Risk factors for the development of HFrEF include hypertension, coronary artery disease, diabetes, obesity, and valvular heart disease. 2 HFrEF is associated with high morbidity and mortality rates, ...with a 5-year mortality rate of around 50% and a high risk of hospitalization. 3,4 It is also a leading cause of hospitalization in people over the age of 65. Research has highlighted the significance of a board treatment foundation in HF, as the more comprehensive the approach, the greater the degree of progressive improvement in outcome. 6 Vericiguat is a novel drug that has shown promising results in the treatment of HF. 7 It is a soluble guanylate cyclase (sGC) stimulator that works by increasing the production of cyclic guanosine monophosphate (cGMP), a molecule that promotes vasodilation and reduces oxidative stress and inflammation. 8 Endothelial NO synthase induces the production of nitric oxide (NO) in response to laminar flow and shear stress. NO diffuses to nearby cells and binds to the haem group of sGC, which in turn produces cGMP, activating protein kinase G. Protein kinase G phosphorylates proteins in the heart and vessels to promote diastolic relaxation, improve coronary blood flow, inhibit inflammation, hypertrophy, and fibrosis in response to cardiac damage, and improve ventricular-arterial coupling. 8 In the heart, there are seven isoforms of phosphodiesterase (PDE) that inactivate cGMP to GMP. 9 PDE3 inhibitors like milrinone and enoximone are used in acute HF, and PDE5 inhibitors such as sildenafil and udenafil improve contractile function in systolic HF, blunt left ventricular hypertrophic remodelling, reduce myocardial infarct size, and suppress ventricular arrhythmias, although neither class of drugs improves the outcome of HF patients. 9 Natriuretic peptides (NPs), particularly atrial NP or B-type NP, act on transmembrane receptors (NR-A and NR-B) with GC activity (particulate GC) to exert their biological effects, while NR-C receptors act as clearance receptors, decreasing plasma NP concentration, together with enzymatic cleavage by vasopeptidases like neprilysin. 10 In HFrEF, impaired left ventricular systolic function leads to tissue hypoperfusion, inflammation, and oxidative stress, resulting in decreased NO bioavailability and cGMP deficiency. 11 This cGMP deficiency has deleterious effects on the heart, kidneys, and vessels (including the pulmonary circulation), which may contribute to HF progression. 12,13 HFrEF patients commonly exhibit a reduced response to NPs, which may be due to various mechanisms, including altered production or clearance of active NPs, their binding to membrane receptors, or intracellular effects. 14 sGC modulators acting on a downstream target of the NO-sGC-cGMP pathway may circumvent NP resistance more effectively than other therapeutic strategies that aim to increase NP concentration, such as the administration of pharmacological doses of recombinant B-type NP (nesiritide and ularitide), which is associated with worsening renal function and no effect on outcome. 8,15,16 The sGC activator cinaciguat increases cGMP levels by directly activating sGC, independent of NO, and has a high risk of hypotension. 8 Conversely, sGC stimulators enhance sGC sensitivity to endogenous NO, which possibly explains their neutral effects on blood pressure. 8 While the sGC stimulator riociguat requires three administrations per day due to its shorter half-life, vericiguat has a more favourable pharmacology, which makes it more feasible for daily use considering drug compliance and adherence. 2,8 Efficacy and safety of vericiguat in heart failure with reduced ejection fraction Vericiguat has undergone phase 2 (SOCRATES-REDUCED) 17 and phase 3 (VICTORIA) 7 trials in the context of HFrEF. ...despite substantial advances in managing patients with HFrEF, there remains a demand for innovative treatments, particularly directed towards those with eGFR <30 mL/min/1.73 m2 and severe HFrEF.
Abstract Background Post-infarction cardiac rupture (CR) such as ventricular septal rupture (VSR), free wall rupture (FWR), atrial septal rupture (ASR) or papillary muscle rupture (PMR) is a rare but ...dreaded complication in patients with acute myocardial infarction (AMI) associated with a very poor prognosis with reported mortality rates between 60 and 100%. Therefore suitable risk stratification for secondary prevention seems crucial, but data on long-term survival und risk prediction in this especially vulnerable patient collective remains scarce. Methods Out of 11 641 patients presenting with AMI a total of 28 individuals suffering post-infarction CR were identified and stratified in “acute survivors of CR” (n = 10) and “non-survivors of CR” (n = 18). Cox regression hazard analysis was used to assess prognosticators on long-term survival. Results Ten patients (35.7%) survived the initial event. After a median follow-up time of 9 years 2 (20%) of the survivors died, both due to cardiovascular causes. Younger age (p = 0.023) and higher systolic blood pressure at admission (p = 0.018) turned out to be significant predictors of long-term survival. Systolic blood pressure 48 hours after CR proved to be a strong and independent predictor for survival with an adjusted hazard ratio per one standard deviation of 0.89 (95% CI: 0.72-0.99; 0.048). Conclusion Hemodynamic stabiliziation and severity of cardiogenic shock were detected as clinically most common among patients suffering post-infarction CR and proved to be of major importance for survival. If survival of the initial event was achieved, satisfying long-term mortality could be reached.
In cancer patients, thrombocytopenia can result from bone marrow infiltration or from anticancer medications and represents an important limitation for the use of antithrombotic treatments, including ...anticoagulant, antiplatelet, and fibrinolytic agents. These drugs are often required for prevention or treatment of cancer‐associated thrombosis or for cardioembolic prevention in atrial fibrillation in an increasingly older cancer population. Data indicate that cancer remains an independent risk factor for thrombosis even in case of thrombocytopenia, since mild‐to‐moderate thrombocytopenia does not protect against arterial or venous thrombosis. In addition, cancer patients are at increased risk of antithrombotic drug‐associated bleeding, further complicated by thrombocytopenia and acquired hemostatic defects. Furthermore, some anticancer treatments are associated with increased thrombotic risk and may generate interactions affecting the effectiveness or safety of antithrombotic drugs. In this complex scenario, the European Hematology Association in collaboration with the European Society of Cardiology has produced this scientific document to provide a clinical practice guideline to help clinicians in the management of patients with cancer and thrombocytopenia. The Guidelines focus on adult patients with active cancer and a clear indication for anticoagulation, single or dual antiplatelet therapy, their combination, or reperfusion therapy, who have concurrent thrombocytopenia because of either malignancy or anticancer medications. The level of evidence and the strength of the recommendations were discussed according to a Delphi procedure and graded according to the Oxford Centre for Evidence‐Based Medicine.
OBJECTIVE—Interleukin (IL)-33 is the most recently described member of the IL-1 family of cytokines and it is a ligand of the ST2 receptor. While the effects of IL-33 on the immune system have been ...extensively studied, the properties of this cytokine in the cardiovascular system are much less investigated.
METHODS/RESULTS—We show here that IL-33 promoted the adhesion of human leukocytes to monolayers of human endothelial cells and robustly increased vascular cell adhesion molecule-1, intercellular adhesion molecule-1, endothelial selectin, and monocyte chemoattractant protein-1 protein production and mRNA expression in human coronary artery and human umbilical vein endothelial cells in vitro as well as in human explanted atherosclerotic plaques ex vivo. ST2-fusion protein, but not IL-1 receptor antagonist, abolished these effects. IL-33 induced translocation of nuclear factor-κB p50 and p65 subunits to the nucleus in human coronary artery endothelial cells and human umbilical vein endothelial cells and overexpression of dominant negative form of IκB kinase 2 or IκBα in human umbilical vein endothelial cells abolished IL-33-induced adhesion molecules and monocyte chemoattractant protein-1 mRNA expression. We detected IL-33 and ST2 on both protein and mRNA level in human carotid atherosclerotic plaques.
CONCLUSION—We hypothesize that IL-33 may contribute to early events in endothelial activation characteristic for the development of atherosclerotic lesions in the vessel wall, by promoting adhesion molecules and proinflammatory cytokine expression in the endothelium.
Deleterious inflammatory responses are seen to be the trigger of heart failure in myocarditis and therapies directed towards immunomodulation have been assumed to be beneficial. The objective of the ...present review was to systematically assess the effect of immunomodulation in lymphocytic myocarditis. Studies were included if diagnosis of lymphocytic myocarditis was based on EMB as well as on the exclusion of other etiologies of heart failure and if the patients had at least moderately decreased left ventricular ejection fraction (< 45%). All immunomodulatory treatments at any dose that target the cause of myocarditis leading to cardiomyopathy were included. Retrieval of PUBMED, SCOPUS, Cochrane Central Register of Controlled Trials, and LILACs from January 1950 to January 2016 revealed 444 abstracts of which nine studies with a total of 612 patients were included. As primary effectivity endpoint, a change in left ventricular ejection was chosen. No benefits of corticosteroids or intravenous immunoglobulin alone were reported. Immunoadsorption and subsequent IVIG substitution was associated with a greater improvement in left ventricular ejection fraction (LVEF) in one study. Single studies found a beneficial effect of interferon and statins on LVEF. We performed a meta-analysis for the combination of corticosteroids with immunosuppressants and found a non-significant increase of LVEF of + 13.06% favoring combined treatment (95%CI 1.71 to + 27.84%,
p =
0.08). The current evidence does not support the routine use of immunosuppression in traditional lymphocytic myocarditis. Nevertheless, in histologically proven virus-negative myocarditis of high-risk patients, combined immunosuppression might be beneficial. Future research should focus on translation of these effects to clinical outcome.
Background:
The propensity of serum to calcify, as assessed by the T
50
-test, associates with mortality in patients with chronic kidney disease. In chronic heart failure, phosphate and fibroblast ...growth factor-23 (FGF-23), which are important components of the vascular calcification pathway, have been linked to patient survival. Here, we investigated whether T
50
associates with overall and cardiovascular survival in patients with chronic heart failure with reduced ejection fraction (HFrEF).
Methods:
We measured T
50
, intact and c-terminal FGF-23 levels in a cohort of 306 HFrEF patients. Associations with overall and cardiovascular mortality were analyzed in survival analysis and Cox-regression models.
Results:
After a median follow-up time of 3.2 years (25th−75th percentile: 2.0–4.9 years), 114 patients (37.3%) died due to any cause and 76 patients (24.8%) died due to cardiovascular causes. 139 patients (45.4%) had ischemic and 167 patients (54.6%) had non-ischemic HFrEF. Patients with ischemic HFrEF in the lowest T
50
-tertile had significantly greater 2-year cardiovascular mortality compared to patients in higher tertiles (
p
= 0.011). In ischemic but not in non-ischemic HFrEF, T
50
was significantly associated with cardiovascular mortality in univariate (
p
= 0.041) and fully adjusted (
p
= 0.046) Cox regression analysis. Significant associations of intact and c-terminal FGF-23 with all-cause and cardiovascular mortality in univariate Cox regression analysis did not remain significant after adjustment for confounding factors.
Conclusion:
T
50
is associated with 2-year cardiovascular mortality in patients with ischemic HFrEF but not in non-ischemic HFrEF. More research on the role of T
50
measurements in coronary artery disease is warranted.
Objectives: Secondary prevention is crucial for reducing morbidity and mortality in patients following acute myocardial infraction (MI). However, adherence to cardiac rehabilitation (CR) and ...pharmacotherapy remains suboptimal despite strong guideline recommendations. This study investigated the adherence to CR, dual antiplatelet therapy (DAPT), and statins following acute MI and evaluated their impact on patient outcomes from a nationwide perspective in Austria. Methods: In this national observational study, all patients diagnosed with acute MI, defined as STEMI or NSTEMI, between April 2011 and August 2015 in Austria were included. Patient characteristics and comorbidities were derived from the Austrian national health insurance system using ICD-10 codes. Adherence to CR, high-intensity statins, and DAPT was assessed based on health insurance records and pharmacy prescription submissions. Cox Regression hazard analysis was used to explore the impact of non-adherence to CR on mortality. Results: Among 16,518 acute MI patients, only 13.4% adhered to the recommended CR programs, which was associated with a significantly lower risk of mortality (adjusted hazard ratio HR 0.73; 95% CI: 0.54–0.98; p = 0.036). In contrast, 66.4% of 23,240 patients did not comply with high-intensity statin therapy, correlating with an increased mortality risk (adjusted HR 1.16; 95% CI: 1.06–1.25; p < 0.001). Furthermore, among 22,331 patients analyzed for DAPT adherence, only 29.3% followed the guidelines, yet this adherence was linked to a 21% reduction in mortality over the observation period (adjusted HR 0.79; 95% CI: 0.72–0.88; p < 0.001). Conclusions: This nationwide study reveals alarmingly low adherence to CR and secondary preventive medications among acute MI patients, which is significantly linked to higher mortality rates. Enhanced efforts to promote awareness and adherence are crucial, involving structured referrals and personalized follow-ups to improve patient outcomes. Addressing these gaps through comprehensive healthcare strategies could substantially enhance cardiovascular health.
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