A Randomized, double-blind, dose ranging clinical trial of intravenous FDY-5301 in acute STEMI patients undergoing primary PCI.

BACKGROUND: Ischemia-reperfusion injury remains a major clinical problem in patients with ST-elevation myocardial infarction (STEMI), leading to myocardial damage despite early reperfusion by primary percutaneous coronary intervention (PPCI). There are no effective therapies to limit ischemia-reperfusion injury, which is caused by multiple pathways activated by rapid tissue reoxygenation and the generation of reactive oxygen species (ROS). FDY-5301 contains sodium iodide, a ubiquitous inorganic halide and elemental reducing agent that can act as a catalytic anti-peroxidant. We tested the feasibility, safety and potential utility of FDY-5301 as a treatment to limit ischemia-reperfusion injury, in patients with first-time STEMI undergoing emergency PPCI. METHODS: STEMI patients (n = 120, median 62 years) presenting within 12 h of chest pain onset were randomized at 20 PPCI centers, in a double blind Phase 2 clinical trial, to receive FDY-5301 (0.5, 1.0 or 2.0 mg/kg) or placebo prior to reperfusion, to evaluate the feasibility endpoints. Participants underwent continuous ECG monitoring for 14 days after PPCI to address pre-specified cardiac arrhythmia safety end points and cardiac magnetic resonance imaging (MRI) at 72 h and at 3 months to assess exploratory efficacy end points. RESULTS: Intravenous FDY-5301 was delivered before re-opening of the infarct-related artery in 97% participants and increased plasma iodide levels ~1000-fold within 2 min. There was no significant increase in the primary safety end point of incidence of cardiac arrhythmias of concern. MRI at 3 months revealed median final infarct sizes in placebo vs. 2.0 mg/kg FDY-5301-treated patients of 14.9% vs. 8.5%, and LV ejection fractions of 53.9% vs. 63.2%, respectively, although the study was not powered to detect statistical significance. In patients receiving FDY-5301, there was a significant reduction in the levels of MPO, MMP2 and NTproBNP after PPCI, but no reduction with placebo. CONCLUSIONS: Intravenous FDY-5301, delivered immediately prior to PPCI in acute STEMI, is feasible, safe, and shows potential efficacy. A larger trial is justified to test the effects of FDY-5301 on acute ischemia-reperfusion injury and clinical outcomes. CLINICAL TRIAL REGISTRATION: CT.govNCT03470441; EudraCT 2017-000047-41.

Modern therapeutic approaches of cardiac arrhythmias in pregnancy / Terhességi ritmuszavarok modern terápiás megközelítései.

Összefoglaló. A ritmuszavarok elofordulása gyakoribb a terhes nok esetén, mint a nem várandósok körében. A legtöbb esetben terápiás beavatkozás nélkül is kihordható a magzat. Hemodinamikai instabilitás és magzatkárosodáshoz vezeto fetalis hypoperfusio jöhet létre, amennyiben tartós, magas kamrai frekvenciával járó epizódok jelentkeznek. Ezekben az esetekben a ritmuszavar megszüntetése indokolttá válhat. Az antiarrhythmiás gyógyszerek korlátozottan és nagy körültekintéssel alkalmazhatók a gyermeket várók körében, így a katéterablatio jelenthet biztonságos és használható alternatívát. Ezen beavatkozásokat hagyományosan röntgensugár segítségével végzik, ez azonban az ionizáló sugárzásnak a magzati fejlodésre gyakorolt hatása miatt magas rizikót jelentene. Több éve elérheto a szív-elektrofiziológiában az ún. zéró fluoroszkópiás ablatio, mely a pitvarfibrilláció kezelésében és más ritmuszavarok esetében egyaránt alkalmazható. A terheseknél alkalmazott eljárást két eseten keresztül mutatjuk be. A röntgensugár használatát, a jelen cikkben bemutatott beavatkozások esetén is, sikerült teljesen kiküszöbölnünk. Az elso, 23 hetes gravid páciensnél recidív paroxysmalis supraventricularis tachycardia miatt végeztünk elektrofiziológiai vizsgálatot. E vizsgálat során atrioventricularis nodalis reentry tachycardiát igazoltunk és abláltunk sikerrel. Második esetbemutatásunkban egy anteroseptalis járulékos köteg katéterablatiós megoldását mutatjuk be. A terhesség során jelentkezo, az anyára és/vagy magzatára veszélyt jelento ritmuszavar esetén a háromdimenziós térképezo rendszer (szükség esetén intracardialis ultrahangvizsgálattal kiegészítve) biztonságos és hatásos alternatívát jelent, olyan esetekben, ha röntgensugár nem használható. Orv Hetil. 2021; 162(41): 1643-1651. Summary. Arrhythmias are more common in pregnant women than in others. In most cases, the fetus can be delivered without therapeutic intervention. Hemodynamic instability and fetal hypoperfusion leading to fetal harm may occur if persistent episodes of high ventricular rate occur. In these cases, resolution of the arrhythmia may be advised. Antiarrhythmic drugs can be used with limitations and great caution in those expecting a child, so catheter ablation may be a safe and usable alternative. These interventions are traditionally performed using X-ray, however, due to the effect of ionizing radiation on fetal development, this would pose a high risk. Zero-fluoroscopic ablation has been available for several years in cardiac electrophysiology, which can be used both in the treatment of atrial fibrillation and in other arrhythmias. The procedure which we used in pregnant women is presented in two cases. We also managed to completely eliminate the use of X-ray during the interventions presented in this article. In the first case, a 23-week-old gravid patient underwent electrophysiological examination for recurrent paroxysmal supraventricular tachycardia. In the electrophysiological study, atrioventricular nodal reentry tachycardia was confirmed and successfully ablated. In our second case study, we present a catheter ablation for anteroseptal accessory pathway. Three-dimensional mapping system (supplemented with intracardiac ultrasound, if necessary), in the case of significant arrhythmia, is a safe and effective alternative where X-rays, which poses a risk to the mother and/or the fetus, cannot be used during pregnancy. Orv Hetil. 2021; 162(41): 1643-1651.

Implementation of a zero fluoroscopic workflow using a simplified intracardiac echocardiography guided method for catheter ablation of atrial fibrillation, including repeat procedures.

OBJECTIVE: Pulmonary vein isolation (PVI) is the cornerstone of the interventional treatment of atrial fibrillation (AF). Traditionally, during these procedures the catheters are guided by fluoroscopy, which poses a risk to the patient and staff by ionizing radiation. Our aim was to describe our experience in the implementation of an intracardiac echocardiography (ICE) guided zero fluoroscopic (ZF) ablation approach to our routine clinical practice. METHODS: We developed a simplified ICE guided technique to perform ablation procedures for AF, with the aid of a 3D electroanatomical mapping system. The workflow was implemented in two phases: (1) the Introductory phase, where the first 16 ZF PVIs were compared with 16 cases performed with fluoroscopy and (2) the Extension phase, where 71 consecutive patients (including repeat procedures) with ZF approach were included. Standard PVI (and redoPVI) procedures were performed, data on feasibility of the ZF approach, complications, acute and 1-year success rates were collected. RESULTS: In the Introductory phase, 94% of the procedures could be performed with complete ZF with a median procedure time of 77.5 (73.5-83) minutes. In one case fluoroscopy was used to guide the ICE catheter to the atrium. There was no difference in the complication, acute and 1-year success rates, compared with fluoroscopy guided procedures. In the Extension phase, 97% of the procedures could be completed with complete ZF. In one case fluoroscopy was used to guide the transseptal puncture and in another to position the ICE catheter. Acute success of PVI was achieved in all cases, 64.4% patients were arrhythmia free at 1-year. Acute major complications were observed in 4 cases, all of these occurred in the redo PVI group and consisted of 2 tamponades, 1 transient ischemic attack and 1 pseudoaneurysm at the puncture site. The procedures were carried out by all members of the electrophysiology unit in the Extension phase, including less experienced operators and electrophysiology fellows (3 physicians) under the supervision of the senior electrophysiologist. Consequently, procedure times became longer [90 (75-105) vs 77.5 (73.5-85) min, p = 0.014]. CONCLUSIONS: According to our results, a ZF workflow of AF ablations can be successfully implemented into the routine practice of an electrophysiology laboratory, without compromising safety and effectivity.

[Myocardial infarction without obstructive coronary artery disease (MINOCA) - prevalence and prognosis]. / Obstruktív koszorúér-betegség nélkül kialakuló heveny szívizominfarktus (MINOCA) ­ gyakoriság és prognózis.

Introduction: There are conflicting data on the prevalence and prognosis of AMI patients with non-obstructive coronary artery disease (MINOCA). Aim: We studied the prevalence and prognosis of MINOCA patients. Method: In the Hungarian Myocardial Infarction Registry (HUMIR) 45,223 patients (pts) with acute myocardial infarction (AMI) were found who were treated between Jan 1, 2014, and June 30, 2018, and coronary arteriography was performed. ST-elevation myocardial infarction was diagnosed in 22,469 pts (49.7%). Patients without obstructive coronary artery disease who had no previous myocardial infarction, heart failure, PCI and CABG procedure were selected to the MINOCA group (n = 2003). Patients with obstructive coronary artery disease belonged to the MICAD group (n = 43,220). We investigated clinical characteristics of the patients, overall survival and reinfarction. Survival curves were estimated with the Kaplan-Meier method and were modeled with the Cox proportional hazards model. Results: The proportion of MINOCA pts among all myocardial infarction was by 4.4% higher in the STEMI pts compared to the NSTEMI group (2.0% vs. 6.8%). The MINOCA pts were younger (age 64.0 ± 14.4 vs. 65.5 ± 12.2 years), and the proportion of women was higher (55.7% vs. 36.5%). Hypertension, diabetes mellitus and peripheral artery disease were more common in the MICAD group (79.1% vs. 73.7%, 33.0% vs. 21.2%, and 12% vs. 8%). The mortality was higher among the MICAD pts. In the MINOCA group, the mortality of men did not differ between STEMI and NSTEMI, as opposed to women: women with STEMI had higher mortality than women with NSTEMI. The risk of reinfarction was higher in the MICAD group, especially in NSTEMI, the risk in the MINOCA group was lower, and there was no substantial difference between types. Conclusion: In this real word, retrospective, observational study, we found a significant difference in the prevalence of MINOCA pts according to different types of myocardial infarction. In the MINOCA group, the mortality of women with STEMI was substantially higher. Orv Hetil. 2019; 160(45): 1791-1797.

Does Gender Have Prognostic Value Among Patients with Myocardial Infarction? Analysis of the Data from the Hungarian Myocardial Infarction Registry.

Background: The authors analyzed data from the Hungarian Myocardial Infarction Registry (HUMIR) to examine the potential impact of gender on the treatment and 30-day and 1-year mortality of patients with myocardial infarction (MI). Materials and Methods: The National Registry of Myocardial Infarction included 42,953 patients between January 1, 2013 and December 31, 2016; 19,875 of whom were diagnosed with ST-elevation myocardial infarction (STEMI) and 23,078 with non-ST-elevation myocardial infarction (NSTEMI). The proportion of women was 39% and 41.9% in the two groups, respectively. Logistic regression analysis was performed adjusting for age, the year and month of hospital admission, smoking, as well as for five concomitant diseases and anamnestic data. We found that the odds ratio (OR) of performing percutaneous coronary intervention (PCI) was influenced by age, the year of treatment, prior stroke, and peripheral artery disease (PAD) in both patient groups. Results: Gender had an impact on treatment in both cases; women had significantly fewer PCIs (OR = 0.86 confidence interval [95% CI: 0.77-0.95] in the STEMI group, OR = 0.75 [95% CI: 0.70-0.82] in the NSTEMI group). Age and PCI, PAD, and diabetes mellitus proved to be prognostic factors for 30-day and 1-year mortality in both groups. In the STEMI group, hypertension proved to be of prognostic value for both 30-day and 1-year mortality, whereas prior MI, stroke, and smoking only affected 1-year mortality. Similarly, in the NSTEMI group, prior stroke was also of prognostic value for 30-day and 1-year mortality, whereas prior MI, hypertension and smoking were only associated with 1-year mortality. Conclusions: The independent prognostic value of gender could not be proven for any of the MI types or follow-up periods. In conclusion, gender influenced the treatment of patients with MI but had no significant impact on prognosis in itself.

Comparison of Platelet Function Guided Versus Unguided Treatment With P2Y12 Inhibitors in Patients With Acute Myocardial Infarction (from the Hungarian Myocardial Infarction Registry).

Evidence is conflicting regarding the clinical benefits of selecting P2Y12 inhibitors based on platelet function testing (PFT). Between March 1, 2013 and March 1, 2014, we collected clinical characteristics and platelet function data in a nationwide acute myocardial infarction (AMI) registry from 15 interventional cardiology centers in Hungary. The risk of all-cause mortality at 1 year were compared after propensity score (PS) matching between patients receiving PFT-guided and unguided P2Y12-inhibitor therapies. High platelet reactivity on clopidogrel (HPRoC) was uniformly defined with the Multiplate assay. A total of 5,583 patients with AMI and coronary intervention were registered. After exclusion of cases with contraindication to prasugrel, propensity matching resulted in a sample of 2,104 patients with well-adjusted characteristics. Clopidogrel was the dominant P2Y12 inhibitor in both groups (unguided: 96% vs PFT guided: 85%, p <0.001). In the PFT-guided group, 19% of patients had HPRoC and 77% of them were switched to prasugrel. According to the adjusted analysis, all-cause mortality at 1 year was significantly lower in the PFT-guided compared with the unguided group (hazard ratio 0.57 [95% confidence interval 0.43 to 0.77], p <0.001). Although prasugrel treatment was not associated with lower all-cause mortality in the overall cohort, patients with HPRoC who switched to prasugrel had significantly lower mortality when compared with those continuing clopidogrel (hazard ratio 0.33 [95% confidence interval 0.12 to 0.92], p <0.05). In conclusion, in patients with AMI, PFT-guided treatment with a high rate of switchover to prasugrel was associated with a lower risk of mortality. Prasugrel was a predictor of lower mortality in patients with HPRoC but not in the overall cohort of AMI.

[Patient care of patients with myocardial infarction in Hungary. Analysis of National Myocardial Infarction Registry data collecting in 2015]. / A szívinfarktus miatt kezelt betegek ellátása Magyarországon. A Nemzeti Szívinfarktus Regiszter 2015. évi adatainak elemzése.

The authors summarize the most relevant data of myocardial infarction patients according to the National Myocardial Infarction Registry data base. In 2015 12,681 patients had 12,941 acute myocardial infarctions. Less than half of patients (44.4%) were treated with ST elevation myocardial infarction. National Ambulance Service was the first medical contact of more than half (51.4%) of patients with ST elevation infarction. Prehospital thrombolysis was occasionally done (0.23%), but 91.6% of the patients were treated in hospital with invasive facilities. The median of the ischaemic time (time between onset of symptoms and arrival at the invasive laboratory) was 223 minutes. Most of the patients (94%) with positive coronary arteriography were treated with percutaneous coronary intervention. The 30 day mortality of the whole group was 12.8% vs. 8.6% of patients treated with an invasive procedure. CONCLUSION: comparing the national and international registry data we conclude that we should analyse and decrease the prehospital delay time to improve the patient care in Hungary. Orv. Hetil., 2017, 158(3), 90-93.

Underuse of coronary intervention and its impact on mortality in the elderly with myocardial infarction. A propensity-matched analysis from the Hungarian Myocardial Infarction Registry.

BACKGROUND: Data are limited on the real-life use of coronary intervention (PCI) and on its long-term efficacy and safety in elderly patients with acute myocardial infarction (AMI). METHODS: Data from a nation-wide registry of patients treated due to an AMI event in centers of invasive cardiology were analyzed for the potential interaction of age on the utilization of invasive therapy and outcome. Follow-up data of consecutive patients between March 1, 2013, and March 1, 2014 were analyzed. Differences in the risk of all-cause death at 1year between patients undergoing PCI versus others receiving conservative treatment were determined from vital records and were compared with propensity score matching. RESULTS: A total of 8485 consecutive patients were enrolled at 19 centers. Sixty-three percent of the patients were male; the mean age was 65.1±12.4years. The proportion of STEMI cases was 51%. STEMI cases were treated with primary PCI in 91.0% while patients with NSTEACS underwent PCI in 71.0%. The age of patients was a significant determinant of deferring coronary angiography (Hazard ratio (HR): 0.524 95% confidence interval (CI) 0.47-0.59, p<0.001) and PCI (HR: 0.76 95% CI 0.73-0.80, p<0.001). One-year survival after PCI was significantly better both in the overall and in the propensity matched cohort (HR: 0.44 [95% CI: 0.39-0.49] and HR: 0.59 [95% CI: 0.50-0.69], p<0.001, both). This benefit remained consistent in age-dependent subgroup analyses. CONCLUSION: Coronary intervention is underused among the elderly despite the mortality benefit of interventional therapy in myocardial infarction that is consistent in all age groups.

[Short and long term prognosis of patients with myocardial infarction. Hungarian Myocardial Infarction Registry]. / Szívinfarktus miatt kezelt betegek korai és késoi prognózisa. Magyar Infarctus Regiszter Vizsgálat.

INTRODUCTION: Mortality data of patients with acute myocardial infarction are incomplete in Hungary. AIM: The aim of the authors was to analyse the data of 8582 myocardial infarction patients (4981 with ST-elevation myocardial infarction) registered in the Hungarian Myocardial Infarction Register in order to define the hospital, 30-day, and 1-year mortality. To evaluate the prehospital mortality of myocardial infarction, all myocardial infarction and sudden death were registered in five districts of Budapest. METHOD: Multivariate logistic regression was performed to define risk factors of mortality and the model were assessed using c statistics. RESULTS: The hospital, 30-day and 1-year mortality of patients with ST elevation myocardial infarction were 3.7%, 9.5% and 16.5%, respectively. In patients without ST elevation myocardial infarction these figures were 4%, 9.8% and 21.7%, respectively. The 1-year mortality of patients without ST elevation was higher than those of with ST elevation and the difference was statistically significant. Age, Killip class, diabetes mellitus, history of stroke and myocardial infarction were independent predictors of death. Coronary intervention improved the prognosis of patients with myocardial infarction significantly. CONCLUSIONS: The rate of pre-hospital mortality was considerably high; 72.5% of 30 day mortality occurred before admission to hospital.

[Mortality rate of acute heart attack in Zalaegerszeg micro-region. Results of the first Hungarian 24-hour acute ST-elevation myocardial infarction intervention care unit]. / A heveny szívinfarktus halálozásának alakulása Zalaegerszeg kistérségben. Az elso magyarországi 24 órás ST-elevációs akut myocardialis infarctus intervenciós ügyelet hatásai.

UNLABELLED: Morbidity and mortality rates of acute heart attack emphasize the significance of this patient group worldwide. The prompt and exact diagnosis and the timing of adequate therapy is crucial for this patients. Modern supply of acute heart attack includes invasive cardiology intervention, primer percutaneous coronary intervention. In year 1999, American and European recommendations suggested primer percutaneous coronary intervention only as an alternative possibility instead of thrombolysis, or in case of cardiogenic shock. 24 hour intervention unit for patients with acute heart attack was first organized in Hungary in Zala County Hospital's Cardiology Department, in year 1998. Our present study confirms, that since the intervention treatment has been introduced, average mortality rate has been reduced considerably in our area comparing to the national average. METHODS: Mortality rates in West Transdanubian region and in Zalaegerszeg's micro-region were studied and compared for the period between 1997-2004, according to the data of National Public Health and Medical Officer Service. These data were then compared with the national average mortality data of Hungarian Central Statistical Office. With the help of our own computerized database we examined this period and compared the number of the completed invasive interventions to the mortality statistics. RESULTS: In the first full year, in 1998, we completed 82 primer and 283 elective PCIs; these number increased to 318 and 1265 by year 2005. At the same time, significant decrease of acute infarction related mortality was detectable among men of the Zalaegerszeg micro-region, comparing to the national average (p<0.001). CONCLUSION: The first Hungarian 24 hour acute heart attack intervention care improved the area's mortality statistics significantly, comparing to the national average. The skilled work of the experienced team means an important advantage to the patients in Zalaegerszeg micro-region.

Defibrillator implantation early after myocardial infarction.

BACKGROUND: The rate of death, including sudden cardiac death, is highest early after a myocardial infarction. Yet current guidelines do not recommend the use of an implantable cardioverter-defibrillator (ICD) within 40 days after a myocardial infarction for the prevention of sudden cardiac death. We tested the hypothesis that patients at increased risk who are treated early with an ICD will live longer than those who receive optimal medical therapy alone. METHODS: This randomized, prospective, open-label, investigator-initiated, multicenter trial registered 62,944 unselected patients with myocardial infarction. Of this total, 898 patients were enrolled 5 to 31 days after the event if they met certain clinical criteria: a reduced left ventricular ejection fraction (< or = 40%) and a heart rate of 90 or more beats per minute on the first available electrocardiogram (ECG) (criterion 1: 602 patients), nonsustained ventricular tachycardia (> or = 150 beats per minute) during Holter monitoring (criterion 2: 208 patients), or both criteria (88 patients). Of the 898 patients, 445 were randomly assigned to treatment with an ICD and 453 to medical therapy alone. RESULTS: During a mean follow-up of 37 months, 233 patients died: 116 patients in the ICD group and 117 patients in the control group. Overall mortality was not reduced in the ICD group (hazard ratio, 1.04; 95% confidence interval [CI], 0.81 to 1.35; P=0.78). There were fewer sudden cardiac deaths in the ICD group than in the control group (27 vs. 60; hazard ratio, 0.55; 95% CI, 0.31 to 1.00; P=0.049), but the number of nonsudden cardiac deaths was higher (68 vs. 39; hazard ratio, 1.92; 95% CI, 1.29 to 2.84; P=0.001). Hazard ratios were similar among the three groups of patients categorized according to the enrollment criteria they met (criterion 1, criterion 2, or both). CONCLUSIONS: Prophylactic ICD therapy did not reduce overall mortality among patients with acute myocardial infarction and clinical features that placed them at increased risk. (ClinicalTrials.gov number, NCT00157768.)

Aspirin resistance: focus on clinical endpoints.

INTRODUCTION: Via its antiplatelet effect, aspirin reduces the odds of an arterial thrombotic event in high-risk patients by approximately 25%. However, 10% to 20% of patients with an arterial thrombotic event who are treated with aspirin have a recurrent arterial thrombotic event during long-term follow-up. Nevertheless, the effectiveness of aspirin has been questioned by the emergence of the concept of aspirin resistance, which has been introduced as an explanation of the fact that a considerable proportion of patients treated with aspirin exhibit normal platelet function. OBJECTIVES AND METHODS: We systematically reviewed all available evidence till March 2008 on prevalence of aspirin resistance and its association with clinical outcome. We also collected articles showing the possible way of treatment. CONCLUSION: Analyzing the data of different laboratory methods aspirin resistance seems to be associated with poor clinical outcome, although currently no standardized or widely accepted definition of aspirin resistance exists. The widely used laboratory methods might not be comparable with each other; therefore, specific treatment recommendations for patients who exhibit high platelet reactivity during aspirin therapy or who have poor platelet inhibition by aspirin are not established.

Experience with Endeavor stent implantations.

UNLABELLED: Restenosis is the most common disadvantage of percutaneous coronary interventions. The incidence of restenosis can be lowered with the use of stents. After the use of stents, 'in-stent' restenosis can occur. To avoid it drug-eluting stents were developed, but the occurrence of stent thrombosis is higher than observed in case of bare-metal stents. Endeavor is a new zotarolimus-eluting stent developed to reduce the stent thrombosis. AIMS: In a prospective study we aimed to follow-up our patients regarding the incidence of in-stent restenosis, stent thrombosis, and clinical end points after Endeavor stent implantation. PATIENTS AND METHODS: Endeavor stents have been implanted in patients undergoing coronary angiography with the following indications: complex lesions susceptible to restenosis and after recanalization of chronic total occlusions. RESULTS: Endeavor stent implantations were successfully performed in 99 patients and has been successful in 98% of cases, two stents could not be implanted because of technical difficulties. Significant restenosis was observed in eight patients (8.1%). Subacute stent thrombosis (within 10 days) occurred in two patients (2.0%). Any late stent thrombosis was not observed. CONCLUSION: Our registry affirmed the results of the Endeavor I trial in a population with more severe and longer coronary stenosis. We can conclude that the Endeavor stent is suitable for implantation in complex, longer coronary lesions. Our long-term follow-up data do not prove those opinions which prefer bare-metal stent implantation in all patients because of the late adverse events of the drug-eluting stents.