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Background: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. Results: The median age was 68 years, 23% of participants were women, 51% had ST-segment–elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71–1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69–1.61]). Conclusions: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search ; Unique identifier: 2019-003244-79.

Cil: Zjistit, jestli je možne předpovědět non-adherenci (NA) k lecbě chronickeho srdecniho selhani (CHSS) na zakladě výsledků běžně provaděných vysetřeni. Metody: Byly analyzovany výsledky klinických a laboratornich vysetřeni a data z pacientskeho dotazniku. Soucasti bylo subjektivni hodnoceni adherence (A) pacientem a lekařem. Referencni metodou pro průkaz NA bylo vysetřeni serových hladin leků (SHL). Výsledky: Bylo zařazeno 81 pacientů. Stanovenim SHL byla NA zjistěna u 25 %. Vsichni pacienti uvedli, že leky uživaji spravně, vynechani některe davky v týdnu připustilo 18 % A a 25 % NA (p = 0,53). Lekař předpokladal NA spravně u 40 % NA a chybně u 10 % A. Byl trend k castějsi NA u žen (p = 0,055), meně casta byla u pacientů z vesnice nebo maleho města (p = 0,031). NA měli vyssi systolický (137 ± 13 vs. 124 ± 15 mmHg, p = 0,001) i diastolický (83 ± 11 vs. 75 ± 9 mmHg, p = 0,002) krevni tlak. Byl trend k vyssi tepove frekvenci u NA (83 ± 18 vs. 73 ± 13, p = 0,052), v podskupině lecených betablokatory byl rozdil signifikantni (94 ± 19 vs. 73±12, p < 0,001). Adherentni nesignifikantně lepe hodnotili svůj zdravotni stav (p = 0,052). V ostatnich parametrech nebyl nalezen rozdil. Zavěr: NA můžeme předpokladat u lecených pacientů s přetrvavajicim vyssim TK a u pacientů s vyssi TF při lecbě betablokatory. NA lze potvrdit stanovenim SHL.

Aim. Understanding cardiac electronic device infective endocarditis epidemiology is essential for the management of this serious complication. Only monocentric and limited data have been published regarding patients in the Czech republic so far. The aim of this study was to describe the current profile, microbiology and clinical characteristics of this population. Patients and Methods. National data from the prospective ESC-EORP EURO-ENDO registry were collected. 57 consecutive patients with a diagnosis of cardiac device-related infective endocarditis (CDRIE) from 11 Czech centres were included. Results. Staphylococcus spp. was responsible for 43.9% of isolates, whereas Culture negative endocarditis was documented in 26.3% episodes. The most frequent complications under therapy were acute renal failure (17.5%), septic shock and heart failure (both 10.5%). Extraction of device was performed in 75.4% of all patients, and the 1-year mortality was 22.5%. Conclusions. The high proportion of culture-negative endocarditis is alarming and warrants further investigation. Cardiac device related infective endocarditis is a serious complication with a high 1-year mortality in a highly polymorbid spectrum of patients.

Background: The aim of our study was to evaluate the prevalence of drug non-adherence in stable chronic heart failure (CHF) patients using serum drug levels (SDL) assessment. Methods: CHF patients were prospectively enrolled during scheduled outpatient visit. Except standard procedures an unanticipated blood sampling for the SDL assessment was obtained. Analysis was focused on the prescribed heart failure and antihypertensive medication and was performed by liquid chromatography coupled with mass spectrometry. The patient was labelled as non-adherent if at least one of drugs assessed was not found in the serum. In the first half of patients multiple SDL have been evaluated during the follow-up. Results: Eighty one patients were enrolled. The non-adherence was proven in twenty of them (25%). In the subgroup of thirty eight patients with multiple SDL evaluation the non-adherence raised significantly with increasing number of visits assessed together (21% for single visit, 29% for two of three visits assessed together and 34% for all three visits evaluated together, all p < 0.001). Conclusion: The non-adherence was proven in significant part of stable CHF patients using SDL assessment. This method seems to be reliable and effective and should be a part of clinical assessment in selected patients with CHF.

Infekcni endokarditida (IE) je zavažne onemocněni, jehož incidence v case pravděpodobně mirně narůsta a mortalita zůstava vysoka. Významně se změnily zakladni charakteristiky IE. Pacienti jsou dnes starsi a castěji polymorbidni. Zvysuje se podil IE ziskaných v souvislosti s poskytovanou zdravotni peci. Nejcastějsim etiologickým agens jsou stafylokoky, předevsim Staphylococcus aureus. Hemokultivacni a echokardiograficke vysetřeni jsou zakladnimi kameny diagnostiky IE. Předevsim v přitomnosti intrakardialně uložených cizich materialů (chlopenni protezy, elektrody kardiostimulatorů) se stale castěji uplatňuji i jina vysetřeni (CT, nuklearni metody). Pokud jsou hemokultury negativni, je vhodne doplnit některa serologicka vysetřeni. Přinosne může být vysetřeni pomoci polymerazove řetězove reakce (PCR) z operacně ziskaneho materialu. Zakladem lecby je dlouhodobe podavani antibiotik a až polovina pacientů je v akutni fazi onemocněni operovana. Vzhledem k nedostatku dat založených na důkazech zůstava v lecbě IE mnoho otazek nezodpovězených (kombinace antibiotik, delka lecby, přechod na peroralni antibiotika, domaci parenteralni lecba, nacasovani kardiochirurgickeho výkonu). Pacienti s IE vyžaduji komplexni peci. Je při ni nezbytna mezioborova spoluprace, ktera může zlepsit jejich prognozu.

BackgroundRegular physical activity is recommended for patients with chronic heart failure to improve their functional capacity, and walking is a popular, effective, and safe form of physical activity. Pedometers have shown potential to increase the amount of walking across a range of chronic diseases, but it is unknown whether a pedometer-based intervention improves functional capacity and neurohumoral modulation in heart failure patients.MethodsTwo multicenter randomized controlled trials will be conducted in parallel: one in patients with chronic heart failure with reduced ejection fraction (HFrEF), the other in patients with chronic heart failure with preserved ejection fraction (HFpEF). Each trial will consist of a 6-month intervention with an assessment at baseline, at 3 months, at the end of the intervention, and 6 months after completing the intervention. Each trial will aim to include a total of 200 physically inactive participants with chronic heart failure who will be randomly assigned to intervention or control arms. The 6-month intervention will consist of an individualized pedometer-based walking program with weekly step goals, behavioral face-to-face sessions with a physician, and regular telephone calls with a research nurse. The intervention will be based on effective behavioral principles (goal setting, self-monitoring, personalized feedback). The primary outcome is the change in 6-min walk distance at the end of the 6-month intervention. Secondary outcomes include changes in serum biomarkers levels, pulmonary congestion assessed by ultrasound, average daily step count measured by accelerometry, anthropometric measures, symptoms of depression, health-related quality of life, self-efficacy, and MAGGIC risk score.DiscussionTo our knowledge, these are the first studies to evaluate a pedometer-based walking intervention in patients with chronic heart failure with either reduced or preserved ejection fraction. The studies will contribute to a better understanding of physical activity promotion in heart failure patients to inform future physical activity recommendations and heart failure guidelines.Trial registrationThe trials are registered in ClinicalTrials.gov, identifiers: NCT03041610, registered 29 January 2017 (HFrEF), NCT03041376, registered 1 February 2017 (HFpEF)

Aim: To compare clinical complications and outcomes of infective endocarditis (IE) episodes caused by Staphylococcus aureus (S. aureus) and other most frequent aetiological agents (streptococci, enterococci, coagulase-negative staphylococci, and culture-negative IE). Methods: A total of 117 IE episodes assessed by all internal medicine services of a major teaching institution in the Czech Republic over an eight-year period were identified. Results: We found that S. aureus IE episodes (n = 36) were significantly more associated with systemic embolism (41.7% vs 18.5%, P = 0.01), severe sepsis/septic shock (33.3% vs 3.7%, P < 0.0001), and in-hospital mortality (33% vs 12.3%, P = 0.01). No differences in local, structural, and/or functional complications (cardiac abscess formation, impaired integrity of the valvular apparatus, conduction disturbances, or incidence of heart failure) were observed between studied groups. Long-term survival estimates were significantly improved in patients with IE caused by agents other than S. aureus (13.78 median years vs 5.48 median years, P=0.03). Conclusions: IE episodes caused by S. aureus are associated with both increased short-term and long-term mortality. Of all the studied parameters, only systemic embolism and severe sepsis/septic shock predicted in-hospital mortality.

Liver cirrhosis is associated with severe hemodynamic changes which include hyperdynamic circulation with increased cardiac output, heart rate and reduced systemic vascular resistance. The term cirrhotic cardiomyopathy is defined as the presence of chronic cardiac dysfunction, characterized by blunted contractile responsiveness to stress and altered diastolic relaxation with electrophysiological abnormalities (QT interval prolongation), all occurring in the absence of any other cardiac disease. The key role in diagnosis is played by 2-dimensional echocardiography, electrocardiography and various serum markers (natriuretic peptides). The prognosis of the patients with cirrhotic cardiomyopathy is affected by heart failure, which can develop during invasive procedures (surgery, insertion of a transjugular intrahepatic portosystemic shunting and liver transplantation). No accepted specific treatment of cirrhotic cardiomyopathy exists. The therapy should follow the recommendations for the treatment of liver cirrhosis and heart failure.

Myeloproliferative disorders (MPDs) are defined as clonal stem cell diseases. the cardiovascular system is involved in 4 to 21% of MPD cases, presenting as acute ischemic coronary artery disease, valvular heart involvement, pericardial involvement, aortitis, thrombosis of major vessels, pulmonary embolism, systemic and pulmonary hypertension. Acute coronary syndrome may be the first manifestation of myeloproliferation.

Difficult-to-control arterial hypertension is a common medical problem that may result from severe hypertensive disease or from poor adherence to the recommended medical treatment. The identification of non-adherent patients is challenging, especially when non-adherence is intentional. The current report describes the use of serum levels of prescribed antihypertensive drugs to evaluate the adherence in individuals with difficult-to-control arterial hypertension. Serum drug levels (SDLs) were evaluated by liquid chromatography with mass spectrometry. The chromatographic separation was performed on a reversed-phase column with a gradient flow of the mobile phase. The detection of analyzed substances was accomplished on a linear ion-trap mass spectrometer. The subjects were labeled as non-adherent when the serum level of at least one of the evaluated drugs was below the limit of quantification. The study used data from 84 patients with arterial hypertension who underwent SDL assessment to verify compliance with the recommended treatment. Patients who presented with uncontrolled blood pressure despite the recommended combination of at least three antihypertensives were enrolled in the analysis. Based on the evaluation of the SDLs, all of the evaluated drugs were found in the sera of 29 (34.5%) of the study patients. In the remaining 55 (65.5%) patients, non-adherence was diagnosed. None of the prescribed antihypertensive drugs was detected in the sera of the 29 (34.5%) patients. Our data suggest that an assessment of SDLs might be helpful before an extensive evaluation is initiated for difficult-to-control hypertension.