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Frontiers in Cardiovascular Medicine 2020The restoration of coronary circulation plays a crucial role in treating ST-segment elevation myocardial infarction (STEMI), however successful reperfusion with primary...
The restoration of coronary circulation plays a crucial role in treating ST-segment elevation myocardial infarction (STEMI), however successful reperfusion with primary percutaneous coronary intervention (PPCI) may induce life-threatening arrhythmias. The relation between myocardial electrical instability, as a background factor in reperfusion arrhythmia, and magnesium administered periprocedurally is still questionable. Several randomized clinical trials have been conducted predominantly in the thrombolysis era. Due to the contradictory results of these studies, there is little evidence of the potential preventive effect of magnesium on reperfusion arrhythmias. The aim of our study is to review and meta-analytically analyze data from all studies published so far in the PPCI era, comparing STEMI patients who have undergone primary PCI and received either magnesium or a placebo before the reperfusion procedure. Our meta-analysis follows the points in the PRISMA protocol and, meets all of their criteria. We conducted a search in five scientific databases using the following keyword combination: (myocardial infarction OR myocardial injury OR acute coronary syndrome OR acs OR stemi) AND magnesium. The 7,295 collected publications were filtered with the Endnote program by title, abstract and full-text based on predefined criteria. A statistical analysis was performed on three randomized-controlled trials using three common parameters, involving 336 patients Trial sequential analysis (TSA) was applied to assess the risk of random error associated with sparse data and multiple testing which can affect cumulative meta-analysis. The incidence of ventricular tachycardias (VTs) was not significantly increased in the non-magnesium control group. (OR: 1.36; CI: 0.619; -2.986, = 0.263). For the ejection fraction (EF), a non-significant decrease was observed in the magnesium group by weighted mean difference calculation. (WMD: 7.262, 95% CI: -0.238; 0.053; = 0.057). There was significant decrease in the infarct zone wall motion index (IZWMSI) in the magnesium treatment group. (WMD: 0.384, 95% CI: -0.042; 0.811, = 0.015). Based on the TSA assessments, the results of all parameters are not significant, objectively demonstrating the lack of reasonable data pertaining to our question. The preventive effect of magnesium on reperfusion arrhythmia associated with primary PCI can still be considered contradictory based on previous studies. In our study, we found, that magnesium is ineffective with a very weak evidence, due to the small number of patients and the biases of the included studies, and a well-designed clinical trial is needed in this area, based on the TSA.
PubMed: 33585581
DOI: 10.3389/fcvm.2020.608193 -
Diabetologia Apr 2021Large cardiovascular outcome trials demonstrated that the cardioprotective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors might reach beyond... (Meta-Analysis)
Meta-Analysis
AIMS/HYPOTHESIS
Large cardiovascular outcome trials demonstrated that the cardioprotective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors might reach beyond glucose-lowering action. In this meta-analysis, we sought to evaluate the potential infarct size-modulating effect of SGLT2 inhibitors in preclinical studies.
METHODS
In this preregistered meta-analysis (PROSPERO: CRD42020189124), we included placebo-controlled, interventional studies of small and large animal models of myocardial ischaemia-reperfusion injury, testing the effect of SGLT2 inhibitor treatment on myocardial infarct size (percentage of area at risk or total area). Standardised mean differences (SMDs) were calculated and pooled using random-effects method. We evaluated heterogeneity by computing Τ and I values. Meta-regression was performed to explore prespecified subgroup differences according to experimental protocols and their contribution to heterogeneity was assessed (pseudo-R values).
RESULTS
We identified ten eligible publications, reporting 16 independent controlled comparisons on a total of 224 animals. Treatment with SGLT2 inhibitor significantly reduced myocardial infarct size compared with placebo (SMD = -1.30 [95% CI -1.79, -0.81], p < 0.00001), referring to a 33% [95% CI 20%, 47%] difference. Heterogeneity was moderate (Τ = 0.58, I = 60%). SGLT2 inhibitors were only effective when administered to the intact organ system, but not to isolated hearts (p interaction <0.001, adjusted pseudo-R = 47%). While acute administration significantly reduced infarct size, chronic treatment was superior (p interaction <0.001, adjusted pseudo-R = 85%). The medications significantly reduced infarct size in both diabetic and non-diabetic animals, favouring the former (p interaction = 0.030, adjusted pseudo-R = 12%). Treatment was equally effective in rats and mice, as well as in a porcine model. Individual study quality scores were not related to effect estimates (p = 0.33). The overall effect estimate remained large even after adjusting for severe forms of publication bias.
CONCLUSIONS/INTERPRETATION
The glucose-lowering SGLT2 inhibitors reduce myocardial infarct size in animal models independent of diabetes. Future in vivo studies should focus on clinical translation by exploring whether SGLT2 inhibitors limit infarct size in animals with relevant comorbidities, on top of loading doses of antiplatelet agents. Mechanistic studies should elucidate the potential relationship between the infarct size-lowering effect of SGLT2 inhibitors and the intact organ system.
Topics: Animals; Cardiovascular Agents; Disease Models, Animal; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Sodium-Glucose Transporter 2 Inhibitors; Translational Research, Biomedical
PubMed: 33483761
DOI: 10.1007/s00125-020-05359-2 -
The Journal of International Medical... Nov 2020There is controversy whether nicorandil treatment has cardioprotective effects in patients with acute myocardial infarction (AMI) following percutaneous coronary... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
There is controversy whether nicorandil treatment has cardioprotective effects in patients with acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI). This meta-analysis was conducted to assess the efficacy of nicorandil on functional and clinical outcomes after PCI.
METHODS
Systematic databases were searched to retrieve studies that compared the effect of nicorandil with a control group in patients with AMI who underwent PCI. Outcomes related to coronary blood flow, and functional and clinical outcomes were extracted and a meta-analysis was performed. Trial sequential analysis was conducted to estimate the required sample size for statistical power.
RESULTS
Twenty-four trials involving 2965 patients with AMI were enrolled. Pooled results showed that nicorandil treatment significantly suppressed the incidence of no-reflow phenomenon and reperfusion arrhythmia after reperfusion, improved the left ventricular ejection fraction and left ventricular end-systolic volume index, and reduced major adverse cardiovascular events and cardiovascular death. Trial sequential analysis confirmed the effect of nicorandil in reducing the incidence of no-reflow phenomenon and follow-up major adverse cardiovascular events in patients with AMI after PCI.
CONCLUSION
Our findings suggest that nicorandil treatment adjunctive to reperfusion therapy improves myocardial reperfusion, cardiac function, and clinical outcomes in patients with AMI.
Topics: Humans; Myocardial Infarction; Nicorandil; Percutaneous Coronary Intervention; Stroke Volume; Ventricular Function, Left
PubMed: 33249959
DOI: 10.1177/0300060520967856 -
European Heart Journal. Quality of Care... Jan 2021The COVID-19 pandemic has disrupted healthcare services around the world, which may have serious implications for the prognosis of patients with acute cardiovascular...
The COVID-19 pandemic has disrupted healthcare services around the world, which may have serious implications for the prognosis of patients with acute cardiovascular disease. We conducted a systematic review to assess the extent to which health services related to the care and management of acute cardiovascular events have been impacted during the COVID-19 pandemic. PubMed, MedRxiv, and Google Scholar were searched for observational studies published up to 12 August 2020 for studies that assessed the impact of the pandemic on the care and management of people with acute cardiovascular disease (CVD). In total, 27 articles were included. Of these, 16 examined the impact on acute coronary syndromes (ACS), eight on strokes, one on ACS and strokes, and two on other types of CVD. When comparing the COVID-19 period to non-COVID-19 periods, 11 studies observed a decrease in ACS admissions ranging between 40% and 50% and 5 studies showed a decrease in stroke admissions of between 12% and 40%. Four studies showed a larger reduction in non-ST-segment elevation myocardial infarctions compared to ST-segment elevation myocardial infarctions. A decrease in the number of reperfusion procedures, a shortening in the lengths of stay at the hospital, and longer symptom-to-door times were also observed. The COVID-19 pandemic has led to a substantial decrease in the rate of admissions for acute CVD, reductions in the number of procedures, shortened lengths of stay at the hospital, and longer delays between the onset of the symptoms and hospital treatment. The impact on patient's prognosis needs to be quantified in future studies.
Topics: COVID-19; Cardiovascular Diseases; Delayed Diagnosis; Hospitalization; Humans; Length of Stay; Pandemics; Patient Acceptance of Health Care; Prognosis; SARS-CoV-2; Time-to-Treatment
PubMed: 33151274
DOI: 10.1093/ehjqcco/qcaa084 -
Diagnostics (Basel, Switzerland) Nov 2020The complement system has a significant role in myocardial ischemia/reperfusion injury, being responsible for cell lysis and amplification of inflammatory response. In... (Review)
Review
The complement system has a significant role in myocardial ischemia/reperfusion injury, being responsible for cell lysis and amplification of inflammatory response. In this context, several studies highlight that terminal complement complex C5b-9, also known as the membrane attack complex (MAC), is a significant contributor. The MAC functions were studied by many researchers analyzing the characteristics of its activation in myocardial infarction. Here, a systematic literature review was reported to evaluate the principal features, advantages, and limits (regarding the application) of complement components and MAC in post mortem settings to perform the diagnosis of myocardial ischemia/infarction. The review was performed according to specific inclusion and exclusion criteria, and a total of 26 studies were identified. Several methods studied MAC, and each study contributes to defining better how and when it affects the myocardial damage in ischemic/reperfusion injury. The articles were discussed, focusing on the specificity, sensibility, and post mortem stability of MAC as a marker of myocardial ischemia/infarction, supporting the usefulness in routine post mortem investigations.
PubMed: 33147886
DOI: 10.3390/diagnostics10110898 -
Biochimica Et Biophysica Acta.... Jan 2021The mitochondrial permeability transition pore (mPTP) opening is involved in the pathophysiology of multiple cardiac diseases, such as ischemia/reperfusion injury and...
The mitochondrial permeability transition pore (mPTP) opening is involved in the pathophysiology of multiple cardiac diseases, such as ischemia/reperfusion injury and heart failure. A growing number of evidence provided by proteomic screening techniques has demonstrated the role of post-translational modifications (PTMs) in several key components of the pore in response to changes in the extra/intracellular environment and bioenergetic demand. This could lead to a fine, complex regulatory mechanism that, under pathological conditions, can shift the state of mitochondrial functions and, thus, the cell's fate. Understanding the complex relationship between these PTMs is still under investigation and can provide new, promising therapeutic targets and treatment approaches. This review, using a systematic review of the literature, presents the current knowledge on PTMs of the mPTP and their role in health and cardiac disease.
Topics: Heart Failure; Humans; Mitochondria, Heart; Mitochondrial Permeability Transition Pore; Myocardial Reperfusion Injury; Protein Processing, Post-Translational; Proteomics
PubMed: 33091565
DOI: 10.1016/j.bbadis.2020.165992 -
Advanced Drug Delivery Reviews 2020Myocardial infarction (MI) is one of the leading causes of mortality worldwide. It is caused by an acute imbalance between oxygen supply and demand in the myocardium,...
Myocardial infarction (MI) is one of the leading causes of mortality worldwide. It is caused by an acute imbalance between oxygen supply and demand in the myocardium, usually caused by an obstruction in the coronary arteries. The conventional therapy is based on the application of (a combination of) anti-thrombotics, reperfusion strategies to open the occluded artery, stents and bypass surgery. However, numerous patients cannot fully recover after these interventions. In this context, new therapeutic methods are explored. Three decades ago, the first biologicals were tested to improve cardiac regeneration. Angiogenic proteins gained popularity as potential therapeutics. This is not straightforward as proteins are delicate molecules that in order to have a reasonably long time of activity need to be stabilized and released in a controlled fashion requiring advanced delivery systems. To ensure long-term expression, DNA vectors-encoding for therapeutic proteins have been developed. Here, the nuclear membrane proved to be a formidable barrier for efficient expression. Moreover, the development of delivery systems that can ensure entry in the target cell, and also correct intracellular trafficking towards the nucleus are essential. The recent introduction of mRNA as a therapeutic entity has provided an attractive intermediate: prolonged but transient expression from a cytoplasmic site of action. However, protection of the sensitive mRNA and correct delivery within the cell remains a challenge. This review focuses on the application of synthetic delivery systems that target the myocardium to stimulate cardiac repair using proteins, DNA or RNA.
Topics: Biological Products; DNA; Drug Delivery Systems; Genetic Therapy; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardium; Nanoparticles; Proteins; RNA, Messenger; Regeneration; Tissue Scaffolds
PubMed: 33039498
DOI: 10.1016/j.addr.2020.10.003 -
BMJ Open Sep 2020To summarise existing data on the relation between the time from symptom onset until revascularisation (time to reperfusion) and the myocardial salvage index (MSI)...
OBJECTIVE
To summarise existing data on the relation between the time from symptom onset until revascularisation (time to reperfusion) and the myocardial salvage index (MSI) calculated as proportion of non-necrotic myocardium inside oedematous myocardium on T2-weighted and T1-weighted late gadolinium enhancement MRI after ST-segment elevation myocardial infarction (STEMI).
METHODS
Studies including patients with revascularised STEMI and stating both the time to reperfusion and the MSI measured by T2-weighted and T1-weighted late gadolinium enhancement MRI were searched in MEDLINE, EMBASE and ISI Web of Science until 16 May 2020. A mixed effects model was used to evaluate the relation between the time to reperfusion and the MSI. The gender distribution and mean age in included patient groups, the timing of MRI, used MRI sequences and image interpretation methodology were included in the mixed effects model to explore between-study heterogeneity.
RESULTS
We included 38 studies with 5106 patients. The pooled MSI was 42.6% (95% CI: 38.1 to 47.1). The pooled time to reperfusion was 3.8 hours (95% CI: 3.5 to 4.0). Every hour of delay in reperfusion was associated with an absolute decrease of 13.1% (95% CI: 11.5 to 14.6; p<0.001) in the MSI. Between-study heterogeneity was considerable (σ=167.8). Differences in the gender distribution, timing of MRI and image interpretation among studies explained 45.2% of the between-study heterogeneity.
CONCLUSIONS
The MSI on T2-weighted and T1-weighted late gadolinium enhancement MRI correlates inversely with the time to reperfusion, which indicates that cardioprotection achieved by minimising the time to reperfusion leads to a higher MSI. The analysis revealed considerable heterogeneity between studies. The heterogeneity could partly be explained by differences in the gender distribution, timing and interpretation of MRI suggesting that the MRI-assessed MSI is not only influenced by cardioprotective therapy but also by patient characteristics and MRI parameters.
Topics: Contrast Media; Gadolinium; Humans; Magnetic Resonance Imaging; Myocardium; Regression Analysis; ST Elevation Myocardial Infarction; Treatment Outcome
PubMed: 32988935
DOI: 10.1136/bmjopen-2019-034359 -
Journal of Cardiovascular Translational... Jun 2021We conducted a meta-analysis of preclinical studies that tested left ventricular assist device (LVAD) therapy for reducing myocardial infarct size in experimental acute... (Meta-Analysis)
Meta-Analysis
We conducted a meta-analysis of preclinical studies that tested left ventricular assist device (LVAD) therapy for reducing myocardial infarct size in experimental acute myocardial infarction (AMI). Twenty-six articles were included with a total of 488 experimental animal subjects. The meta-analysis showed that infarct size was significantly decreased by LVAD support compared to control animals (SDM, - 2.19; 95% CI, - 2.70 to - 1.69; P < 0.001). The meta-regression analysis demonstrated a high degree of heterogeneity associated with time from coronary artery occlusion to LVAD support, which correlated positively with infarct size. Subgroup analysis suggested smaller infarct size in LVAD therapies that withdrew blood from left heart than those from right heart. The proportion of left ventricular support relative to total cardiac output was positively correlated with infarct size reduction in Impella studies. Thus, early initiation of LVAD after ischemia and effective left ventricular venting may be important factors to reduce infarct size in AMI.
Topics: Animals; Disease Models, Animal; Heart-Assist Devices; Myocardial Infarction; Myocardium; Prosthesis Design; Prosthesis Implantation; Ventricular Function, Left
PubMed: 32860130
DOI: 10.1007/s12265-020-10068-7 -
Nutrients Jul 2020Percutaneous coronary intervention (PCI) is the preferred treatment for acute coronary syndrome (ACS) secondary to atherosclerotic coronary artery disease. This...
Percutaneous coronary intervention (PCI) is the preferred treatment for acute coronary syndrome (ACS) secondary to atherosclerotic coronary artery disease. This nonsurgical procedure is also used for selective patients with stable angina. Although the procedure is essential for restoring blood flow, reperfusion can increase oxidative stress as a side effect. We address whether intravenous infusion of vitamin C (VC) prior to PCI provides a benefit for cardioprotection. A total of eight randomized controlled trials (RCT) reported in the literature were selected from 371 publications through systematic literature searches in six electronic databases. The data of VC effect on cardiac injury biomarkers and cardiac function were extracted from these trials adding up to a total of 1185 patients. VC administration reduced cardiac injury as measured by troponin and CK-MB elevations, along with increased antioxidant reservoir, reduced reactive oxygen species (ROS) and decreased inflammatory markers. Improvement of the left ventricular ejection fraction (LVEF) and telediastolic left ventricular volume (TLVV) showed a trend but inconclusive association with VC. Intravenous infusion of VC before PCI may serve as an effective method for cardioprotection against reperfusion injury.
Topics: Acute Coronary Syndrome; Antioxidants; Ascorbic Acid; Biomarkers; Coronary Artery Disease; Creatine Kinase, MB Form; Databases, Factual; Heart; Humans; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Stroke Volume; Troponin; Ventricular Function, Left
PubMed: 32718091
DOI: 10.3390/nu12082199