Echocardiographic features of Fabry cardiomyopathy-Comparison with hypertrophy-matched sarcomeric hypertrophic cardiomyopathy.

BACKGROUND: The concept of "red flags" has been particularly useful in the etiologic diagnosis of cardiomyopathies such as Fabry disease, as early detection is often essential for treatment response and outcomes. The present study sought to describe the echocardiographic features that may differentiate Fabry cardiomyopathy from sarcomeric hypertrophic cardiomyopathy (HCM). METHODS: Forty patients with left ventricular (LV) hypertrophy were prospectively included and divided into two groups: the Fabry group (20) and the sarcomeric HCM group (20). The two groups were matched for LV hypertrophy (similar maximum wall thickness and indexed LV mass) and age. All patients underwent full echocardiographic evaluation including ventricular strain analysis. RESULTS: The Fabry group had significantly lower LV ejection fraction (63 ± 7 vs 72 ± 7%, P = .001) and higher LV end-systolic diameter (28 ± 7 vs 22 ± 5 mm, P = .004). LV hypertrophy in Fabry patients was more often concentric, with a significantly lower interventricular septum/posterior wall ratio (1.22 ± 0.63 vs 1.55 ± 0.66, P = .001). Fabry patients had more reduced regional longitudinal strain in the inferolateral part of the LV (-9 ± 5 vs -16 ± 7%), and RV free wall longitudinal strain was also worse in Fabry patients (-23 ± 6 vs -28 ± 5%, P = .027). CONCLUSION: These parameters are promising echocardiographic features to identify patients with Fabry cardiomyopathy and may help for the detection and subsequent management of these patients.

Too young for an acquired cardiomyopathy? Cobalt metallosis as a cardiac amyloidosis mimicker.

Metallosis with subsequent cardiac involvement is a possible long-term complication of hip arthroplasty. We report the case of a young female referred to our centre for the suspicion of cardiac amyloidosis presenting with low electrocardiogram voltage, left ventricular hypertrophy, pericardial effusion, and global and longitudinal systolic impairment with apical sparing pattern. Her medical history was remarkable for arthroplasty in the context of congenital hip dysplasia. Two years prior to presentation, she underwent revision surgery for prosthesis malfunction, and tissue metallosis was initially documented. At the current presentation, cobalt metallosis was confirmed, as the circulating cobalt and chromium levels were severely elevated. The accurate diagnosis prompted the removal of the cobalt source with extensive tissue debridement and the use of chelating agents. Reversal of the cardiac abnormalities occurred as the circulating cobalt levels returned to normal.

Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature Review.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder, most often caused by sarcomeric gene mutations, with a small proportion due to variants in non-sarcomeric loci. Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of cardiac contractility and relaxation. We conducted a retrospective study to determine the prevalence, phenotypical spectrum and clinical course of patients carrying the PLN p.Leu39* variant. A cohort including 11 PLN patients was identified among all patients with HCM (9/189, 4.8%) and DCM (2/62, 3.2%) who underwent genetic testing from two tertiary centers and five more were detected through cascade screening. Complete phenotyping was performed. PLN p.Leu39* variant-driven cardiomyopathy presented mostly as hypertrophic, with frequent progression to end-stage dilated HCM. We proceeded to compare these results to a similar analysis of a control cohort consisting of age-matched individuals that inherited pathogenic or likely pathogenic variants in common sarcomeric genes (MYBPC3/MYH7). Overall, the clinical characteristics and examination findings of patients carrying PLN p.Leu39* were not different from patients with cardiomyopathy related to sarcomeric mutations except for the presence of pathological Q waves and the incidence of non-sustained ventricular arrhythmias, which were higher in PLN patients than in those with MYBPC3/MYH7-related diseases.

Association between Left Atrial Function and Survival in Systemic Sclerosis.

Systemic sclerosis (SSc) is a multisystemic autoimmune disorder in which cardiac involvement is frequent and portends negative prognosis. Left ventricular (LV) diastolic dysfunction is one of the most common cardiac alterations in these patients, and left atrial (LA) reservoir strain (ƐR) measurement using speckle tracking echocardiography has been proposed as a novel parameter for a better assessment of LV diastolic function. Therefore, the aim of this study was to test the prognostic value of ƐR in a large multicenter cohort of SSc patients. In total, 311 SSc patients (54 ± 14 years, 85% female) were included from two different centers. Echocardiography was performed at the time of first visit, including ƐR measurement. Over a median follow-up of 132 (interquartile range: 110 to 157) months, 67 (21.5%) patients experienced the outcome of all-cause mortality. Spline curve analysis identified an optimal cut-off value of 30% for ƐR, and patients with ƐR ≤ 30% showed a 10-year cumulative survival rate of 71% as compared to 88% for patients with ƐR > 30% (log-rank p < 0.001). At the multivariable Cox regression analysis, ƐR was independently associated with the endpoint (HR 1.830; 95% confidence interval (CI) 1.031-3.246; p = 0.039) together with age (HR 1.071, 95% CI 1.043 to 1.099; p < 0.001), sex (female) (HR 0.444, 95% CI 0.229 to 0.861; p = 0.016), and diffusing lung capacity for carbon monoxide (HR 0.969 95% CI 0.956 to 0.982; p < 0.001). ƐR is of independent prognostic value in SSc and might help optimizing risk stratification in these patients.

Cardiac amyloidosis is not a single disease: a multiparametric comparison between the light chain and transthyretin forms.

AIMS: Systemic amyloidosis represents a heterogeneous group of diseases resulting from amyloid fibre deposition. The purpose of this study is to establish a differential diagnosis algorithm targeted towards the two most frequent subtypes of CA. METHODS AND RESULTS: We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in two centres in a score derivation cohort and a different validation sample. All patients had a complete clinical, biomarker, electrocardiographic, and imaging evaluation. Confirmation of the final diagnosis with amyloid typing was performed according to the current international recommendations. The study population included 81 patients divided into two groups: ATTR (group 1, n = 32: 28 variant and 4 wild type) and AL (group 2, n = 49). ATTR patients were younger (50.7 ± 13.9 vs. 60.2 ± 7.3 years, P = 0.0001), and significantly different in terms of NT-proBNP [ATTR: 1472.5 ng/L (97-4218.5) vs. AL 8024 ng/L (3058-14 069) P = 0.001], hs-cTn I [ATTR: 10 ng/L (4-20) vs. AL 78 ng/L (32-240), P = 0.0002], GFR [ATTR 95.4 mL/min (73.8-105.3) vs. AL: 68.4 mL/min (47.8-87.4) P = 0.003]. At similar left ventricular (LV) wall thickness and ejection fraction, the ATTR group had less frequently pericardial effusion (ATTR: 15% vs. AL: 33% P = 0.0027), better LV global longitudinal strain (ATTR: -13.1% ± 3.5 vs. AL: -9.1% ± 4.3 P = 0.04), RV strain (ATTR: -21.9% ± 6.2 vs. AL: -16.8% ± 6 P = 0.03) and better reservoir function of the LA strain (ATTR: 22% ± 12 vs. AL: 13.6% ± 7.8 P = 0.02). Cut-off points were calculated based on the Youden method. We attributed to 2 points for parameters having an AUC > 0.75 (NT-proBNP AUC 0.799; hs-cTnI AUC 0.87) and 1 point for GFR (AUC 0.749) and TTE parameters (GLS AUC 0.666; RV FWS AUC 0.649, LASr AUC 0.643). A score of equal or more than 4 points has been able to differentiate between AL and ATTR (sensitivity 80%, specificity 62%, AUC = 0.798). The differential diagnosis score system was applied to the validation cohort of 52 CA patients showing a sensitivity of 81% with specificity of 77%. CONCLUSIONS: CA is a complex entity and requires extensive testing for a positive diagnosis. This study highlights a series of non-invasive checkpoints, which can be useful in guiding the decision-making process towards a more accurate and rapid differential diagnosis.

Sclerodermic Cardiomyopathy-A State-of-the-Art Review.

Systemic sclerosis (SSc) is a chronic autoimmune disorder with unknown triggering factors, and complex pathophysiologic links which lead to fibrosis of skin and internal organs, including the heart, lungs, and gut. However, more than 100 years after the first description of cardiac disease in SSc, sclerodermic cardiomyopathy (SScCmp) is an underrecognized, occult disease with important adverse long-term prognosis. Laboratory tests, electrocardiography (ECG) and cardiovascular multimodality imaging techniques (transthoracic 2D and 3D echocardiography, cardiac magnetic resonance (CMR), and novel imaging techniques, including myocardial deformation analysis) provide new insights into the cardiac abnormalities in patients with SSc. This state-of-the-art review aims to stratify all the cardiac investigations needed to diagnose and follow-up the SScCmp, and discusses the epidemiology, risk factors and pathophysiology of this important cause of morbidity of the SSc patient.

Screening for Pulmonary Hypertension in Systemic Sclerosis-A Primer for Cardio-Rheumatology Clinics.

Systemic sclerosis (SSc) is a rare disease, with unfavorable clinical course and prognosis, characterized by progressive multisystemic involvement. SSc associated pulmonary hypertension (SSc-PAH) and interstitial lung disease (ILD) are the most important factors for morbi-mortality in these patients, being responsible for more than 60% of total deaths. Though pulmonary arterial hypertension (PAH) is the dominant subtype seen in SSc, PH secondary to ILD, left-heart pathology, and pulmonary veno-occlusive disease (PVOD) are also possible occurrences. Initial evaluation of a SSc case is complex and should be performed with a multidisciplinary approach. Early detection of SSc-PAH is imperative, given the fact that new and effective medications are available and early treatment was shown to improve outcomes. Therefore, screening algorithms must be used adequately and in a cost-effective manner. Sensitivity and negative predictive value (NPV) are the most important performance measures in a screening test. Several algorithms were developed in the last decade (e.g., DETECT and ASIG) and demonstrated higher efficiency when compared to older algorithms. The present manuscript details the risk factors for SSc-PAH and includes a critical description of current detection algorithms, as a primer for clinicians working in the field of cardio-rheumatology.

Acute Myocarditis-Like Episode in a Curly-Haired Young Boy-Red Flags for Familial Arrhythmogenic Cardiomyopathy.

The present case report describes a mother and son with arrhythmogenic cardiomyopathy (ACM) with early and greater left ventricle (LV) involvement. The presence of curly hair in both, together with the resuscitated sudden cardiac death of the mother, allowed timely genetic testing, which found a pathogenic nonsense mutation of the desmoplakin gene. While asymptomatic from an arrhythmic point of view, the son's evolution was characterized by a well-documented exercise-induced myocarditis-like stage.