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Several treatments have demonstrated safety and effectiveness in the treatment of patients with hypertrophic cardiomyopathy; however, no drug has been shown to modify the natural history of the disease or to decrease maximal wall thickness. Improvement in our knowledge of the physiopathology of the disease has permitted the development of new therapeutical approaches, including sarcomere modulators and gene therapy. A sarcomere modulator - mavacamten - has been shown to improve exercise capacity, left ventricular outflow tract obstruction, New York Heart Association functional class and health status in a phase 3 trial. Gene therapy - although still far from human experimentation - also has promising characteristics that may radically revolutionize the treatment of hypertrophic cardiomyopathy in the future. This therapy is currently approved for the treatment of select haematological malignancies, inherited retinal dystrophy and spinal muscular atrophy, and could potentially correct the genetic alterations of the most frequent sarcomeric forms of hypertrophic cardiomyopathy. This review provides an overview of current conventional therapies for the management of patients with hypertrophic cardiomyopathy, discusses emerging therapeutic approaches and presents future perspectives.

Cardiomyopathies are mostly determined by genetic mutations affecting either cardiac muscle cell structure or function. Nevertheless, cardiomyopathies may also be part of complex clinical phenotypes in the spectrum of neuromuscular (NMD) or mitochondrial diseases (MD). The aim of this study is to describe the clinical, molecular, and histological characteristics of a consecutive cohort of patients with cardiomyopathy associated with NMDs or MDs referred to a tertiary cardiomyopathy clinic. Consecutive patients with a definitive diagnosis of NMDs and MDs presenting with a cardiomyopathy phenotype were described. Seven patients were identified: two patients with ACAD9 deficiency (Patient 1 carried the c.1240C>T (p.Arg414Cys) homozygous variant in ACAD9; Patient 2 carried the c.1240C>T (p.Arg414Cys) and the c.1646G>A (p.Ar549Gln) variants in ACAD9); two patients with MYH7-related myopathy (Patient 3 carried the c.1325G>A (p.Arg442His) variant in MYH7; Patient 4 carried the c.1357C>T (p.Arg453Cys) variant in MYH7); one patient with desminopathy (Patient 5 carried the c.46C>T (p.Arg16Cys) variant in DES); two patients with mitochondrial myopathy (Patient 6 carried the m.3243A>G variant in MT-TL1; Patient 7 carried the c.253G>A (p.Gly85Arg) and the c.1055C>T (p.Thr352Met) variants in MTO1). All patients underwent a comprehensive cardiovascular and neuromuscular evaluation, including muscle biopsy and genetic testing. This study described the clinical phenotype of rare NMDs and MDs presenting as cardiomyopathies. A multidisciplinary evaluation, combined with genetic testing, plays a main role in the diagnosis of these rare diseases, and provides information about clinical expectations, and guides management.

Introduction Myhre syndrome (MS) is an ultra‐rare disorder due to pathogenic variants in the SMAD4 gene that encodes a protein regulating the TGF‐β pathway and extra‐cellular matrix (ECM) homeostasis. Main clinical features of MS include thickening of skin and joint stiffness. Previous studies showed that losartan improved ECM deposition in MS fibroblasts. Materials and methods Four molecularly confirmed MS subjects (mean age 23.8 ± 17 years) were evaluated for: (a) skin thickness by Rodnan score, (b) joint range of motion (ROM) by goniometry, and (c) speckle‐tracking echocardiogram. Following baseline evaluations, three MS individuals received losartan for 12 months and pre‐defined endpoints were monitored after 6 and 12 months of treatment. Results At baseline, Rodnan scores were increased, joint ROM was reduced, and speckle‐tracking echocardiogram revealed reduced myocardial strain. In three MS subjects, improvements in skin thickness, joint ROM and to a lesser extent of myocardial strain, were observed after 6 and 12 months of losartan treatment. Conclusions Although further long‐term controlled clinical trials with a larger number of affected individuals are needed, the present study suggests that losartan might improve skin, joint and heart abnormalities of MS.

Introduction: We sought to determine prevalence and predictive accuracy of clinical markers (red flags, RF), known to be associated with specific systemic disease in a consecutive cohort of patients with hypertrophic cardiomyopathy (HCM). Methods: We studied 129 consecutive patients (23.7 ± 20.9 years, range 0–74 years; male/female 68%/32%). Pre-specified RF were categorized into five domains: family history; signs/symptoms; electrocardiography; imaging; and laboratory. Sensitivity (Se), specificity (Sp), negative predictive value (NPV), positive predictive value (PPV), and predictive accuracy of RF were analyzed in the genotyped population. Results: In the overall cohort of 129 patients, 169 RF were identified in 62 patients (48%). Prevalence of RF was higher in infants (78%) and in adults >55 years old (58%). Following targeted genetic and clinical evaluation, 94 patients (74%) had a definite diagnosis (sarcomeric HCM or specific causes of HCM). We observed 14 RF in 13 patients (21%) with sarcomeric gene disease, 129 RF in 34 patients (97%) with other specific causes of HCM, and 26 RF in 15 patients (45%) with idiopathic HCM (p < 0.0001). Non-sarcomeric causes of HCM were the most prevalent in ages 55yo. Se, Sp, PPV, NPV and PA of RF were 97%, 70%, 55%, 98% and 77%, respectively. Single and clinical combination of RF (clusters) had an high specificity, NPV and predictive accuracy for the specific etiologies (syndromes/metabolic/infiltrative disorders associated with HCM). Conclusions: An extensive diagnostic work up, focused on analysis of specific diagnostic RF in patients with unexplained LVH facilitates a clinical diagnosis in 74% of patients with HCM.

The term arrhythmogenic cardiomyopathy (ACM) describes a large spectrum of myocardial diseases characterized by progressive fibrotic or fibrofatty replacement, which gives the substrate for the occurrence of ventricular tachyarrhythmias and the development of ventricular dysfunction. This condition may exclusively affect the left ventricle, leading to the introduction of the term arrhythmogenic left ventricular cardiomyopathy (ALVC). The clinical features of ALVC are progressive fibrotic replacement with the absence or mild dilation of the LV and the occurrence of ventricular arrhythmias within the left ventricle. In 2019, the diagnostic criteria for the diagnosis of ALVC, based on family history and clinical, electrocardiographic, and imaging features, have been proposed. However, since the significant clinical and imaging overlap with other cardiac diseases, genetic testing with the demonstration of a pathogenic variant in an ACM-related gene is required for diagnostic confirmation. In ALVC, the multimodality imaging approach comprises different imaging techniques, such as echocardiography, cardiac magnetic resonance, and cardiac nuclear imaging. It provides essential information for the diagnosis, differential diagnosis, sudden cardiac death risk stratification, and management purposes. This review aims to elucidate the current role of the different multimodality imaging techniques in patients with ALVC.

Gastrointestinal involvement is a common clinical feature of patients with systemic amyloidosis. This condition is responsible for invalidating gastrointestinal symptoms, a significant macro and micronutrient deficit, and is a marker of disease severity. Gastrointestinal involvement should be actively sought in patients with systemic amyloidosis, while its diagnosis is challenging in patients with isolated gastrointestinal symptoms. The nutritional status in systemic amyloidosis plays an essential role in the clinical course and is considered a significant prognostic factor. However, the definition of nutritional status is still challenging due to the lack of internationally accepted thresholds for anthropometric and biochemical variables, especially in specific populations such as those with systemic amyloidosis. This review aims to elucidate the fundamental steps for nutritional assessment by using clinical and instrumental tools for better prognostic stratification and patient management regarding quality of life and outcomes.

Aims This study aimed to validate the increased wall thickness (IWT) score, a multiparametric echocardiographic score to facilitate diagnosis of cardiac amyloidosis (CA), in an independent population of patients with increased LV wall thickness suspicious for CA. Methods and results Between January 2019 and December 2020, 152 consecutive patients with increased LV wall thickness suspicious for CA were included. For all patient, the multiparametric echocardiographic score (IWT score) was calculated. To validate the diagnostic accuracy of an IWT score ≥8 to predict the diagnosis of CA, sensibility (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and predictive accuracy (PA) were calculated. Among the 152 patients included in the study, 50 (33%) were diagnosed as CA, 25 (16%) had severe aortic stenosis, 25 (16%) had hypertensive remodelling, and 52 (34%) had hypertrophic cardiomyopathy. Among the 50 and 102 patients with and without CA, 19 (38%) and 1 (1%) showed an IWT score ≥8, respectively. Overall, the diagnostic accuracy of an IWT score ≥8 for the diagnosis of CA in our population was the following: Se 38% (95% CI: 25–53%); Sp 99% (95% CI: 95–100%); PPV 95% (95% CI: 72–99%); NPV 77% (95% CI: 73–80%); PA 79% (95% CI: 72–85%). Conclusions This study reports the first external validation of the IWT score for the diagnosis of CA in patients with increased LV wall thickness. A score ≥8 showed a high Sp, PPV and PA, suggesting that the IWT score can be used to identify CA patients in those with increased LV wall thickness.

Aims To evaluate to role of bisoprolol to control symptoms and left ventricular outflow tract obstruction (LVOTO) in a consecutive cohort of adults with hypertrophic cardiomyopathy (HCM). Methods and results In this retrospective study, patients with HCM with an LVOT gradient ≥50mmHg after Valsalva manoeuvre and New York Heart Association (NYHA) class II-III symptoms were assigned to receive bisoprolol (starting at 1.25 mg daily). The initial dose was increased every two weeks to achieve the target in LVOT gradient Conclusions Treatment with bisoprolol was well-tolerated and effective in relieving obstruction and improving symptoms in a significant proportion of patients with symptomatic obstructive HCM.

Aims: Children presenting with hypertrophic cardiomyopathy (HCM) in infancy are reported to have a poor prognosis, but this heterogeneous group has not been systematically characterized. This study aimed to describe the aetiology, phenotype, and outcomes of infantile HCM in a well-characterized multicentre European cohort. Methods and results: Of 301 children diagnosed with infantile HCM between 1987 and 2019 presenting to 17 European centres [male n=187 (62.1%)], underlying aetiology was non-syndromic (n=138, 45.6%), RASopathy (n=101, 33.6%), or inborn error of metabolism (IEM) (n=49, 16.3%). The most common reasons for presentation were symptoms (n=77, 29.3%), which were more prevalent in those with syndromic disease (n=62, 61.4%, P&nbsp

Aims This study sought to describe the characteristics and the natural course of left ventricular hypertrophy (LVH) in a well-characterized consecutive cohort of infants of diabetic mothers (IDMs). Methods and results Sixty consecutive IDMs with LVH have been retrospectively identified and enrolled in the study. All IDMs were evaluated at baseline and every 6 months until LV wall thickness regression, defined as the decrease of wall thickness measurement into the normal reference range for cardiac parameters (z-score > −2 and Conclusions LVH in IDMs represents a benign condition with complete regression during the first years of life. In those patients without LV wall thickness regression, combined with clinical markers suggesting a specific disease, a complete work-up is required for a definite diagnosis.

Background Right ventricular (RV) dysfunction in cardiomyopathies is a consequence of chronic overload (i.e. aortic stenosis) or direct involvement of systemic disorders (i.e. cardiac amyloidosis, CA). The Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure ratio (TAPSE/sPAP) has been recently proposed as a surrogate of RV-arterial coupling (RVAC) in many cardiac disorders. Purpose This study aims to compare RVAC between CA subgroups and between CA and other forms of genetic and non-genetic cardiomyopathies with hypertrophic phenotype. Methods We enrolled 50 patients with CA (26 pts with AL and 24 pts with wild type ATTR form), 75 patients with LV hypertrophy (LVH) [25 patients with HCM, 25 with hypertensive cardiomyopathy (HypCM), and 25 with aortic stenosis]. We analysed right chambers dimensions and classical and novel parameters of RV function [TAPSE, TAPSE/sPAP, St (S' wave at RV TDI), global (RVGLS) and free-wall (RVFWS) strain]. Results The ATTR group showed higher right dimensions than AL, without differences in all RV systolic parameters (see Table 1). Compared to the LVH group, CA patients showed no differences in RV dimensions while RV systolic parameters, included the TAPSE/sPAP ratio, were significantly reduced. At ROC curve analysis TAPSE (AUC 0.877; 95% CI: 0.811–0.943; p Discussion The RVAC is significantly impaired in CA compared to the LVH group but not between CA subgroups. TAPSE/sPAP proved to be a novel echocardiographic parameter useful in discriminating CA among genetic and non-genetic forms of LVH, and that also show prognostic significance. Funding Acknowledgement Type of funding sources: None. Figure 1. K-M for TAPSE/sPAP ratio IQ rangesTable 1

Background Hypertrophic cardiomyopathy (HCM) is characterized by extremely varied phenotypic expression ranging from asymptomatic to heart failure (HF) to sudden cardiac death (SCD). Although children with HCM are considered in the highest risk spectrum, the most common recommendations on pharmacological and non-pharmacological treatment (i.e. drugs, ICD, septal reduction procedures, inclusion in cardiac transplantation list) are often disregarded or too much postponed in this setting and strong evidence-based risk prediction models are missing. A systematic cardiopulmonary exercise test (CPET) assessment might be helpful to disclose an unsuspected functional limitation. Purpose The aim of our multicenter retrospective study was to investigate possible clinical insights, in terms of functional and prognostic assessment, coming from a full CPET assessment in a cohort of pediatric HCM outpatients aged less than 18 years old. Methods Sixty consecutive pediatric HCM outpatients aged Results An impaired exercise capacity, consisting on peak VO2 values Respect to the control Group, the HCM patients showed a significantly poorer functional status in terms of maximum workload achieved, peak VO2 (regardless the adopted correction), circulatory power and VE/VCO2 slope values (Figure 1, panel A). HCM patients who experience adverse events during the follow-up (Event Group) showed the worst CPET profile (Figure 1, panel B). The composite end-point occurred more frequently in patients with the worst CPETs' profiles. At the univariate analysis, peak VO2% was the variable with the strongest association with adverse events at follow-up (C-index=0.72, p=0.025) and a cut-off value equal to 60% was the most accurate in identifying those patients at the highest risk (Figure 2). Conclusions Our findings support the role of CPET analysis as an insightful approach in the young HCM clinical management. In a group of young asymptomatic or slightly symptomatic HCM patients, the CPET allowed us to estimate accurately their functional capacity and to disclose a portion of un-recognized exercise impairment. Our data argue in favor of a possible role of some CPET-derived variables in the early identification of those young HCM patients at highest risk of HCM related events. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Background Left atrial function (LAF) is emerging as a novel determinant of clinical status and outcome in cardiomyopathies. However, few studies compare LAF between CA subgroups and between CA and other hypertrophic cardiomyopathies. Purpose This study explores the LAF in cardiomyopathies with hypertrophic phenotype and between CA subgroups and its consequences on clinical status, haemodynamic consequences and survival. Methods We enrolled 50 patients with CA (26 with AL and 24 with wild type ATTR form), 75 patients with LV hypertrophy (LVH) [25 with hypertrophic cardiomyopathy (HCM), 25 with hypertensive cardiomyopathy (HypCM), and 25 with aortic stenosis (AS)]. Besides routine echocardiographic measurements, we analysed LAF using the phasic method (LAEI as reservoi, LAPEF as conduit, LAAEF as pump and TLAEF as total emptying LA function). Results The ATTR showed higher atrial dimensions with a significant reduction in the reservoir and total LA emptying function compared to the AL group (see Table 1). Instead, compared to the LVH group, CA patients showed higher atrial dimension with all LAF phasic parameters reduced, higher LV filling pressures and reduced biventricular function. Then, we further divided the CA and LVH group into subgroups based on the presence or absence of LA dysfunction (LADys+) defined as TLAEF values below the median [TLAEF Discussion The LAF is significantly impaired in CA and associated with worst clinical status, higher incidence of RV dysfunction and higher LV filling and pulmonary pressure. Moreover, LADys is significant associated with higher cardiovascular mortality. LADys results from chronic pressure overload due to LA's exposition to the higher LV diastolic pressure due to impaired LV compliance, and from direct infiltration in CA The result is a progressive LA remodelling with an increased LA pressure and consequenT backward transmission to the pulmonary venous system and to RV. Conclusions The TLAEF is a novel parameter of LAF that correlates with increased pulmonary vascular resistance and RV dysfunction. It seems a promising novel prognosticator and amarker of the haemodynamic consequences of LADys. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

Background Cardiac amyloidosis (CA) is an infiltrative disorder characterized by left ventricular (LV) thickening and dysfunction. Due to it poor prognosis its early detection and differential diagnosis among other forms of cardiomyopathies is fundamental. Purpose This study aimed to compare the diagnostic accuracy of LV classical and and novel echocardiographic parameters in differentiating CA from other forms of genetic and non-genetic cardiomyopathies with hypertrophic phenotype. Methods We included 50 patients with CA (26 pts with AL and 24 pts with wild type ATTR form) and 75 patients with LV hypertrophy (LVH) [25 patients with hypertrophic cardiomyopathy (HCM), 25 with hypertensive cardiomyopathy (HypCM), and 25 with aortic stenosis (AS)]. Besides routine echocardiographic measurements, we analysed standard and novel echo parameters implied in LV assessment [LV ejection fraction (LVEF), myocardial contraction fraction (MCF), global longitudinal strain (GLS), relative regional strain ratio (RRSR), ejection fraction on strain ratio (EFSR)], included novel Myocardial Work (MW) parameters [Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), Global Work Efficiency (GWE)]. Results Patients in CA group showed a smallest LV cavity size, higher LV mass and, consequently, a more pronounced concentric hypertrophy compared to LVH group. All LV systolic parameters where more impaired in CA than in LVH group. At ROC curve analysis, among all others, GCW showed the best performance in discriminating CA from LVH (AUC 0.886; 95% CI: 0.819–0.954; P Discussion Although CA and and LVH have with similar phenotype, they differ greatly in terms of systolic function. The MW, estimated by non-invasive pressure-strain loops, is a novel method for a load-independent LV systolic function assessment. In the present study the GCW showed the best ability in detecting CA in comparison to other parameters usually implied in clinical practice. Conclusion Myocardial performance is significantly reduced in CA compared to other forms of LVH. GCW showed to be a promising novel diagnostic and prognostic factor in this setting. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

Background Left ventricular hypertrophy (LVH) in infants of diabetic mothers (IDMs) has been generally considered a benign condition, which usually regresses as the stimulus for the insulin production disappears, resulting in normalized left ventricular wall thickness in the 6 months of life. However, these conclusions have been based on small, mostly outdated cohort studies. Indeed, it has been recently shown that increased left ventricular mass persists in late infancy (6 to 12 months), long after the intrauterine exposure has been removed, suggesting that other factors may potentially contribute. Purpose This study sought to describe the characteristics and the natural course of LVH in a well-characterized consecutive cohort of IDMs. Methods Sixty consecutive IDMs with LVH have been retrospectively identified and enrolled in the study. All IDMs were evaluated at baseline and every 6 months until LV wall thickness regression, defined as the decrease of wall thickness measurement into the normal reference range for cardiac parameters (z-score >−2 and Results At 1-year follow-up, all IDMs showed a significant reduction of maximal wall thickness (MWT) (MWT-mm: 6.67±2.37 vs. 5.83±1.70, p-value At multivariate analysis, MWT was significantly associated with LV wall thickness regression at 1-year follow-up (MWT-mm: OR 0.48 [0.29–0.79], p-value=0.004; MWT-z-score: OR 0.71 [0.56–0.90], p-value=0.004) in an inversely proportional fashion. Overall, 59%, 72% and 79% of IDMs with LVH showed a complete LV wall thickness regression at 1-year, 2-year and 3-year follow-up, respectively (Figure 2). Excluding the two patients with a different cause of LVH, all IDMs showed a LV wall thickness regression in the first 6 years of life. Conclusions LVH in IDMs represents a benign condition with complete regression during the first years of life. In those patients without LV wall thickness regression, combined with clinical markers suggesting a specific disease, a complete work-up is required for a definite diagnosis. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

The usefulness of cardiopulmonary exercise test (CPET) in adult hypertrophic cardiomyopathy (HCM) patients is well-known, whereas its role in pediatric HCM patients has not yet been explored. The present study investigates possible insights from a CPET assessment in a cohort of pediatric HCM outpatients in terms of functional and prognostic assessment. Sixty consecutive pediatric HCM outpatients aged &lt, 18 years old were enrolled, each of them undergoing a full clinical assessment including a CPET, a group of 60 healthy subjects served as controls. A unique composite end-point of heart failure (HF) related and sudden cardiac death (SCD) or SCD-equivalent events was also explored. During a median follow-up of 53 months (25th–75th: 13–84 months), a total of 13 HF- and 7 SCD-related first events were collected. Compared to controls, HCM patients showed an impaired functional capacity with most of them showing peak oxygen uptake (pVO2) values of &lt, 80% of the predicted, clearly discrepant with functional New York Heart Association class assessment. The composite end-point occurred more frequently in patients with the worst CPETs’ profiles. At the univariate analysis, pVO2% was the variable with the strongest association with adverse events at follow-up (C-index = 0.72, p = 0.025) and a cut-off value equal to 60% was the most accurate in identifying those patients at the highest risk. In a pediatric HCM subset, the CPET assessment allows a true functional capacity estimation and it might be helpful in identifying early those patients at high risk of events.

Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by left ventricular hypertrophy not solely explained by abnormal loading conditions. Despite its rare prevalence in pediatric age, HCM carries a relevant risk of mortality and morbidity in both infants and children. Pediatric HCM is a large heterogeneous group of disorders. Other than mutations in sarcomeric genes, which represent the most important cause of HCM in adults, childhood HCM includes a high prevalence of non-sarcomeric causes, including inherited errors of metabolism (i.e., glycogen storage diseases, lysosomal storage diseases, and fatty acid oxidation disorders), malformation syndromes, neuromuscular diseases, and mitochondrial disease, which globally represent up to 35% of children with HCM. The age of presentation and the underlying etiology significantly impact the prognosis of children with HCM. Moreover, in recent years, different targeted approaches for non-sarcomeric etiologies of HCM have emerged. Therefore, the etiological diagnosis is a fundamental step in designing specific management and therapy in these subjects. The present review aims to provide an overview of the non-sarcomeric causes of HCM in children, focusing on the pathophysiology, clinical features, diagnosis, and treatment of these rare disorders.

Introduction: Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy and a common cause of heart failure with preserved and mid-range ejection fraction (HFpEF and HFmrEF). Left ventricular (LV) systolic assessment is pivotal in differential diagnostic and prognostic stratification in CA. However, nondeformation and deformation-based parameters classically implied had many limitations. Myocardial work (MW) has been recently introduced for the evaluation of myocardial performance, in a load-independent fashion, in patients with cardiomyopathies. Aims: This study aimed to evaluate MW parameters in LV performance assessment in CA and their possible role in differential diagnosis between AL and ATTR forms, compared with other echocardiographic parameters, also exploring the possible association between MW parameters and blood biomarkers. Materials and Methods: The study population consisted of 25 patients with CA (10 with AL amyloidosis and 15 with wild-type ATTR [ATTRwt] form) and HFpEF or HFmrHF, enrolled between March 2018 and December 2019, undergoing a comprehensive clinical, biochemical, and imaging evaluation. Ten healthy individuals were studied as controls. ATTR patients had a noninvasive diagnosis of wtATTR-CA (positive 99m Tc-hydroxy methylene-diphosphonate scintigraphy with a negative hematological screening), while AL patients underwent endomyocardial biopsy. All patients underwent standard transthoracic echocardiography. MW and related indices were estimated using a vendor-specific module. Results: Compared to the ATTRwt group, patients in the AL group showed a more pronounced myocardial performance impairment assessed by Global Word Efficiency (GWE: 83.5% ± 6.3% vs. 88.2% ± 3.6%; P = 0.026). In multiple linear regression analysis, cardiac troponin I (B =-0.55; P < 0.0001), global longitudinal strain (B =0.35; P < 0.008), and regional relative strain ratio (B =-0.30; P < 0.016) were significant predictors of GWE reduction in CA patients. At receiver operating characteristics curve analysis, among all other deformation-based and nondeformation-based echocardiographic parameters, GWE showed the highest area under the curve (AUC) (AUC 0.74; 95% CI: 0.55-0.96; P < 0.04). The optimal cutoff was determined by sensitivity/specificity analysis: A GWE < 86.5% identified patients with AL amyloidosis with a sensitivity and specificity, respectively, of 80.0% and 66.7%. Conclusions: The results of our pivotal study seem to highlight the importance of new deformation parameters to study myocardial performance in patients with CA, and to differentiate between AL CA and ATTR CA.

Patients with bicuspid aortic valve (BAV) have an increased risk of aortic dilation and aortic dissection or rupture. The impact of physical training on the natural course of aortopathy in BAV patients remains unclear. The aim of this study was to evaluate the impact of regular physical activity on aortic diameters in a consecutive cohort of paediatric patients with BAV. Consecutive paediatric BAV patients were evaluated and categorized into two groups: physically active and sedentary subjects. Only the subjects with a complete 2-year follow-up were included in the study. To evaluate the potential impact of physical activity on aortic size, aortic diameters were measured at the sinus of Valsalva and mid-ascending aorta using echocardiography. We defined aortic diameter progression the increase of aortic diameter ≥ 10% from baseline. Among 90 BAV patients (11.5 ± 3.4 years of age, 77% males), 53 (59%) were physically active subjects. Compared to sedentary, physically active subjects were not significantly more likely to have > 10% increase in sinus of Valsalva (13% vs. 8%, p-value = 0.45) or mid-ascending aorta diameter (9% vs. 13%, p-value = 0.55) at 2 years follow-up, both in subjects with sinus of Valsalva diameter progression (3.7 ± 1.0 mm vs. 3.5 ± 0.8 mm, p-value = 0.67) and in those with ascending aorta diameter progression (3.0 ± 0.8 mm vs. 3.2 ± 1.3 mm, p-value = 0.83). In our paediatric cohort of BAV patients, the prevalence and the degree of aortic diameter progression was not significantly different between physically active and sedentary subjects, suggesting that aortic dilation is unrelated to regular physical activity over a 2-year period.

Background Right chambers involvement is common in cardiac amyloidosis (CA) but has been ever compared to control groups. Purpose Aim of this study is to compare right heart involvement between CA subgroups (AL vs. ATTR amyloidosis) and between CA and other forms of genetic and non-genetic left ventricular hypertrophy. Methods We enrolled 25 patients with CA (10 pts with AL and 15 pts with wild type ATTR amyloidosis) and 75 patients with LVH (25 HCM pts; 25 HypCMP pts; 25 AS pts). Beside routine echocardiographic measurements, we analysed right chambers dimensions and classical and novel parameters for right ventricular (RV) function [TAPSE (Tricuspid Anulus Plane Systolic Excursion), St (S' wave at RV TDI), global and free-wall strain]. Results ATTR group showed higher right dimensions compared to AL, without differences in RV systolic parameters (see table). CA patients, compared to LVH group, showed no differences in right dimensions. RV systolic parameters were significantly reduced while diastolic Doppler parameters were higher (E/E' 21.7±9.0 vs. 11.2±5.0; p Discussion CA group showed a significantly impaired RV systolic function with higher pulmonary pressures compared to LVH group. TAPSE proved to be the only able to discriminate CA among genetic and non-genetic forms of LVH and also to have prognostic significance. Funding Acknowledgement Type of funding source: None

Cardiomyopathies (CMPs) represent a diverse group of heart muscle diseases, grouped into specific morphological and functional phenotypes. CMPs are associated with mutations in sarcomeric and non-sarcomeric genes, with several suspected epigenetic and environmental mechanisms involved in determining penetrance and expressivity. The understanding of the underlying molecular mechanisms of myocardial diseases is fundamental to achieving a proper management and treatment of these disorders. Among these, inflammation seems to play an important role in the pathogenesis of CMPs. The aim of the present study is to review the current knowledge on the role of inflammation and the immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.

In this report, an atypical case of Noonan syndrome (NS) associated with sarcomeric hypertrophic cardiomyopathy (HCM) in a 33-year-old patient was described. Genetic testing revealed two different disease-causing mutations: a mutation in the PTPN11 gene, explaining NS, and a mutation in the MYBPC3 gene, known to be associated with HCM. This case exemplifies the challenge in achieving a definite etiological diagnosis in patients with HCM and the need to exclude other diseases mimicking this condition (genocopies or phenocopies). Compound heterozygous mutations are rare but possible in HCM patients. In conclusion, this study highlights the important role of genetic testing as a necessary diagnostic tool for performing a definitive etiological diagnosis of HCM.

Multimodality imaging is a comprehensive strategy to investigate left ventricular hypertrophy (LVH), providing morphologic, functional, and often clinical information to clinicians. Hypertrophic cardiomyopathy (HCM) is defined by an increased LV wall thickness not only explainable by abnormal loading conditions. In the context of HCM, multimodality imaging, by different imaging techniques, such as echocardiography, cardiac magnetic resonance, cardiac computer tomography, and cardiac nuclear imaging, provides essential information for diagnosis, sudden cardiac death stratification, and management. Furthermore, it is essential to uncover the specific cause of HCM, such as Fabry disease and cardiac amyloidosis, which can benefit of specific treatments. This review aims to elucidate the current role of multimodality imaging in adult patients with HCM.

Aim: Anderson-Fabry disease (AFD) is a hereditary disorder caused by a deficiency in the lysosomal enzyme α-galactosidase A which causes dysfunctions in multiple organ systems. Cardiac manifestation includes left ventricular hypertrophy, thickening of the valves, conduction disturbances and in the late phase, extensive areas of myocardial fibrosis with increased risk of sudden cardiac death. Case example: A case of AFD with exclusive cardiac involvement is described. During follow-up, due to the high risk of life-threatening arrhythmic events, implantation of an implantable cardioverter defibrillator is performed. Conclusion: AFD patients with advanced cardiac disease might represent a subgroup of patients who may require an implantable cardioverter defibrillator for primary prevention of sudden cardiac death.

Pregnancy exposes women with inherited cardiomyopathies to increased risk for arrhythmias and heart failure. In asymptomatic patients with inherited cardiomyopathies, pregnancy is generally well tolerated. Preconception evaluation, risk assessment and proper counseling by a team of experienced physicians are mandatory in managing women with inherited cardiomyopathies planning pregnancy. In this paper, we reviewed the clinical course, risk assessment and management during pregnancy of women with cardiomyopathies.

Introduction Lysosomal storage diseases (LSDs) are rare inherited metabolic diseases characterized by an abnormal accumulation of various toxic materials in the cells as a result of enzyme deficiencies leading to tissue and organ damage. Among clinical manifestations, cardiac diseases are particularly important in Pompe glycogen storage diseases (PD), in glycosphingolipidosis Fabry disease (FD), and mucopolysaccharidoses (MPS). Here, we evaluated the occurrence of aortopathy in knock out (KO) mouse models of three different LSDs, including PD, FD, and MPS IIIB. Methods We measured the aortic diameters in 15 KO male mice, 5 for each LSD: 5 GLA-/- mice for FD, 5 NAGLU-/- mice for MPS IIIB, 5 GAA-/- mice for PD, and 15 wild type (WT) mice: 5 for each strain. In order to compare the aortic parameters between KO and WT mice deriving from the same colonies, different diameters were echocardiographically measured: aortic annulus, aortic sinus, sino-tubular junction, ascending aorta, aortic arch and descending aorta. Storage material content and aortic defects of the KO mice were also analyzed by histology, when available. Results Compared to their correspondent WT mice: GAA-/- mice showed greater diameters of ascending aorta (1.61mm vs. 1.11mm, p-value = 0.01) and descending aorta (1.17mm vs 1.02mm, p-value 0.04); GLA-/- mice showed greater diameters of aortic annulus (1.35mm vs. 1.22mm, p-value = 0.01), sinus of Valsalva (1.6mm vs. 1.38mm, p-value

Clinical trials have shown the benefits of &beta, blockers therapy in patients with heart failure reduced ejection fraction. These benefits include improved survival and a reduced need for hospitalization. Cardiac resynchronization therapy has emerged as an essential device-based therapy for symptomatic patients with heart failure reduced ejection fraction despite optimal pharmacologic treatment. The extent to which &beta, blockers are being utilized in patients receiving cardiac resynchronization therapy is not well known. In this study, we evaluate the possibility of increasing &beta, blockers doses in an unselected cohort of heart failure reduced ejection patients after cardiac resynchronization therapy capable defibrillator system implantation and the correlation between &beta, blockers treatments and clinical outcome. Methods and results: Patients with heart failure reduced ejection fraction in &beta, blockers therapy that underwent cardiac resynchronization therapy capable defibrillator system implantation between July 2008, and December 2016 were enrolled in the study. The &beta, blockers dose was determined at the time of discharge and during follow-up. Cardiovascular mortality, hospitalization for worsening heart failure or arrhythmic storm and appropriate intervention of the device, were recorded. The study cohort included 480 patients, 289 patients (60.3%) had &beta, blockers doses equal to the dose before CRT (Group 1), 191 patients (39.7%) had higher &beta, blockers doses than those before the CRT implant (Group 2). Comparing the two groups, Group 2 have lower cardiovascular mortality, heart failure-related hospitalization, and arrhythmic events than Group 1. Conclusion: After initiating CRT, &beta, blockers could be safely up-titrated at higher doses with the reduction in mortality, heart failure-related hospitalization, and arrhythmic events.

Coarctation of the aorta is a leading cause of morbidity and mortality among adults with congenital heart disease (ACHD). Lifelong surveillance is mandatory to screen for possible long-term cardiovascular events.Left ventricular systolic dysfunction has been reported in association with recoarctation, and association with dilated cardiomyopathy (DCMP) is very rare. Herein, we report the case of a 19-year-old boy with coarctation of the aorta who complained of mild exertional dyspnea. Cardiac magnetic resonance revealed a moderately dilated, hypokinetic left ventricle (LV), with mildly reduced EF (45%), and residual isthmic coarctation was excluded. Genetic tests revealed a heterozygous missense variant in TNNT2 (NM_001001430.2): c.518G>A (p. Arg173Gln). This case highlights the role of careful history taking: a family history of cardiomyopathy should not be overlooked even when the clinical setting seems to suggest a predisposition to hemodynamic factors for LVSD.

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme, agalactosidase A. The inadequate enzymatic activity leads to systemic storage of glycosphingolipids, mostly globotriaosylceramide, in the lysosomes. As of now, enzyme replacement therapy is the only approved treatment for AFD. However, it does not induce a complete and lasting response in several clinical contexts. Genemediated enzyme replacement is an emerging approach that could overcome these limits. The single gene nature of AFD enhances the possibility to transfect and modify a small number of cells, making them capable to affect the correction of a larger number of cells. This review summarizes the history and the state of the art of gene therapy in AFD, showing potential benefits and limits.