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.

Multimodality Cardiac Imaging in COVID-19 Infection.

COVID-19 infection often produces cardiovascular complications, which can range from mild to severe and influence the overall prognosis. Imaging is the cornerstone for diagnosing initial COVID-19 cardiovascular involvement as well as treatment guidance. In this review, we present the current state of the literature on this subject while also emphasizing possible algorithms for indicating and executing these investigations.

The Value of Multimodal Imaging in Early Phenotyping of Cardiomyopathies: A Family Case Report.

Cardiomyopathies are structural and functional myocardial disorders that are not caused by other specific conditions such as coronary artery disease, arterial hypertension, valvular disease or congenital heart diseases. They are grouped into specific morphological and functional phenotypes, and sub-classified into familial and non-familial forms, with the dilated phenotype being the most frequent. However, there are many overlapping features between these phenotypes, complicating the diagnosis and management of patients. We report here the case of three related patients with different types of cardiomyopathies, emphasizing the importance of a multimodal approach to diagnosis.

Holographic Techniques as a Novel Method for Intervention Planning: A Tertiary Centres Experience.

Advanced holographic visualization techniques are becoming increasingly important in clinical practice, not only for diagnostic purposes but also in the planning of interventional or surgical procedures. The traditional approach for visualizing anatomic structures is based on standard imaging modalities such as echocardiography, cardiac magnetic resonance (CMR) and cardiac CT scan (CCT) which, however, can only provide two-dimensional (2D) images thus limiting 3D perception. Many recent studies have shown that the use of 3D imaging modalities such as augmented reality, virtual reality, mixed reality and holography improve the short and long-term outcome of percutaneous or surgical procedures. In this article, we report our experience on the use of the hologram in different clinical scenarios and in the field of university education.

Intracardiac mass presenting as acute myocardial infarction.

Cardiac tumors, although rare, present intricate diagnostic and therapeutic challenges, necessitating timely intervention for optimal patient outcomes. This case report focuses on a 65-year-old woman admitted with chest pain and loss of consciousness, ultimately diagnosed with a left ventricular cardiac myxoma. The patient's presentation mimicked acute coronary syndrome, highlighting the diagnostic complexity associated with cardiac tumors. Advanced imaging modalities, including transthoracic echocardiography, computed tomography, and invasive coronary angiography, played a pivotal role in characterizing the intracardiac mass. Histopathological (HP) examination, utilizing immunohistochemistry, confirmed the tumor as a cardiac myxoma. The patient management involved a multidisciplinary approach, leading to surgical resection of the mass and mitral valve replacement. The case underscores the importance of the HP confirmation in patients with cardiac masses, especially when multimodality cardiac imaging suggests various tumor types, simultaneously emphasizing the need for a comprehensive diagnostic approach that includes advanced imaging and histopathology to ensure an accurate diagnosis and tailored management of cardiac tumors.

The Dysfunctional Right Ventricle in Dilated Cardiomyopathies: Looking from the Right Point of View.

Dilated cardiomyopathies (DCMs) are a heterogenous group of primary myocardial diseases, representing one of the leading causes of heart failure, and the main indication for heart transplantation. While the degree of left ventricular dilation and dysfunction are two key determinants of adverse outcomes in DCM patients, right ventricular (RV) remodeling and dysfunction further negatively influence patient prognosis. Consequently, RV functional assessment and diagnosing RV involvement by using an integrative approach based on multimodality imaging is of paramount importance in the evaluation of DCM patients and provides incremental prognostic and therapeutic information. Transthoracic echocardiography remains the first-line imaging modality used for the assessment of the RV, and newer techniques such as speckle-tracking and three-dimensional echocardiography significantly improve its diagnostic and prognostic accuracy. Nonetheless, cardiac magnetic resonance (CMR) is considered the gold standard imaging modality for the evaluation of RV size and function, and all DCM patients should be evaluated by CMR at least once. Accordingly, this review provides a comprehensive overview of the anatomy and function of the RV, and the pathophysiology, diagnosis, and prognostic value of RV dysfunction in DCM patients, based on traditional and novel imaging techniques.

Intracardiac mass revealing a rare form of cardiomyopathy.

We present the case of a woman with a 2-month history of exertional dyspnoea and fatigue in which echocardiography revealed a cavity-obliterating right ventricular mass. Further imaging evaluation using cardiac magnetic resonance showed a thrombotic mass as well as diffuse myocardial oedema and endomyocardial fibrosis (EMF) that involved both ventricles. In the absence of any other cause (including peripheral eosinophilia), the diagnosis of idiopathic EMF was established. This case highlights this uncommon disease in non-tropical areas.

Multivendor comparison of global and regional 2D cardiovascular magnetic resonance feature tracking strains vs tissue tagging at 3T.

BACKGROUND: Cardiovascular magnetic resonance (CMR) 2D feature tracking (FT) left ventricular (LV) myocardial strain has seen widespread use to characterize myocardial deformation. Yet, validation of CMR FT measurements remains scarce, particularly for regional strain. Therefore, we aimed to perform intervendor comparison of 3 different FT software against tagging. METHODS: In 61 subjects (18 healthy subjects, 18 patients with chronic myocardial infarction, 15 with dilated cardiomyopathy, and 10 with LV hypertrophy due to hypertrophic cardiomyopathy or aortic stenosis) were prospectively compared global (G) and regional transmural peak-systolic Lagrangian longitudinal (LS), circumferential (CS) and radial strains (RS) by 3 FT software (cvi42, Segment, and Tomtec) among each other and with tagging at 3T. We also evaluated the ability of regional LS, CS, and RS by different FT software vs tagging to identify late gadolinium enhancement (LGE) in the 18 infarct patients. RESULTS: GLS and GCS by all 3 software had an excellent agreement among each other (ICC = 0.94-0.98 for GLS and ICC = 0.96-0.98 for GCS respectively) and against tagging (ICC = 0.92-0.94 for GLS and ICC = 0.88-0.91 for GCS respectively), while GRS showed inconsistent agreement between vendors (ICC 0.10-0.81). For regional LS, the agreement was good (ICC = 0.68) between 2 vendors but less vs the 3rd (ICC 0.50-0.59) and moderate to poor (ICC 0.44-0.47) between all three FT software and tagging. Also, for regional CS agreement between 2 software was higher (ICC = 0.80) than against the 3rd (ICC = 0.58-0.60), and both better agreed with tagging (ICC = 0.70-0.72) than the 3rd (ICC = 0.57). Regional RS had more variation in the agreement between methods ranging from good (ICC = 0.75) to poor (ICC = 0.05). Finally, the accuracy of scar detection by regional strains differed among the 3 FT software. While the accuracy of regional LS was similar, CS by one software was less accurate (AUC 0.68) than tagging (AUC 0.80, p < 0.006) and RS less accurate (AUC 0.578) than the other two (AUC 0.76 and 0.73, p < 0.02) to discriminate segments with LGE. CONCLUSIONS: We confirm good agreement of CMR FT and little intervendor difference for GLS and GCS evaluation, with variable agreement for GRS. For regional strain evaluation, intervendor difference was larger, especially for RS, and the diagnostic performance varied more substantially among different vendors for regional strain analysis.

Prognostic Value of Pulmonary Transit Time by Cardiac Magnetic Resonance on Mortality and Heart Failure Hospitalization in Patients With Advanced Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Pulmonary transit time (PTT) from first-pass perfusion imaging is a novel parameter to evaluate hemodynamic congestion by cardiac magnetic resonance (cMR). We sought to evaluate the additional prognostic value of PTT in heart failure with reduced ejection fraction over other well-validated predictors of risk including the Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. METHODS: We prospectively followed 410 patients with chronic heart failure with reduced ejection fraction (61±13 years, left ventricular (LV) ejection fraction 24±7%) who underwent a clinical cMR to assess the prognostic value of PTT for a primary endpoint of overall mortality and secondary composite endpoint of cardiovascular death and heart failure hospitalization. Normal reference values of PTT were evaluated in a population of 40 asymptomatic volunteers free of cardiovascular disease. Results PTT was significantly increased in patients with heart failure with reduced ejection fraction as compared to controls (9±6 beats and 7±2 beats, respectively, P<0.001), and correlated not only with New York Heart Association class, cMR-LV and cMR-right ventricular (RV) volumes, cMR-RV and cMR-LV ejection fraction, and feature tracking global longitudinal strain, but also with cardiac output. Over 6-year median follow-up, 182 patients died and 200 reached the secondary endpoint. By multivariate Cox analysis, PTT was an independent and significant predictor of both endpoints after adjustment for Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Importantly in multivariable analysis, PTT in beats had significantly higher additional prognostic value to predict not only overall mortality (χ2 to improve, 12.3; hazard ratio, 1.35 [95% CI, 1.16-1.58]; P<0.001) but also the secondary composite endpoints (χ2 to improve=20.1; hazard ratio, 1.23 [95% CI, 1.21-1.60]; P<0.001) than cMR-LV ejection fraction, cMR-RV ejection fraction, LV-feature tracking global longitudinal strain, or RV-feature tracking global longitudinal strain. Importantly, PTT was independent and complementary to both pulmonary artery pressure and reduced RV ejection fraction<42% to predict overall mortality and secondary combined endpoints. CONCLUSIONS: Despite limitations in temporal resolution, PTT derived from first-pass perfusion imaging provides higher and independent prognostic information in heart failure with reduced ejection fraction than clinical and other cMR parameters, including LV and RV ejection fraction or feature tracking global longitudinal strain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03969394.

Test-retest reliability of left and right ventricular systolic function by new and conventional echocardiographic and cardiac magnetic resonance parameters.

AIMS: Reproducible evaluation of left (LV) and right ventricular (RV) function is crucial for clinical decision-making and risk stratification. We evaluated whether speckle-tracking echocardiography (STE) and cardiac magnetic resonance feature-tracking (cMR-FT) global longitudinal (GLS) and circumferential strains allow better test-retest reproducibility of LV and RV systolic function than conventional cMR and echocardiographic parameters. METHODS AND RESULTS: Thirty healthy volunteers and 20 chronic heart failure patients underwent cMR and STE twice on separate days to evaluate test-retest coefficient of variation (CV), intraclass correlation coefficient (ICC) and estimated sample sizes for significant changes in LV and RV function. Among LV parameters, cMR-left ventricular ejection fraction (LVEF) had the highest reproducibility (CV = 6.7%, ICC = 0.98), significantly better than cMR-FT-GLS (CV = 15.1%, ICC = 0.84), global circumferential strains (CV = 11.5%, ICC = 0.94) and echocardiographic LVEF (CV = 11.3%, ICC = 0.93). STE-LV-GLS (CV = 8.9%, ICC = 0.94) had significantly better reproducibility than cMR-FT-LV-GLS. Among RV parameters, STE-RV-GLS (CV = 7.3%, ICC = 0.93) had significantly better CV than cMR-right ventricular ejection fraction (RVEF) (CV = 13%, ICC = 0.82). cMR-FT-RV-GLS (CV = 43%, ICC = 0.39) performed poorly with significantly lower reproducibility than all other RV parameters. Owing to their superior interstudy reproducibility, cMR-LVEF (n = 12), cMR-RVEF (n = 41), STE-LV-GLS and STE-RV-GLS (both n = 14) were the parameters allowing the lowest calculated sample sizes to detect 10% change in LV or RV systolic function. CONCLUSION: STE-LV-GLS and STE-RV-GLS showed higher test-retest reliability than other echocardiographic measurements of LV and RV function. They also allowed smaller calculated sample sizes, supporting the use of STE-LV and RV-GLS for longitudinal follow-up of LV and RV function.

Finite Element Analysis of a Novel Aortic Valve Stent.

Worldwide, one of the leading causes of death for patients with cardiovascular disease is aortic valve failure or insufficiency as a result of calcification and cardiovascular disease. The surgical treatment consists of repair or total replacement of the aortic valve. Artificial aortic valve implantation via a percutaneous or endovascular procedure is the minimally invasive alternative to open chest surgery, and the only option for high-risk or older patients. Due to the complex anatomical location between the left ventricle and the aorta, there are still engineering design optimization challenges which influence the long-term durability of the valve. In this study we developed a computer model and performed a numerical analysis of an original self-expanding stent for transcatheter aortic valve in order to optimize its design and materials. The study demonstrates the current valve design could be a good alternative to the existing commercially available valve devices.

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.

Validation of Semiautomated Quantification of Mitral Valve Regurgitation by Three-Dimensional Color Doppler Transesophageal Echocardiography.

BACKGROUND: The aim of this study was to evaluate the accuracy of mitral regurgitation (MR) volume quantified on three-dimensional (3D) color Doppler transesophageal echocardiography (TEE) using new semiautomated software compared with conventional two-dimensional (2D) proximal isovelocity surface area (PISA) transthoracic echocardiography (TTE) and TEE and cardiac magnetic resonance imaging (CMR). METHODS: Fifty-one patients (mean age, 63 ± 16 years; 35 men) prospectively underwent TTE, TEE, and CMR for MR evaluation. Regurgitant volume (RVol) by 3D MR flow quantification was compared with 2D TTE, TEE, and CMR, and the accuracy of evaluation of severe MR by 3D MR flow quantification was compared against guideline criteria by TEE. RESULTS: Twenty-nine patients had severe MR, 16 had moderate MR, and six had mild MR. Three-dimensional MR flow quantification was feasible in all patients, including prolapse (n = 37), restriction (n = 9), functional MR (n = 5), and eccentric or multiple jects (n = 41). RVol on 3D MR flow quantification correlated well with RVol on 2D PISA TTE (interclass correlation coefficient [ICC] = 0.75, P < .001), quantitatively estimated RVol (ICC = 0.74, P < .001), and 2D PISA TEE (ICC = 0.79, P < .001). Three-dimensional MR flow quantification agreed better with CMR (ICC = 0.86, P < .001) than did RVol on 2D PISA TTE (ICC = 0.66, P < .001) and 2D PISA TEE (ICC = 0.69, P < .001), with narrower limits of agreement on Bland-Altman analysis. Three-dimensional MR flow quantification had high accuracy for diagnosing severe MR using TEE (area under the curve = 0.85, 95% CI 0.74-0.96, P < .001) or CMR (area under the curve = 0.95; 95% CI, 0.89-1.00; P < .001) as the criterion. CONCLUSIONS: The new software enabled semiautomated 3D MR flow quantification in complex MR with multiple and eccentric jets and showed better agreement with CMR than 2D PISA TTE or TEE, suggesting that this method is more accurate than conventional 2D PISA TTE and TEE.

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.

Multimodality imaging in Fabry cardiomyopathy: from early diagnosis to therapeutic targets.

Fabry disease (FD) is a rare genetic X-linked disorder that can impact multiple organs. Cardiac involvement influences the prognosis of patients with FD, being one of the main causes of mortality. Cardiac imaging has proven essential in all aspects of Fabry cardiomyopathy evaluation, such as diagnosis (including detection of early organ changes), disease progression, and guideline for starting enzyme therapy. Imaging techniques used in cardiac evaluation of FD range from 2D and deformation studies in echocardiography to cardiac magnetic resonance (CMR), cardiac scintigraphy and positron emission tomography. The present review summarizes the imaging 'red flags' demonstrated to be able to differentiate early cardiac FD from normal controls and Fabry cardiomyopathy from other causes of hypertrophic cardiomyopathy. Also, it discusses the current evidence for the role of CMR in myocardial tissue characterization, as well as other imaging methods that have shown promise in FD. Current knowledge of the evaluation of the presence and extent of cardiac involvement at baseline and during follow-up of enzyme therapy efficiency are further presented. Multiple studies demonstrated that imaging parameters can be reliably used in establishing diagnosis and monitoring therapy in FD. Given the rarity of this disorder, we conclude that awareness should be raised about these imaging 'red flags' and likely patients sent for evaluation in expert centres.

Romanian Registry of Hypertrophic Cardiomyopathy - overview of general characteristics and therapeutic choices at a national level.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a disease with increased left ventricular (LV) wall thickness not solely explained by abnormal loading conditions, with great heterogeneity regarding clinical expression and prognosis. The aim of the present study was to collect data on HCM patients from different centres across the country, in order to assess the general characteristics and therapeutic choices in this population. METHODS: Between December 2014 and April 2017, 210 patients from 11 Romanian Cardiology centres were enrolled in the National Registry of HCM. All patients had to fulfil the diagnosis criteria for HCM according to the European Society of Cardiology guidelines. Clinical, electrocardiographic, imaging and therapeutic characteristics were included in a predesigned online file. RESULTS: Median age at enrolment was 55 ± 15 years with male predominance (60%). 43.6% of the patients had obstructive HCM, 50% non-obstructive HCM, while 6.4% had an apical pattern. Maximal wall thickness was 20.3 ± 4.8 mm (limits 15-37 mm) while LV ejection fraction was 60 ± 8%. Heart failure symptoms dominated the clinical picture, mainly NYHA functional class II (51.4%). Most frequent arrhythmias were atrial fibrillation (28.1%) and non-sustained ventricular tachycardia (19.9%). Mean sudden cardiac death risk score (SCD-RS) was 3.0 ± 2.3%, with 10.4% of the patients with high risk of SCD. However, only 5.7% received an ICD. Patients were mainly treated with beta-blockers (72.9%), diuretics (28.1%) and oral anticoagulants (28.6%). Invasive treatment of LVOT obstruction was performed in a small number of patients: 22 received myomectomy and 13 septal ablation. Cardiac magnetic resonance was reported in only 14 patients (6.6%). CONCLUSIONS: The Romanian registry of HCM illustrates patient characteristics at a national level as well as the gaps in management which need improvement - accessibility to high-end diagnostic tests and invasive methods of treatment.

New Fabry disease mutation confirms cardiomyopathy aetiology: a case report.

BACKGROUND: Aetiologic diagnosis should be a priority in cardiomyopathy patients, as some of them may benefit from efficient specific treatment. To achieve this, the best approach is to look for clinical and paraclinical 'red flags'. CASE SUMMARY: A 55-year-old woman was referred to our centre with the diagnoses of hypertrophic cardiomyopathy (HCM), high blood pressure and dyslipidaemia. The only symptom she declared was long-term acroparesthaesia with an otherwise normal clinical exam. Lab work-up showed slightly above normal values of troponin and brain natriuretic peptide (BNP), and chronic kidney disease Stage IIIA. Both the electrocardiogram (ECG) and the echocardiography showed signs of biventricular HCM, with short PR interval on the ECG and longitudinal systolic dysfunction on the echo. Family history revealed that her son and brother had been diagnosed with Fabry disease (FD). She was then tested for FD and the results confirmed the diagnosis. Alpha-galactosidase (AGAL) levels were low and she had a severe mutation on the GLA gene (gross deletion of 3' region of the GLA gene including coding parts of exon 7), not described before. The patient was started on specific enzyme therapy. DISCUSSION: Fabry disease is a rare X-linked disease caused by mutations on the GLA gene, which leads to low levels of AGAL and accumulation of globotriaosylceramide in the lysosomes of most tissues. Even though FD is X-linked, current medical knowledge states that most females are not mere carriers, but often present with a milder or later-onset phenotype.

Discovery of a new mutation in the desmin gene in a young patient with cardiomyopathy and muscular weakness.

A 25-year-old woman with a five years history of syncope, mild left ventricular hypertrophy and moderately enlarged atria, was diagnosed with third degree atrioventricular heart block alternating with atrioventricular heart block 2:1, and received a dual chamber pacemaker. After three years of evolution, she developed atrial fibrillation, marked biatrial enlargement, severely depressed longitudinal myocardial velocities, associated with mild girdle weakness and slight increase in creatine kinase level. The diagnosis of restrictive cardiomyopathy with mild skeletal myopathy imposed the screening for a common etiology. Skeletal muscle biopsy revealed the morphological picture of myofibrillar myopathy with sarcoplasmic aggregates, immunoreactive for desmin and other ectopic proteins on immunohistochemistry, appearing as granulofilamentous material at ultrastructural level. Western blot analysis confirmed the desmin overexpression. Genetic testing identified a heterozygous missense variant DES rs869025381, c.1297C>A, p.(Pro433Thr), not previously reported. This is not only the first confirmed Romanian patient with myofibrillar myopathy with clinical features of severe restrictive cardiomyopathy associated with mild skeletal myopathy, but also a case which adds up to the known mutational spectrum in desminopathy.

Predictive factors for obtaining a correct therapeutic range using antivitamin K anticoagulants: a tertiary center experience of patient adherence to anticoagulant therapy.

BACKGROUND: Patient adherence is an essential factor in obtaining efficient oral anticoagulation using vitamin K antagonists (VKAs), a situation with a narrow therapeutic window. Therefore, patient education and awareness are crucial for good management. Auditing the current situation would help to identify the magnitude of the problem and to build tailored education programs for these patients. METHODS: This study included 68 hospitalized chronically anticoagulated patients (mean age 62.6±13.1 years; males, 46%) who responded to a 26-item questionnaire to assess their knowledge on VKA therapy management. Laboratory and clinical data were used to determine the international normalized ratio (INR) at admission, as well as to calculate CHA2DS2-VASC and HAS-BLED scores for patients with atrial fibrillation. RESULTS: The majority of patients (62%) were receiving VKA for atrial fibrillation, the others for a mechanical prosthesis and previous thromboembolic disease or stroke. In the atrial fibrillation group, the mean CHA2DS2-VASC score was 3.1±1.5, while the average HAS-BLED score was 1.8±1.2. More than half of the patients (53%) had an INR outside of the therapeutic range at admission, with the majority (43%) having a low INR. A correct INR value was predicted by education level (higher education) and the diagnostic indication (patients with mechanical prosthesis being best managed). Patients presenting with a therapeutic INR had a trend toward longer treatment duration than those outside the therapeutic range (62±72 months versus 36±35 months, respectively, P=0.06). There was no correlation between INR at admission and the patient's living conditions, INR monitoring frequency, and bleeding history. CONCLUSION: In a tertiary cardiology center, more than half of patients receiving VKAs are admitted with an INR falling outside the therapeutic range, irrespective of the bleeding or embolic risk. Patients with a mechanical prosthesis and complex antithrombotic regimens appear to be the most careful with INR monitoring, especially if they have a higher level of education. Identifying patient groups with the lowest time interval spent in the therapeutic range could help attending physicians educate patients focusing on specific awareness issues.