Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis.

AIMS: The value of elective coronary revascularisation plus medical therapy over medical therapy alone in managing stable patients with coronary artery disease is debated. We reviewed all trials comparing the two strategies in this population. METHODS AND RESULTS: From inception through November 2020, MEDLINE, EMBASE, Google Scholar, and other databases were searched for randomised trials comparing revascularisation against medical therapy alone in clinically stable coronary artery disease patients. Treatment effects were measured by rate ratios (RRs) with 95% confidence intervals, using random-effects models. Cardiac mortality was the pre-specified primary endpoint. Spontaneous myocardial infarction (MI) and its association with cardiac mortality were secondary endpoints. Further endpoints included all-cause mortality, any MI, and stroke. Longest follow-up data were abstracted. The study is registered with PROSPERO (CRD42021225598). Twenty-five trials involving 19 806 patients (10 023 randomised to revascularisation plus medical therapy and 9783 to medical therapy alone) were included. Compared with medical therapy alone, revascularisation yielded a lower risk of cardiac death [RR 0.79 (0.67-0.93), P < 0.01] and spontaneous MI [RR 0.74 (0.64-0.86), P < 0.01]. By meta-regression, the cardiac death risk reduction after revascularisation, compared with medical therapy alone, was linearly associated with follow-up duration [RR per 4-year follow-up: 0.81 (0.69-0.96), P = 0.008], spontaneous MI absolute difference (P = 0.01) and percentage of multivessel disease at baseline (P = 0.004). Trial sequential and sensitivity analyses confirmed the reliability of the cardiac mortality findings. All-cause mortality [0.94 (0.87-1.01), P = 0.11], any MI (P = 0.14), and stroke risk (P = 0.30) did not differ significantly between strategies. CONCLUSION: In stable coronary artery disease patients, randomisation to elective coronary revascularisation plus medical therapy led to reduced cardiac mortality compared with medical therapy alone. The cardiac survival benefit after revascularisation improved with longer follow-up times and was associated with fewer spontaneous MIs.

Role of P2Y Receptors in Platelet Extracellular Vesicle Release.

Platelet extracellular vesicles (PEVs) are potential new biomarkers of platelet activation which may allow us to predict and/or diagnose developing coronary thrombosis before myocardial necrosis occurs. The P2Y1 and P2Y12 receptors play a key role in platelet activation and aggregation. Whereas the P2Y1 antagonists are at the preclinical stage, at present, the P2Y12 antagonists are the most effective treatment strategy to prevent stent thrombosis after percutaneous coronary intervention. Despite an increasing number of publications on PEVs, the mechanisms underlying their formation, including the role of purinergic receptors in this process, remain an active research field. Here, we outline the clinical relevance of PEVs in cardiovascular disease, summarize the role and downstream signalling of P2Y receptors in platelet activation, and discuss the available evidence regarding their role in PEV formation.

Validation of the CREST model & Comparison with SCAI Shock Classification for Prediction of Circulatory Death in Resuscitated Out of Hospital Cardiac Arrest.

OBJECTIVE: We validated the CREST model, a 5 variable score for stratifying risk of circulatory etiology death (CED) following out of hospital cardiac arrest (OHCA), and compared its discrimination with the SCAI shock classification. BACKGROUND: CED occurs in approximately a third of patients admitted after resuscitated OHCA. There is an urgent need for improved stratification of the OHCA patient on arrival to a cardiac arrest centre to improve patient selection for invasive interventions. METHODS: The CREST model and SCAI shock classification were applied to a dual-centre registry of 723 patients with cardiac etiology OHCA, both with and without ST-elevation myocardial infarction, between May 2012 to December 2020. The primary endpoint was 30-day CED. RESULTS: Of 509 patients included (62.3 years, 75.4% male), 125 patients had CREST=0 (24.5%), 162 were CREST=1 (31.8%), 140 were CREST=2 (27.5%), 75 were CREST=3 (14.7%), 7 were CREST of 4 (1.4%) and no patients were CREST=5. CED was observed in 91 (17.9%) patients at 30 days [STEMI - 51/289 (17.6%); NSTEMI - 40/220 (18.2%)]. For the total population, and both NSTEMI & STEMI subpopulations, increasing CREST score was associated with increasing CED (all p<0.001). CREST score and SCAI classification had similar discrimination for the total population (AUC=0.72/calibration slope=0.95), NSTEMI cohort (AUC=0.75/calibration slope=0.940) and STEMI cohort (AUC=0.69 and calibration slope=0.925). AUC meta-analyses demonstrated no significant differences between the two classifications. CONCLUSIONS: The CREST model and SCAI shock classification have similar prediction for the development of CED after OHCA.

Nanoparticles: a breakthrough in COVID-19 prevention, diagnosis and treatment.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared a global pandemic by the World Health Organization (WHO). The three key principles in management of the COVID-19 pandemic are prevention, early detection and targeted treatment. Vaccine-based prevention together with early detection has already proven its efficacy in controlling the pandemic. Early detection of infected patients could substantially accelerate the implementation of treatment, but also help to identify infection hotspots, whereas targeted treatment might destroy the virus and minimize damage to healthy tissue. Nanoparticles hold great promise with respect to these aspects. They may also be the solution to emerging clinical problems such as reinfection, pregnancy-related COVID-19 and coinfection. Here, we aim to discuss the potential applications of nanoparticles to combat the COVID-19 pandemic.

Sodium-Glucose Cotransporter 2 Inhibitors to Decrease the Uric Acid Concentration-A Novel Mechanism of Action.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are glucose-lowering agents whose positive impact on cardiovascular risk has been described extensively. Not only do they influence lipid profile, blood pressure, atherosclerosis risk, hemoglobin level, and insulin resistance, but they also reduce cardiovascular events, all-cause mortality, and hospitalization rates. Some of these effects may be due to their impact on serum uric acid (SUA) concentration. Findings from nine meta-analyses showed that, indeed, SGLT2is significantly reduce SUA. The data on the drug- and dose-dependency of this effect were inconclusive. Several factors alternating the beneficial effects of SGLT2is on SUA, such as glycated hemoglobin concentration (HbA1c), presence of diabetes, and baseline SUA level, were described. Even though there is a consensus that the lowering of SUA by SGLT2is might be due to the increased urinary excretion rate of uric acid (UEUA) rather than its altered metabolism, the exact mechanism remains unknown. The influence of SGLT2is on SUA may not only be used in gout treatment but may also be of huge importance in explaining the observed pleiotropic effects of SGLT2is.

Diagnostic value of soluble urokinase-type plasminogen activator receptor in patients with acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS. METHODS: A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used if I² < 50%; otherwise, the random-effects model was performed. RESULTS: Five studies with 3417 participants were included in the meta-analysis. Pooled analysis showed that mean suPAR levels in the ACS group were statistically significantly higher than in the control group (3.56 ± 1.38 vs. 2.78 ± 0.54 ng/mL, respectively; mean difference: 1.04; 95% confidence interval: 0.64-1.44; I² = 99%; p < 0.001). CONCLUSIONS: In the context of acute coronary syndrome, suPAR is a potential biomarker for the early identification of medical conditions in individuals who are being treated in emergency rooms.

Meta-analysis of chest compression-only versus conventional cardiopulmonary resuscitation by bystanders for adult with out-of-hospital cardiac arrest.

BACKGROUND: According to the guidelines of cardiopulmonary resuscitation (CPR) conducted by bystanders, two methods of CPR are feasible: standard CPR (sCPR) with mouth-to-mouth ventilations and continuous chest compression-only CPR (CCC) without rescue breathing. The goal herein, was to evaluate the effect of sCPR (30:2) and CCC on resuscitation outcomes in patients with out-of-hospital cardiac arrest (OHCA) patients. METHODS: This study was a systematic review and meta-analysis. Using standardized criteria, Pub- Med, Web of Science, Scopus, EMBASE and Cochrane Collaboration were searched for trials assessing the effect of sCPR vs. CCC on resuscitation outcomes after adult OHCA. Random-effects model meta-analysis was applied to calculate the mean deviation (MD), odds ratio (OR) and 95% confidence interval (CI). RESULTS: Overall, 3 randomized controlled trials and 12 non-randomized trials met the inclusion criteria. Survival to hospital discharge with sCPR was 10.2% compared to 9.3% in the CCC group (OR = 1.04; 95% CI: 0.93-1.16; p = 0.46). Survival to hospital discharge with good neurological outcome measured with the cerebral performance category (CPC 1 or 2) was 6.5% for sCPR vs. 5.8% for CCC (OR = 1.00; 95% CI: 0.84-1.20; p = 0.98). Prehospital return of spontaneous circulation (ROSC) in sCPR and CCC groups was 15.9% and 14.8%, respectively (OR = 1.13; 95% CI: 0.91-1.39; p = 0.26). Survival to hospital admission with ROSC occurred in 29.5% of the sCPR group compared to 28.4% in CCC group (OR = 1.20; 95% CI: 0.89-1.63; p = 0.24). CONCLUSIONS: This systematic review and meta-analysis concluded that there were no significant differences in the resuscitation outcomes between the use of standard cardiopulmonary resuscitation and chest compression only.

Emerging Role of Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease-Insights from the 2022 ESC Guidelines.

In this article, we discuss the topic of chronic thromboembolic pulmonary disease (CTEPD) and the growing role of balloon pulmonary angioplasty (BPA) in its treatment. We present the pathophysiology of CTEPD which arises from an incomplete resolution of thrombi in the pulmonary arteries and leads to stenosis and occlusion of the vessels. The article focuses mainly on the chronic thromboembolic pulmonary hypertension (CTEPH) subpopulation for which prognosis is very poor when left untreated. We describe a multimodal approach to treating CTEPH, including pulmonary endarterectomy (PEA), BPA, and pharmacological therapies. Additionally, the benefits of pharmacological pre-treatment before BPA and the technical aspects of the procedure itself are outlined. It is emphasized that BPA does not replace PEA but serves as a complementary treatment option for eligible patients. We summarized efficacy and treatment goals including an improvement in functional and biochemical parameters before and after BPA. Patients who received pre-treatment with riociguat prior to BPA exhibited a notable reduction in the occurrence of less severe complications. However, elderly patients are still perceived as an especially vulnerable group. It is shown that the prognosis of patients undergoing BPA is similar to PEA in the first years after the procedure but the long-term prognosis of BPA still remains unclear. The 2022 ESC/ERS guidelines highlight the significant role of BPA in the multimodal treatment of CTEPH, emphasizing its effectiveness and recommending its consideration as a therapeutic option for patients with CTEPD, both with and without pulmonary hypertension. This review summarizes the available evidence for BPA, patient selection, procedural details, and prognosis and discusses the potential future role of BPA in the management of CTEPH.

Inhibitors of sodium-glucose transport protein 2: A new multidirectional therapeutic option for heart failure patients.

Several mechanisms have been suggested to explain positive cardiovascular effects observed in studies with sodium-glucose co-transporter 2 (SGLT2) inhibitors. The reduction in glucose reabsorption in proximal tubuli induced by SGLT2 inhibitors increases urinary glucose and sodium excretion resulting in increased osmotic diuresis and consequently in decreased plasma volume, followed by reduced preload. In addition, the hemodynamic effects of SGLT2 inhibition were observed in both hyper and euglycemic patients. Due to the complex and multidirectional effects induced by SGLT2 inhibitors, this originally antidiabetic group of drugs has been successfully used to treat patients with heart failure as well as for subjects with chronic kidney disease. Moreover, their therapeutic potential seems to be even broader than the indications studied to date.

The plague of unexpected drug recalls and the pandemic of falsified medications in cardiovascular medicine as a threat to patient safety and global public health: A brief review.

Valsartan, losartan, and irbesartan, are widely used in the treatment strategies of cardiovascular medicine diseases, including hypertension and heart failure. Recently, many formulations for the aforementioned diseases contained active pharmaceutical ingredients and had been abruptly recalled from the market due to safety concerns mainly associated with unwanted impurities - nitrosamines, which are highly carcinogenic substances accidentally produced during manufacturing. Along with cardiovascular medications, formulations containing ranitidine were also recalled from the market. This poses a particular threat to public health due to the non-prescription status of these drugs. Regulatory authorities, including the Food and Drug Administration and European Medicines Agency among others, have taken action to minimize patient risk and improve the manufacturing quality as well as re-checking current guidelines and recommendations. While these steps are necessary to avoid further recalls, authorities should remember the growing concerns of patients regarding the safety and efficacy of pharmacotherapy. Apart from the genuine manufacturing mistakes mentioned above, falsified and counterfeit medications should be at the heart of global attention. The lack of a well-accepted definition of falsified/counterfeit medications has impeded political and scientific efforts to mitigate risk of this phenomenon. Falsified Medicines Directive should be considered the most pivotal legislation recently enacted to harmonize international cooperation. In summary, one should remember that only international and direct collaboration between patients, stakeholders, and authorities be considered a remedy for a pandemic of falsified medicines and plague of unexpected recalls due to safety concerns.

The diagnostic and prognostic value of copeptin in patients with acute ischemic stroke and transient ischemic attack: A systematic review and meta-analysis.

BACKGROUND: Stroke is the second main cause of mortality and the third leading cause of mortality and permanent disability combined. Many potential biomarkers have been described to contribute to the diagnosis, prognosis of outcomes, and risk stratification after stroke. Copeptin is an inactive peptide that is produced in an equimolar ratio to arginine vasopressin (AVP) in response to the activation of the endogenous stress system. METHODS: The present study isa systematic review and meta-analysis to assess plasma copeptin concentrations, diagnostic and prognostic values for risk stratification after acute ischemic stroke and transient ischemic attack. RESULTS: Mean copeptin level in stroke vs. non-stroke groups varied and amounted to 19.8 ± 17.4 vs. 9.7 ± 6.6 pmol/L, respectively (mean differences [MD]: 12.75; 95% confidence interval [CI]: 5.00 to 20.49; p < 0.001), in good vs. poor outcome 12.0 ± 3.6 vs. 29.4 ± 14.5 (MD: -8.13; 95% CI: -8.37 to -7.88; p < 0.001) and in survive vs. non-survive stroke patients: 13.4 ± 3.2 vs. 33.0 ± 12.3, respectively (MD: -13.43; 95% CI: -17.82 to -9.05; p < 0.001). CONCLUSIONS: The above systematic review and meta-analysis suggests that monitoring the copeptin levels may help predict the long-term prognosis of ischemic stroke efficiently. Determining the copeptin level may help individualize the management of ischemic stroke patients, keep stroke risk lower, reduce post-stroke complications, including patient death, and minimize healthcare costs.

Diagnostic value of lactate dehydrogenase in COVID-19: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis outlines the role of elevated lactate dehydrogenase (LDH) levels in assessing the severity of coronavirus disease 2019 (COVID-19). METHODS: The current study was designed as a systematic review and meta-analysis. Embase, Pub- Med, Web of Science, Scopus and Cochrane Central Register of Controlled Trials were searched to identify the usefulness of LDH as a marker of COVID-19 severity. All extracted data were analyzed using RevMan V.5.4 or STATA V.14 software. RESULTS: A total of 264 records were selected for this meta-analysis. Pooled analysis showed that LDH levels were statistically significantly lower in the group of survivors compared to patients who died in hospital (standardized mean differences [SMD] = -3.10; 95% confidence interval [CI]: -3.40 to -2.79; I2 = 99%; p < 0.001). Lower LDH levels were observed in non-severe groups compared to severe course of COVID-19 (SMD = -2.38; 95% CI: -2.61 to -2.14; I2 = 99%; p < 0.001). The level of LDH was statistically significantly lower in the severe group compared to the critical group (SMD = -1.48; 95% CI: -2.04 to -0.92; I2 = 98%; p < 0.001). Patients who did not require treatment in the intensive care unit (ICU) showed significantly lower levels of LDH compared to patients who required treatment in the ICU (SMD = -3.78; 95% CI: -4.48 to -3.08; I2 = 100%; p < 0.001). CONCLUSIONS: This meta-analysis showed that elevated LDH was associated with a poor outcome in COVID-19.

Should targeted temperature management be used in cardiogenic shock patients? Systematic review and meta-analysis.

BACKGROUND: Therapeutic hypothermia, or targeted temperature management (TTM), is a strategy of reducing the core body temperature of survivors of sudden cardiac arrest, cardiogenic shock (CS) or stroke. Therefore, a systematic literature review and meta-analysis were performed to tackle the question about whether the implementation of TTM is actually beneficial for patients with CS. METHODS: Study was designed as a systematic review and meta-analysis. PubMed, Cochrane Library, Web of Science and Scopus were searched from these databases inception to July 17, 2022. Eligible studies were those comparing TTM and non-TTM treatment in CS patients. Data were pooled with the Mantel-Haenszel method. RESULTS: Thirty-day mortality was reported in 3 studies. Polled analysis of 30-day mortality was 44.2% for TTM group and 48.9% for non-TTM group (risk ratio: 0.90; 95% confidence interval: 0.75 to 1.08; p = 0.27). Other mortality follow-up periods showed also no statistically significant differences (p > 0.05). The occurrence of adverse events in the studied groups also did not show statistically significant differences between TTM and non-TTM groups (p > 0.05 for myocardial infarction, stent thrombosis, sepsis, pneumonia, stroke or bleeding events). CONCLUSIONS: The present analysis shows no significant benefit of TTM in patients with CS. Moreover, no statistically significant increase of the incidence of adverse effects was found. However, further randomized studies with higher sample size and greater validity are needed to determine if TTM is worth implementing in CS patients.