Efficiency and safety of various dual antiplatelet therapy strategies in patients undergoing percutaneous coronary intervention due to myocardial infarction

Aim. To compare the efficacy and safety of prasugrel, ticagrelor, or clopidogrel as part of dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) due to myocardial infarction (MI).Material and methods. The observational study included 74 patients who underwent PCI due to MI within the first 24 hours after the onset. The patients were devided into 3 groups: group 1 — patients who received ticagrelor as part of DAPT; group 2 — clopidogrel, group 3 — prasugrel. The follow-up period was 28 days. To assess the efficacy and safety of therapy, a composite endpoint was assessed (death + nonfatal recurrent MI (and/or stent rethrombosis) + nonfatal ischemic stroke (IS). Additional secondary endpoints were any moderate and severe (major) bleeding according to the GUSTO and/or TIMI scales. We assessed the incidence of reperfusion arrhythmias, an opening of an infarct-related coronary artery (IRCA), and non-ST elevation myocardial infarction (non-STEMI).Results. The analysis showed no significant differences in the cumulative incidence of adverse outcomes in the study groups within 28 days. The prevalence of secondary endpoints over a 28-day follow-up period was 3,1% in the ticagrelor group and 5,9% in the clopidogrel group, while no moderate and life-threatening bleeding was recorded in the prasugrel group during. There were no significant differences in the incidence of reperfusion arrhythmias, opening of an IRCA, and non-STEMI between the groups.Conclusion. The obtained results suggest the comparable efficacy and safety profiles of prasugrel, ticagrelor and clopidogrel as a part of DAPT in patients undergoing PCI due to MI. There were no significant differences in endpoint event rates. In particular, prasugrel has been shown to be as effective and safe as ticagrelor.

Percutaneous management of reperfusion arrhythmias during primary percutaneous coronary intervention: a case report

Background Myocardial reperfusion may cause profound electrophysiological alterations and can lead to serious reperfusion arrhythmias (RA). Management of RA and the accompanying electrical storm that may occur remains a problem. To our knowledge, the role of balloon re-inflation of the infarct-related artery (IRA) has never been addressed as a treatment modality for RA presenting as ventricular tachycardia (VT) with pulse or supraventricular tachycardia (SVT). Case presentation Six patients presenting with ST elevation myocardial infarction (STEMI) in the first 12 h, who underwent successful primary percutaneous coronary intervention (PCI), developed RA in the cathlab after restoration of flow in the IRA. The RA was in the form of VT with pulse, except in one patient who had SVT. In four patients, the RA was associated with hemodynamic instability. The mean age of the studied patients was 59.16 ± 7.94 years, and four were males. Coronary artery disease risk factors were prevalent, with four patients being hypertensive, two dyslipidemic, one diabetic, and 2 current smokers. One patient had a history of prior myocardial infarction (MI), and none had a history of congestive heart failure. The coronary angiography showed 100% occlusion of IRA in all patients and 2–3-vessel disease was present in 50%. PCI was successful with restoration of thrombolysis in myocardial infarction (TIMI) 2–3 flow in IRA in all cases. The mean time to revascularization from the onset of chest pain was 4.88 ± 2.68 h. In all cases, balloon re-inflation was successful in terminating the arrhythmias. None of the patients needed direct current cardioversion or anti-arrhythmic drugs for management of the acute arrhythmia. Conclusion Balloon re-inflation of IRA was successful in terminating RA that develop in the form of VT with pulse or SVT.

The Effect of Magnesium on Reperfusion Arrhythmias in STEMI Patients, Treated With PPCI. A Systematic Review With a Meta-Analysis and Trial Sequential Analysis

Aims: 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.Methods and Results: 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, P = 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; P = 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, P = 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.Conclusions: 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.

PREVENTION OF COMPLICATIONS IN PATIENTS WITH MYOCARDIAL INFARCTION AND CONCOMITANT METABOLIC SYNDROME

In Ukraine, coronary heart disease is still occupying the first place in the structure of the causes of death and primary disability (22.8%), and the incidence of myocardial infarction among people of working age is 48.9 per 100 thousand. The aim of this study was to increase the effectiveness of the treatment and prevention of complications in patients with acute coronary syndrome (myocardial infarction) and concomitant metabolic syndrome by including L-carnitine and L-arginine to the integrated therapy. The study involved 71 patients with acute coronary syndrome (ACS) with ST-segment elevation and concomitant metabolic syndrome. Among the 37 individuals who were prescribed a course of cytoprotective therapy additional to the standard drug therapy according to the protocol of the Ministry of Health, formed a test group. The control group consisted of 34 patients who only received standard protocol treatment with corticosteroids (MI). The diagnosis of acute myocardial infarction was verified according to the ESC recommendations (2017). Diagnosis of metabolic syndrome (MS) was established based on the recommendations of the International Diabetes Federation (IDF, 2016). It was found that due to the integrated therapy including L-arginine and L-carnitine, the patients with ACS (MI) and concomitant MS achieved a significant improvement in central cardiohemodynamics and the restoration of vascular endothelial function that was often accompanied by the following complications of corticosteroids (MI) as reperfusion arrhythmias and blockades and acute heart (left ventricular) failure. The patients with acute myocardial infarction and concomitant MS demonstrated pronounced deterioration of morpho-functional parameters of the heart, and namely the development of its post infarction remodelling with subsequent impairments of systolic and diastolic heart function and the development of heart failure and endothelial vascular dysfunction. A mixture of L-arginine and L-carnitine added to the standard therapy significantly reduces the incidence and severity of complications of acute MI such as reperfusion arrhythmias and acute left ventricular failure.

Reperfusion Arrhythmias Increase after Superior Cervical Ganglionectomy Due to Conduction Disorders and Changes in Repolarization

Pharmacological concentrations of melatonin reduce reperfusion arrhythmias, but less is known about the antiarrhythmic protection of the physiological circadian rhythm of melatonin. Bilateral surgical removal of the superior cervical ganglia irreversibly suppresses melatonin rhythmicity. This study aimed to analyze the cardiac electrophysiological effects of the loss of melatonin circadian oscillation and the role played by myocardial melatonin membrane receptors, SERCA2A, TNFα, nitrotyrosine, TGFβ, KATP channels, and connexin 43. Three weeks after bilateral removal of the superior cervical ganglia or sham surgery, the hearts were isolated and submitted to ten minutes of regional ischemia followed by ten minutes of reperfusion. Arrhythmias, mainly ventricular tachycardia, increased during reperfusion in the ganglionectomy group. These hearts also suffered an epicardial electrical activation delay that increased during ischemia, action potential alternants, triggered activity, and dispersion of action potential duration. Hearts from ganglionectomized rats showed a reduction of the cardioprotective MT2 receptors, the MT1 receptors, and SERCA2A. Markers of nitroxidative stress (nitrotyrosine), inflammation (TNFα), and fibrosis (TGFβ and vimentin) did not change between groups. Connexin 43 lateralization and the pore-forming subunit (Kir6.1) of KATP channels increased in the experimental group. We conclude that the loss of the circadian rhythm of melatonin predisposes the heart to suffer cardiac arrhythmias, mainly ventricular tachycardia, due to conduction disorders and changes in repolarization.

Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of KATP Channels or Connexin 43

Ischemic postconditioning (IPoC) reduces reperfusion arrhythmias but the antiarrhythmic mechanisms remain unknown. The aim of this study was to analyze IPoC electrophysiological effects and the role played by adenosine A1, A2A and A3 receptors, protein kinase C, ATP-dependent potassium (KATP) channels, and connexin 43. IPoC reduced reperfusion arrhythmias (mainly sustained ventricular fibrillation) in isolated rat hearts, an effect associated with a transient delay in epicardial electrical activation, and with action potential shortening. Electrical impedance measurements and Lucifer-Yellow diffusion assays agreed with such activation delay. However, this delay persisted during IPoC in isolated mouse hearts in which connexin 43 was replaced by connexin 32 and in mice with conditional deletion of connexin 43. Adenosine A1, A2A and A3 receptor blockade antagonized the antiarrhythmic effect of IPoC and the associated action potential shortening, whereas exogenous adenosine reduced reperfusion arrhythmias and shortened action potential duration. Protein kinase C inhibition by chelerythrine abolished the protective effect of IPoC but did not modify the effects on action potential duration. On the other hand, glibenclamide, a KATP inhibitor, antagonized the action potential shortening but did not interfere with the antiarrhythmic effect. The antiarrhythmic mechanisms of IPoC involve adenosine receptor activation and are associated with action potential shortening. However, this action potential shortening is not essential for protection, as it persisted during protein kinase C inhibition, a maneuver that abolished IPoC protection. Furthermore, glibenclamide induced the opposite effects. In addition, IPoC delays electrical activation and electrical impedance recovery during reperfusion, but these effects are independent of connexin 43.

A clinical study of hemodynamically significant arrhythmias and QTc interval associated with thrombolysed and non thrombolysed acute myocardial infarction patients

Background: Arrhythmias are a common occurrence in acute myocardial infarction. Objectives of this study the hemodynamically significant arrhythmias and QTc interval in thrombolysed and non thrombolysed acute myocardial infarction patients.Methods: Two hundred patients of AMI were enrolled. ECG and cardiac parameters were examined. Arrhythmias and its various parameters like its incidence, type, frequency associated with site of infarction were recorded in thrombolysed and non thrombolysed patients of AMI.Results: AMI was more prevalent in the males (63.3%) and those with 41-50 years of age. Hypertension (35.7%), smoking (34.2%), and diabetes (23.1%) were the major risk factor. Incidence of AWMI (30.7%) is higher than IWMI (25.1%). Out of 200 subjects 130 were thrombolysed. Arrhythmias was observed in total 164 patients while 36 patients has no documentation of arrhythmias. Mean QTc was prolonged (546.88ms vs 404.33ms) in patients documented with arrhythmia compared with those who has no arrhythmia. Out of all arrhythmias, ventricular tachycardia was seen in 38% cases with 50% mortality and preponderance to antero lateral MI. Sinus Tachycardia was seen in 22% of cases with preponderance to Antero Lateral MI and persistence of Sinus Tachycardia was a prognostic sign, mortality being 12%. Complete Heart Block were seen with IWMI, incidence being 26%. Bundle Branch Block was common in AWMI (31%) than IWMI (10%).Conclusion: Tachyarrhythmias are common with AWMI and bradyarrhythmia’s in IWMI. Reperfusion arrhythmias are a benign phenomenon and good indicator of successful reperfusion.

Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia–reperfusion arrhythmias

Background: Increasing evidences have verified that microRNAs (miRNAs) play an important role in formation and progression of various cardiac diseases including arrhythmias. Existing research has showed that certain miRNAs exhibit significantly different expressions and effects in arrhythmias. However, the effect of miRNAs in the progression of hypothermic ischemic–reperfusion arrhythmias (RA) and its potential mechanism remains to be further discussed. Methods: By utilizing a model for hypothermic ischemia–reperfusion of rats, miRNAs expression profiles of ventricular myocardium with global hypothermic ischemia–reperfusion and those of ventricular myocardium with hypothermic ischemia–RA were established through high-throughput sequencing. Furthermore, the aberrantly expressed miRNAs in myocardium with and without hypothermic ischemia–RA were screened and verified. By applying RNAhybrid, MiRanda, and TargetScan software, the target genes of these aberrantly expressed miRNAs were predicted. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, the mRNA targets associated with these miRNAs were determined and the miRNA–mRNA interaction during the progression of cardiovascular diseases was explored. The aberrantly expressed miRNAs related to hypothermic ischemia–RA were validated by employing quantitative fluorescence polymerase chain reaction (PCR). Results: Eight significantly aberrantly expressed miRNAs were identified(novel-miR-1 、novel-miR-16、novel-miR-17、novel-miR-19、novel-miR-30、novel-miR-43、rno-miR-122-5p、rno-miR-429), in which six were up-regulated and two were down-regulated. Moreover, target genes and signaling pathways associated with these aberrantly expressed miRNAs were predicted and analyzed. According to miRNA–mRNA interaction network graph, it was revealed that GJA1 gene was considered as the target of novel-miR-17. Conclusions: Aberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia–RA. Specific miRNAs, such as novel-miR-17 and rno-miR-429 are probably new potential targets for further conducting functional study on hypothermic ischemia–RA.