Genetic Characterization of Dilated Cardiomyopathy in Romanian Adult Patients.

Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of <35% was observed in 41.9% of patients with disease-causing variants and 55% with negative or uncertain findings. Further genotype-phenotype correlations were explored in this study population. The substantial percentage (50.8%) of disease-causing variants identified in patients with DCM acknowledges the importance of genetic investigations. This study highlights the genetic landscape in genes associated with DCM in the Romanian population.

High penetrance and similar disease progression in probands and in family members with arrhythmogenic cardiomyopathy.

AIMS: We aimed to assess structural progression in arrhythmogenic cardiomyopathy (AC) patients and mutation-positive family members and its impact on arrhythmic outcome in a longitudinal cohort study. METHODS AND RESULTS: Structural progression was defined as the development of new Task Force imaging criteria from inclusion to follow-up and progression rates as annual changes in imaging parameters. We included 144 AC patients and family members (48% female, 47% probands, 40 ± 16 years old). At genetic diagnosis and inclusion, 58% of family members had penetrant AC disease. During 7.0 [inter-quartile range (IQR) 4.5-9.4] years of follow-up, 47% of family members without AC at inclusion developed AC criteria, resulting in a yearly new AC penetrance of 8%. Probands and family members had a similar progression rate of right ventricular outflow tract diameter (0.5 mm/year vs. 0.6 mm/year, P = 0.28) by mixed model analysis of 598 echocardiographic examinations. Right ventricular fractional area change progression rate was even higher in family members (-0.6%/year vs. -0.8%/year, P < 0.01). Among 86 patients without overt structural disease or arrhythmic history at inclusion, a first severe ventricular arrhythmic event occurred in 8 (9%), of which 7 (88%) had concomitant structural progression. Structural progression was associated with higher incidence of severe ventricular arrhythmic events adjusted for age, sex, and proband status (HR 21.24, 95% CI 2.47-182.81, P < 0.01). CONCLUSION: More than half of family members had AC criteria at genetic diagnosis and yearly AC penetrance was 8%. Structural progression was similar in probands and family members and was associated with higher incidence of severe ventricular arrhythmic events.

Novel FHL1 mutation variant identified in a patient with nonobstructive hypertrophic cardiomyopathy and myopathy - a case report.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disorder mostly caused by sarcomeric gene mutations, but almost 10% of cases are attributed to inherited metabolic and neuromuscular disorders. First described in 2008 in an American-Italian family with scapuloperoneal myopathy, FHL1 gene encodes four-and-a-half LIM domains 1 proteins which are involved in sarcomere formation, assembly and biomechanical stress sensing both in cardiac and skeletal muscle, and its mutations are responsible for a large spectrum of neuromuscular disorders (mostly myopathies) and cardiac disease, represented by HCM, either isolated, or in conjunction with neurologic and skeletal muscle impairment. We thereby report a novel mutation variant in FHL1 structure, associated with HCM and type 6 Emery-Dreifuss muscular dystrophy (EDMD). CASE PRESENTATION: We describe the case of a 40 year old male patient, who was referred to our department for evaluation in the setting of NYHA II heart failure symptoms and was found to have HCM. The elevated muscular enzymes raised the suspicion of a neuromuscular disease. Rigid low spine and wasting of deltoidus, supraspinatus, infraspinatus and calf muscles were described by the neurological examination. Electromyography and muscle biopsy found evidence of chronic myopathy. Diagnosis work-up was completed by next-generation sequencing genetic testing which found a likely pathogenic mutation in the FHL1 gene (c.157-1G > A, hemizygous) involved in the development of X-linked EDMD type 6. CONCLUSION: This case report highlights the importance of multimodality diagnostic approach in a patient with a neuromuscular disorder and associated hypertrophic cardiomyopathy by identifying a novel mutation variant in FHL1 gene. Raising awareness of non-sarcomeric gene mutations which can lead to HCM is fundamental, because of diagnostic and clinical risk stratification challenges.

Quality of life status determinants in hypertrophic cardiomyopathy as evaluated by the Kansas City Cardiomyopathy Questionnaire.

PURPOSE: The present study evaluated how heart failure (HF) negatively impacts health-related quality of life (HRQoL) in hypertrophic cardiomyopathy (HCM) patients and explored the major clinical determinants associated with HRQoL impairment in this population. METHODS: This was a cross-sectional single-center study of health-related HRQoL that included 91 consecutive patients with HCM. Evaluation was performed based on a comprehensive protocol that included the recommended diagnostic studies, as well as administration of the translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ) (CV Outcomes Inc) as a health status measure. RESULTS: The cohort included 52 (57%) males, median age 58 (20-85) years. The median global KCCQ score was 67 (12.5-100) corresponding to a moderate impairment in HRQoL. There was an inverse correlation between the median global KCCQ score and NYHA class (Kendall's tau b coefficient r - 0.33, p = 0.001). Patients with pulmonary hypertension (PHT), defined as resting pulmonary artery systolic pressure of ≥ 45 mmHg, presented a significantly worse HRQoL as compared to those without PHT (median KCCQ score 56.2 vs 77.5, p = 0.013). The KCCQ score mildly correlated with age (r - 0.18, p = 0.014), history of syncope (r - 0.18, p = 0.045), estimated glomerular filtration rate (eGFR) (r 0.31, p < 0.001), plasmatic creatinine (r - 0.18, p = 0.017) and urea levels (r - 0.27, p < 0.001), left ventricular (LV) end-systolic dimensions (r - 0.18, p = 0.014), maximal provoked intraventricular gradient (r 0.20, p = 0.039), LV ejection fraction (r 0.15, p = 0.04), average E/e' (r - 0.16, p = 0.039), pulmonary acceleration time (r 0.21, p = 0.007), pulmonary artery systolic pressure (r - 0.20, p = 0.016). In ordinal regression, the independent predictors of HRQoL were NYHA class and eGFR. CONCLUSIONS: Patients with HCM and HF present a moderate degree of alteration in HRQoL. This is especially true for patients with PHT and more severe functional impairment. Renal failure and NYHA class are potential markers of HRQoL in clinical practice.

Impaired ankle-brachial index in antiphospholipid syndrome: Beyond the traditional risk factors.

INTRODUCTION: The patients with antiphospholipid syndrome (APS) associate an increased risk of atherosclerosis. OBJECTIVE: To determine the predictors of an abnormal ankle-brachial index (ABI), surrogate measure of atherosclerosis, in patients with APS. METHODS: The ABI was measured according to standard recommendations in 106 patients. Traditional cardiovascular risk factors were assessed in all cases. A large spectrum of APS antibodies was determined in 73 patients. RESULTS: A total of 106 patients diagnosed with APS were included. 28.3% patients included were found to have low ABI. Anti-beta 2-glycoprotein I (aß2GPI) IgG antibodies [4.00 (1.00-79.00) vs 3.00 (0.00-29.00) U/mL, P = 0.02] and antiprothrombin (aPT) IgM antibodies [4.50 (0.00-82.00) vs 3.00 (0.00-14.00) U/mL, P = 0.05] titers were found to be higher in patients with abnormal ABI. However, after multivariate regression analysis, only the aß2GPI IgG titer remained predictor of low ABI (P = 0.04). CONCLUSIONS: aß2GPI IgG associated with impaired ABI in patients with APS. This relation might reflect their involvement in the atherosclerosis occurrence.

The Cardiomyopathy Registry of the EURObservational Research Programme of the European Society of Cardiology: baseline data and contemporary management of adult patients with cardiomyopathies.

Aims: The Cardiomyopathy Registry of the EURObservational Research Programme is a prospective, observational, and multinational registry of consecutive patients with four cardiomyopathy subtypes: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). We report the baseline characteristics and management of adults enrolled in the registry. Methods and results: A total of 3208 patients were enrolled by 69 centres in 18 countries [HCM (n = 1739); DCM (n = 1260); ARVC (n = 143); and RCM (n = 66)]. Differences between cardiomyopathy subtypes (P < 0.001) were observed for age at diagnosis, history of familial disease, history of sustained ventricular arrhythmia, use of magnetic resonance imaging or genetic testing, and implantation of defibrillators. When compared with probands, relatives had a lower age at diagnosis (P < 0.001), but a similar rate of symptoms and defibrillators. When compared with the Long-Term phase, patients of the Pilot phase (enrolled in more expert centres) had a more frequent rate of familial disease (P < 0.001), were more frequently diagnosed with a rare underlying disease (P < 0.001), and more frequently implanted with a defibrillator (P = 0.023). Comparing four geographical areas, patients from Southern Europe had a familial disease more frequently (P < 0.001), were more frequently diagnosed in the context of a family screening (P < 0.001), and more frequently diagnosed with a rare underlying disease (P < 0.001). Conclusion: By providing contemporary observational data on characteristics and management of patients with cardiomyopathies, the registry provides a platform for the evaluation of guideline implementation. Potential gaps with existing recommendations are discussed as well as some suggestions for improvement of health care provision in Europe.

Right ventricular remodeling in athletes and in arrhythmogenic cardiomyopathy.

OBJECTIVE: Changes in right ventricular (RV) structure and function following prolonged endurance training in athletes arise due to its unique anatomy and physiology. Arrhythmogenic cardiomyopathy (AC) should be differentiated from electrical, functional and structural adaptation of the heart in response to repetitive intense physical activity due to the negative contribution of exercise on AC progression and arrhythmic risk. DESIGN: For this review we performed a systematic search of the PubMed database up to October 2017 using terms and keywords pertaining to RV, athlete's heart (AH), AC, sudden cardiac death. RESULTS: This review summarizes currently available data on the impact of exercise on cardiac structure and function, discusses the debatable hypothesis of exercise-induced RV remodeling, compares the common features and search for distinctive characteristics between AH and AC. CONCLUSION: Exercise has a more profound impact on the structure and function of the RV than of the left ventricle. Differentiating physiologic RV remodeling following prolonged endurance exercise from subclinical cardiac pathology can be challenging. A multimodality approach is recommended to differentiate between exercise-induced physiological adaptations and cardiomyopathy.

Following up adult patients with tetralogy of fallot: The role of echocardiography.

Tetralogy of Fallot (TOF) is one of the most common cyanotic congenital heart diseases. With surgical repair and the advances in postoperative care, contemporary mortality has dramatically improved and an increasing number of patients survive into adulthood, leading to a growing number of adult TOF. However, residual anatomic and hemodynamic abnormalities are encountered in nearly all patients, making follow-up mandatory. Furthermore, mortality starts to increase 25 years after surgery, emphasizing that, in adult TOF, closer monitoring is necessary. We review here the role of echocardiography in the follow-up of the TOF patients, emphasizing the role of multiple echocardiographic techniques. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:79-95, 2017.

Is Right Ventricular Remodeling in Pulmonary Hypertension Dependent on Etiology? An Echocardiographic Study.

AIMS: Survival in patients (pts) with pulmonary hypertension (PH) differs between subgroups at similar levels of pressure overload. We set to analyze right ventricular (RV) morphology and function in different types of PH using conventional and deformation imaging echocardiography. MATERIAL AND METHODS: Thirty-four pts with PH: 12 pts with idiopathic pulmonary arterial hypertension (IPAH, 42.2 ± 13 years), 11 pts with chronic thromboembolic PH (CTEPH, 50.8 ± 12 years), 11 pts with Eisenmenger syndrome [ES 41.2 ± 15 years, 4 with atrial septal defect (ASD) and 7 with ventricular septal defect (VSD)], and 13 age-matched healthy individuals (38.1 ± 15 years) were evaluated. The following echocardiographic parameters were measured: echo-derived systolic pulmonary pressure (sPAPecho), RV end-diastolic diameter (RVEDD), RV wall thickness (RVWT), TAPSE, RV fractional area change (RVFAC), Tei index, peak systolic velocity of the tricuspid ring (S't), and speckle tracking-derived RV free wall strain. Furthermore, right heart catheterization (RHC) was performed in pts with PH and mean, and systolic pulmonary artery pressure (mPAPcath, sPAPcath), cardiac output (CO), cardiac index (COi), and pulmonary vascular resistance (PVR) were noted. RESULTS: The levels of mPAPcath and sPAPcath were similar between pts with PH (pANOVA = NS). Patients with ES had higher COi compared to other groups (2.94 ± 0.79, 2.28 ± 0.69, and 1.74 ± 0.46 L/min/m(2) for pts with ES, IPAH, and CTEPH respectively, pANOVA = 0.004, P post hoc ES versus all other groups < 0.05). TAPSE, Tei index, and S't were similar between groups and impaired versus controls (pANOVA < 0.001, P post hoc between groups of patients = NS). Patients with ES had better RVFAC (41.1 ± 9, 30.5 ± 10.8, 23.2 ± 9.8%) and RV free wall strain (-20.6 ± 3.5, -16.3 ± 7.5, -10.8 ± 5%), as well as an increased thickness of the RV free wall compared to other groups of patients (9.2 ± 1.5, 7.2 ± 1 and 7.2 ± 1.6 mm for pts with ES, IPAH and CTEPH, respectively) (pANOVA<0.001, P post hoc <0.05 ES versus all other groups). RVFAC and RV free wall strain significantly correlated with COi (r = 0.53, P = 0.006 and r = -0.77, P < 0.001, respectively). CONCLUSION: Patients with ES have a more hypertrophied RV free wall, better RV performance as assessed by RVFAC and RV free wall strain and increased COi compared to other types of PH. Furthermore, RV performance appears to be less dependent on the level of pressure overload. These findings could contribute to the better survival profile of patients with ES.

Pregnancy in women with dilated cardiomyopathy genetic variants.

INTRODUCTION AND OBJECTIVES: Limited information is available on the safety of pregnancy in patients with genetic dilated cardiomyopathy (DCM) and in carriers of DCM-causing genetic variants without the DCM phenotype. We assessed cardiac, obstetric, and fetal or neonatal outcomes in this group of patients. METHODS: We studied 48 women carrying pathogenic or likely pathogenic DCM-associated variants (30 with DCM and 18 without DCM) who had 83 pregnancies. Adverse cardiac events were defined as heart failure (HF), sustained ventricular tachycardia, ventricular assist device implantation, heart transplant, and/or maternal cardiac death during pregnancy, or labor and delivery, and up to the sixth postpartum month. RESULTS: A total of 15 patients, all with DCM (31% of the total cohort and 50% of women with DCM) experienced adverse cardiac events. Obstetric and fetal or neonatal complications were observed in 14% of pregnancies (10 in DCM patients and 2 in genetic carriers). We analyzed the 30 women who had been evaluated before their first pregnancy (12 with overt DCM and 18 without the phenotype). Five of the 12 (42%) women with DCM had adverse cardiac events despite showing NYHA class I or II before pregnancy. Most of these women had a history of cardiac events before pregnancy (80%). Among the 18 women without phenotype, 3 (17%) developed DCM toward the end of pregnancy. CONCLUSIONS: Cardiac complications during pregnancy and postpartum were common in patients with genetic DCM and were primarily related to HF. Despite apparently good tolerance of pregnancy in unaffected genetic carriers, pregnancy may act as a trigger for DCM onset in a subset of these women.

Proposed diagnostic criteria for arrhythmogenic cardiomyopathy: European Task Force consensus report.

Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent "non-ischemic" myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the "Padua criteria" were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late­gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other "non-scarring" myocardial disease. The "ring-like' pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients.

Right ventricular function predicts clinical response to specific vasodilator therapy in patients with pulmonary hypertension.

INTRODUCTION: We followed patients with pulmonary arterial hypertension (PAH) receiving specific vasodilator therapy and tested for predictors of clinical outcome. METHODS: Thirty-two patients (mean age 39 ± 15 years, 22 women, diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with inoperable chronic thromboembolic PH received therapy with either bosentan, sildenafil, or both and were evaluated with clinical parameters, biomarkers (B-type natriuretic peptide values), and echocardiography before receiving specific medication and every 3 months thereafter. A right heart catheterization was performed at baseline. A composite endpoint of death, worsening of functional class, or the need of a second vasodilator agent was used to define the clinical nonresponders. RESULTS: Patients were followed for 14 months (7.5-21). The endpoint was reached by 15 patients: four patients died (two idiopathic PAH and two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional class worsening, and four patients needed to be switched to combination therapy. Patients who remained clinically stable or improved had at baseline a better cardiac output with a less remodeled right ventricle (RV) and better functioning RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV global strain value higher than -13.4% predict with 87% sensitivity and 83% specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC 84.2%, P = 0.003), respectively, patients who will deteriorate clinically under specific vasodilator therapy. A multivariate model showed RVFAC to be the only independent predictor of the endpoint with a HR of 0.87 (0.8-0.96), P = 0.007. CONCLUSIONS: Over an average period of 1 year, almost half of patients showed signs of clinical deterioration despite specific vasodilator therapy. Parameters of right ventricular morphology and function had prognostic value in these patients.

Sex-specific difference in cardiac function in patients with systemic sclerosis: association with cardiovascular outcomes.

BACKGROUND: Cardiovascular involvement is one of the leading causes of mortality in systemic sclerosis (SSc) and is reported to be higher in men as compared with women. However, the cause of this difference is largely unknown. The objective of this study was to assess sex differences in echocardiographic characteristics, including left ventricular global longitudinal strain (LV GLS), as a potential explanation of sex differences in outcomes. METHODS: A total of 746 patients with SSc from four centres, including 628 (84%, 54±13 years) women and 118 (16%, 55±15 years) men, were evaluated with standard and advanced echocardiographic examinations. The independent association of the echocardiographic parameters with the combined endpoint of cardiovascular events-hospitalisation/death was evaluated. RESULTS: Men and women with SSc showed significant differences in disease characteristics and cardiac function. After adjusting for the most important clinical characteristics, while LV ejection fraction and diastolic function were not significantly different anymore, men still presented with more impaired LV GLS as compared with women (-19% (IQR -20% to -17%) vs -21% (IQR: -22% to -19%), p<0.001). After a median follow-up of 48 months (IQR: 26-80), the combined endpoint occurred in 182 patients. Men with SSc experienced higher cumulative rates of cardiovascular events-hospitalisation/mortality (χ2=8.648; Log-rank=0.003), and sex differences were maintained after adjusting for clinical confounders, but neutralised when matching the groups for LV GLS. CONCLUSION: In patients with SSc, male sex is associated with worse cardiovascular outcomes even after adjusting for important clinical characteristics. LV GLS was more impaired in men as compared with women and potentially explains the sex difference in cardiovascular outcomes.

Awareness of Nuclear Medicine Physicians in Romania Regarding the Diagnostic of Cardiac Amyloidosis-A Survey-Based Study.

Amyloidosis is a heterogeneous group of diseases caused by the extracellular deposition of amyloid insoluble fibrils in multiple organs, resulting in various clinical manifestations. Cardiac amyloidosis (CA) occurs mainly in primary light-chain (AL) amyloidosis, hereditary transthyretin (ATTRv) amyloidosis and senile or wild-type transthyretin (ATTRwt) amyloidosis. Knowing that myocardial uptake at bone scintigraphy is an essential step in the ATTR-CA diagnostic algorithm, the level of awareness among nuclear medicine physicians (NMPs) using bone tracer scintigraphy is of great importance. The objective of the study was to evaluate NMPs' awareness of scintigraphy with bisphosphonates for the detection of CA. We conducted an online survey among NMPs from Romania to assess their current awareness and state of knowledge of nuclear techniques used in CA. Among the total 65 Romanian NMPs, 35 (53%) responded to this questionnaire. Approximately three-quarters of participants (74%) found a diffuse accumulation of bisphosphonates in the heart on scintigraphy performed for bone pathology as an incidental discovery. Detection of myocardial uptake of 99mTc-labeled bisphosphonates on scintigraphy suggests CA-AL for 3% of participants and for 9% of respondents, the appearance is of uncertain cardiac amyloidosis, while 5% of participants observed cardiac uptake but did not report it as CA. Even if more than half of those who responded to this survey (54%) found abnormal cardiac uptake and interpreted it as CA-ATTR, only 14% contacted the referring physician to draw attention to the incidental discovery to refer the patient to a specialist in rare genetic cardiomyopathy. Regarding the knowledge about the categories of bisphosphonates recommended in the diagnosis of CA-ATTR, 54% answered inadequately that methylene diphosphonate (MDP) could be used. Romanian nuclear physicians are partially familiar with CA diagnosis by scintigraphy, but its diagnostic potential and standardization, recommended radiotracers and acquisition times and interpretation algorithms are known in varying proportions. Therefore, there is a need to enhance knowledge through continuing medical education programs in order to standardize the protocols for the acquisition, processing and interpretation of bisphosphonate scintigraphy for the detection of cardiac ATTR amyloidosis.

Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation-Family Case Report and Review of the Literature.

PRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), that mainly presents with ventricular pre-excitation, cardiac hypertrophy and progressive conduction system degeneration. Its natural course, treatment and prognosis are significantly different from sarcomeric HCM. The clinical phenotypes of PRKAG2 syndrome often overlap with HCM due to sarcomere protein mutations, causing this condition to be frequently misdiagnosed. The syndrome is caused by mutations in the gene encoding for the γ2 regulatory subunit (PRKAG2) of 5' Adenosine Monophosphate-Activated Protein Kinase (AMPK), an enzyme that modulates glucose uptake and glycolysis. PRKAG2 mutations (OMIM#602743) are responsible for structural changes of AMPK, leading to an impaired myocyte glucidic uptake, and finally causing storage cardiomyopathy. We describe the clinical and investigative findings in a family with several affected members (NM_016203.4:c.905G>A or p.(Arg302Gln), heterozygous), highlighting the various phenotypes even in the same family, and the utility of genetic testing in diagnosing PS. The particularity of this family case is represented by the fact that the index patient was diagnosed at age 16 with cardiac hypertrophy and ventricular pre-excitation while his mother, by age 42, only had Wolff−Parkinson−White syndrome, without left ventricle hypertrophy. Both the grandmother and the great-grandmother underwent pacemaker implantation at a young age because of conduction abnormalities. Making the distinction between PS and sarcomeric HCM is actionable, given the early-onset of the disease, the numerous life-threatening consequences and the high rate of conduction disorders. In patients who exhibit cardiac hypertrophy coexisting with ventricular pre-excitation, genetic screening for PRKAG2 mutations should be considered.

Cardiovascular Disease in Primary Sjögren's Syndrome: Raising Clinicians' Awareness.

In the ever evolving landscape of systemic immune mediated diseases, an increased awareness regarding the associated cardiovascular system impairment has been noted in recent years. Even though primary Sjögren's Syndrome (pSS) is one of the most frequent autoimmune diseases affecting middle-aged individuals, the cardiovascular profile of this specific population is far less studied, at least compared to other autoimmune diseases. Traditional cardiovascular risk factors and disease specific risk factors are inextricably intertwined in this particular case. Therefore, the cardiovascular risk profile in pSS is a multifaceted issue, sometimes difficult to assess. Furthermore, in the era of multimodality imaging, the diagnosis of subclinical myocardial and vascular damage is possible, with recent data pointing that the prevalence of such involvement is higher in pSS than in the general population. Nevertheless, when approaching patients with pSS in terms of cardiovascular diseases, clinicians are often faced with the difficult task of translating data from the literature into their everyday practice. The present review aims to synthesize the existing evidence on pSS associated cardiovascular changes in a clinically relevant manner.

The Impact of Kidney Biopsy for Fabry Nephropathy Evaluation on Patients' Management and Long-Term Outcomes: Experience of a Single Center.

BACKGROUND: Fabry disease (FD) is a rare lysosomal storage disease causing progressive loss of target organ function. All renal cell types are involved from the early stages, even before clinical signs can be detected. FD-specific therapies can stop/mitigate disease progression. Thus, it is important to validate early markers of renal lesions so that they can be adopted as criteria for timely treatment initiation. MATERIALS AND METHODS: We retrospectively analyzed and extensively evaluated 21 FD case patients; this evaluation included a kidney biopsy. We looked for the influence of pathological findings on the management of FD patients. In addition, we investigated the association between general and FD-specific features and long-term patients' outcomes. We defined a combined endpoint as being at least one of the following: 50% decrease of estimated glomerular filtration rate (eGFR) from baseline, kidney failure (KF), end-stage kidney disease (ESKD), or death and mortality. RESULTS: Our cohort of 21 FD patients (11 males and 10 females) was stratified according to the presence of the combined endpoint: group 1 (n = 15) included patients without the combined endpoint, while group 2 (n = 6) patients reached the combined endpoint outcome. Patients from group 2 presented lower mean baseline eGFR (72.2 ± 38.7 mL/min/1.73 m2 vs. 82.5 ± 26.4 mL/min/1.73 m2) without statistical significance (p = 0.44), but significantly (p = 0.22) higher median baseline proteinuria (2.7 g/24 h vs. 0.4 g/24 h). Specific lysosomal deposits were identified in all patients. Segmental sclerosis was present in all patients with the combined endpoint and in only 33% of patients without the combined endpoint (p = 0.009). Global sclerosis and interstitial fibrosis were present in both groups, with no significant differences. A total of 15 out of the 16 treatment-naïve patients (7 males and 9 females) started FD-specific therapy after kidney biopsy. Treatment was initiated in all male FD patients and in 8 female patients. In 2 females, pathological findings in kidney biopsy offered important reasons to start FD treatment, although specific criteria of the Romanian protocol for prescription of FD-specific therapy were still not fulfilled. Cox univariate analysis showed that every increase in 24 h proteinuria with 1 g is associated with a 65% risk of developing the combined endpoint (HR = 1.65; 95%CI: 1.05-2.58; p = 0.02), and that the presence of segmental sclerosis increased the risk of developing the combined endpoint by 51.3 times (HR = 51.3; 95% CI: 95% CI: 1.67-103.5; p = 0.01). Kaplan-Meier analysis showed that the cumulative risk of developing the combined endpoint was higher in patients in whom segmental sclerosis (100% vs. 0%, log-rank test, p = 0.03) was present. CONCLUSIONS: Histological evaluation is an important tool for the detection of early kidney involvement and provides additional support to the early initiation of FD-specific therapy. Presence of segmental sclerosis can predict the long-term outcomes of kidney disease deterioration and mortality and may be used as an early indicator of disease progression. Additionally, in the absence of other criteria according to current guidelines, specific FD renal lesions as revealed by kidney biopsy might become a distinct criterion to initiate FD therapy.

Electrocardiographic and Echocardiographic Predictors of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy.

Background: Patients with hypertrophic cardiomyopathy (HCM) have an increased prevalence of atrial fibrillation (AF) compared to the general population, and left atrium (LA) remodeling is strongly correlated with the risk of AF. This prospective, monocentric study aimed to assess the role of LA electrocardiographic and echocardiographic (structural and functional) parameters in predicting the risk for incident AF in patients with HCM. Methods and Results: The study population consisted of 126 HCM patients in sinus rhythm (52.6 ± 16.2 years, 54 men), 118 of them without documented AF. During a median follow-up of 56 (7-124) months, 39 (30.9%) developed a new episode of AF. Multivariable analysis showed that LA booster pump function (assessed by ASr, HR = 4.24, CI = 1.84-9.75, and p = 0.038) and electrical dispersion (assessed by P wave dispersion - Pd, HR = 1.044, CI = 1.029-1.058, and p = 0.001), and not structural parameters (LA diameter, LA volume) were independent predictors of incident AF. Seventy-two patients had a LA diameter < 45 mm, and 16 of them (22.2%) had an AF episode during follow-up. In this subgroup, only Pd emerged as an independent predictor for incident AF (HR = 1.105, CI = 1.059-1.154, and p = 0.002), with good accuracy (AUC = 0.89). Conclusion: Left atrium booster pump function (ASr) and electrical dispersion (Pd) are related to the risk of incident AF in HCM patients. These parameters can provide further stratification of the risk for AF in this setting, including in patients considered at lower risk for AF based on the conventional assessment of LA size.

EACVI survey on the multi-modality imaging assessment of the right heart.

AIMS: The European Association of Cardiovascular Imaging (EACVI) Scientific Initiatives Committee performed a global survey to evaluate the use of different cardiac imaging modalities for the evaluation of the right heart. METHODS AND RESULTS: Delegates from 250 EACVI registered centres were invited to participate in a survey which was also advertised on the EACVI bulletin and on social media. One hundred and thirty-eight respondents from 46 countries across the world responded to the survey. Most respondents worked in tertiary centres (79%) and echocardiography was reported as the commonest imaging modality used to assess the right ventricle (RV). The majority of survey participants (78%) included RV size and function in >90% of their echocardiographic reports. The RV basal diameter obtained from the apical four-chamber view and the tricuspid annular plane systolic excursion were the commonest parameters used for the echocardiographic assessment of RV size and function as reported by 82 and 97% respondents, respectively. Survey participants reported arrhythmogenic cardiomyopathy as the commonest condition (88%) where cardiac magentic resonance (CMR) imaging was used for right heart assessment. Only 52% respondents included RV volumetric and ejection fraction assessments routinely in their CMR reports, while 30% of respondents included these parameters only when RV pathology was suspected. Finally, 73% of the respondents reported pulmonary hypertension as the commonest condition where right heart catheterization was performed. CONCLUSION: Echocardiography remains the most frequently used imaging modality for the evaluation of the right heart, while the use of other imaging techniques, most notably CMR, is increasing.