Cardiovascular Therapeutics

Objectives. To observe the effect of avβ3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. Background. Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avβ3, which is widely expressed on various cell surfaces, plays an important role in the proliferation and migration of VSMCs. Methods. In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avβ3 ssDNA, which has high affinity and specificity to the avβ3 protein. MTT, Transwell, and cell scratch assays were carried out to examine the effect of avβ3 ssDNA on the proliferation and migration of VSMCs. Flow cytometry was performed to detect apoptosis and cell cycle progression. The effect of avβ3 ssDNA on the Ras-phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) signaling pathway was evaluated by quantitative reverse transcription polymerase chain reaction and western blot. Results. In the present study, we found that avβ3 ssDNA significantly decreased the expression of osteopontin, focal adhesion kinase, Ras, p-PI3K, and p-MAPK at both mRNA and protein levels (). Avβ3 ssDNA also inhibited VSMC proliferation and migration while promoting apoptosis (), as demonstrated by the upregulation of the proapoptotic proteins Bax and active caspase 3 (). Conclusions. The findings suggest that avβ3 ssDNA inhibited the proliferation and migration of VSMCs by suppressing the activation of Ras-PI3K/MAPK signaling.

Read the full article

Objective. This study aimed to compare the effectiveness of drug-coated balloons (DCB) with everolimus-eluting stents (EES) in the treatment of in-stent restenosis (ISR) and the differential relative effect of DCB in patients with drug-eluting stents (DES)-ISR and bare metal stents (BMS)-ISR. Background. The efficiency and safety of DCB and EES need to be assessed for the treatment of ISR. Methods. A systematic literature search was conducted using PubMed and EMBASE to identify all relevant studies. Angiographic results and clinical events were separately assessed. Subgroup meta-analyses were performed according to the type of restenosed stent. Results. Six randomized trials with 1134 patients were included. The overall pooled outcomes indicated that DCB was associated with lower minimum lumen diameter (mean difference , 95% CI = −0.29 to −0.05, ) and higher target lesion revascularization (risk ratio , 95% CI = 1.36 to 4.18, ) than EES. However, the subgroup meta-analyses showed that DCB was inferior to EES only in DES-ISR patients, with lower minimum lumen diameter (, 95% CI = −0.37 to −0.14, ), higher percent diameter stenosis (, 95% CI = 1.33 to 9.42, ), more binary restenosis (, 95% CI = 1.20 to 3.58, ), and higher incidence of target vessel revascularization (, 95% CI = 1.22 to 3.50, ) and target lesion revascularization (, 95% CI = 1.28 to 4.22, ). No differences in angiographic results and clinical events were found between DCB and EES in BMS-ISR patients. Conclusions. DCB was inferior to EES in DES-ISR and comparable in BMS-ISR in terms of angiographic results and clinical events.

Read the full article

Introduction. Including healthcare professionals dealing with cardiovascular diseases, Heart Team is a concept/structure designed for selecting diagnostic strategies, facilitating therapeutic decisions, and improving cardiovascular outcomes in patients with complex heart pathologies, requiring input from different subspecialties and the necessity of a multidisciplinary approach. The aim of this narrative review is to search for and to summarize current evidence regarding Heart Team and to underline the future directions for the development of this concept. Methods. We searched the electronic database of PubMed, SCOPUS, and Cochrane CENTRAL for studies including Heart Team. Forty-eight studies were included, if reference was made to Heart Team structure and functionality. Results. We depicted the structure and the timeline of Heart Team, along with actual evidence-based recommendations from European Guidelines. We underlined the importance of quality of knowledge-sharing and decision-making inside the Team, analyzing bad decisions which did not reflect members’ true beliefs due to “uniformity pressure, closed mindedness, and illusion of invulnerability.” The observation that Guidelines’ indications regarding Heart Team carry a level C indication underlines the very future of this Team: randomized controlled trials proving solid benefits in an evidence-based world. Conclusions. Envisioned as a tool for optimizing the management of various complex cardiovascular pathologies, Heart Team should simplify and facilitate the activity in the cardiovascular ward. Finally, these facts should be translated into better cardiovascular outcomes and a lower psychological distress among Team participants. Despite all future changes, there must always be a constant part: the patient should remain at the very center of the Team.

Read the full article

Objective. This prospective study aimed to evaluate the value of the cardiac cycle time-corrected electromechanical activation time (EMATc) measured at admission for predicting major cardiac adverse events (MACEs) in hospitalized patients with chronic heart failure (CHF). Methods. CHF patients with a left ventricular ejection fraction (LVEF) lower than 50% were enrolled in this study. Documented clinical end-points (MACEs) included cardiogenic death, onset of acute HF as assessed with invasive and noninvasive mechanical ventilation, and cardiogenic shock. According to the different clinical end-points, patients were divided into two groups: a MACE group and a nonMACE group . EMATc, LVEF, and circulating levels of B type natriuretic peptide (BNP) and Troponin I (TnI) were measured. Multivariate logistic regression analysis was used to examine the association between EMATc and MACEs. The parameters adjusted in the multivariable model included EMATc, BNP, and heart rate. The predictive value of EMATc was evaluated by receiver operating characteristic (ROC) curve analysis. Results. Elevated EMATc was an independent risk factor for MACEs (odds ratio [OR] 1.1443, 95% confidence interval [CI] 1.016–1.286, ). The area under the ROC curve for EMATc was 0.799 (95% CI 0.702–0.896, ). The optimal cutoff EMATc value was >13.8% with a sensitivity of 81.8% and a specificity of 65.9%. Conclusions. We demonstrated that an elevated EMATc measured at admission is an independent risk factor for MACEs among hospitalized CHF patients. Acoustic cardiography measured at admission may provide a simple, noninvasive method for risk stratification of CHF patients. This trial is registered with ChiCTR1900021470.

Read the full article

Introduction. The current use of lipid lowering therapies and the eligibility for proprotein convertase subtilisin/kexin-9 (PCSK9) inhibitors of patients surviving a myocardial infarction (MI) is poorly known. Methods. Using the data from two contemporary, nationwide, prospective, real-world registries of patients with stable coronary artery disease, we sought to describe the lipid lowering therapies prescribed by cardiologists in patients with a prior MI and the resulting eligibility for PCSK9 inhibitors according to the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) and the Italian regulatory agency (Agenzia Italiana del Farmaco; AIFA) criteria. The study cohort was stratified according to the following low-density lipoprotein cholesterol (LDL-C) levels at the time of enrolment: <70 mg/dl; 70–99 mg/dl and ≥100 mg/dl. Results. Among the 3074 post-MI patients with LDL-C levels available, a target level of LDL-C < 70 mg/dl was present in 1186 (38.6%), while 1150 (37.4%) had LDL-C levels ranging from 70 to 99 mg/dl and the remaining 738 (24.0%) an LDL-C ≥ 100 mg/dl. A statin was prescribed more frequently in post-MI patients with LDL-C levels <70 mg/dl (97.1%) compared to the other LDL-C groups (). A low dose of statin was prescribed in 9.3%, while a high dose in 61.4% of patients. Statin plus ezetimibe association therapy was used in less than 18% of cases. In the overall cohort, 293 (9.8%) and 450 (22.2%) resulted eligible for PCSK9 inhibitors, according to ESC/EAS and AIFA criteria, respectively. Conclusions. Post-MI patients are undertreated with conventional lipid lowering therapies. A minority of post-MI patients would be eligible to PCSK9 inhibitors according to ESC/EAS guidelines and Italian regulatory agency criteria.

Read the full article

Aim. Myocarditis and cardiomyopathy impose a substantial economic burden on society. Many studies have examined the effects of various predictors on the prognosis of these diseases, such as the left ventricular systolic function, the New York Heart Association glomerular filtration rate, the QT interval, and the presence of viruses. In the present study, we conducted a meta-analysis of cohort studies to investigate the significance of the presence of viruses in the myocardial tissue on the prognosis of these diseases. Methods. The Embase, PubMed, and Cochrane library databases were searched for relevant literature that had been published between January 1, 1964 and August 14, 2018. The inclusion criteria were patients over 18 years of age, suspected myocarditis or dilated cardiomyopathy, accepted myocardial biopsy, and the detection of virus in the myocardial tissue. Results. In total, 10 studies met the inclusion criteria. These studies included 1006 patients with suspected myocarditis or idiopathic heart disease for whom the primary endpoint was all-cause death, heart transplant, or re-hospitalization due to fatal arrhythmia and heart failure. There was no significant difference in the prognosis of virus-positive and virus-negative patients with myocarditis or dilated cardiomyopathy confirmed by endomyocardial biopsy (EMB) [hazard ratio (HR) = 1.40, 95% confidence interval (CI) = 0.93–2.12, ]. However, virus-negative patients had a better prognosis following nonspecific treatment (HR = 1.40, 95% CI = 1.06–1.86, ) and right ventricular biopsy (HR = 2.08, 95% CI = 1.07–4.04, ). Conclusions. The presence of a virus did not worsen the long-term prognosis of patients with suspected myocarditis or dilated cardiomyopathy. However, virus-positive patients who did not undergo specific treatment or who underwent right ventricular biopsy did have a worse prognosis. Thus, the early diagnosis of the presence of viral infection in the myocardium will improve the prognosis of patients.

Read the full article