Therapeutic Advances in Cardiovascular Disease最新文献

Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: 'dabigatran', 'apixaban', 'rivaroxaban', 'edoxaban', 'gene polymorphism', 'pharmacogenetics', 'ABCB1', 'CES1', 'SULT1A', 'ABCG2', and 'CYP3A4'. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.

Background: Although guidelines recommend intracoronary acetylcholine (ACh) and ergonovine (ER) provocation testing for diagnosis of vasospastic angina, the feasibility and safety of sequential (combined) use of both pharmacological agents during the same catheterization session remain unclear.

Objectives: In this study, we investigated the feasibility and safety of sequential intracoronary ACh and ER administration for coronary spasm provocation testing.

Methods: The study included 235 patients who showed positive results on ACh and ER provocation testing. Initial intracoronary ACh administration was followed by ER administration for left coronary artery (LCA) spasm provocation testing. Subsequently, the right coronary artery (RCA) was subjected to sequential ACh and ER administration for provocation testing. The primary outcome of the study was the safety of sequential intracoronary ACh and ER provocation testing, which was assessed based on a composite of all-cause death, sustained ventricular tachycardia and fibrillation, and cardiogenic shock.

Results: Even in patients with negative results on sequential intracoronary ACh and ER provocation testing in the LCA and only ACh administration into the RCA, additional administration of ER into the RCA showed a positive provocation test result in 33 of 235 (14.0%) patients; three (1.3%) patients developed adverse effects (cardiogenic shock occurred in all cases) during LCA provocation testing. We observed no deaths attributable to spasm provocation testing.

Conclusion: Sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of vasospastic angina.

Background: Inflammation has been suggested to play a role in heart failure (HF) pathogenesis. However, the role of platelet-to-lymphocyte ratio (PLR), as a novel biomarker, to assess HF prognosis needs to be investigated. We sought to evaluate the impact of PLR on HF clinical outcomes.

Methods: English-published records in PubMed/Medline, Scopus, and Web-of-science databases were screened until December 2023. Relevant articles evaluated PLR with clinical outcomes (including mortality, rehospitalization, HF worsening, and HF detection) were recruited, with PLR difference analysis based on death/survival status in total and HF with reduced ejection fraction (HFrEF) patients.

Results: In total, 21 articles (n = 13,924) were selected. The total mean age was 70.36 ± 12.88 years (males: 61.72%). Mean PLR was 165.54 [95% confidence interval (CI): 154.69-176.38]. In total, 18 articles (n = 10,084) reported mortality [either follow-up (PLR: 162.55, 95% CI: 149.35-175.75) or in-hospital (PLR: 192.83, 95% CI: 150.06-235.61) death rate] and the mean PLR was 166.68 (95% CI: 154.87-178.50). Further analysis revealed PLR was significantly lower in survived HF patients rather than deceased group (152.34, 95% CI: 134.01-170.68 versus 194.73, 95% CI: 175.60-213.85, standard mean difference: -0.592, 95% CI: -0.857 to -0.326, p < 0.001). A similar trend was observed for HFrEF patients. PLR failed to show any association with mortality risk (hazard ratio: 1.02, 95% CI: 0.99-1.05, p = 0.289). Analysis of other aforementioned outcomes was not possible due to the presence of few studies of interest.

Conclusion: PLR should be used with caution for prognosis assessment in HF sufferers and other studies are necessary to explore the exact association.

Background: The prevalence of heart failure (HF) is increasing among young adults in the United States with pervasive racial and ethnic differences in this population.

Objective: To evaluate contemporary associations between race and ethnicity, clinical comorbidities, and outcomes among young to middle-aged adults with HF.

Methods: A retrospective analysis was performed using the National Health and Nutrition Examination Survey. All participants with a self-report of HF aged 20-64 years from 2005 to 2018 were included and stratified by race and ethnicity [non-Hispanic (NH) Whites, NH Blacks, and Hispanics]. Data on baseline characteristics including age, sex, marital status, citizenship, education level, body mass index, insurance, waist circumference, cigarette smoking, marijuana use, and relevant clinical comorbidities were included. Weighted logistic regression was performed to estimate adjusted odds ratios (aOR) to determine the association of race and ethnicity with HF. Cox proportional-hazards models were used to assess the association of race and ethnicity with all-cause and cardiac mortality.

Results: A total of 1,940,447 young to middle-aged adults had self-reported HF between 2005 and 2018, of whom 61% were NH White, 40% were NH Black, and 22% were Hispanic. When compared with NH White adults, NH Black adults had higher odds of HF adjusted for age, sex, insurance status, marital status, education level, citizenship status, and clinical comorbidities (adjusted aOR 2.63, 95% CI: 1.71-4.05, p < 0.001). There was no significant difference in the odds of HF between Hispanic and NH White adults (aOR 1.18, 95% CI: 0.64-2.18, p = 0.585). NH Black adults had higher mean systolic and diastolic blood pressure, and a comparable or lower burden of cardiovascular and non-cardiovascular clinical comorbidities compared with NH White and Hispanic adults. No statistical significance was noted by race and ethnicity for all-cause and cardiac mortality during a follow-up of 5 years.

Conclusion: NH Black young to middle-aged adults were more likely to have HF which may be related to higher blood pressure given the largely similar burden of clinically relevant comorbidities compared with other racial and ethnic groups.

Background: Currently, no pharmacological or device-based intervention has been fully proven to reverse the no-reflow phenomenon.

Objectives: To assess the efficacy and safety of intracoronary (IC) epinephrine in the management of no-reflow phenomenon following percutaneous coronary intervention (PCI), either as first-line treatment or after the failure of conventional agents.

Design: Systematic review.

Data sources and methods: PubMed and Scopus databases were systematically searched up to 28 May 2022, with additional manual search on the Google Scholar and review of the reference lists of the relevant studies to identify all published studies. Cohort studies, case series, and interventional studies written in English which evaluated the efficacy and safety of IC epinephrine in patients with no-flow phenomenon were included in our review.

Results: Six of the 646 articles identified in the initial search met our inclusion criteria. IC epinephrine was used either as a first-line treatment [two randomized clinical trials (RCTs)] or after the failure of conventional agents (two cohort studies and two case series) for restoring the coronary flow, mainly after primary PCI. As first-line therapy, IC epinephrine successfully restored coronary flow in over 90% of patients in both RCTs, which significantly outperformed IC adenosine (78%) but lagged behind combination of verapamil and tirofiban (100%) in this regard. In the refractory no-flow phenomenon, successful reperfusion [thrombolysis in myocardial infarction (TIMI) flow grade = 3] was achieved in three out of four patients after the administration of IC epinephrine based on the results from both case series. Their findings were confirmed by a recent cohort study that further compared IC epinephrine with IC adenosine and found significant differences between them in terms of efficacy [% TIMI flow grade 3: (69.1% versus 52.7%, respectively; p value = 0.04)] and 1-year major adverse cardiac event (MACE) outcomes (11.3% versus 26.7%, respectively; p value ⩽ 0.01). Overall, malignant ventricular arrhythmias were reported in none of the patients treated with IC epinephrine.

Conclusion: Results from available evidence suggest that IC epinephrine might be an effective and safe agent in managing the no-reflow phenomenon.

Diabetic cardiomyopathy (DCM) is characterized by structural and functional abnormalities in the myocardium affecting people with diabetes. Treatment of DCM focuses on glucose control, blood pressure management, lipid-lowering, and lifestyle changes. Due to limited therapeutic options, DCM remains a significant cause of morbidity and mortality in patients with diabetes, thus emphasizing the need to develop new therapeutic strategies. Ongoing research is aimed at understanding the underlying molecular mechanism(s) involved in the development and progression of DCM, including oxidative stress, inflammation, and metabolic dysregulation. The goal is to develope innovative pharmaceutical therapeutics, offering significant improvements in the clinical management of DCM. Some of these approaches include the effective targeting of impaired insulin signaling, cardiac stiffness, glucotoxicity, lipotoxicity, inflammation, oxidative stress, cardiac hypertrophy, and fibrosis. This review focuses on the latest developments in understanding the underlying causes of DCM and the therapeutic landscape of DCM treatment.

Background: Myocarditis is now one of the most fatal and morbid complications of COVID-19. Many scientists have recently concentrated on this problem.

Objectives: This study assessed the effects of Remdesivir (RMS) and Tocilizumab (TCZ) in COVID-19 myocarditis.

Design: Observational, cohort study.

Methods: Patients with COVID-19 myocarditis were enrolled in the study and divided into three groups, TCZ-treated, RMS-treated, and Dexamethasone-treated patients. After 7 days of treatment, patients were reassessed for improvement.

Results: TCZ significantly improved patients' ejection fraction in 7 days, but it had limited efficacy. RMS improved inflammatory characteristics of the disease, but RMS-treated patients showed exacerbated cardiac function over 7 days, and the mortality rate with RMS was higher than TCZ. TCZ protects the heart by decreasing the miR-21 expression rate.

Conclusion: Using Tocilizumab in early diagnosed COVID-19 myocarditis patients can save their cardiac function after hospitalization and decrease the mortality rate. miR-21 level determines the outcome and responsiveness of COVID-19 myocarditis to treatment.

Infective endocarditis is a complex heterogeneous condition involving the infection of the endocardium and heart valves, leading to severe complications, including death. Surgery is often indicated in patients with infective endocarditis but is associated with elevated risk compared with other forms of cardiac surgery. Risk models play an important role in many cardiac surgeries as they can help inform clinicians and patients regarding procedural risk, decision-making to proceed or not, and influence perioperative management; however, they remain under-utilized in the infective endocarditis settings. Another crucial role of such risk models is to assess predicted versus found mortality, thereby allowing an assessment of institutional performance in infective endocarditis surgery. Traditionally, general cardiac surgery risk models such as European System for Cardiac Operative Risk Evaluation (EuroSCORE), EuroSCORE II, and Society of Thoracic Surgeon's score have been applied to endocarditis surgery. However, there has been the development of many endocarditis surgery-specific scores over the last decade. This review aims to discuss clinical characteristics and applications of all contemporary risk scores in the setting of surgical treatment of infective endocarditis.

G protein-coupled receptors (GPCRs) play pivotal roles in regulation of cardiac function and homeostasis. To function properly, every cell needs these receptors to be stimulated only when a specific extracellular stimulus is present, and to be silenced the moment that stimulus is removed. The regulator of G protein signaling (RGS) proteins are crucial for the latter to occur at the cell membrane, where the GPCR normally resides. Perturbations in both activation and termination of G protein signaling underlie numerous heart pathologies. Although more than 30 mammalian RGS proteins have been identified, each RGS protein seems to interact only with a specific set of G protein subunits and GPCR types/subtypes in any given tissue or cell type, and this applies to the myocardium as well. A large number of studies have provided substantial evidence for the roles various RGS proteins expressed in cardiomyocytes play in cardiac physiology and heart disease pathophysiology. This review summarizes the current understanding of the functional roles of cardiac RGS proteins and their implications for the treatment of specific heart diseases, such as heart failure and atrial fibrillation. We focus on cardiac RGS4 in particular, since this isoform appears to be selectively (among the RGS protein family) upregulated in human heart failure and is also the target of ongoing drug discovery efforts for the treatment of a variety of diseases.