ERRATUM: Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Transthyretin amyloid cardiomyopathy in patients with unexplained increased left ventricular wall thickness.

Amyloid cardiomyopathy (CA) was previously considered a rare disease; however, rapid advancements in imaging modalities have led to an increased frequency of its diagnosis. The aim of this prospective study was to assess the prevalence and clinical phenotype of transthyretin amyloidosis (ATTR) cardiomyopathy in patients exhibiting unexplained increased left ventricular (LV) wall thickness. From 2020 to 2022, we enrolled 100 consecutive adults with unexplained increased LV wall thickness in the study. The analysis included clinical data, electrocardiography, transthoracic echocardiography, single-photon emission computed tomography/computed tomography with 3,3-disphono-1,2-propanodicarboxylic acid, genetic testing. Overall, 18% of patients were diagnosed with CA, comprising 5% with light-chain amyloidosis, and 12% with ATTR. To evaluate associations with the ATTR diagnosis, a LOGIT model and multivariate analysis were applied. Notably, age, polyneuropathy, gastropathy, carpal tunnel syndrome, lumbar spine stenosis, low voltage, ventricular arrhythmia, LV mass, LV ejection fraction, global longitudinal strain (GLS), E/A, E/E', right ventricle (RV) thickness, right atrium area, RV VTI, TAPSE, apical sparing, ground glass appearance of myocardium, thickening of interatrial septum, thickening of valves, and the "5-5-5" sign were found to be significantly associated with ATTR (p < 0.05). The best predictive model for ATTR diagnoses exhibited an area under the curve of 0.99, including LV mass, GLS and RV thickness. This study, conducted at a cardiology referral center, revealed that a very considerable proportion of patients with unexplained increased LV wall thickness may suffer from underlying CA. Moreover, the presence of ATTR should be considered in patients with increased LV mass accompanied by reduced GLS and RV thickening.

Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Diagnosis and treatment of transthyretin amyloidosis cardiomyopathy: A position statement of the Polish Cardiac Society.

Considering the rare incidence of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in Poland, patients encounter difficulties at the stages of diagnosis and treatment. For successful diagnosis, it is vital to raise the suspicion of ATTR-CM, that is, to identify typical clinical scenarios such as heart failure with preserved ejection fraction or the red flags of amyloidosis. In most cases, it is possible to establish the diagnosis on the basis of noninvasive tests. This article presents the recommended diagnostic algorithms including laboratory workup, imaging tests (in particular, isotope scanning), and genetic tests. Since ATTR-CM should be differentiated from light chain amyloidosis, we also discuss aspects related to hematological manifestations and invasive diagnosis. We describe neurological signs and symptoms in patients with amyloidosis and present therapeutic options, including the causative treatment of ATTR-CM with the only currently approved drug, tafamidis. We also discuss drugs that are being assessed in ongoing clinical trials. We outline differences in the symptomatic treatment of heart failure in ATTR-CM and recommendations for nonpharmacological treatment and monitoring of the disease. Finally, we underline the need for providing access to the causative treatment with tafamidis as part of a drug program, as in other rare diseases, so that patients with ATTR-CM can be treated according to the European Society of Cardiology guidelines on heart failure and cardiomyopathy.

Cardiac Disease: Diagnosis, Treatment, and Outcomes.

Although the epidemiology-as well as the morbidity and mortality-of cardiovascular diseases (CVD) is a subject of constant change, nevertheless, CVDs are still the primary (or secondary at best after neoplasms) cause of deaths in developed countries [...].

Twelve-month kinetics of circulating fibrosis-linked microRNAs (miR-21, miR-29, miR-30, and miR-133a) and the relationship with extracellular matrix fibrosis in dilated cardiomyopathy.

Introduction: A single measurement of any biomarker may not reflect its full biological meaning. The kinetics of fibrosis-linked microRNAs and their relationship with extracellular matrix (ECM) fibrosis in dilated cardiomyopathy (DCM) have not been explored. Material and methods: We evaluated 70 consecutive DCM patients (48 ±12.1 years, left ventricular ejection fraction 24.4 ±7.4%). All patients underwent right ventricular endomyocardial biopsy in order to quantify ECM fibrosis and measure collagen volume fraction (CVF). Circulating microRNAs (miR-21-5p, miR-29b, miR-30c-5p, and miR-133a-3p) were measured with quantitative polymerase chain reaction (PCR) at baseline and at 3 and 12 months. Results: Based on the biopsy results, two groups of patients were identified: with (n = 24, 34.3%) and without (n = 46, 65.7%) ECM fibrosis. Except for a single measurement of miR-29b at 3 months (DCM with fibrosis: 6.03 ±0.72 vs. DCM without fibrosis: 6.4 ±0.75 ΔCq; p < 0.05), baseline, 3- and 12-month kinetics of microRNAs did not differ between the two groups. Moreover, 12-month microRNA kinetics did not differ in patients with new-onset DCM (duration < 6 months; n = 35) and chronic DCM (> 6 months; n = 35). Only miR-29 at 3 months correlated with CVF (r = -0.31; p < 0.05), whereas other microRNAs did not correlate with CVF either at 3 or at 12 months. Conclusions: Regardless of ECM fibrosis status or duration of the disease, 12-month patterns of circulating microRNAs are similar in DCM. Correlations between microRNAs, measured at 3 and 12 months, are lower than expected. In this study, regardless of the time point, circulating microRNAs were not able to differentiate between DCM patients with versus without fibrosis.

Spectrum of transthyretin gene mutations and clinical characteristics of Polish patients with cardiac transthyretin amyloidosis.

BACKGROUND: Transthyretin amyloidosis (ATTR) is a rare, life-threatening systemic disorder. We present first findings on the cardiac hereditary ATTR in Poland. METHODS: Sixty-eight consecutive patients with suspected or known cardiac amyloidosis were evaluated, including blood tests, standard 12-lead electrocardiography (ECG) and transthoracic echocardiography. ATTR was confirmed histologically or non-invasively using 99mTc-DPD scintigraphy. Transthyretin (TTR) gene sequencing was performed. RESULTS: In 2017-2019, 10 unrelated male patients were diagnosed with hereditary ATTR. All patients had very uncommon TTR gene mutations: 7 patients had p.Phe53Leu mutation, 2 patients had p.Glu109Lys mutation and 1 patient had p.Ala101Val mutation. The age of onset ranged from 49 to 67 years (mean [SD] age, 58.7 [6.4] years). On ECG, most patients (70%) had pseudoinfarct pattern and/or low QRS voltage. The maximal wall thickness (MWT) on echocardiography varied considerably among the patients from moderate (16 mm) to massively increased (30 mm). Most patients (90%) had decreased left ventricular ejection fraction (mean [SD], 43 [11] %). On follow-up, we observed progressive heart failure in almost all cases. The first patient with p.Phe53Leu mutation died of heart failure, the second died suddenly, the third successfully underwent combined heart and liver transplant with 15 months survival from the surgery. The patient with p.Ala101Val mutation died of stroke. CONCLUSIONS: According to available data, this is the first time that the types of TTR mutations and the clinical characteristics of Polish patients with cardiac hereditary ATTR have been described. Previous literature data about Polish background in families with p.Phe53Leu mutation and the present results, suggest that this TTR mutation might be endemic in the Polish population.

Trans-endocardial delivery of progenitor cells to compromised myocardium using the "needle technique"and risk of myocardial injury.

Introduction: Recent analysis from CHART-1 study indicated that the therapeutic effects of trans-endocardial cardiopoetic cell transplantation in chronic ischemic heart failure (iCHF) may be lost with an increasing number of injections perfomed to deliver therapeutic cells. Aim: To evaluate global and regional contractility and diastolic function of the left ventricle of patients with iCHF who received trans-endomyocardial cardiopoietic stem cells (CSCs) delivery or sham procedures. Material and methods: The study included patients (mean age: 60.8 ±7.1 years) with iCHF (left ventricular ejection fraction (LVEF) < 35%) and a history of hospitalization for worsening heart failure within 12 months despite optimal medical therapy. The patients underwent transmyocardial CSCs transplantation using perforated needle technique or a sham procedure. The wall motion score index (WMSI), LVEF, transmitral E-velocity, E-wave deceleration time, E/A-ratio, and E/e'-mean value were measured with two-dimensional echocardiography on days 1 and 30. Results: A total of 170 segments were analyzed, including 48 targeted segments where 92 injections of 0.5 ml of CSCs were performed. In the transendocardial injections cohort, a decrease in regional contractility was observed in 30.6% (26/85) and 18.9% (16/85) of the segments on days 1 and 30, respectively. This was accompanied by an increase in WMSI by 0.32 ±0.06 and 0.19 ±0.18 (day 1, p = 0.02, day 30, p = 0.03) and a reduction in LVEF (-3.15 ±1.23%, p = 0.065). Conclusions: Transendocardial injections performed to deliver therapeutic cells were associated with myocardial injury. This adverse effect remained, albeit at a lesser degree, at 30-days. Mechanical injury with trans-endocardial delivery of progenitor cells using the "needle technique" may counterbalance, at least in part, any cell-related benefit(s).

Mitral regurgitation severity dynamic during acute decompensated heart failure treatment.

Acute decompensated heart failure (ADHF) treatment leads to significant hemodynamic changes. The aim of our study was to quantitatively analyze the dynamics of mitral regurgitation (MR) severity (evaluated by transthoracic echocardiography) which occur during the treatment of ADHF and to correlate these changes with the clinical condition of patients as well as heart failure biochemical markers. The study included 27 consecutive adult patients (40.7% females, mean age 71.19 ± 11.2 years) who required hospitalization due to signs of acute HF. Echocardiographic assessment was performed upon admission and discharge together with clinical and laboratory evaluation. Significant reduction in dyspnea intensity [0-100 scale] (81.48 ± 9.07 vs. 45.00 ± 11.04 pts, p < 0.001), body weight (84.98 ± 18.52 vs. 79.77 ± 17.49 kg, p < 0.001), and NT-proBNP level (7520.56 ± 5288.62 vs. 4949.88 ± 3687.86 pg/ml, p = 0.001) was found. The severity of MR parameters decreased significantly (MR volume 44.92 ± 22.83 vs. 30.88 ± 18.77 ml, p < 0.001; EROA 0.37 ± 0.17 vs. 0.25 ± 0.16 cm2, p < 0.001; VC 6.21 ± 1.48 vs. 5.26 ± 1.61 mm, p < 0.001). Left atrial area (35.86 ± 9.11 vs. 32.47 ± 9.37, p < 0.001) and mitral annular diameter (42.33 ± 6.63 vs. 39.72 ± 5.05. p < 0.001) also underwent statistically significant reductions. An increase in LVEF was observed (34.73 ± 13.88 vs. 40.24 ± 13.19%, p < 0.001). In 40.7% of patients, a change in MR severity class (transition from a higher class to a lower one) was observed: 6/8 (75%) patients transitioned from severe to moderate and 6/18 (33.3%) patients transitioned from moderate to mild class. Treatment of ADHF leads to a significant reduction in MR severity, together with significant reductions in left atrial and mitral annular dimensions. Quantitative measurement of MR dynamics offer valuable assistance for ADHF management.

Relationships between circulating galectin-3, extracellular matrix fibrosis and outcomes in dilated cardiomyopathy.

BACKGROUND: Galectin-3 is an emerging biomarker in cardiovascular disease. Myocardial galectin-3 is involved in the pathology of cardiac fibrosis; however, the role of circulating galectin-3 is not yet established. OBJECTIVES: To assess the relationships between circulating galectin-3, fibrosis and outcomes in dilated cardiomyopathy (DCM). MATERIAL AND METHODS: We included 70 patients (age: 48 ±12.1 years, ejection fraction (EF) 24.4 ±7.4%) with new-onset DCM (n = 35, ≤6 months). Galectin-3 and procollagen type I and III (PICP, PINP, PIIICP, and PIIINP), transforming growth factor ß (TGF-ß), connective tissue growth factor (CTGF), osteopontin (OPN), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitor (TIMP-1) were determined in serum at baseline and after 3 and 12 months. Patients underwent endomyocardial biopsy. The endpoint was a combination of death and urgent hospitalization at 12 months. RESULTS: Galectin-3 did not correlate with biopsy-determined fibrosis. Baseline galectin-3 correlated with OPN,, TIMP-1, PIIICP, and MMP-2. In new-onset DCM, galectin-3 levels at baseline were higher than at 3 and 12 months, whereas in chronic DCM there was no difference. Galectin-3 was a predictor of the endpoint (hazard ratio (HR) = 1.115; 95% confidence interval (95% CI) = 1.009-1.231; p < 0.05). The best cut-off value was 14.54 ng/mL (area under the curve (AUC) = 0.67). Patients with galectin-3 ≥14.54 ng/mL had an increased risk of events (HR = 2.569; 95% CI = 1.098-6.009; p < 0.05). CONCLUSIONS: Circulating galectin-3 is unrelated to fibrosis. Serial measurements of galectin-3 correlated with markers of fibrosis, including markers of collagen synthesis and OPN. Circulating galectin-3 was independently associated with cardiovascular (CV) outcomes in DCM.

Expert opinion of the Heart Failure Working Group of the Polish Cardiac Society on the use of dapagliflozin in the treatment of heart failure with reduced ejection fraction.

Heart failure (HF) is a global health problem inherent in an aging population with coexisting cardiovascular diseases. Based on data from the Polish National Health Fund (Polish, Narodowy Fundusz Zdrowia), approximately 1.2 million people in Poland currently suffer from HF, and 140 000 of them die annually. Recently, Poland was ranked fifth among the European Union countries regarding the number of patients with diagnosed HF and first in terms of the number of HF hospitalizations (547 per 100 000 population) among 34 countries associated in the Organization for Economic Cooperation and Development. In recent years, a significant progress has been made in the diagnosis and treatment of HF with reduced left ventricular ejection fraction (HFrEF), which has resulted in a reduction in cardiovascular and total mortality. Despite these advantages, 5-year survival in the course of HF is still worse than that observed in some types of cancer, both in the populations of men and women. Hence, the search for drugs improving the prognosis in this group of patients is still ongoing. Sodium-glucose cotransporter 2 inhibitors represent a new group of drugs that will undoubtedly be a milestone in the treatment of patients with HFrEF. This expert opinion covers the history of dapagliflozin, which, from a drug dedicated to the treatment of type 2 diabetes, has become one of the most effective drugs improving prognosis and quality of life as well as reducing the number of hospitalizations in patients with HF. This document presents the opinion from the experts of the Heart Failure Working Group of the Polish Cardiac Society on the most relevant studies on dapagliflozin and indications for its use.

Relations between circulating and myocardial fibrosis-linked microRNAs with left ventricular reverse remodeling in dilated cardiomyopathy.

BACKGROUND: Left ventricular reverse remodeling (LVRR) determines clinical status and outcomes in dilated cardiomyopathy (DCM). The extent of myocardial fibrosis is connected to the systolic function of the heart. The recent discovery of the contribution of microRNAs (miRs) to the regulation of cardiac remodeling, LVRR and fibrosis warrants exploration. OBJECTIVES: The aim of the study was to examine the predictive value of circulating and myocardial miR expression for LVRR in DCM. MATERIAL AND METHODS: Seventy consecutive DCM patients (age 48 ±12.1 years, 90% male, ejection fraction (EF) 24.4% ±7.4%) were included in the study. At baseline, all patients underwent clinical assessment, echocardiography, venous blood sampling, and right ventricular endomyocardial biopsy. Circulating and myocardial miRs (miR-21, -26, -29, -30, -133a, and -423) were measured with quantitative real-time polymerase chain reaction (qRT-PCR). LVRR was defined as an increase in EF ≥ 10%, accompanied by a decrease in left ventricle end-diastolic diameter (LVEDd) ≥10% or LVEDd ≤ 33 mm/m2 between baseline and 3-month follow-up. RESULTS: At the 3-month follow-up, 4 patients had died and 3 patients had incomplete data. The remaining patients were divided according to the presence of LVRR into LVRR-present (n = 32, 51%) and LVRR-absent (n = 31, 49%) groups. Out of all the circulating and tissue miRs under study, only myocardial expression of miR-133a significantly differed between the LVRR-present and LVRR-absent group (1.22 (0.47-1.90) vs 0.61 (0.25-0.99) ΔCq, respectively, p < 0.01). miR-133a was found to be a significant LVRR predictor in unadjusted (odds ratio (OR) = 2.81 (1.23-6.40), p < 0.05) and adjusted for duration of disease, left ventricle end-diastolic (LVED) volume (LVEDvol), hs-troponin-T, and NT-proBNP (OR = 5.20 (1.13-24.050, p < 0.05) models. CONCLUSIONS: From all of the circulating and tissue miRs, only myocardial miR-133a showed increased expression in LVRR-present patients and was found an independent LVRR predictor. This indicates a link between miR-133 and cardiac remodeling in DCM.

Identification of a variant hotspot in MYBPC3 and of a novel CSRP3 autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a heart disorder caused by autosomal dominant alterations affecting both sarcomeric genes and other nonsarcomeric loci in a minority of cases. However, in some patients, the occurrence of the causal pathogenic variant or variants in homozygosity, compound heterozygosity, or double heterozygosity has also been described. Most of the HCM pathogenic variants are missense and unique, but truncating mutations of the MYBPC3 gene have been reported as founder pathogenic variants in populations from Finland, France, Japan, Iceland, Italy, and the Netherlands. OBJECTIVES: This study aimed to assess the genetic background of HCM in a cohort of Polish patients. PATIENTS AND METHODS: Twenty­nine Polish patients were analyzed by a next generation sequencing panel including 404 cardiovascular genes. RESULTS: Pathogenic variants were found in 41% of the patients, with ultra­ rare MYBPC3 c.2541C>G (p.Tyr847Ter) mutation standing for a variant hotspot and correlating with a lower age at HCM diagnosis. Among the nonsarcomeric genes, the CSRP3 mutation was found in a single case carrying the novel c.364C>T (p.Arg122Ter) variant in homozygosity. With this finding, the total number of known HCM cases with human CSRP3 knockout cases has reached 3. CONCLUSIONS: This report expands the mutational spectrum and the inheritance pattern of HCM.

Cardiac implantable electronic devices with a defibrillator component and all-cause mortality in left ventricular assist device carriers: results from the PCHF-VAD registry.

AIMS: To compare characteristics of left ventricular assist device (LVAD) recipients receiving a cardiac implantable electronic device (CIED) with a defibrillator component (implantable cardioverter-defibrillator and cardiac resynchronization therapy with defibrillation, CIED-D) vs. those without one, and to assess whether carrying such a device contiguously with an LVAD is associated with outcomes. METHODS AND RESULTS: Overall, 448 patients were analysed (mean age 52 ± 13 years, 82% male) in the multicentre European PCHF-VAD registry. To account for all active CIED-Ds during ongoing LVAD treatment, outcome analyses were performed by a time-varying analysis with active CIED-D status post-LVAD as the time-varying covariate. At the time of LVAD implantation, 235 patients (52%) had an active CIED-D. Median time on LVAD support was 1.1 years (interquartile range 0.5-2.0 years). A reduction of 36% in the risk of all-cause mortality was observed in patients with an active CIED-D [hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.46-0.91; P = 0.012), increasing to 41% after adjustment for baseline covariates (HR 0.59, 95% CI 0.40-0.87; P = 0.008) and 39% after propensity score adjustment (HR 0.61, 95% CI 0.39-0.94; P = 0.027). Other than CIED-D, age, LVAD implant as redo surgery, number of ventricular arrhythmia episodes and use of vasopressors pre-LVAD were remaining significant risk factors of all-cause mortality. Incident ventricular arrhythmias post-LVAD portended a 2.4-fold and 2.6-fold increased risk of all-cause and cardiovascular death, respectively; carrying an active CIED-D remained associated with a 47% and 43% reduction in these events, respectively. CONCLUSIONS: In an analysis accounting for all active CIED-Ds, including those implanted during LVAD support, carrying such a device was associated with significantly better survival during LVAD support.

Clinical classification of rare cardiac arrhythmogenic and conduction disorders, and rare arrhythmias.

INTRODUCTION Rare cardiovascular diseases and disorders (RCDDs) constitute an important clinical problem, and their proper classification is crucial for expanding knowledge in the field of RCDDs. OBJECTIVES The aim of this paper is to provide an updated classification of rare arrhythmogenic and conduction disorders, and rare arrhythmias (RACDRAs). METHODS We performed a search for RACDRAs using the Orphanet inventory of rare diseases, which includes diseases with a prevalence of no more than 5 per 10 000 in the general population. We supplemented this with a search of PubMed and Scopus databases according to a wider definition proposed by the European Parliament and the Council of the European Union. RESULTS RACDRAs are categorized into 2 groups, primary electrical disorders of the heart and arrhythmias in specific clinical settings. The first group is further divided into subgroups of major clinical presentation: disorders predisposing to supraventricular tachyarrhythmias, ventricular tachyarrhythmias, bradyarrhythmias, and others. The second group includes iatrogenic arrhythmias or heart rhythm disturbances related to medical treatment, arrhythmias associated with metabolic disorders, and others. We provide a classification of RACDRAs and supplement them with respective RCDDs codes. CONCLUSION The clinical classification of RACDRAs may form a basis to facilitate research and progress in clinical practice, both in diagnostic and therapeutic approaches.

The relationship between myocardial fibrosis and myocardial microRNAs in dilated cardiomyopathy: A link between mir-133a and cardiovascular events.

It is unknown whether fibrosis-associated microRNAs: miR-21, miR-26, miR-29, miR-30 and miR-133a are linked to cardiovascular (CV) outcome. The study evaluated the levels of extracellular matrix (ECM) fibrosis and the prevalence of particular microRNAs in patients with dilated cardiomyopathy (DCM) to investigate any correlation with CV events. METHODS: Seventy DCM patients (48 ± 12 years, EF 24.4 ± 7.4%) underwent right ventricular biopsy. The control group was comprised of 7 patients with CAD who underwent CABG and intraoperative biopsy. MicroRNAs were measured in blood and myocardial tissue via qPCR. The end-point was a combination of CV death and urgent HF hospitalization at the end of 12 months. There were differential levels of circulating and myocardial miR-26 and miR-29 as well as myocardial miR-133a when the DCM and CABG groups were compared. Corresponding circulating and myocardial microRNAs did not correlate with one another. There was no correlation between microRNA and ECM fibrosis. By the end of the 12-month period of the study, CV death had occurred in 6 patients, and a further 19 patients required urgent HF hospitalization. None of the circulating microRNAs was a predictor of the combined end-point; however, myocardial miR-133a was an independent predictor in unadjusted models (HR 1.53; 95% CI 1.14-2.05; P < .004) and adjusted models (HR 1.57; 95% CI 1.14-2.17; P < .005). The best cut-off value for the miR-133a level for the prediction of the combined end-point was 0.74 ΔCq, with an AUC of 0.67. The absence of a correlation between the corresponding circulating and myocardial microRNAs calls into question their cellular source. This study sheds new light on the role of microRNAs in ECM fibrosis in DCM, which warrants further exploration.

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.