Oral anticoagulation in patients with left ventricular thrombus - a systematic review and meta-analysis.

AIMS: Direct oral anticoagulants (DOACs) are increasingly used off-label to treat patients with left ventricular thrombus (LVT). We analyzed available meta-data comparing DOACs and vitamin K antagonists (VKAs) for efficacy and safety. METHODS: We conducted a systematic search and meta-analysis of observational and randomized data comparing DOACs versus VKAs in patients with LVT. Endpoints of interest were stroke or systemic embolism, thrombus resolution, all-cause death, and a composite bleeding endpoint. Estimates were pooled using a random-effect model meta-analysis, and their robustness was investigated using sensitivity and influential analyses. RESULTS: We identified 22 articles (18 observational studies, 4 small randomized clinical trials) reporting on a total of 3,587 patients (2,489 VKA vs. 1,098 DOAC therapy). The pooled estimates for stroke or systemic embolism (OR 0.81; 95% CI [0.57, 1.15]) and thrombus resolution (OR 1.12; 95% CI [0.86; 1.46]) were comparable, and there was low heterogeneity overall across the included studies. DOAC use was associated with lower odds of all-cause death (OR 0.65; 95%CI [0.46; 0.92]) and a composite bleeding endpoint (OR 0.67; 95%CI [0.47; 0.97]). A risk of bias was evident particularly for observational reports, with some publication bias suggested in funnel plots. CONCLUSION: In this comprehensive analysis of mainly observational data, the use of DOACs was not associated with a significant difference in stroke or systemic embolism, or thrombus resolution compared to VKA therapy. The use of DOACs was associated with a lower rate of all-cause death and fewer bleeding events. Adequately sized randomized clinical trials are needed to confirm these findings, which could allow a wider adoption of DOACs in patients with LVT.

Same-day discharge after percutaneous coronary procedures-Consensus statement of the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology.

INTRODUCTION: Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. Recent technical advances such as radial access, third generation drug-eluting stents and highly effective antiplatelet therapy have substantially improved the safety profile of coronary procedures. Despite several practice guidelines and a clear patient preference of early hospital discharge, the percentage of coronary procedures performed in an outpatient setting in Austria remains low, mostly due to safety concerns. METHODS: The aim of this consensus statement is to provide a practical framework for the safe and effective implementation of coronary outpatient clinics in Austria. Based on a structured literature review and an in-depth analysis of available practice guidelines a consensus statement was developed and peer-reviewed within the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology. RESULTS: Based on the available literature same-day discharge coronary procedures show a favorable safety profile with no increase in the risk of major adverse events compared to an overnight stay. This document provides a detailed consensus in various clinical settings. The most important prerequisite for same-day discharge is, however, adequate selection of suitable patients and a structured peri-interventional and postinterventional management plan. CONCLUSION: Based on the data analysis this consensus document provides detailed practice guidelines for the safe operation of daycare cathlab programs in Austria.

Same-day discharge after percutaneous coronary procedures-Structured review and comprehensive meta-analysis.

INTRODUCTION: Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. The safety and feasibility of performing these procedures on a same-day discharge basis for selected patients has been studied in a large number of mostly nonrandomized trials. An up to date literature review should focus on trials with radial access, representing the current standard for coronary procedures in Austria and other European countries. METHODS: The aim of this consensus statement is to review the most recent evidence for the safety and feasibility of performing same-day discharge procedures in selected patients. A structured literature search was performed using prespecified search criteria, focusing on trials with radial access procedures. RESULTS: A total of 44 clinical trials and 4 large meta-analyses were retrieved, spanning 21 years of clinical evidence from 2001 to 2022. The outcome data from a wide range of clinical settings were unanimous in showing no negative effect on early (24 h) or late (30 day) major adverse events after same-day discharge coronary procedures. Based on nine prospective trials a comprehensive meta-analysis was compiled. Using 1­month major adverse events data the pooled odds ratio of same-day discharge versus overnight stay procedures was 0.66 (95% confidence interval, CI 0.35-01.24; p = 0.19; I2 0%), indicating a noninferiority in carefully selected patients. CONCLUSION: Outcome data from same-day discharge coronary intervention trials with radial access confirm the robust safety profile showing no increase in the risk of major adverse events compared to overnight stay.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023.

Although cardiovascular diseases (CVDs) are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of CVDs.

Decreased percentages of plasmacytoid dendritic cells predict survival in critically ill patients.

Critically ill patients admitted to intensive care units (ICUs) experience a broad variety of life-threatening conditions. Irrespective of the initial cause of hospitalization, many experience systemic immune dysregulation. Dendritic cells (DCs) are the most potent antigen-presenting cells and play a pivotal role in regulating the immune response by linking the innate to the adaptive immune system. The aim of this study was to analyze whether DCs or their respective subsets are associated with 30-d mortality in an unselected patient cohort admitted to a medical ICU with a cardiovascular focus. A total of 231 patients were included in this single-center prospective observational study. Blood was drawn at admission and after 72 h. Subsequently, flow cytometry was utilized for the analysis of DCs and their respective subsets. In the total cohort, low percentages of DCs were significantly associated with sepsis, respiratory failure, and septic shock. In particular, a significantly lower percentage of circulating plasmacytoid DCs (pDCs) was found to be a strong and independent predictor of 30-d mortality after adjustment for demographic and clinical variables with an hazard ratio of 4.2 (95% confidence interval: 1.3-13.3, P = 0.015). Additionally, low percentages of pDCs were correlated with additional markers of inflammation and organ dysfunction. In conclusion, we observed low percentages of DCs in patients admitted to an ICU experiencing sepsis, respiratory failure, and cardiogenic shock, suggesting their depletion as a contributing mechanism for the development of immune paralysis. In our cohort, pDCs were identified as the most robust subset to predict 30-d mortality.

Development of Cross-Sector Health Care Quality Indicators Based on Claims Data.

Quality indicators serve as a tool to measure and improve evidence-based health care. Often the transition from inpatient to outpatient care is not sufficiently included. The focus of this work was to develop and to evaluate methods to define relevant cross-sector quality indicators based on Austrian claims data, using myocardial infarction as tracer.

Analysis of type 2 diabetes heterogeneity with a tree-like representation: insights from the prospective German Diabetes Study and the LURIC cohort.

BACKGROUND: Heterogeneity in type 2 diabetes can be represented by a tree-like graph structure by use of reversed graph-embedded dimensionality reduction. We aimed to examine whether this approach can be used to stratify key pathophysiological components and diabetes-related complications during longitudinal follow-up of individuals with recent-onset type 2 diabetes. METHODS: For this cohort analysis, 927 participants aged 18-69 years from the German Diabetes Study (GDS) with recent-onset type 2 diabetes were mapped onto a previously developed two-dimensional tree based on nine simple clinical and laboratory variables, residualised for age and sex. Insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, insulin secretion was assessed by intravenous glucose tolerance test, hepatic lipid content was assessed by 1 H magnetic resonance spectroscopy, serum interleukin (IL)-6 and IL-18 were assessed by ELISA, and peripheral and autonomic neuropathy were assessed by functional and clinical measures. Participants were followed up for up to 16 years. We also investigated heart failure and all-cause mortality in 794 individuals with type 2 diabetes undergoing invasive coronary diagnostics from the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort. FINDINGS: There were gradients of clamp-measured insulin sensitivity (both dimensions: p<0·0001) and insulin secretion (pdim1<0·0001, pdim2=0·00097) across the tree. Individuals in the region with the lowest insulin sensitivity had the highest hepatic lipid content (n=205, pdim1<0·0001, pdim2=0·037), pro-inflammatory biomarkers (IL-6: n=348, pdim1<0·0001, pdim2=0·013; IL-18: n=350, pdim1<0·0001, pdim2=0·38), and elevated cardiovascular risk (nevents=143, pdim1=0·14, pdim2<0·00081), whereas individuals positioned in the branch with the lowest insulin secretion were more prone to require insulin therapy (nevents=85, pdim1=0·032, pdim2=0·12) and had the highest risk of diabetic sensorimotor polyneuropathy (nevents=184, pdim1=0·012, pdim2=0·044) and cardiac autonomic neuropathy (nevents=118, pdim1=0·0094, pdim2=0·06). In the LURIC cohort, all-cause mortality was highest in the tree branch showing insulin resistance (nevents=488, pdim1=0·12, pdim2=0·0032). Significant gradients differentiated individuals having heart failure with preserved ejection fraction from those who had heart failure with reduced ejection fraction. INTERPRETATION: These data define the pathophysiological underpinnings of the tree structure, which has the potential to stratify diabetes-related complications on the basis of routinely available variables and thereby expand the toolbox of precision diabetes diagnosis. FUNDING: German Diabetes Center, German Federal Ministry of Health, Ministry of Culture and Science of the state of North Rhine-Westphalia, German Federal Ministry of Education and Research, German Diabetes Association, German Center for Diabetes Research, European Community, German Research Foundation, and Schmutzler Stiftung.

Early Initiation of SGLT2 Inhibitors in Acute Heart Failure: a Focus on Diuresis and Renal Protection.

PURPOSE: Acute heart failure (AHF) represents a critical and life-threatening condition characterized by the sudden onset or exacerbation of symptoms, such as dyspnea and fluid retention, due to impaired cardiac function. Despite advances in the treatment of chronic heart failure (HF), the management of AHF remains challenging, with limited therapeutic options available. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a promising drug class in AHF management. METHODS/RESULTS: The objective of this article was to conduct a comprehensive review of the existing literature in the domain of SGLT2 inhibitors and their relevance in the context of AHF. CONCLUSION: The existing evidence underscores the importance of SGLT2 inhibitors in enhancing decongestive therapy for AHF patients. Early initiation appears both practical and beneficial, leading to improved and sustained decongestion, a reduction in heart failure-related events, enhanced quality of life, and decreased mortality rates, all while maintaining a favorable safety profile. Consequently, it should be considered to initiate SGLT2 inhibitor treatment as early and as safely as possible to facilitate effective decongestion. However, careful patient selection and monitoring are essential when considering the use of these drugs in the management of AHF.

Sex-Related Disparities in Prescription Patterns of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Type 2 Diabetes and Heart Failure.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF). In consideration of emerging evidence that there are clinically relevant sex-related differences in the course of T2DM and subsequent cardiovascular outcomes, it is unknown if SGLT2i therapy is sex-independently utilized in daily clinical practice. Methods: Patients with T2DM and HF admitted to a tertiary academic center between January 2014 and April 2020 were identified through a search of electronic health records. Data on antidiabetic therapy were acquired at discharge and were screened for SGLT2i prescription. Results: Overall, 812 patients (median age 70 years, 29.7% female) were included in the present analysis. Only 17.3% of the study population received an SGLT2i. In comparison between sexes, females show lower rates of SGLT2i prescription (11.2% vs. 19.8%, p = 0.003), despite comparable patient characteristics. Furthermore, male HF patients showed a significantly higher probability of SGLT2i prescription with an adjusted odds ratio of 2.59 (95% confidence interval 1.29-5.19; p = 0.008). Females who did not receive an SGLT2i showed higher rates of chronic kidney disease (25.2% vs. 7.4%, p = 0.039) and greater levels of N-terminal pro b-type natriuretic peptide (NT-proBNP; 2092 vs. 825 pg/mL, p = 0.011) as compared to female SGLT2i recipients, which did not explain the observed sex-related disparities. Conclusion: SGLT2i are potentially underutilized in female patients with HF and T2DM, despite an overall increasing prescription trend during the observation period. Reasons for withholding therapy could not be objectified. The present data indicate a major need to increase awareness of guideline-directed therapy, especially in female HF patients.

The Impact of Preclinical High Potent P2Y12 Inhibitors on Decision Making at Discharge and Clinical Outcomes in Patients with Acute Coronary Syndrome.

BACKGROUND: Purinergic signaling receptor Y12 (P2Y12) inhibitors are a fundamental part of pharmacological therapy in acute coronary syndrome (ACS) for preventing recurrent ischemic events. Current guidelines support the use of prasugrel over ticagrelor-however, ticagrelor is widely used for preclinical loading during ACS due to its ease of administration. In this regard, it remains unknown whether the preclinical loading with P2Y12 inhibitors impacts decision-making for the long-term dual antiplatelet strategy, as well as cardiovascular outcomes, including re-percutaneous coronary intervention in real-world settings. METHODS: Within this population-based prospective observational study, all patients with ACS who received medical care via the Emergency Medical Service (EMS) in the city of Vienna between January 2018 and October 2020 were enrolled. Patients were stratified according to their P2Y12 inhibitor loading regimen. Subsequently, the association of P2Y12 inhibitor loading on long-term prescription at discharge and outcome was assessed. RESULTS: The entire study cohort consisted of 1176 individuals with ST-elevation myocardial infarction (STEMI), of whom 47.5% received prasugrel and 52.5% ticagrelor. The likelihood of adhering to the initial P2Y12 inhibitor strategy during the clinical stay was high for both ticagrelor (84%; OR: 10.00; p < 0.001) and prasugrel (77%; OR: 21.26; p < 0.001). During patient follow-up (median follow-up time three years), 84 (7.1%) patients died due to cardiovascular causes, and 82 (7.0%) patients required re-PCI. Notably, there was no difference in cardiovascular mortality (6.6% ticagrelor vs. 7.7% prasugrel) or re-PCI rates (6.6% ticagrelor vs. 7.3% prasugrel) addressing the P2Y12 inhibition strategy. CONCLUSION: We observed that, regardless of the initial antiplatelet inhibitor strategy, the in-hospital P2Y12 adherence was exceedingly high, and there was a minimal occurrence of switching to another P2Y12 inhibitor. Most importantly, no significant difference in cardiovascular death/re-PCI between ticagrelor and prasugrel-based preclinical loading has been observed. Consequently, the choice of high potent P2Y12 did not influence the cardiac outcome from a long-term perspective.

Rivaroxaban in Valvular Atrial Fibrillation - a Critical Appraisal of the INVICTUS Trial.

PURPOSE: The efficacy of factor Xa inhibitors in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD) is unknown. METHODS/RESULTS: The objective of this article was to conduct a comprehensive evaluation of the INVICTUS trial, an open-label randomized controlled study that compared vitamin K antagonists (VKA) to rivaroxaban in patients with AF and RHD while also considering the existing evidence from literature in this particular area of research. CONCLUSION: The findings of the INVICTUS trial indicated that rivaroxaban was found to be inferior in efficacy to VKA. However, it is important to note that the primary outcome of the trial was driven by sudden death and death caused by mechanical pump failure. As a result, it is necessary to approach the data from this study with caution, and it would be inappropriate to draw parallel conclusions for other causes of valvular AF. Particularly, the perplexing issue of how rivaroxaban could have contributed to both pump failure and sudden cardiac death requires further explanation. Additional data regarding changes in heart failure medication and ventricular function would be essential for proper interpretation.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022 including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of "old" drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensin receptor blockers plus ß-blockers), and secondary cardiovascular prevention (i.e. low-dose aspirin, ramipril and atorvastatin), thereby filling existing gaps in knowledge, and opening new avenues for the treatment of CVD. Clinical trials confirming the role of dapagliflozin in patients with HF and mildly reduced or preserved ejection fraction, long-term evolocumab to reduce the risk of cardiovascular events, vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation, antibiotic prophylaxis in patients at high risk for infective endocarditis before invasive dental procedures, and vutrisiran for the treatment of hereditary transthyretin-related amyloidosis with polyneuropathy were also reviewed. Finally, we briefly discuss recent clinical trials suggesting that FXIa inhibitors may have the potential to uncouple thrombosis from hemostasis and attenuate/prevent thromboembolic events with minimal disruption of hemostasis.

Relationship of Fibroblast Growth Factor 23 With Hospitalization for Heart Failure and Cardiovascular Outcomes in Patients Undergoing Cardiac Surgery.

Background Fibroblast growth factor 23 (FGF-23) is crucial in regulating phosphate and vitamin D metabolism and is moreover associated with an increased cardiovascular risk. The specific objective of this study was to investigate the influence of FGF-23 on cardiovascular outcomes, including hospitalization for heart failure (HHF), postoperative atrial fibrillation, and cardiovascular death, in an unselected patient population after cardiac surgery. Methods and Results Patients undergoing elective coronary artery bypass graft and/or cardiac valve surgery were prospectively enrolled. FGF-23 blood plasma concentrations were assessed before surgery. A composite of cardiovascular death/HHF was chosen as primary end point. A total of 451 patients (median age 70 years; 28.8% female) were included in the present analysis and followed over a median of 3.9 years. Individuals with higher FGF-23 quartiles showed elevated incidence rates of the composite of cardiovascular death/HHF (quartile 1, 7.1%; quartile 2, 8.6%; quartile 3, 15.1%; and quartile 4, 34.3%). After multivariable adjustment, FGF-23 modeled as a continuous variable (adjusted hazard ratio for a 1-unit increase in standardized log-transformed biomarker, 1.82 [95% CI, 1.34-2.46]) as well as using predefined risk groups and quartiles remained independently associated with the risk of cardiovascular death/HHF and the secondary outcomes, including postoperative atrial fibrillation. Reclassification analysis indicated that the addition of FGF-23 to N-terminal pro-B-type natriuretic peptide provides a significant improvement in risk discrimination (net reclassification improvement at the event rate, 0.58 [95% CI, 0.34-0.81]; P<0.001; integrated discrimination increment, 0.03 [95% CI, 0.01-0.05]; P<0.001). Conclusions FGF-23 is an independent predictor of cardiovascular death/HHF and postoperative atrial fibrillation in individuals undergoing cardiac surgery. Considering an individualized risk assessment, routine preoperative FGF-23 evaluation may improve detection of high-risk patients.