Reviewing the Modern Therapeutical Options and the Outcomes of Sacubitril/Valsartan in Heart Failure.

Sacubitril/valsartan (S/V) is a pharmaceutical strategy that increases natriuretic peptide levels by inhibiting neprilysin and regulating the renin-angiotensin-aldosterone pathway, blocking AT1 receptors. The data for this innovative medication are mainly based on the PARADIGM-HF study, which included heart failure with reduced ejection fraction (HFrEF)-diagnosed patients and indicated a major improvement in morbidity and mortality when S/V is administrated compared to enalapril. A large part of the observed favorable results is related to significant reverse cardiac remodeling confirmed in two prospective trials, PROVE-HF and EVALUATE-HF. Furthermore, according to a subgroup analysis from the PARAGON-HF research, S/V shows benefits in HFrEF and in many subjects having preserved ejection fraction (HFpEF), which indicated a decrease in HF hospitalizations among those with a left ventricular ejection fraction (LVEF) < 57%. This review examines the proven benefits of S/V and highlights continuing research in treating individuals with varied HF characteristics. The article analyses published data regarding both the safeness and efficacy of S/V in patients with HF, including decreases in mortality and hospitalization, increased quality of life, and reversible heart remodeling. These benefits led to the HF guidelines recommendations updating and inclusion of S/V combinations a key component of HFrEF treatment.

Acute Coronary Syndromes in Chronic Kidney Disease: Clinical and Therapeutic Characteristics.

Background and Objectives: This study evaluated the clinical characteristics of the acute coronary syndromes (ACS) in chronic kidney disease (CKD) patients and established prognostic values of the biomarkers and echocardiography. Materials and Methods: 273 patients admitted to the cardiology department of the Clinical County Emergency Hospital of Oradea, Romania, with ACS diagnosis were studied. Two study groups were formed according to the presence of CKD (137 patients with ACS + CKD and 136 with ACS without CKD). Kidney Disease: Improving Global Outcomes (KDIGO) threshold was used to assess the stages of CKD. Results: Data regarding the medical history, laboratory findings, biomarkers, echocardiography, and coronary angiography were analysed for both groups. ACS parameters were represented by ST-segment elevation myocardial infarction (STEMI), which revealed a greater incidence in subjects without CKD (43.88%); non-ST-segment elevation myocardial infarction (NSTEMI), characteristic for the CKD group (28.47%, with statistically significance p = 0.04); unstable angina and myocardial infarction with nonobstructive coronary arteries (MINOCA). Diabetes mellitus, chronic heart failure, previous stroke, and chronic coronary syndrome were more prevalent in the ACS + CKD group (56.93%, p < 0.01; 41.61%, p < 0.01; 18.25%, p < 0.01; 45.26%, p < 0.01). N-terminal pro b-type natriuretic peptide (NT-proBNP) was statistically higher (p < 0.01) in patients with CKD; Killip class 3 was evidenced more frequently in the same group (p < 0.01). Single-vessel coronary artery disease (CAD) was statistically more frequent in the ACS without CKD group (29.41%, p < 0.01) and three-vessel CAD or left main coronary artery disease (LMCA) were found more often in the ACS + CKD group (27.01%, 14.6%). Conclusions: Extension of the CAD in CKD subjects revealed an increased prevalence of the proximal CAD, and the involvement of various coronary arteries is characteristic in these patients. Biomarkers and echocardiographic elements can outline the evolution and outcomes of ACS in CKD patients.

Oxidative stress - Complex pathological issues concerning the hallmark of cardiovascular and metabolic disorders.

Oxidative stress is a complex biological process characterized by the excessive production of reactive oxygen species (ROS) that act as destroyers of the REDOX balance in the body and, implicitly, inducing oxidative damage. All the metabolisms are impaired in oxidative stress and even nucleic acid balance is influenced. ROS will promote structural changes of the tissues and organs due to interaction with proteins and phospholipids. The constellation of the cardiovascular risk factors (CVRFs) will usually develop in subjects with predisposition to cardiac disorders. Oxidative stress is usually related with hypertension (HTN), diabetes mellitus (DM), obesity and cardiovascular diseases (CVDs) like coronary artery disease (CAD), cardiomyopathy or heart failure (HF), that can develop in subjects with the above-mentioned diseases. Elements describing the complex relationship between CVD and oxidative stress should be properly explored and described because prevention may be the optimal approach. Our paper aims to expose in detail the complex physiopathology of oxidative stress in CVD occurrence and novelties regarding the phenomenon. Biomarkers assessing oxidative stress or therapy targeting specific pathways represent a major progress that actually change the outcome of subjects with CVD. New antioxidants therapy specific for each CVD represents a captivating and interesting future perspective with tremendous benefits on subject's outcome.

Acute coronary syndromes in diabetic patients, outcome, revascularization, and antithrombotic therapy.

Diabetes exacerbates the progression of atherosclerosis and is associated with increased risk of developing acute coronary syndrome (ACS). Approximatively 25-30% of patients admitted for ACS have diabetes. ACS occurs earlier in diabetics and is associated with increased mortality and a higher risk of recurrent ischemic events. An increased proinflammatory and prothrombotic state is involved in the poorer outcomes of diabetic patients. In the past decade advancement in both percutaneous coronary intervention (PCI) and coronary artery by-pass graft (CABG) techniques and more potent antiplatelet drugs like prasugrel and ticagrelor improved outcomes of diabetic patients with ACS, but this population still experiences worse outcomes compared to non-diabetic patients. While in ST elevation myocardial infarction urgent PCI is the method of choice for revascularization, in patients with non-ST elevation ACS an early invasive approach is suggested by the guidelines, but in the setting of multivessel (MV) or complex coronary artery disease (CAD) the revascularization strategy is less clear. This review describes the accumulating evidence regarding factors involved in promoting increased incidence and poor prognosis of ACS in patients with diabetes, the evolution over time of prognosis and outcomes, revascularization strategies and antithrombotic therapy studied until now.

Use of anticoagulant drugs in patients with atrial fibrillation. Does adherence to therapy have a prognostic impact?

Anticoagulant therapy represents a pivotal element that strongly influences the thromboembolic risk of non-valvular atrial fibrillation (NVAF) subjects. The main purpose of this review was to identify issues and suggest strategies to improve the oral anticoagulants (OACs) treatment adherence, which is the most important predictor of NVAF outcome. Advantages, efficacy, and impact of these drugs on patients' prognosis were revealed in important clinical trials on large cohorts of patients and are often prescribed nowadays. A real-life data registry, the Global Anticoagulant Registry in the Field-Atrial Fibrillation (GARFIELD-AF) analyzed the profile and outcome of patients diagnosed with NVAF receiving oral antithrombotic treatment. The observations gathered in the registry were crucial for identifying relevant elements that clinicians must improve, such as adherence strategies and predisposing factors that correlated with stroke. Adherence to OACs in AF patients is essential from the viewpoint of clinical efficacy and safety. Major adverse events and negative outcome are correlated with a weak anticoagulation control caused by an ineffective treatment adherence strategy. Solving the issue of oral anticoagulation adherence is possible using new technologies, but future directions should be explored. Mobile phone applications centered on patients' needs, telemedicine programs that evaluate patients' evolution and detect adverse reactions or events, encouraging an adequate management of the event without interruption of OACs, represent perspectives with a major impact on treatment adherence.

A Narrative Review of the Classical and Modern Diagnostic Methods of the No-Reflow Phenomenon.

The incidence of the no-reflow (NR) phenomenon varies depending on the diagnostic criteria used. If just the angiographic criteria are considered (i.e., a degree of thrombolysis in myocardial infarction ≤2), it will be found that the incidence of NR is quite low; on the other hand, when the myocardial NR is taken into account (i.e., a decrease in the quality of myocardial reperfusion expressed by the degree of myocardial blush), the real incidence is higher. Thus, the early establishment of a diagnosis of NR and the administration of specific treatment can lead to its reversibility. Otherwise, regardless of the follow-up period, patients with NR have a poor prognosis. In the present work, we offer a comprehensive perspective on diagnostic tools for NR detection, for improving the global management of patients with arterial microvasculature damage, which is a topic of major interest in the cardiology field, due to its complexity and its link with severe clinical outcomes.

Framing Cause-Effect Relationship of Acute Coronary Syndrome in Patients with Chronic Kidney Disease.

The main causes of death in patients with chronic kidney disease (CKD) are of cardiovascular nature. The interaction between traditional cardiovascular risk factors (CVRF) and non-traditional risk factors (RF) triggers various complex pathophysiological mechanisms that will lead to accelerated atherosclerosis in the context of decreased renal function. In terms of mortality, CKD should be considered equivalent to ischemic coronary artery disease (CAD) and properly monitored. Vascular calcification, endothelial dysfunction, oxidative stress, anemia, and inflammatory syndrome represents the main uremic RF triggered by accumulation of the uremic toxins in CKD subjects. Proteinuria that appears due to kidney function decline may initiate an inflammatory status and alteration of the coagulation-fibrinolysis systems, favorizing acute coronary syndromes (ACS) occurrence. All these factors represent potential targets for future therapy that may improve CKD patient's survival and prevention of CV events. Once installed, the CAD in CKD population is associated with negative outcome and increased mortality rate, that is the reason why discovering the complex pathophysiological connections between the two conditions and a proper control of the uremic RF are crucial and may represent the solutions for influencing the prognostic. Exclusion of CKD subjects from the important trials dealing with ACS and improper use of the therapeutical options because of the declined kidney functioned are issues that need to be surpassed. New ongoing trials with CKD subjects and platelets reactivity studies offers new perspectives for a better clinical approach and the expected results will clarify many aspects.

Atherosclerosis Burden and Therapeutic Challenges Regarding Acute Coronary Syndromes in Chronic Kidney Disease Patients.

The major cause of death in patients with chronic kidney disease is represented by cardiovascular events. Atherosclerosis is usually initiated by the association of traditional and non-traditional risk factors, and the acute thrombotic complications are more frequent in subjects with reduced glomerular filtration rate. The diagnosis of acute coronary syndromes is challenging due to the increased values of cardiac necrosis enzymes correlated with reduced renal function.