (p < 0.001). The LVEDV, LVSV, and LVEF were significantly lower in HCM patients than in controls (all p < 0.001). In HCM patients, the LPSS-api, LPSS-mid, LPSS-bas, CPSS-api, CPSS-mid, and CPSS-bas and the LPSS and CPSS of LV segments with different thicknesses were all significantly reduced (all p < 0.001). CONCLUSIONS: In HCM patients, myocardial dysfunction was widespread not only in the obviously hypertrophic segments but also in the non-hypertrophic segments; the LV systolic and diastolic functions were damaged, even with a normal LVEF. LV diastolic dysfunction, systolic dysfunction, and myocardial deformation impairment in HCM patients can be sensitively revealed by RT-3PE-QTVI, RT-3DE, and 2D-STI.

Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe).

Background: A better understanding of the factors that contribute to heterogeneous outcomes and lifetime disease burden in hypertrophic cardiomyopathy (HCM) is critically needed to improve patient management and outcomes. The Sarcomeric Human Cardiomyopathy Registry (SHaRe) was established to provide the scale of data required to address these issues, aggregating longitudinal datasets curated by eight international HCM specialty centers. Methods: Data on 4591 HCM patients (2763 genotyped), followed for a mean of 5.4±6.9 years (24,791 patient-years; median [interquartile range] 2.9 [0.3-7.9] years) were analyzed regarding cardiac arrest, cardiac transplantation, appropriate implantable cardioverter-defibrillator (ICD) therapy, all-cause death, atrial fibrillation, stroke, New York Heart Association Functional Class III/IV symptoms (all comprising the overall composite endpoint), and left ventricular ejection fraction (LVEF)<35%. Outcomes were analyzed individually and as composite endpoints. Results: Median age of diagnosis was 45.8 [30.9-58.1] years and 37% of patients were female. Age of diagnosis and sarcomere mutation status were predictive of outcomes. Patients <40 years old at diagnosis had a 77% [95% confidence interval: 72%, 80%] cumulative incidence of the overall composite outcome by age 60, compared to 32% [29%, 36%] by age 70 for patients diagnosed >60 years. Young HCM patients (20-29 years) had 4-fold higher mortality than the general United States population at a similar age. Patients with pathogenic/likely pathogenic sarcomere mutations had two-fold greater risk for adverse outcomes compared to patients without mutations; sarcomere variants of uncertain significance were associated with intermediate risk. Heart failure and atrial fibrillation were the most prevalent adverse events, although typically not emerging for several years after diagnosis. Ventricular arrhythmias occurred in 32% [23%, 40%] of patients <40 years at diagnosis, but in 1% [1%, 2%] >60 years. Conclusions: The cumulative burden of HCM is substantial and dominated by heart failure and atrial fibrillation occurring many years following diagnosis. Young age of diagnosis and the presence of a sarcomere mutation are powerful predictors of adverse outcomes. These findings highlight the need for close surveillance throughout life, and the need to develop disease-modifying therapies.

Biventricular assessment of light-chain amyloidosis using 3D speckle tracking echocardiography: Differentiation from other forms of myocardial hypertrophy.

BACKGROUND: Given that in patients with cardiac amyloidosis (CA), deposition of amyloid protein is not restricted to the left ventricular (LV) myocardium, it can be hypothesized that the diagnostic value of deformation mechanics would be enhanced by considering right ventricular (RV) strain measures. The aim of the present study was to examine the potential utility of left ventricular (LV) and right ventricular (RV) deformation and rotational parameters derived from three-dimensional speckle-tracking echocardiograph (3DSTE) to diagnose cardiac amyloidosis and differentiate this disease from other forms of myocardial hypertrophy. METHODS: Twenty-three patients with biopsy-proven light-chain (AL) amyloidosis, 23 patients with systemic arterial hypertension (HTN), 23 patients with hypertrophic cardiomyopathy (HCM), 23 athletes and 23 normal controls were prospectively studied by conventional echocardiography and 3DSTE. LV longitudinal strain (LV LS), LV circumferential strain (LV CS), RV global longitudinal strain and RV free-wall longitudinal strain (RV FW LS) were obtained by 3DSTE, as well as LV rotation and rotational velocities. RESULTS: LV and RV longitudinal strains were reduced in cardiac amyloidosis (CA) patients compared to controls. By multivariate analysis, LV basal LS (p = 0.002), LV peak basal rotation (p = 0.003), and RV basal FW LS (p = 0.014) were independently associated with CA in the overall population. A significant improvement in global χ2 value was noted with RV 3D-strain parameters over only LV-3DSTE + conventional indices for detection of CA (p < 0.001). Comparison of ROC curves showed that the AUC using combined LV basal LS, LV basal rotation and RV basal FW LS had a higher discriminative value than the other echocardiographic parameters used for detecting CA (AUC 0.93, 95%CI 0.81-0.97). CONCLUSIONS: Three-dimensional speckle tracking echocardiography reveals regional and global biventricular dysfunction in CA. Assessment of RV ventricular dysfunction has an additive value in differentiating CA from other causes of myocardial wall thickening.

Vortical features for myocardial rotation assessment in hypertrophic cardiomyopathy using cardiac tagged magnetic resonance.

Left ventricular rotational motion is a feature of normal and diseased cardiac function. However, classical torsion and twist measures rely on the definition of a rotational axis which may not exist. This paper reviews global and local rotation descriptors of myocardial motion and introduces new curl-based (vortical) features built from tensorial magnitudes, intended to provide better comprehension about fibrotic tissue characteristics mechanical properties. Fifty-six cardiomyopathy patients and twenty-two healthy volunteers have been studied using tagged magnetic resonance by means of harmonic phase analysis. Rotation descriptors are built, with no assumption about a regular geometrical model, from different approaches. The extracted vortical features have been tested by means of a sequential cardiomyopathy classification procedure; they have proven useful for the regional characterization of the left ventricular function by showing great separability not only between pathologic and healthy patients but also, and specifically, between heterogeneous phenotypes within cardiomyopathies.

Assessment of left atrial function in patients with hypertrophic cardiomyopathy using two-dimensional strain: a comparison with volume-derived values.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common heart disease. Left atrial (LA) function plays an important role in the diastolic function in patients with HCM. In this study, two-dimensional speckle tracking imaging (2D-STI) was used to assess left atrial (LA) function in patients with HCM. METHODS: Thirty-four patients with HCM and thirty-four age- and gender-matched normal subjects were studied. The LA Volume-Derived Index was measured using 2D ultrasonic images. The LA strain (S-reservoir, S-conduit, S-booster pump) and the strain rate (SR-reservoir, SR-conduit, SR-booster pump), representing the reservoir, conduit and booster pump functions, respectively, were measured. RESULTS: The LA reservoir, conduit and booster pump functions were significantly different between patients with HCM and normal subjects. The values in patients with HCM were less than those in normal subjects. In patients with HCM, S-reservoir and SR-reservoir were significantly correlated with the total LA ejection fraction (LAEF), LA Expansion Index and left ventricular (LV) global longitudinal strain. S-conduit and SR-conduit were significantly correlated with e' and LV global longitudinal strain. S-booster pump and SR-booster pump were significantly correlated with the A, a', active LAEF and LA Expansion Index. S-booster pump was significantly correlated with the LV global longitudinal strain. CONCLUSIONS: 2D-STI conveniently demonstrated the LA dysfunction in patients with HCM by detecting the LA strain and strain rate. The accurate assessment of LA function could have potential clinical value for the treatment of patients with HCM.

CMR assessment and clinical outcomes of hypertrophic cardiomyopathy with or without ventricular remodeling in the end-stage phase.

End-stage phase of hypertrophic cardiomyopathy (ES-HCM) is a recognized part of HCM disease spectrum. Information on cardiac magnetic resonance (CMR) studies for ES-HCM especially for those without ventricular remodeling has been limited. We aimed to evaluate the morpho-functional and tissue features of ES-HCM with or without ventricular remodeling and to explore CMR prognostic value in these patients. We analysed CMR scans of sixty-three ES-HCM patients and divided them into those with ventricular dilatation (D-ES, n = 41) and those with normal ventricular size (N-ES, n = 22). Cox proportional hazards models were used to assess the association between CMR parameters and outcomes. Patients in D-ES showed hypokinetic-dilated HCM phenotype, while patients in N-ES showed hypokinetic-restrictive HCM phenotype. LGE extent was significantly larger in D-ES (34.7% ± 15.4% vs. 22.8% ± 7.7%; P < 0.01). Atrial fibrillation and edema of lower extremity were more common in N-ES (72.7 vs. 29.3% and 54.5 vs. 24.4%, respectively; P < 0.05). Log-rank test found no significant difference between 2 groups in combined end point of cardiovascular events (χ2 = 0.66, P = 0.418). In multivariate analysis, LGE (HR 1.57-1.83 per 10% LGE increase, P < 0.01) and indexed left atrial volume (LAVI) (HR 1.14-1.21 per 20 mL/m2 increase, P < 0.05) remained independently associated with combined end point when adjusted by other risk factors. The CMR features of HCM in end-stage span between two extremes. LGE is more extensive in those with ventricular remodeling and LAVI is larger in those with normal ventricular size. Both LGE and LAVI are significant predictors of poor outcomes.

Atrial Enlargement in the Athlete's Heart: Assessment of Atrial Function May Help Distinguish Adaptive from Pathologic Remodeling.

Intensive training is associated with hemodynamic changes that typically induce an enlargement of cardiac chambers, involving not only the ventricles but also the atria. The hearts of competitive athletes are characterized by increases in left and right atrial dimensions that have been interpreted as a physiologic adaptation to training. Conversely, some authors have hypothesized maladaptive remodeling; furthermore, the extent of left atrial dimensional remodeling may overlap atrial dilation observed in patients with cardiac disease, representing a challenge for clinicians. However, studies investigating left and right atrial function in athletes have demonstrated that atrial size is insufficient to provide mechanistic information about the atrium itself, and an increase in atrial size is not intrinsically an expression of atrial dysfunction. The authors critically analyze training-induced atrial remodeling, taking into account not only the assessment of atrial size but also the evaluation of atrial function, suggesting that the characterization of atrial function plays a fundamental role in the evaluation of athlete's heart, being useful to differentiate physiologic remodeling induced by exercise from pathologic changes occurring in cardiac disorders.