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. 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). 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.

Aims: The clinical outcomes for patients with worsening chronic heart failure (WCHF) remain exceedingly poor despite contemporary evidence-based therapies, and effective therapies are urgently needed. Accumulating evidence supports augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential therapeutic strategy for HF with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively). Direct soluble guanylate cyclase (sGC) stimulators target reduced cGMP generation due to insufficient sGC stimulation and represent a promising method for cGMP enhancement. Methods: The phase II SOluble guanylate Cyclase stimulatoR in heArT failurE Study (SOCRATES) programme consists of two randomized, parallel-group, placebo-controlled, double-blind, multicentre studies, SOCRATES-REDUCED (in patients with LVEF <45%) and SOCRATES-PRESERVED (in those with LVEF ≥45%), that will explore the pharmacodynamic effects, safety and tolerability, and pharmacokinetics of four dose regimens of the once-daily oral sGC stimulator vericiguat (BAY 1021189) over 12 weeks compared with placebo. These studies will enrol patients stabilized during hospitalization for HF at the time of discharge or within 4 weeks thereafter. The primary endpoint in SOCRATES-REDUCED is change in NT-proBNP at 12 weeks. The primary endpoints in SOCRATES-PRESERVED are change in NT-proBNP and left atrial volume at 12 weeks. Perspectives: SOCRATES will be the first programme to enrol specifically both inpatients and outpatients with WCHF and patients with reduced or preserved ejection fraction. Results will inform the benefits of pursuing subsequent event-driven clinical outcome trials with sGC stimulators in this patient population. Trial registration: NCT01951625 (SOCRATES-REDUCED) and NCT01951638 (SOCRATES-PRESERVED)

The study aimed to evaluate the effects of a 3‐week n‐3 polyunsaturated fatty acids (n‐3 PUFA) supplementation on serum nitric oxide (NO), asymmetric dimethyloarginine (ADMA), ultrasound indices of endothelial function and maximal oxygen uptake () of elite cyclists. The effects of dietary supplementation (n‐3 PUFA at a dose of 1.3 g twice daily for 3 weeks) and placebo administration on flow‐mediated dilatation (FMD), pulse wave velocity, serum markers (NO, ADMA), lipid profile, and were analysed in 13 cyclists both before and after dietary protocols. Significant differences between pre‐ and post‐intervention baseline NO levels were observed after n‐3 PUFA dietary protocol (13.9 ± 4.2 vs. 23.5 ± 3.6 µmol·l⁻¹; P < 0.001). Higher post‐intervention baseline NO level was observed after n‐3 PUFA diet compared with placebo (23.5 ± 3.6 vs. 15.3 ± 3.0 µmol·l ⁻¹; P < 0.01, respectively). The n‐3 PUFA increased baseline NO concentration (ΔNO) by 6.7 ± 3.8 µmol·l⁻¹ and placebo by 1.6 ± 4.4 µmol·l⁻¹. The positive correlation was observed between baseline post‐intervention NO concentration and maximal oxygen uptake (r = 0.72; P < 0.01) and also between ΔNO and (r = 0.54; P < 0.05) in response to omega‐3 fatty acids supplementation. There was an association between a 5.25% higher FMD (P < 0.05) and higher (P < 0.001) after n‐3 PUFA diet compared with lower values of placebo (r = 0.68; P < 0.05). These findings suggest that an increase in NO release in response to n‐3 PUFA supplementation may play a central role in cardiovascular adaptive mechanisms and enhanced exercise performance in cyclists.

Dynamic instability of coronary atherosclerotic plaque results in the development of both unstable angina and myocardial infarction. The aim of the study was to investigate the dynamics of serum concentrations of tumour necrosis factor (TNF)alpha, interleukin (IL)-10, and IL-2 in patients with myocardial infarction (MI) and unstable angina (UA) as compared to stable angina (SA) patients and healthy volunteers. A total of 189 patients with coronary artery disease (CAD) were studied: 100 patients with SA (class II/III according to CCS), 57 patients with UA (Braunwald class IIIB; determinations at 6, 24, and 48 h after chest pain), and 32 patients with MI (determinations at admission, on the 7th and 30th days after MI). Twenty healthy volunteers acted as controls. Serum TNFalpha levels were elevated in all CAD groups (SA: 17.3+/-4; UA: 18.7+/-4; MI: 22.0+/-3 pg/ml; p<0.001) in comparison to the controls (8.3+/-1.4 pg/ml). However, the highest values were characteristic of MI patients, especially values obtained at admission (p<0.01 versus SA and UA). Mean serum concentrations of IL-2 were significantly higher in patients with MI and UA (89.6+/-40; 87.0+/-24 pg/ml, respectively; p<0.01) when compared to SA and the control group (58.3+/-49; and 51.5+/-39, respectively). Serum IL-10 levels were also higher in MI and UA patients. Levels of IL-2 and IL-10 measured following chest pain in unstable patients, as well as their consecutive determinations in MI patients did not show any change dynamics, that is, they were persistently elevated. When compared to stable CAD and healthy subjects, acute coronary syndromes are associated with long-term increase of serum concentrations of pro- and anti-inflammatory cytokines. It seems likely that sudden CAD progression leading to acute coronary syndromes is triggered/accompanied by prolonged immune activation.

Current knowledge of pulmonary arterial hypertension (PAH) epidemiology is based mainly on data from Western populations, and therefore we aimed to characterize a large group of Caucasian PAH adults of Central-Eastern European origin. We analyzed data of incident and prevalent PAH adults enrolled in a prospective national registry involving all Polish PAH centers. The estimated prevalence and annual incidence of PAH were 30.8/mln adults and 5.2/mln adults, respectively and they were the highest in females ≥65 years old. The most frequent type of PAH was idiopathic (n = 444; 46%) followed by PAH associated with congenital heart diseases (CHD-PAH, n = 356; 36.7%), and PAH associated with connective tissue disease (CTD-PAH, n = 132; 13.6%). At enrollment, most incident cases (71.9%) were at intermediate mortality risk and the prevalent cases had most of their risk factors in the intermediate or high risk range. The use of triple combination therapy was rare (4.7%). A high prevalence of PAH among older population confirms the changing demographics of PAH found in the Western countries. In contrast, we found: a female predominance across all age groups, a high proportion of patients with CHD-PAH as compared to patients with CTD-PAH and a low use of triple combination therapy.

Background: The purpose of this review was to summarize the up-to-date knowledge on clinical presentation and management of neurocardiogenic injury and to deliver the evidence of common pathophysiology of this broad spectrum of disorders. Methods: Medline and EmBase databases were searched to obtain original research articles and review papers using the following key words: neurocardiogenic injury, stress cardiomyopathy,tako-tsubo, subarachnoid hemorrhage, ECG abnormalities, catecholamine toxicity, neuropulmonary edema. Results: Various forms of cerebral pathology, most importantly subarachnoid hemorrhage (SAH), are accompanied by transient cardiac dysfunction with ST-segment elevation and QT interval prolongation and T wave inversion with simultaneous release of cardiac troponin. In the past 20 years a great deal of data emerged concerning stress cardiomyopathy (‘tako-tsubo’) presenting as a rare transient apical ballooning syndrome following stressful life events with symptoms and signs resembling acute myocardial infarction (AMI), yet without significant coronary artery stenosis. Both forms of cardiac dysfunction are mediated by catecholamine toxicity, triggered by physical and psychological distress, leading to a specific type of neurogenic myocardial stunning reflected by histopathological image of contraction band necrosis. Conclusions: Neurocardiogenic injury should be carefully differentiated from AMI. Cardiac dysfunction in SAH heralds increased mortality. The criteria for the diagnosis of stress cardiomyopathy should be revised to comprise the diversity of its clinical symptomatology and to include cardiac dysfunction accompanying cerebral pathology. Background: The purpose of this review was to summarize the up-to-date knowledge on clinical presentation and management of neurocardiogenic injury and to deliver the evidence of common pathophysiology of this broad spectrum of disorders. Methods: Medline and EmBase databases were searched to obtain original research articles and review papers using the following key words: neurocardiogenic injury, stress cardiomyopathy,tako-tsubo, subarachnoid hemorrhage, ECG abnormalities, catecholamine toxicity, neuropulmonary edema. Results: Various forms of cerebral pathology, most importantly subarachnoid hemorrhage (SAH), are accompanied by transient cardiac dysfunction with ST-segment elevation and QT interval prolongation and T wave inversion with simultaneous release of cardiac troponin. In the past 20 years a great deal of data emerged concerning stress cardiomyopathy (‘tako-tsubo’) presenting as a rare transient apical ballooning syndrome following stressful life events with symptoms and signs resembling acute myocardial infarction (AMI), yet without significant coronary artery stenosis. Both forms of cardiac dysfunction are mediated by catecholamine toxicity, triggered by physical and psychological distress, leading to a specific type of neurogenic myocardial stunning reflected by histopathological image of contraction band necrosis. Conclusions: Neurocardiogenic injury should be carefully differentiated from AMI. Cardiac dysfunction in SAH heralds increased mortality. The criteria for the diagnosis of stress cardiomyopathy should be revised to comprise the diversity of its clinical symptomatology and to include cardiac dysfunction accompanying cerebral pathology.