Nitric oxide (NO)-stimulated cyclic guanosine monophosphate (cGMP) is a key regulator of cardiovascular health, as NO-cGMP signalling is impaired in diseases like pulmonary hypertension, heart failure and chronic kidney disease. The development of NO-independent sGC stimulators and activators provide a novel therapeutic option to restore altered NO signalling. sGC stimulators have been already approved for the treatment of pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH), and chronic heart failure (HFrEF), while sGC activators are currently in phase-2 clinical trials for CKD. The best characterized effect of increased cGMP via the NO-sGC-cGMP pathway is vasodilation. However, to date, none of the sGC agonists are in development for hypertension (HTN). According to WHO, the global prevalence of uncontrolled HTN continues to rise, contributing significantly to cardiovascular mortality. While there are effective antihypertensive treatments, many patients require multiple drugs, and some remain resistant to all therapies. Thus, in addition to improved diagnosis and lifestyle changes, new pharmacological strategies remain in high demand. In this review we explore the potential of sGC stimulators and activators as novel antihypertensive agents, starting with the overview of NO-sGC-cGMP signalling, followed by potential mechanisms by which the increase in cGMP may regulate vascular tone and BP. These effects may encompass not only acute vasodilation, but also mid-term and chronic effects, such as the regulation of salt and water balance, as well as mitigation of vascular ageing and remodelling. The main section summarizes the preclinical and clinical evidence supporting the BP-lowering efficacy of sGC agonists.

• MeSH
• agonisté guanylátcyklázy terapeutické užití   farmakologie   MeSH
• aktivátory enzymů terapeutické užití   farmakologie   MeSH
• antihypertenziva * terapeutické užití   farmakologie   MeSH
• guanosinmonofosfát cyklický * metabolismus   MeSH
• hypertenze * farmakoterapie   patofyziologie   MeSH
• lidé MeSH
• oxid dusnatý metabolismus   MeSH
• rozpustná guanylátcyklasa * metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Limited data are available to guide the management of coronary artery aneurysms (CAAs). OBJECTIVES: The authors sought to define the clinical characteristics, identify variables that predict outcomes, and provide long-term data on CAAs. METHODS: We describe outcomes from 1,729 consecutive patients with CAAs included in an ambispective international registry (CAAR [Coronary Artery Aneurysm Registry]; NCT02563626) involving 33 hospitals across 9 countries in America and Europe. RESULTS: Patients were predominantly male (78.6%; 1,359/1,729) with a mean age of 66 years. Classic cardiovascular risk factors were common, as well as coronary artery disease (85.8%; 1,484/1,729), peripheral vascular disease (10.9%; 188/1,729), and chronic kidney disease (8.0%; 138/1,729). The median number of aneurysms per patient was 1.0 (Q1-Q3: 1.0-1.0), with the most affected territory being the left anterior descending artery (49.6%; 857/1,729). The majority underwent any revascularization procedure (68.5%; 1,184/1,729), mainly percutaneous coronary intervention (50.7%; 877/1,729), and were discharged on dual antiplatelet therapy (65.6%; 1,134/1,729). After a median follow-up of 44.8 months (Q1-Q3: 14.9-88.1), 379 died (21.9%), and 641 (37.1%) developed a major adverse cardiovascular event (MACE) (all-cause death, heart failure, unstable angina, and reinfarction). In a multivariable analysis, age (HR: 1.03; 95% CI: 1.02-1.04; P < 0.001), diabetes mellitus (HR: 1.47; 95% CI: 1.23-1.75; P < 0.001), renal insufficiency (HR: 1.53; 95% CI: 1.19-1.96; P = 0.010), peripheral vessel disease (HR: 1.43; 95% CI: 1.13-1.82; P = 0.003), reduced left ventricular ejection fraction (HR: 0.98; 95% CI: 0.98-0.99; P < 0.001), acute indication for the index coronary angiography (HR: 1.30; 95% CI: 1.08-1.55; P = 0.005), and the number of coronary vessels presenting severe stenosis (HR: 1.11; 95% CI: 1.02-1.20; P = 0.015) were independent predictors of MACEs. Remarkably, only 37 patients presented with local aneurysm complications during follow-up. CONCLUSIONS: The long-term prognosis of CAAs is not favorable, with MACEs associated with the underlying risk factor profile for atherosclerotic heart disease.

• MeSH
• časové faktory MeSH
• hodnocení rizik MeSH
• kohortové studie MeSH
• koronární aneurysma * diagnostické zobrazování   mortalita   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• registrace * MeSH
• rizikové faktory MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Evropa MeSH
• Severní Amerika MeSH

BACKGROUND: The clinical impact of a chronic total occlusion (CTO) in patients with 3-vessel coronary artery disease undergoing fractional flow reserve-guided percutaneous coronary intervention (PCI) with current-generation drug-eluting stents or coronary artery bypass grafting (CABG) is unclear. METHODS: The FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) compared fractional flow reserve-guided PCI with CABG in patients with 3-vessel coronary artery disease. The primary end point was major adverse cardiac and cerebrovascular events, a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. In this substudy, the 3-year outcomes were analyzed in patients with or without a CTO. RESULTS: Of the patients randomized to PCI or CABG in the FAME 3 trial, 305 (21%) had a CTO. In the PCI arm, revascularization of the CTO was attempted in 61% with a procedural success rate of 88%. The incidence of major adverse cardiac and cerebrovascular events at 3 years was not significantly different between those with or without a CTO in both the PCI (15.2% versus 20.1%; adjusted hazard ratio, 0.62 [95% CI, 0.38-1.03]; P=0.07) and the CABG (13.0% versus 12.9%; adjusted hazard ratio, 0.96 [95% CI, 0.55-1.66]; P=0.88) arms. In those without a CTO, PCI was associated with a significantly higher risk of major adverse cardiac and cerebrovascular events compared with CABG (adjusted hazard ratio, 1.61 [95% CI, 1.20-2.17]; P<0.01) but not in those with a CTO (adjusted hazard ratio, 1.21 [95% CI, 0.64-2.28]; P=0.56; Pinteraction=0.31). CONCLUSIONS: The presence of a CTO did not significantly impact the treatment effect of PCI versus CABG at 3 years in patients with 3-vessel coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02100722.

• MeSH
• časové faktory MeSH
• chronická nemoc MeSH
• frakční průtoková rezerva myokardu * MeSH
• koronární angiografie * MeSH
• koronární angioplastika * škodlivé účinky   mortalita   MeSH
• koronární bypass * škodlivé účinky   mortalita   MeSH
• koronární okluze * diagnostické zobrazování   mortalita   terapie   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci koronárních tepen terapie   mortalita   diagnostické zobrazování   patofyziologie   MeSH
• prediktivní hodnota testů MeSH
• rizikové faktory MeSH
• senioři MeSH
• stenty uvolňující léky * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

BACKGROUND: Heart failure (HF) is becoming an increasingly prevalent issue, particularly among the elderly population. Lipids are closely associated with cardiovascular disease (CVD) pathology. Lipidomics as a comprehensive profiling tool is showing to be promising in the prediction of events and mortality due to CVD as well as identifying novel biomarkers. MATERIALS AND METHODS: In this study, eicosanoids and lipid profiles were measured in order to predict survival in patients with de novo or acute decompensated HF. Our study included 50 patients (16 females, mean age 73 years and 34 males, mean age 71 years) with de novo or acute decompensated chronic HF with a median follow-up of 7 months. Lipids were semiquantified using targeted lipidomic liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Eicosanoid concentrations were determined using a commercially available sandwich ELISA assay. RESULTS: From 736 lipids and 3 eicosanoids, 39 significant lipids were selected (by using the Mann-Whitney U test after Benjamini-Hochberg correction) with the highest number of representatives belonging to the polyunsaturated (PUFA) phosphatidylcholines (PC). PC 42:10 (p = 1.44 × 10-4) was found to be the most statistically significantly elevated in the surviving group with receiver operating characteristics of AUC = 0.84 (p = 3.24 × 10-7). A multivariate supervised discriminant analysis based on the aforementioned lipid panel enabled the classification of the groups of surviving and non-surviving patients with 90 % accuracy. CONCLUSIONS: In the present study we describe a trend in PUFA esterified in PC that were systematically increased in surviving patients with HF. This trend in low-abundant and rarely identified PUFA PC (mainly very long chain PUFA containing PC such as PC 42:10 or PC 40:9 containing FA 22:6, FA 20:5 and FA 20:4) suggests candidate biomarkers.

• Publikační typ
• časopisecké články MeSH

Cardiogenic shock (CS) is a devastating and fatal complication of acute myocardial infarction (AMI). CS can affect the pharmacokinetics and pharmacodynamics of medications. The unique properties of cangrelor make it the optimal P2Y12 inhibitor for CS-AMI, in terms of both efficacy and safety. The DAPT-SHOCK-AMI trial (ClinicalTrials.gov: NCT03551964; EudraCT: 2018-002161-19) will assess the benefits of cangrelor in patients with an initial CS-AMI undergoing primary angioplasty. This randomised, multicentre, placebo-controlled trial of approximately 550 patients (with an allowed 10% increase) in 5 countries using a double-blind design will compare initial P2Y12 inhibitor treatment strategies in patients with CS-AMI of (A) intravenous cangrelor and (B) ticagrelor administered as crushed tablets at a loading dose of 180 mg. The primary clinical endpoint is a composite of all-cause death, myocardial infarction (MI), or stroke within 30 days. The main secondary endpoints are (1) the net clinical endpoint, defined as death, MI, urgent revascularisation of the infarct-related artery, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium criteria; (2) cardiovascular-related death, MI, urgent revascularisation, or heart failure; (3) heart failure; and (4) cardiovascular-related death, all (1-4) within 1 year after study enrolment. A platelet reactivity study that tests the laboratory antiplatelet benefits of cangrelor, when given in addition to standard antiplatelet therapy, will be conducted using vasodilator-stimulated phosphoprotein phosphorylation. The primary laboratory endpoints are the periprocedural rate of onset and the proportion of patients who achieve effective P2Y12 inhibition. The DAPT-SHOCK-AMI study is the first randomised trial to evaluate the benefits of cangrelor in patients with CS-AMI.

• MeSH
• adenosinmonofosfát * analogy a deriváty   terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• dvojitá slepá metoda MeSH
• fosfoproteiny MeSH
• infarkt myokardu * komplikace   MeSH
• inhibitory agregace trombocytů * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• kardiogenní šok * mortalita   MeSH
• koronární angioplastika škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• purinergní receptory P2Y - antagonisté aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři MeSH
• ticagrelor * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

A short-term mortality of patients with acute myocardial infarction (AMI) without cardiogenic shock (CS) and treated with PCI is 5%, mortality of those with CS is 10 times higher. Rapid and effective antiplatelet therapy (acetylsalicylic acid and P2Y12 inhibitor) is of essential importance for an early coronary flow renewal and perfusion of microcirculation, and is as such highly important for patient’s prognosis. Patients with CS are the population with the highest thrombotic risk. CS is an exclusion criterion for participation in randomized studies. Relevant evidence resulting from comparison of antiplatelets in these patients is entirely missing. The project is a randomized study, comparing efficacy of cangrelor and ticagrelor. It is based on an assumption that cangrelor, parenteral and direct-acting P2Y12 inhibitor, has a potential to be an optimal drug for patients with AMI complicated with CS. With regards to hypoperfusion of the splanchnic area, the preferred drug application is the parenteral route while in case of drugs, those not requiring metabolisation, are being preferred.

Krátkodobá mortalita pacientů s akutním infarktem myokardu (AIM), kteří jsou léčeni perkutánní koronární intervencí bez kardiogenního šoku (KŠ) je 5%, mortalita těch s komplikujícím KŠ je desetinásobně vyšší. Rychlá a efektivní kombinovaná protidestičková léčba (kyselina acetylsalicylová a inhibitor P2Y12) má zásadní význam pro časné obnovení průtoku v koronární tepně a perfuzi mikrocirkulace, a tím pro prognózu nemocných. Pacienti s KŠ jsou populací s nejvyšším trombotickým rizikem. Přesto je KŠ vyřazovacím kritériem pro účast v randomizovaných studiích. Relevantní evidence o srovnání efektivity protidestičkových léků u této subpopulace pacientů zcela chybí. Projekt je randomizovanou multicentrickou dvojitě zaslepenou studií srovnávající efektivitu cangreloru a ticagreloru. Vychází z předpokladu, že cangrelor, parenterální a přímý inhibitor P2Y12, má potenciál být optimálním lékem pro pacienty s AIM komplikovaným iniciálně KŠ, kteří podstupují PCI. Vzhledem k hypoperfuzy splanchnika je totiž preferovanou aplikací intravenózní a z léků mají přednost ty, jež nevyžadují metabolizaci.

• Klíčová slova
• prognóza, mortalita, mortality, Outcome, akutní infarkt myokardu, kardiogenní šok, protidestičková léčba, velké kardiovaskulární příhody, cardiogenic shock, antiplatelet therapy, major cardiovascular events, acute myocardial infartion,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

• MeSH
• intervenční ultrasonografie * metody   MeSH
• koronární nemoc diagnostické zobrazování   MeSH
• lidé MeSH
• optická koherentní tomografie * metody   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Complete revascularization is the standard treatment for patients with ST-segment-elevation myocardial infarction and multivessel disease. The FIRE trial (Functional Assessment in Elderly Myocardial Infarction Patients With Multivessel Disease) confirmed the benefit of complete revascularization in a population of older patients, but the follow-up is limited to 1 year. Therefore, the long-term benefit (>1 year) of this strategy in older patients is debated. To address this, an individual patient data meta-analysis was conducted in patients with ST-segment-elevation myocardial infarction ≥75 years of age enrolled in randomized clinical trials investigating complete versus culprit-only revascularization strategies. METHODS: PubMed, Embase, and the Cochrane database were systematically searched to identify randomized clinical trials comparing complete versus culprit-only revascularization. Individual patient-level data were collected from the relevant trials. The primary end point was death, myocardial infarction, or ischemia-driven revascularization. The secondary end point was cardiovascular death or myocardial infarction. RESULTS: Data from 7 randomized clinical trials encompassing 1733 patients (917 randomized to culprit-only and 816 to complete revascularization) were analyzed. The median age was 79 [interquartile range, 77-83] years. Of the patients, 595 (34%) were female. Follow-up ranged from a minimum of 6 months to a maximum of 6.2 years (median, 2.5 [interquartile range, 1-3.8] years). Complete revascularization reduced the primary end point up to 4 years (hazard ratio, 0.78 [95% CI, 0.63-0.96]) but not at the longest available follow-up (hazard ratio, 0.83 [95% CI, 0.69-1.01]). Complete revascularization significantly reduced the occurrence of cardiovascular death or myocardial infarction at the longest available follow-up (hazard ratio, 0.76 [95% CI, 0.58-0.99]). This was observed even when censoring the follow-up at each year. Long-term rate of death did not differ between complete and culprit-only revascularization arms. CONCLUSIONS: In this individual patient data meta-analysis of older patients with ST-segment-elevation myocardial infarction and multivessel disease, complete revascularization reduced the primary end point of death, myocardial infarction, or ischemia-driven revascularization up to 4 years. At the longest follow-up, complete revascularization reduced the composite of cardiovascular death or myocardial infarction but not the primary end point. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022367898.

• MeSH
• infarkt myokardu s elevacemi ST úseků * mortalita   chirurgie   terapie   MeSH
• koronární angioplastika mortalita   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma * MeSH
• revaskularizace myokardu * metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

• MeSH
• infarkt myokardu * epidemiologie   terapie   MeSH
• lidé MeSH
• nemocnice MeSH
• poskytování zdravotní péče MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Traditionally, aborted cardiac arrest (ACA) due to documented ventricular fibrillation (VF) in the absence of structural heart disease has been termed idiopathic VF. By careful evaluation, a specific etiology can be found in a substantial proportion of patients. The aim of this survey was to assess the yield of an advanced diagnostic work-up to reveal a causative etiology in a real-life clinical setting. Patients from the University Hospital Brno's ACA database were analyzed (514 patients in total). Forty-six patients (31 males) fulfilled the inclusion criteria, which were: (1) absence of structural pathology on echocardiography; (2) absence of coronary artery disease; and (3) absence of reversible cause of ACA. The diagnostic work-up consisted in cardiac magnetic resonance imaging, stress testing, sodium channel blocker challenge, and genetic testing according to the availability of the method and patient compliance. A specific disease was found in 17 individuals (37.0%), although at least one diagnostic step was refused by 13 patients (28.3%). True idiopathic VF was confirmed in 7 patients (15.2%), for whom the entire diagnostic work-up did not reveal any specific pathology. Our real-life survey shows that, even with an incomplete diagnostic work-up (due to the unavailability of a particular method or variable patient compliance), a specific diagnosis can be identified in more than one third of the cases of "idiopathic" VF, which can thus enable targeted treatment and family screening.

• MeSH
• dospělí MeSH
• echokardiografie MeSH
• fibrilace komor * diagnóza   MeSH
• genetické testování metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• senioři MeSH
• zátěžový test MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH