Clinical staging of Anderson-Fabry cardiomyopathy: An operative proposal.

As a slowly progressive form of hypertrophic cardiomyopathy (HCM), Anderson-Fabry disease (FD) resembles the phenotype of the most common sarcomeric forms, although significant differences in presentation and long-term progression may help determine the correct diagnosis. A variety of electrocardiographic and imaging features of FD cardiomyopathy have been described at different times in the course of the disease, and considerable discrepancies remain regarding the assessment of disease severity by individual physicians. Therefore, we here propose a practical staging of FD cardiomyopathy, in hopes it may represent the standard for cardiac evaluation and facilitate communication between specialized FD centres and primary care physicians. We identified 4 main stages of FD cardiomyopathy of increasing severity, based on available evidence from clinical and imaging studies: non-hypertrophic, hypertrophic - pre-fibrotic, hypertrophic - fibrotic, and overt dysfunction. Each stage is described and discussed in detail, following the principle that speaking a common language is critical when managing such complex patients in a multi-disciplinary and sometimes multi-centre setting.

Inflammation across the spectrum of hypertrophic cardiac phenotypes.

The hypertrophic cardiomyopathy phenotype encompasses a heterogeneous spectrum of genetic and acquired diseases characterized by the presence of left ventricular hypertrophy in the absence of abnormal cardiac loading conditions. This "umbrella diagnosis" includes the "classic" hypertrophic cardiomyopathy (HCM), due to sarcomere protein gene mutations, and its phenocopies caused by intra- or extracellular deposits, such as Fabry disease (FD) and cardiac amyloidosis (CA). All these conditions share a wide phenotypic variability which results from the combination of genetic and environmental factors and whose pathogenic mediators are poorly understood so far. Accumulating evidence suggests that inflammation plays a critical role in a broad spectrum of cardiovascular conditions, including cardiomyopathies. Indeed, inflammation can trigger molecular pathways which contribute to cardiomyocyte hypertrophy and dysfunction, extracellular matrix accumulation, and microvascular dysfunction. Growing evidence suggests that systemic inflammation is a possible key pathophysiologic process potentially involved in the pathogenesis of cardiac disease progression, influencing the severity of the phenotype and clinical outcome, including heart failure. In this review, we summarize current knowledge regarding the prevalence, clinical significance, and potential therapeutic implications of inflammation in HCM and two of its most important phenocopies, FD and CA.

Echocardiography in Anderson-Fabry Disease.

Echocardiography is the most common diagnostic tool to screen for Fabry cardiomyopathy as it is fast, non-invasive, low-cost, widely available, easily applicable and reproducible. Echocardiography is the first-line investigation, being useful in all the stages of the disease: (1) in gene-positive patients, to unveil signs of early cardiac involvement and allowing timely treatment; (2) in patients with overt cardiomyopathy to estimate the severity of cardiac involvement, the possible related complications, and the effect of treatment. Recently, advanced echocardiographic techniques, such as speckle tracking analysis, are offering new insights in the assessment of Fabry disease patients and in the differential diagnosis of cardiomyopathies with hypertrophic phenotype. The aim of this review is to provide a comprehensive overview on the cardiac structural and functional abnormalities described in Fabry disease by means of echocardiography.

The Heart in Fabry Disease: Mechanisms Beyond Storage and Forthcoming Therapies.

In patients with Fabry disease (FD), cardiovascular involvement is the main cause of death and reduction of quality of life. Left ventricular hypertrophy mimicking hypertrophic cardiomyopathy is the main feature of FD cardiac involvement although glycolipid storage occurs in all cardiac cellular types. Accumulation of lysosomal globotriasylceramide represents the main mechanism of cardiac damage in early stages, but secondary pathways of cellular and tissue damage, triggered by lysosomal storage, and including altered energy production, inflammation and cell death, contribute to cardiac damage and disease progression. These mechanisms appear prominent in more advanced stages, hampering and reducing the efficacy of FD-specific treatments. Therefore, additional cardiovascular therapies are important to manage cardiovascular symptoms and reduce cardiovascular events. Although new therapies targeting lysosomal storage are in development, a better definition and comprehension of the complex pathophysiology of cardiac damage in FD, may lead to identify new therapeutic targets beyond storage and new therapeutic strategies.

Transcatheter aortic valve implantation in pure aortic regurgitation: Hemodynamic and echocardiographic findings in bioprosthesis vs. native valve.

OBJECTIVE: The objective of this study is to compare hemodynamic and echocardiographic findings between valve-in-valve (VIV) and native-valve (NV) patients submitted to transcatheter aortic valve implantation (TAVI) due to pure aortic regurgitation (AR). BACKGROUND: Patients with severe AR are surgically treated with variable postinterventional left-ventricular (LV) "reverse remodeling." TAVI might be considered in selected AR patients. METHODS: Twenty-eight patients with pure severe AR caused by either degenerated bioprosthesis or NV disease were successfully treated by TAVI at our institution. LV catheterization before and after TAVI and echocardiography before, after (24-72 h), and at follow-up (3-12 months) were performed. RESULTS: Baseline clinical, hemodynamic, and echocardiographic characteristics were comparable between the two study groups, except for a younger age, higher proto-diastolic LV pressure, and higher LV end-systolic diameter in the NV group. At catheterization, an immediate hemodynamic impact of TAVI in both groups was noticed, with a trend toward better postprocedural residual regurgitation index and significantly lower LV dP/dT values (666.0 ± 177.9 vs. 883.5 ± 259.7 mmHg/s, p = 0.04) in VIV. At echocardiography, both NV and VIV patients showed favorable (early and sustained) post-TAVI echocardiographically detectable reverse remodeling. VIV patients also showed more pronounced early reduction in indexed LV end-diastolic volume (68.1 ± 27.4 vs. 86.5 ± 28.9 ml/m2 in VIV, p < 0.001 and 81.0 ± 29.0 vs. 95.2 ± 37.8 ml/m2 in NV, p = 0.043). CONCLUSIONS: Successful TAVI induces a striking hemodynamic impact with major structural (reverse remodeling) consequences in patients with pure AR caused by both bioprosthesis degeneration or NV disease. In the immediate postrelease phase, VIV patients might exhibit a more pronounced early LV contractile and structural benefit.

An unusual case of mitral valve chordal rupture.

In this report, we present a rare case of severe mitral regurgitation due to isolated mitral valve chordal rupture without valve leaflet prolapse in a patient with Fabry cardiomyopathy. This finding could be due to subvalvular apparatus storage of glycosphingolipids rather than fibro-elastic deficiency, underlying how close cardiological follow-up of Fabry patients must be comprehensive and not only focused on left ventricular hypertrophy and arrhythmias.

Cardiac Output Measurement With Echocardiography and Pressure Recording Analytical Method in Pediatric Patients Admitted to the Cardiac Intensive Care Unit: A Retrospective Assessment of Bias Between the Two Methods.

OBJECTIVES: This study aimed to compare, in a cohort of critically ill children with biventricular anatomy and no cardiovascular shunt, cardiac output (CO) and cardiac index (CI) assessed by echocardiography and a continuous pulse-contour method, MostCareUP, to measure the differences between these techniques (biasCO and biasCI), and their association with clinical variables. DESIGN: Retrospective study. SETTING: Tertiary pediatric cardiac intensive care unit. PARTICIPANTS: Children admitted to the pediatric cardiac intensive care unit who underwent echocardiography with CO measurement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-five patients were included. BiasCO was -0.02 (0.26) L/min (percentage error 36%). BiasCI was 0.07 (0.34) L/min/m2 (percentage error 18%). Biases and percentage errors were higher in 24 nonsupervised echocardiographies. A negative biasCO (overestimation by MostCareUP) was associated with post-surgical status (v cardiomyopathy), higher systolic arterial pressure, and spontaneous breathing (v intubation). When only absolute values were considered, biasCONONEG correlated with age, weight, arterial pressure, and heart rate, whereas biasCINONEG was associated with a femoral arterial cannula, no use of inotropes, and the absence of mechanical ventilation. After adjustment, biasCONONEG remained independently associated with patients' body weight(p = 0.0001). BiasCINONEG showed a nonlinear relationship with weight below 20 kg and above 40 kg. CONCLUSIONS: Children with extreme low or high weights, those who are extubated, and those with a femoral cannula carry the highest bias. When younger patients are considered, CI should be evaluated instead of CO, because biases are better highlighted by indexing data on body surface area. In children, both echocardiography and MostCareUP may be responsible of inaccurate CO/CI assessment.

Variable selection with P-splines in functional linear regression: Application in graft-versus-host disease.

This paper focuses on the problems of estimation and variable selection in the functional linear regression model (FLM) with functional response and scalar covariates. To this end, two different types of regularization (L1 and L2 ) are considered in this paper. On the one hand, a sample approach for functional LASSO in terms of basis representation of the sample values of the response variable is proposed. On the other hand, we propose a penalized version of the FLM by introducing a P-spline penalty in the least squares fitting criterion. But our aim is to propose P-splines as a powerful tool simultaneously for variable selection and functional parameters estimation. In that sense, the importance of smoothing the response variable before fitting the model is also studied. In summary, penalized (L1 and L2 ) and nonpenalized regression are combined with a presmoothing of the response variable sample curves, based on regression splines or P-splines, providing a total of six approaches to be compared in two simulation schemes. Finally, the most competitive approach is applied to a real data set based on the graft-versus-host disease, which is one of the most frequent complications (30% -50%) in allogeneic hematopoietic stem-cell transplantation.

Early cardiac mechanics abnormalities in patients with mitochondrial diseases.

BACKGROUND: Evidence about early cardiac mechanics abnormalities in patients with mitochondrial diseases (MDs) before overt cardiomyopathy is limited. METHODS: In this prospective study, we performed a comparative analysis of conventional and speckle tracking echocardiographic parameters between patients with genetically identified MDs and no overt cardiomyopathy vs controls matched for age, sex and cardiovascular risk factors. The Newcastle mitochondrial disease adult scale (NMDAS) was calculated, using a threshold of > 21 as indicator of high disease severity. RESULTS: We enrolled 24 MDs patients (50 % males, mean age 47.2 ± 14.3 years), the most prevalent mutation was the MT-TL1 m.3243A>G (37.5 %). In MDs patients all dimensional echocardiographic parameters were similar to controls. Conversely, albeit normal, Tissue Doppler septal systolic (p = 0.002) and early diastolic velocities (p = 0.016) were significantly lower and E/e' ratio was higher (p = 0.032) in MDs. Moreover, LV-GLS was significantly reduced in MDs as compared to their counterparties (20.2 ± 1.6 vs 22.6 ± 1.5, p < 0.001). Similarly, LA reservoir and conduit strain were significantly lower in MDs (31.7 ± 7.0 vs 35.9 ± 6.6, p = 0.038; 19.7 ± 5.6 vs 23.1 ± 6.0, p = 0.049 respectively), while LA contractile strain was similar between the two groups. Lower values of LV-GLS were observed in patients with NMDAS > 21 vs patients with NMDAS ≤ 21 (19.0 ± 1.2 vs 21.0 ± 1.3, p = 0.001). CONCLUSIONS: In patients with MDs and no overt cardiomyopathy Tissue Doppler and speckle tracking analysis unveil worse LV systolic and diastolic function indices as compared to controls. Reduced LV-GLS values were found especially in those with worse disease burden.

Valvular heart disease and cardiomyopathy: reappraisal of their interplay.

Cardiomyopathies and valvular heart diseases are typically considered distinct diagnostic categories with dedicated guidelines for their management. However, the interplay between these conditions is increasingly being recognized and they frequently coexist, as in the paradigmatic examples of dilated cardiomyopathy and hypertrophic cardiomyopathy, which are often complicated by the occurrence of mitral regurgitation. Moreover, cardiomyopathies and valvular heart diseases can have a shared aetiology because several genetic or acquired diseases can affect both the cardiac valves and the myocardium. In addition, the association between cardiomyopathies and valvular heart diseases has important prognostic and therapeutic implications. Therefore, a better understanding of their shared pathophysiological mechanisms, as well as of the prevalence and predisposing factors to their association, might lead to a different approach in the risk stratification and management of these diseases. In this Review, we discuss the different scenarios in which valvular heart diseases and cardiomyopathies coexist, highlighting the need for an improved classification and clustering of these diseases with potential repercussions in the clinical management and, particularly, personalized therapeutic approaches.

Performance and explainability of feature selection-boosted tree-based classifiers for COVID-19 detection.

In this paper, we evaluate the performance and analyze the explainability of machine learning models boosted by feature selection in predicting COVID-19-positive cases from self-reported information. In essence, this work describes a methodology to identify COVID-19 infections that considers the large amount of information collected by the University of Maryland Global COVID-19 Trends and Impact Survey (UMD-CTIS). More precisely, this methodology performs a feature selection stage based on the recursive feature elimination (RFE) method to reduce the number of input variables without compromising detection accuracy. A tree-based supervised machine learning model is then optimized with the selected features to detect COVID-19-active cases. In contrast to previous approaches that use a limited set of selected symptoms, the proposed approach builds the detection engine considering a broad range of features including self-reported symptoms, local community information, vaccination acceptance, and isolation measures, among others. To implement the methodology, three different supervised classifiers were used: random forests (RF), light gradient boosting (LGB), and extreme gradient boosting (XGB). Based on data collected from the UMD-CTIS, we evaluated the detection performance of the methodology for four countries (Brazil, Canada, Japan, and South Africa) and two periods (2020 and 2021). The proposed approach was assessed in terms of various quality metrics: F1-score, sensitivity, specificity, precision, receiver operating characteristic (ROC), and area under the ROC curve (AUC). This work also shows the normalized daily incidence curves obtained by the proposed approach for the four countries. Finally, we perform an explainability analysis using Shapley values and feature importance to determine the relevance of each feature and the corresponding contribution for each country and each country/year.

Pulmonary congestion assessed by lung ultrasound in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: Prevalence and prognostic implications.

AIMS: Lung ultrasound (LUS) is a sensitive tool to assess pulmonary congestion (PC). Few data are available on LUS-PC evaluation in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the prevalence and prognostic impact of LUS-PC in patients with severe AS before and after TAVI. METHODS AND RESULTS: We designed a single-centre prospective study in patients referred for TAVI for severe AS (ClinicalTrials.gov identification number: NCT05024942). All patients underwent echocardiography and LUS (according to a simplified 8-zone scanning protocol) the day before and within 72 h after the procedure. The primary endpoint was the composite of all-cause mortality, hospitalization for heart failure and urgent medical visits for worsening dyspnoea at 12-month follow-up. A total of 127 patients were enrolled (mean age 81.1 ± 5.8 years; 54.3% female). Pre-TAVI LUS-PC was documented in 65 patients (51%). After TAVI, the prevalence of LUS-PC significantly decreased as compared to pre-TAVI evaluation, being documented in only 28 patients (22% vs. 51%, p < 0.001) with a median B-lines score of 4 (interquartile range [IQR] 0-11) versus 11 (IQR 6-19) pre-TAVI (p < 0.001). During a median follow-up of 12 (12-17) months, 25 patients (19.6%) met the composite endpoint. On multivariable Cox regression analysis, pre-TAVI LUS-PC was independently associated with cardiovascular events (hazard ratio 2.764, 95% confidence interval 1.114-6.857; p = 0.028). CONCLUSIONS: Lung ultrasonography reveals a high prevalence of PC in patients with severe AS undergoing TAVI, which is significantly reduced by the procedure. Pre-TAVI PC, measured by LUS, is an independent predictor of 1-year clinical outcome.

Emerging multisystem biomarkers in hereditary transthyretin amyloidosis: a pilot study.

Hereditary transthyretin (ATTRv) amyloidosis is a rare, adult-onset, progressive, multisystemic condition caused by TTR pathogenic variants. Reliable biomarkers are needed to allow early diagnosis and to monitor disease severity and progression. We measured serum concentrations of growth differentiation factor-15 (GDF-15) and uromodulin (Umod) in ATTRv patients to evaluate correlations with standard markers of disease severity (FAP stage and PND score). Blood samples were collected from 16 patients diagnosed with ATTRv amyloidosis and a verified TTR variant and from 26 healthy controls. ATTRv patients were stratified by clinical phenotype (neurologic vs. mixed), genotype (V30M vs. non-V30M), and disease severity. We found significantly higher levels of serum GDF-15 in ATTRv patients compared with controls. Mean serum Umod levels were significantly lower in patients with ATTRv than controls. A positive correlation was found between serum Umod and estimated glomerular filtration rate (eGFR), while an inverse correlation was found with cystatin C levels. Conversely, GDF-15 showed a negative correlation with eGFR, and a direct correlation with cystatin C levels. No correlation was demonstrated between GDF-15 or Umod levels and traditional cardiac biomarkers. The results identify alteration of serum levels of GDF-15 and Umod in ATTRv amyloidosis.

Left atrial structural and functional remodelling in Fabry disease and cardiac amyloidosis: A comparative analysis.

BACKGROUND: Fabry disease (FD) and transthyretin cardiac amyloidosis (TTR CA) are cardiomyopathies with hypertrophic phenotype that share several features, including left atrial (LA) enlargement and dysfunction, but direct comparative data are lacking. Aim of the present study was to perform a comparative analysis of LA remodelling between the two diseases. METHODS AND RESULTS: In this prospective study, a total of 114 patients (31 FD and 83 TTR CA) were included; all of them had left ventricular hypertrophy (LVH), defined as left ventricular (LV) wall thickness ≥ 12 mm. Despite similar degree of LVH, patients with TTR CA showed worse LV systolic and diastolic function. LA maximal volume index was not significantly different between the two groups (p = 0.084), while patients with TTR CA showed larger LA minimal volume index (p = 0.001). Moreover, all phases of LA mechanics were more impaired in the TTR CA group vs FD (reservoir: 6.9[4.2-15.5] vs 19.0[15.5-29.5], p < 0.001). After excluding patients with atrial fibrillation (AF), these differences remained clearly significant. In multivariable regression analyses, LA reservoir strain showed an independent correlation with TTR CA, controlling for demographic characteristics, AF and LV systolic and diastolic performance (p ≤ 0.001), whereas LV global longitudinal strain did not. Finally, among echocardiographic parameters, LA function demonstrated the highest accuracy in discriminating the two diseases. CONCLUSIONS: TTR CA is characterized by a more advanced LA structural and functional remodelling in comparison to patients with FD and similar degree of LVH. The association between TTR CA and LA dysfunction remains consistent after adjustment for potential confounders.

NN2Poly: A Polynomial Representation for Deep Feed-Forward Artificial Neural Networks.

Interpretability of neural networks (NNs) and their underlying theoretical behavior remain an open field of study even after the great success of their practical applications, particularly with the emergence of deep learning. In this work, NN2Poly is proposed: a theoretical approach to obtain an explicit polynomial model that provides an accurate representation of an already trained fully connected feed-forward artificial NN a multilayer perceptron (MLP). This approach extends a previous idea proposed in the literature, which was limited to single hidden layer networks, to work with arbitrarily deep MLPs in both regression and classification tasks. NN2Poly uses a Taylor expansion on the activation function, at each layer, and then applies several combinatorial properties to calculate the coefficients of the desired polynomials. Discussion is presented on the main computational challenges of this method, and the way to overcome them by imposing certain constraints during the training phase. Finally, simulation experiments as well as applications to real tabular datasets are presented to demonstrate the effectiveness of the proposed method.

Consistent comparison of symptom-based methods for COVID-19 infection detection.

BACKGROUND: During the global pandemic crisis, various detection methods of COVID-19-positive cases based on self-reported information were introduced to provide quick diagnosis tools for effectively planning and managing healthcare resources. These methods typically identify positive cases based on a particular combination of symptoms, and they have been evaluated using different datasets. PURPOSE: This paper presents a comprehensive comparison of various COVID-19 detection methods based on self-reported information using the University of Maryland Global COVID-19 Trends and Impact Survey (UMD-CTIS), a large health surveillance platform, which was launched in partnership with Facebook. METHODS: Detection methods were implemented to identify COVID-19-positive cases among UMD-CTIS participants reporting at least one symptom and a recent antigen test result (positive or negative) for six countries and two periods. Multiple detection methods were implemented for three different categories: rule-based approaches, logistic regression techniques, and tree-based machine-learning models. These methods were evaluated using different metrics including F1-score, sensitivity, specificity, and precision. An explainability analysis has also been conducted to compare methods. RESULTS: Fifteen methods were evaluated for six countries and two periods. We identify the best method for each category: rule-based methods (F1-score: 51.48% - 71.11%), logistic regression techniques (F1-score: 39.91% - 71.13%), and tree-based machine learning models (F1-score: 45.07% - 73.72%). According to the explainability analysis, the relevance of the reported symptoms in COVID-19 detection varies between countries and years. However, there are two variables consistently relevant across approaches: stuffy or runny nose, and aches or muscle pain. CONCLUSIONS: Regarding the categories of detection methods, evaluating detection methods using homogeneous data across countries and years provides a solid and consistent comparison. An explainability analysis of a tree-based machine-learning model can assist in identifying infected individuals specifically based on their relevant symptoms. This study is limited by the self-report nature of data, which cannot replace clinical diagnosis.

Using survey data to estimate the impact of the omicron variant on vaccine efficacy against COVID-19 infection.

Symptoms-based detection of SARS-CoV-2 infection is not a substitute for precise diagnostic tests but can provide insight into the likely level of infection in a given population. This study uses symptoms data collected in the Global COVID-19 Trends and Impact Surveys (UMD Global CTIS), and data on variants sequencing from GISAID. This work, conducted in January of 2022 during the emergence of the Omicron variant (subvariant BA.1), aims to improve the quality of infection detection from the available symptoms and to use the resulting estimates of infection levels to assess the changes in vaccine efficacy during a change of dominant variant; from the Delta dominant to the Omicron dominant period. Our approach produced a new symptoms-based classifier, Random Forest, that was compared to a ground-truth subset of cases with known diagnostic test status. This classifier was compared with other competing classifiers and shown to exhibit an increased performance with respect to the ground-truth data. Using the Random Forest classifier, and knowing the vaccination status of the subjects, we then proceeded to analyse the evolution of vaccine efficacy towards infection during different periods, geographies and dominant variants. In South Africa, where the first significant wave of Omicron occurred, a significant reduction of vaccine efficacy is observed from August-September 2021 to December 2021. For instance, the efficacy drops from 0.81 to 0.30 for those vaccinated with 2 doses (of Pfizer/BioNTech), and from 0.51 to 0.09 for those vaccinated with one dose (of Pfizer/BioNTech or Johnson & Johnson). We also extended the study to other countries in which Omicron has been detected, comparing the situation in October 2021 (before Omicron) with that of December 2021. While the reduction measured is smaller than in South Africa, we still found, for instance, an average drop in vaccine efficacy from 0.53 to 0.45 among those vaccinated with two doses. Moreover, we found a significant negative (Pearson) correlation of around - 0.6 between the measured prevalence of Omicron in several countries and the vaccine efficacy in those same countries. This prediction, in January of 2022, of the decreased vaccine efficacy towards Omicron is in line with the subsequent increase of Omicron infections in the first half of 2022.

Comparison of De-Kay repair versus De Vega suture for functional tricuspid regurgitation: a preliminary experience.

BACKGROUND: In patients undergoing mitral valve surgery, restrictive suture annuloplasty (De Vega) for less-than-severe functional tricuspid regurgitation has been proven to be safe and effective. The aim of this study is to determine whether the adjunct of the plication of the posterior tricuspid leaflet with the same running suture (bicuspidized De Vega or "De Kay") is equally safe and effective. METHODS: Single center, retrospective study on patients submitted to suture repair of the tricuspid valve during mitral valve surgery, with either conventional or De Kay, between January 2014 and December 2020. Comparison was based on degree of residual tricuspid valve regurgitation and right ventricular assessment at discharge. RESULTS: Over the course of the study period, 255 patients undergoing mitral valve surgery had a dilated (>40 mm or >20 mm/m2) tricuspid valve annulus, with less-than-severe tricuspid regurgitation. Conventional De Vega was employed in 166 patients (65.1%) and De Kay in the remaining 89 (34.9%). At discharge the adjunct of postero-septal commissure plication has similar outcomes to the classic De Vega repair. It seems to preserve right ventricular function. CONCLUSIONS: De Kay repair guarantees the same tricuspidal regurgitation reduction as compared with conventional De Vega early after surgery.

Comparative analysis of right ventricular strain in Fabry cardiomyopathy and sarcomeric hypertrophic cardiomyopathy.

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 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 α-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 (ΔRV strain), in comparison to individuals with HCM (P < 0.001 and P = 0.002, respectively). RV-FWS and ΔRV 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 ΔRV 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 ΔRV strain in comparison to patients with HCM, which may be helpful in the differential diagnosis between these two diseases.