Aims:To perform a comparative analysis of right ventricle (RV) myocardial mechanics, assessed by 2D speckle-tracking echocardiography (2D-STE), between patients with Fabry disease and patients with... Show moreAims:To perform a comparative analysis of right ventricle (RV) myocardial mechanics, assessed by 2D speckle-tracking echocardiography (2D-STE), between patients with Fabry disease and patients with sarcomeric disease.Methods and results: Patients with Fabry cardiomyopathy (FC) (n = 28) were compared with patients with sarcomeric hypertrophic cardiomyopathy (HCM), matched for degree of left ventricle hypertrophy (LVH) and demographic characteristics (n = 112). In addition, patients with Fabry disease and no LVH [phenotype-negative carriers of pathogenic alpha-galactosidase gene mutations (GLA LVH-)] (n = 28) were compared with age and sex-matched carriers of sarcomeric gene mutations without LVH [Phenotype-negative carriers of pathogenic sarcomeric gene mutations (Sarc LVH-)] (n = 56). Standard echocardiography and 2D-STE were performed in all participants. Despite a subtle impairment of RV global longitudinal strain (RV-GLS) was common in both groups, patients with FC showed a more prominent reduction of RV free wall longitudinal strain (RV-FWS) and lower values of difference between RV-FWS and RV-GLS (Delta RV strain), in comparison to individuals with HCM (P <0.001 and P = 0.002, respectively). RV-FWS and Delta RV strain demonstrated an independent and additive value in discriminating FC from HCM, over the presence of symmetric LVH, systolic anterior motion of the mitral valve and RV hypertrophy. Similar results were found in GLA LVH- patients: they had worse RV-FWS and lower values of Delta RV strain as compared to Sarc LVH- patients (both P <0.001).Conclusion: Patients with FC show a specific pattern of RV myocardial mechanics, characterized by a larger impairment of RV-FWS and lower Delta RV strain in comparison to patients with HCM, which may be helpful in the differential diagnosis between these two diseases.[GRAPHICS]. Show less
Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular... Show moreBackground: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. Methods: The study cohort comprised 1075 children (mean age, 10.2 years [+/- 4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). Results: MLVWT Z score was <10 in 598 (58.1%), >= 10 to <20 in 334 (31.1%), and >= 20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score >= 20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, >= 10 to <20, and >= 20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM. Show less
Schuldt, M.; Driel, B. van; Alguel, S.; Parbhudayal, R.Y.; Barge-Schaapveld, D.Q.C.M.; Gueclue, A.; ... ; Velden, J. van der 2021
Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype-phenotype correlations. Advanced imaging... Show moreHypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype-phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To determine whether disturbed myocardial energetics with the potential to serve as biomarkers are also reflected in the serum metabolome, we analyzed the serum metabolome of asymptomatic carriers in comparison to healthy controls and obstructive HCM patients (HOCM). We performed non-quantitative direct-infusion high-resolution mass spectrometry-based untargeted metabolomics on serum from fasted asymptomatic gene variant carriers, symptomatic HOCM patients and healthy controls (n = 31, 14 and 9, respectively). Biomarker panels that discriminated the groups were identified by performing multivariate modeling with gradient-boosting classifiers. For all three group-wise comparisons we identified a panel of 30 serum metabolites that best discriminated the groups. These metabolite panels performed equally well as advanced cardiac imaging modalities in distinguishing the groups. Seven metabolites were found to be predictive in two different comparisons and may play an important role in defining the disease stage. This study reveals unique metabolic signatures in serum of preclinical carriers and HOCM patients that may potentially be used for HCM risk stratification and precision therapeutics. Show less
Tjahjadi, C.; Hiemstra, Y.L.; Bijl, P. van der; Pio, S.M.; Bootsma, M.; Marsan, N.A.; ... ; Bax, J.J. 2021
Aims Atrial fibrillation (AF) is frequently observed in hypertrophic cardiomyopathy (HCM) and is associated with poor clinical outcome. Total atrial conduction time, estimated by tissue Doppler... Show moreAims Atrial fibrillation (AF) is frequently observed in hypertrophic cardiomyopathy (HCM) and is associated with poor clinical outcome. Total atrial conduction time, estimated by tissue Doppler imaging (TDI), the so-called PA-TDI duration, reflects the left atrial (LA) structural and electrical remodelling. The aim of this study was to evaluate the association between PA-TDI and new-onset AF in patients with HCM.Methods and results From a large cohort of patients with HCM, 208 patients (64% male, mean age 53 +/- 14 years) without AF were selected. PA-TDI duration was measured from the onset P wave on electrocardiogram to the peak A' wave of the lateral LA wall using TDI. The incidence of new-onset AF was 20% over a median follow-up of 7.3 (3.5-10.5) years. Patients with incident AF had longer PA-TDI duration when compared with patients without AF (133.7 +/- 23.0 vs. 110.5 +/- 30.0 ms, P < 0.001). PA-TDI duration was independently associated with new-onset AF (hazard ratio: 1.03, 95% confidence interval: 1.01-1.05, P < 0.001).Conclusion Prolonged PA-TDI duration was independently associated with new-onset AF in patients with HCM. This novel parameter could be useful to risk-stratify patients with HCM who are at risk of having AF. Show less
OBJECTIVES This study hypothesized that paroxysmal atrial fibrillation (PAF) reflects the presence of a more severe cardiac hypertrophic cardiomyopathy (HCM) phenotype.BACKGROUND HCM is... Show moreOBJECTIVES This study hypothesized that paroxysmal atrial fibrillation (PAF) reflects the presence of a more severe cardiac hypertrophic cardiomyopathy (HCM) phenotype.BACKGROUND HCM is characterized by myocyte hypertrophy, fibrosis, and a high prevalence of PAF. It is currently unresolved whether atrial fibrillation (AF) is a marker or a mediator of adverse outcomes in HCM.METHODS This study retrospectively examined 45 HCM patients who underwent cardiovascular magnetic resonance (CMR) imaging in sinus rhythm. The function of all 4 cardiac chambers was assessed, as well as late gadolinium enhancement (LGE) in the left atrium (LA) and left ventricle (LV), as indicators of fibrosis. A fat-saturated, 3-dimensional inversion recovery-prepared, fast-spoiled, gradient-recalled echo sequence, and the image intensity ratio method were used to measure LA-LGE; LGE in the LV was quantified using a semi-automated threshold technique.RESULTS HCM patients (n = 45) were divided into 2 groups (PAF, no AF) based on history of PAF. All HCM patients had LGE in the LA posterior wall. The PAF group (n = 18) had higher LA volume, a lower LA ejection fraction, a lower global peak longitudinal LA strain (PLAS), and a higher amount of LA-LGE compared with the no AF group (n = 27). A modest inverse association was noted between the LA ejection fraction, PLAS, and LA-LGE; a positive association was present between LV-LGE and LA-LGE. The PAF group had lower ejection fractions in the LV, right atrium, and right ventricle compared with those in the no AF group.CONCLUSIONS PAF is associated with a greater degree of structural LA remodeling and global myopathy, which suggests a more severe cardiac HCM phenotype. (c) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
