BACKGROUND: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified. OBJECTIVE: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs. METHODS: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC). RESULTS: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92). CONCLUSIONS: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment.
- MeSH
- Androstenes MeSH
- Androgen Receptor Antagonists * adverse effects therapeutic use MeSH
- Benzamides adverse effects MeSH
- Phenylthiohydantoin MeSH
- Cardiovascular Diseases * chemically induced epidemiology MeSH
- Humans MeSH
- Prostatic Neoplasms * drug therapy pathology MeSH
- Nitriles adverse effects MeSH
- Randomized Controlled Trials as Topic MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Network Meta-Analysis MeSH
- Systematic Review MeSH
AIMS: Among patients with cardiogenic shock, immediate initiation of extracorporeal membrane oxygenation (ECMO) did not demonstrate any benefit at 30 days. The present study evaluated 1-year clinical outcomes of the Extracorporeal Membrane Oxygenation in the therapy of Cardiogenic Shock (ECMO-CS) trial. METHODS AND RESULTS: The ECMO-CS trial randomized 117 patients with severe or rapidly progressing cardiogenic shock to immediate initiation of ECMO or early conservative strategy. The primary endpoint for this analysis was 1-year all-cause mortality. Secondary endpoints included a composite of death, resuscitated cardiac arrest or implantation of another mechanical circulatory support device, duration of mechanical ventilation, and the length of intensive care unit (ICU) and hospital stays. In addition, an unplanned post-hoc subgroup analysis was performed. At 1 year, all-cause death occurred in 40 of 58 (69.0%) patients in the ECMO arm and in 40 of 59 (67.8%) in the early conservative arm (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.66-1.58; p = 0.93). The composite endpoint occurred in 43 (74.1%) patients in the ECMO group and in 47 (79.7%) patients in the early conservative group (HR 0.83, 95% CI 0.55-1.25; p = 0.29). The durations of mechanical ventilation, ICU stay and hospital stay were comparable between groups. Significant interaction with treatment strategy and 1-year mortality was observed in subgroups according to baseline mean arterial pressure (MAP) indicating lower mortality in the subgroup with low baseline MAP (<63 mmHg: HR 0.58, 95% CI 0.29-1.16; pinteraction = 0.017). CONCLUSIONS: Among patients with severe or rapidly progressing cardiogenic shock, immediate initiation of ECMO did not improve clinical outcomes at 1 year compared to the early conservative strategy. However, immediate ECMO initiation might be beneficial in patients with advanced haemodynamic compromise.
- MeSH
- Time Factors MeSH
- Intensive Care Units MeSH
- Shock, Cardiogenic * therapy mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Extracorporeal Membrane Oxygenation * methods MeSH
- Survival Rate trends MeSH
- Aged MeSH
- Respiration, Artificial methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Pokroky ve farmakoterapii přinesly nové možnosti léčby srdečního selhání. Léčba srdečního selhání se sníženou ejekční frakcí má čtyři základní pilíře – základní léky. Aktualizace doporučených postupů rozšířila možnosti léčby pro srdeční selhání s mírně sníženou a zachovalou ejekční frakcí levé komory. Kromě inhibitorů sodíkoglukózového ko-transportéru 2 je novou nadějí pro pacienty se srdečním selháním a ejekční frakcí levé komory nad 40 % selektivní nesteroidní antagonista mineralokortikoidních receptorů – finerenon.
Advances in pharmacotherapy have brought new possibilities in the treatment of heart failure. Therapy of heart failure with reduced ejection fraction has four basic pillars - fundamental drugs. Update of heart failure guidelines extended new options in the treatment of heart failure with preserved and mildly reduced ejection fraction. In additon to sodium glucose co-transporter 2 inhibitors, it is a hope for patients with heart failure and ejection fraction over 40 % selective non-steroideal mineralocorticoid receptro antagonist - finerenon.
- Keywords
- finerenon,
- MeSH
- Sodium-Glucose Transporter 2 Inhibitors pharmacokinetics therapeutic use MeSH
- Humans MeSH
- Naphthyridines pharmacology therapeutic use MeSH
- Heart Failure * drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
UNLABELLED: Despite significant advances in knowledge and the development of guidelines, the management of hypoplastic left heart syndrome (HLHS) remains highly variable. A structured questionnaire was circulated across European Association of Paediatric & Congenital Cardiology (AEPC) affiliated centres. The aims were to evaluate standards in pre-operative assessment, types of surgery, follow-up and medical practices in children with HLHS. Thirty-one centres from 20 countries completed the survey. Delivery of babies with HLHS occurred in co-located maternity hospitals in 74% of centres; 29% were planned for spontaneous onset of labour, while 54% decided on a case-by-case basis. The preferred initial palliation was a right ventricle-pulmonary artery conduit in 55% of cases, modified Blalock-Thomas Taussig shunt (mBTTS) in 35%, and hybrid in 15% of cases. Timing for Glenn varied from 3 to 6 months of age and preoperative examination varied greatly: 65% performed cardiac catheterization and only 19% performed cardiac magnetic resonance. Stage III palliation was performed at a highly variable interval (2-6 years of age), nearly always employing an extracardiac conduit. Fenestration was routinely performed in 61% and reserved for borderline cases in 39%. All the centers adopted warfarin for the first 3-12 months after Fontan completion, and continued if a fenestration was present, while in non-fenestrated aspirin was left by most centers (e.g. 68%). However, there was a high disparity in the use of heart failure medications (e.g. in interstage I-II 35% use ACE-inhibitors, and only 26% digoxin). Follow-up practice also varied widely with only 60% employing specific protocols. CONCLUSION: This first multi-centre European survey from 31 centres from 20 different European countries highlighted a high practice variation in HLHS management across all the stages of Single Ventricle (Fontan) palliation. Major variations pertained to pre- and post-surgical investigations, surgical strategy for stage I and III, medical treatment regimens, and follow-up programs. WHAT IS KNOWN: • Hypoplastic left heart syndrome (HLHS) remains one of the most complex and challenging congenital cardiac defects to manage. • Investigating the management of children with HLHS across different European centres can facilitate study of the most effective management strategies. WHAT IS NEW: • Significant variation in HLHS management were reported in relation to pre- and post-surgical examinations, surgical strategy at stage I and III, medical treatment regimens, and follow-up programs. • Greater standardisation of imaging and diagnostic evaluation, medical treatment and follow-up surveillance may improve outcomes for these vulnerable patients and warrants further study.
- MeSH
- Child MeSH
- Infant MeSH
- Practice Patterns, Physicians' * statistics & numerical data MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Palliative Care MeSH
- Child, Preschool MeSH
- Surveys and Questionnaires MeSH
- Hypoplastic Left Heart Syndrome * surgery diagnosis therapy MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
Anderson-Fabry disease (AFD) is a rare genetic disease with X-linked transmission characterized by a defect in the enzyme alpha-galactosidase A, which impairs glycosphingolipid metabolism and leads to an excessive storage of globotriaosylceramide (Gb3) within lysosomes. AFD involves renal, cardiac, vascular, and nervous systems and is mainly observed in male patients with onset in childhood, although cardiac manifestation is often shown in adults. AFD cardiomyopathy is caused by the accumulation of Gb3 within myocytes first showed by left ventricular hypertrophy and diastolic dysfunction, leading to restrictive cardiomyopathy and systolic heart failure with biventricular involvement. The diagnosis of AFD cardiomyopathy may be insidious in the first stages and requires accurate differential diagnosis with other cardiomyopathies with hypertrophic phenotype. However, it is fundamental to promptly initiate specific therapies that have shown promising results, particularly for early treatment. A careful integration between clinical evaluation, genetic tests, and cardiac imaging is required to diagnose AFD with cardiac involvement. Basic and advanced echocardiography, cardiac magnetic resonance, and nuclear imaging may offer pivotal information for early diagnosis (Graphical Abstract), and the management of these patients is often limited to centres with high expertise in the field. This clinical consensus statement, developed by experts from the European Society of Cardiology (ESC) Working Group on Myocardial and Pericardial Diseases and the European Association of Cardiovascular Imaging of the ESC, aims to provide practical advice for all clinicians regarding the use of multimodality imaging to simplify the diagnostic evaluation, prognostic stratification, and management of cardiac involvement in AFD.
- MeSH
- Early Diagnosis MeSH
- Diagnosis, Differential MeSH
- Child MeSH
- Adult MeSH
- Echocardiography methods standards MeSH
- Fabry Disease * diagnostic imaging therapy MeSH
- Consensus MeSH
- Humans MeSH
- Multimodal Imaging * methods standards MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Consensus Development Conference MeSH
Heart failure (HF) is a leading cause of morbidity and mortality, often driven by prolonged exposure to pathological stimuli such as pressure and volume overload. These factors contribute to excessive oxidative stress, adverse cardiac remodeling, and dysregulation of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling pathway. Given the urgent need for effective treatments, this study investigated the potential of sGC stimulators to mitigate HF progression. We utilized male hypertensive Ren-2 transgenic (TGR) rats and a volume-overload HF model induced by an aortocaval fistula (ACF). Rats received the sGC stimulator BAY 41-8543 (3 mg/kg/day) for 30 weeks, while normotensive Hannover Sprague-Dawley rats served as controls. At the study endpoint (40 weeks of age), left ventricular tissue was analyzed using mass spectrometry, Western blotting, and histological assessment. TGR rats treated with sGC stimulators exhibited a significant increase in key antioxidant proteins (SOD1, CH10, ACSF2, NDUS1, DHE3, GSTM2, and PCCA), suggesting enhanced resistance to oxidative stress. However, sGC stimulator treatment also upregulated extracellular matrix remodeling markers (MMP-2, TGF-β, and SMAD2/3), which are typically associated with fibrosis. Despite this, Masson's trichrome staining revealed reduced collagen deposition in both TGR and TGR-ACF rats receiving sGC stimulators. Notably, all untreated TGR-ACF rats succumbed before the study endpoint, preventing direct assessment of sGC stimulator effects in advanced HF. These findings highlight the therapeutic potential of sGC stimulators in HF, particularly through their antioxidant effects. However, their concurrent influence on fibrosis warrants further investigation to optimize treatment strategies.
- MeSH
- Chronic Disease MeSH
- Fibrosis MeSH
- Cyclic GMP metabolism MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Morpholines MeSH
- Oxidative Stress * drug effects MeSH
- Rats, Sprague-Dawley * MeSH
- Rats, Transgenic MeSH
- Pyridines pharmacology therapeutic use MeSH
- Pyrimidines MeSH
- Ventricular Remodeling drug effects MeSH
- Soluble Guanylyl Cyclase * metabolism MeSH
- Signal Transduction drug effects MeSH
- Heart Failure * drug therapy MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Farmakoterapie pacientů se srdečním selháním se sníženou ejekční frakcí (heart failure with reduced ejection fraction, HFrEF) je velmi dynamickým odvětvím kardiologie s intenzivním výzkumem. Doporučené postupy European Society of Cardiology (ESC) z roku 2021 byly významně aktualizovány dodatkem z roku 2023. Mezi současné základní pilíře léčby HFrEF patří inhibitory anglotenzin konvertujícího enzymu (angiotensin-converting enzyme inhibitor, ACEI), blokátory receptoru AT1 pro anglotenzin II (anglotensin II receptor 1 blockers, ARB) (sartany) nebo inhibitor angiotenzinových receptorů a nepriiysinu (angiotensin receptor-nepriiysin inhibitor, ARNI), beta-blokátory, inhibitory sodíko-glukózového kotransportéru 2 (sodium-glucose co-transporter 2, SGLT2) (giifloziny) a antagonisté mineralokortikoidních receptorů (mineralocorticoid receptor antagonist, MRA). Diuretika jsou doporučena při známkách městnání. K dispozici jsou i další přípravky, které si již získaly své místo v celkové strategii léčby. Jedná se především o intravenózní přípravky pro substituci železa, vericiguat a tafamidis. Důležitý je správný management léčby HFrEF včetně prevence, včasného nasazení léčby a uptitrace dávky.
Pharmacotherapy of patients with heart failure with reduced ejection fraction (HFrEF) is a very dynamic branch of cardiology with intensive research. The European Society of Cardiology (ESC) guidelines from 2021 were significantly updated in the 2023 supplement. Current mainstays of HFrEF treatment include angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) or angiotensin receptor/neprilysin inhibitor (ARNI), beta-blockers, sodium-glucose cotransporter-2 inhibitors (SGLT2) (gliflozins) and mineralocorticoid receptor antagonist (MRA). Diuretics are recommended for patients with congestion. There are also other medicaments that have already gained their place in the treatment strategy. These are mainly intravenous iron preparations, vericiguat and tafamidis. Proper management of HFrEF treatment is including prevention, early initiation of treatment and proper dose uptitration.
- MeSH
- Adrenergic beta-Antagonists administration & dosage pharmacology therapeutic use MeSH
- Drug Therapy methods MeSH
- Sodium-Glucose Transporter 2 Inhibitors administration & dosage pharmacology therapeutic use MeSH
- Angiotensin-Converting Enzyme Inhibitors administration & dosage pharmacology therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Medication Therapy Management MeSH
- Heart Failure, Systolic * diagnosis drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
IMPORTANCE: The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance. OBJECTIVE: To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD. DESIGN, SETTING, AND PARTICIPANTS: This was an international, multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial including patients implanted with a de novo HM3 LVAD across 51 centers. Data analysis was conducted from April to July 2024. INTERVENTIONS: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg per day) or placebo, in addition to a vitamin K antagonist (VKA) targeted to an international normalized ratio of 2 to 3 in both groups. MAIN OUTCOMES AND MEASURES: Primary end point (assessed for noninferiority) was a composite of survival free of any nonsurgical (>14 days after implant) HRAEs including stroke, pump thrombosis, bleeding, and arterial peripheral thromboembolism at 12 months. Secondary end points included nonsurgical bleeding, stroke, and pump thrombosis events. RESULTS: Among 589 of 628 patients (mean [SD] age, 57.1 [13.7] years; 456 male [77.4%]) who contributed to the primary end point analysis, a history of PCI, CABG, stroke, or PVD was present in 41% (240 of 589 patients). There was no interaction between the presence of an atherosclerotic vascular condition and effect of aspirin compared with placebo (P for interaction= .23). The preset 10% noninferiority margin was not crossed for the studied subgroup of patients. Thrombotic events were rare, with no differences between aspirin and placebo in patients with and without vascular disease (P for interaction = .77). Aspirin treatment was associated with a higher rate of nonsurgical major bleeding events in the group with prior vascular condition history compared with those without aspirin (rate ratio for placebo compared with aspirin, 0.52; 95% CI, 0.35-0.79). CONCLUSIONS AND RELEVANCE: Results of this prespecified analysis of the ARIES-HM3 randomized clinical trial demonstrate that in patients with advanced heart failure who have classical indications for antiplatelet therapy use at the time of LVAD implantation, aspirin avoidance was safe and not associated with increased thrombosis risk. Importantly, elimination of aspirin was associated with no increased thrombosis but a reduction in nonsurgical bleeding events in patients with a history of PCI, CABG, stroke, or PVD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.
- MeSH
- Aspirin * therapeutic use MeSH
- Atherosclerosis MeSH
- Stroke prevention & control MeSH
- Double-Blind Method MeSH
- Fibrinolytic Agents therapeutic use MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Percutaneous Coronary Intervention methods MeSH
- Hemorrhage chemically induced MeSH
- Middle Aged MeSH
- Humans MeSH
- Heart-Assist Devices * MeSH
- Prospective Studies MeSH
- Aged MeSH
- Heart Failure MeSH
- Thrombosis prevention & control MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comment MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Myelodysplastic Syndrome (MDS) is a devastating hematologic malignancy associated with advanced age. Diabetes Mellitus (DM) is one of the most common morbidities worldwide, with metformin serving as the first line therapy for several decades. However, the potential association between previous metformin use and the risk of developing MDS remains uncertain. METHODS: This cross-sectional study addressed the possible association between prior metformin use in DM patients and the subsequent development of MDS. RESULTS: Data from 54,869 DM patients was retrieved from their medical records from a tertiary medical center. Of these, 20,318 patients had been exposed at some point in time to metformin, with 133 (0.7%) subsequently developing MDS. In contrast, among 34,551 DM patients with no prior exposure to metformin, only 154 (0.4%) developed MDS later in life. The Odds Ratio (OR) for MDS development amongst metformin users compared to the entire study population was 1.48 (95% CI 1.17-1.86; p = 0.001). A multivariate analysis adjusting for gender, age, congestive heart failure and chronic kidney disease, past exposure to metformin remained an independent risk factor for MDS development (OR = 1.6, 95% CI 1.26-2.03; p < 0.001). CONCLUSION: Previous exposure to metformin amongst DM patients is associated with an increased risk for MDS development later in life. This is a preliminary, cross-sectional study that show that larger studies in variable MDS patient populations are warranted.
- MeSH
- Diabetes Mellitus epidemiology chemically induced MeSH
- Adult MeSH
- Hypoglycemic Agents * therapeutic use adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Metformin * therapeutic use adverse effects MeSH
- Myelodysplastic Syndromes * epidemiology chemically induced MeSH
- Cross-Sectional Studies MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: This cross-sectional analysis from the CZecking Heart Failure in patients with advanced Chronic Kidney Disease trial (ISRCTN18275480) examined pulmonary hypertension and right ventricular-pulmonary arterial coupling in patients on chronic hemodialysis. The aims of this analysis were: 1. To analyze relations between pulmonary hypertension and right ventricular-pulmonary arterial coupling with dialysis access flow and current hydration; 2. To analyze structural heart changes associated with right ventricular-pulmonary arterial uncoupling; 3. To reveal the prevalence, etiology and severity of pulmonary hypertension in the Czech hemodialysis population. METHODS: We performed expert echocardiography, vascular access flow measurements, bioimpedance analysis, and laboratory testing in 336 hemodialysis patients. RESULTS: Pulmonary hypertension was present in 34% (114/336) patients and right ventricular-pulmonary arterial uncoupling was present in 25% of patients with pulmonary hypertension. Only weak associations between the flow of the dialysis arteriovenous access and estimated pulmonary arterial systolic pressure and right ventricular-pulmonary arterial coupling was proved. There was a strong association between hydration status assessed by estimated central venous pressure with pulmonary arterial systolic pressure (Rho 0.6, p < 0.0001) and right ventricular-pulmonary arterial coupling (Rho -0.52, p < 0.0001) and association between overhydration to extracellular water ratio with pulmonary arterial systolic pressure (Rho 0.31, p = 0.0001) and right ventricular-pulmonary arterial coupling (Rho -0.29, p = 0.002). The prevalence of heart failure was significantly higher in patients with right ventricular-pulmonary arterial uncoupling (88% vs. 52%, p = 0.0003). CONCLUSION: These findings suggest that optimizing volume status and treating heart failure should be prioritized in hemodialysis patients to prevent pulmonary hypertension progression and right ventricular-pulmonary arterial uncoupling.
- MeSH
- Pulmonary Artery * physiopathology MeSH
- Kidney Failure, Chronic * therapy complications physiopathology MeSH
- Renal Dialysis * adverse effects MeSH
- Echocardiography MeSH
- Middle Aged MeSH
- Humans MeSH
- Hypertension, Pulmonary * etiology physiopathology MeSH
- Cross-Sectional Studies MeSH
- Aged MeSH
- Heart Ventricles physiopathology diagnostic imaging MeSH
- Heart Failure physiopathology complications etiology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH