Ishod bolesti u bolesnika s akutnim infarktom miokarda sa ST-elevacijom i šećernom bolesti tipa 2 liječenih primarnom perkutanom koronarnom intervencijom i ishemijskim postkondicioniranjem

Hukeljić Berberović, Behija (2016) Ishod bolesti u bolesnika s akutnim infarktom miokarda sa ST-elevacijom i šećernom bolesti tipa 2 liječenih primarnom perkutanom koronarnom intervencijom i ishemijskim postkondicioniranjem. PhD thesis, Sveučilište u Zagrebu.

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Abstract

INTRODUCTION: Data from the World Health Organization (WHO) for 2005 indicates that 17.5 million people died of cardiovascular diseases in the world, of which 7.6 million died from coronary heart disease. Diseases of the heart and blood vessels are not only the leading cause of death and hospital treatment, but also rank second in terms of number of days of hospitalization and morbidity registered in the sectors of primary health care. Myocardial infarction is a common and dangerous complication of ischemic diseases. It consists of myocardial necrosis due to critical ischemia usually resulting from atherosclerotic narrowing of the blood vessels with the addition of a thrombus. Myocardial infarction is extremely significant due to high mortality (approximately a quarter of the total mortality in developed countries is caused by acute myocardial infarction) and disability. Patients usually die within the first hour of the occurrence of acute myocardial infarction (about 50% of the total mortality of acute myocardial infarction) due to cardiac arrhythmias. It is diagnosed by changes on the ECG, elevated troponin T and I, CK-MB, and invasive diagnostic method – cardiac catheterization. The goal of the treatment is to achieve rapid, complete and stable blood flow in the infarction affected coronary artery in order to limit infarct size, improvement of left ventricular function and reduction in mortality and disability. Primary PCI (primary percutaneous coronary intervention PPCI) is the golden standard in reperfusion treatment of acute myocardial infarction with ST–segment elevation (STEMI) one of the specific risk factors for myocardial infarction is diabetes. Several studies demonstrate that atherosclerotic changes in the coronary arteries of diabetics are severe, diffusely distributed, often in small blood vessels and are usually unsuitable for percutaneous coronary intervention procedure. Diabetic patients with coronary heart disease, when compared with patients without diabetes, tend to have double or triple vessel coronary disease. A quarter of patients with acute myocardial infarction suffer from type 2 diabetes. A significant feature of these patients is the presence of atypical symptoms of the disease and the development of heart failure, a common complication of acute myocardial infarction. Diabetic patients with acute myocardial infarction have two times higher mortality rate than patients without diabetes. Ischemic postconditioning is an intervention in which brief, intermittent periods of reocclusion at the onset of reperfusion protect myocardium from lethal reperfusion injury. It consists of four balloon occlusions, each lasting 30 seconds, followed by 30 seconds of reperfusion The mechanism of the cardio protective effects of ischemic postconditioning is 81 still not completely understood, however, it is perceived that ischemic postconditioning begins with specific cell-surface receptors responsible for activating a number of signalling pathways, many of which appear to converge at the mitochondrial level GOAL: The aim of this paper is to examine whether the use of ischemic postconditioning during primary percutaneous coronary intervention in patients with type 2 diabetes and acute myocardial infarction – STEMI results in reduction in the incidence of restenosis, the reduced area of the lesion of myocardial infarction, and improvement of the overall outcomes of cardiovascular disease, when compared to patients with type 2 diabetes and acute myocardial infarction – STEMI treated with primary percutaneous coronary intervention without the use of ischemic postconditioning. METHODS: The study included 100 patients with acute myocardial infarction – STEMI and type 2 diabetes who were divided into two groups: 50 patients with an average age of 60 treated with ischemic postconditioning during primary percutaneous coronary intervention and 50 patients with an average age of 60 years treated with primary percutaneous coronary intervention without the use of ischemic postconditioning. Study inclusion criteria for patients were as follows. Patients involved in the study had to be treated with insulin therapy for at least one year prior to study entry. The time elapsed from the onset of symptoms to the start of primary percutaneous coronary intervention in all patients included in the study had to be <120 min, as recommended by ACC / AHA. All patients had “drug-eluting stent” planted on the target lesion i.e. – drug-coated stent (Cypher stent). Study exclusion criteria for patients were: previously suffered myocardial infarction, coronary bypass grafting done, prior cardiac decompensation (i.e. patients with NYHA class III and IV) and those patients who, due to the severity of coronarography findings, had to have an immediate coronary artery bypass grafting – CABG. During the first hospitalization data analysis was carried out: anamnesis of the therapy before hospitalization, and TIMI risk score was used to assess the risk of cardiovascular events in both groups of patients. Coronary angiography was graded according to Syntax score. Recording the increase in the biohumoral enzymes (troponin, CK-MB), measuring the initial troponin and CK-MB, then measuring 24 h later and every other day up to 7th day of hospitalization. Echocardiography confirmed the EF (per Simpson) and WMSI, and they recorded cardiac incidents occurred during the hospitalization of the patient (arrhythmias – VF, VT, early stent restenosis, decompensation, ...). Follow up was undertaken after a year when the echocardiography found EF and WMSI. The anamnesis review determined the existence of what was up to that point potential previous cardiac incidents, hence the ergometry exercise test was carried out to objectify the existence of post-infarction angina pectoris. RESULTS: The values of troponin were measured from the date of occurrence of the myocardial infarction up to 7th day following the infarction. There was no statistically significant difference between the values of troponin between the two groups. The study noted a significant statistical difference in the values of troponin on the fourth day following the infarction. The subjects in the control group had higher values than those in the experimental group. The values of creatine kinase muscle fraction were presented, also from the occurrence of the myocardial infarction up to the 7th day following the infarction. There were, also, no differences between the control and experimental groups of subjects. The study has not proven the difference in the EF and WMSI between groups. The total number of complications up to seven day following the myocardial infarction did not differ between the patients in the control and experimental group. There was no difference in the frequency of arrhythmias within seven days of myocardial infarction between the groups of subjects; the incidence of stenosis within seven days of myocardial infarction in the examination group, as well as the difference in rates of heart decompensation within seven days of myocardial infarction did not defer from those in the control group. There were no fatal outcomes in the control group of patients, while two patients died in the experimental group. After a year, the follow-up examination did not show significant differences in ejection fraction and WMSI between the two groups of subjects. A statistically significant negative correlation between the sum of the TIMI risk and ejection fraction in myocardial infarction (rs = - 0.262; P = 0.009).The higher the TIMI risk score was the value of the ejection fraction was lower. A similar correlation has been demonstrated for Syntax sum and ejection fraction in myocardial infarction (rs = - 0.318; P = 0.001), and in the follow-up examination (rs = - 0.293; P = 0.004). Analysis of the complications in the follow-up examination revealed that there were no repeated myocardial infarctions (Table 16). The differences in the incidence of restenosis of blood vessels between the subjects in the examination and the control group were not demonstrated at follow-up examination, and there was no difference in the outcome of ergonomics at the follow up examination between patients in the examination and the control group.

Abstract in Croatian

UVOD. Podaci Svjetske Zdravstvene Organizacije (SZO) za 2005. godinu pokazuju da je od srčanožilnih bolesti u cijelom svijetu umrlo 17,5 milijuna ljudi, od čega 7,6 milijuna ljudi od koronarne bolesti srca. Bolesti srca i krvnih žila nisu samo vodeći uzrok smrti i bolničkog liječenja, nego su na drugom mjestu i po broju dana bolničkog liječenja i morbiditetu registriranom u djelatnostima primarne zdravstvene zaštite. Infarkt miokarda je česta i opasna komplikacija ishemijske bolesti. Čini ga nekroza miokarda nastala zbog kritične ishemije najčešće nastala uslijed aterosklerotskog suženja krvne žile s dodatkom tromba. Izuzetna je važnost infarkta miokarda zbog velike smrtnosti (približno četvrtina ukupne smrtnosti u razvijenim zemljama uzrokuje akutni infarkt miokarda) te invalidnosti. Bolesnici umiru najčešće u prvom satu od nastanka akutnog infarkta miokarda (oko 50% ukupnog letaliteta od akutnog infarkta miokarda) zbog srčanih aritmija. Dijagnosticira se promjenama na EKG-u, povišenim troponinom T i I, CK-MB, te invazivnom dijagnostičkom metodom – kateterizacijom srca. Cilj liječenja predstavlja postizanje brzog, potpunog i postojanog protoka krvi u koronarnoj arteriji zahvaćenoj infarktom, radi ograničenja veličine infarkta, poboljšanja funkcije lijeve klijetke i smanjenja smrtnosti i invalidnosti. Primarna PCI (primarna perkutana koronarna intervencija, PPCI) je zlatni standard u reperfuzijskom liječenju akutnog infarkta miokarda s elevacijom ST–segmenta (STEMI) Jedan od posebnih rizičnih čimbenika za nastanak infarkta miokarda je šećerna bolest. Više studija dokazalo je da su aterosklerotske promjene u koronarnim arterijama kod bolesnika sa šećernom bolesti teže, difuzno rasprostranjene, često na malim krvnim žilama i obično nepogodne za postupak perkutane koronarne intervencije. Bolesnici sa šećernom bolesti i s koronarnom bolesti srca, u odnosu na bolesnike bez šećerne bolesti, češće imaju dvožilnu ili trožilnu bolest koronarnih krvnih žila. Četvrtina bolesnika s akutnim infarktom miokarda boluje od šećerne bolesti tipa 2. Značajna osobitost tih bolesnika je postojanje atipičnih simptoma bolesti i razvoj srčanog zatajivanja, kao česte komplikacije akutnog infarkta miokarda. Bolesnici sa šećernom bolesti i s akutnim infarktom miokarda imaju dvostruko veću smrtnost u odnosu na bolesnike bez šećerne bolesti. Ishemijsko postkondicioniranje je intervencija u kojoj intermitentni periodi reokluzije u početku reperfuzije štite miokard od letalne reperfuzijske ozljede. Čine ga četiri balon okluzije u trajanju po 30 sekundi, praćene s po četiri balon reperfuzije. Mehanizam kardioprotektivnog djelovanja ishemičnog postkondicioniranja je još uvijek nedovoljno objašnjen, iako se čini da ishemijsko postkondicioniranje počinje specifičnim receptorima koji se nalaze na površinama stanica koje su odgovorne za aktiviranje određenog broja signalnih puteva, a mnogi se od njih odvijaju na mitohondrijalnom nivou. CILJ. Cilj ovog rada je ispitati da li uporaba ishemijskog postkondicioniranja u toku primarne perkutane koronarne intervencije u bolesnika sa šećernom bolesti tipa 2 i akutnim infarktom miokarda – STEMI, rezultira u smanjenju incidencije restenoza, smanjenu zone lezije infarkta miokarda, te poboljšanju ukupnog ishoda kardiovaskularne bolesti, u odnosu na bolesnike sa šećernom bolesti tipa 2 i akutnim infarktom miokarda – STEMI, koji su liječeni primarnom perkutanom koronarnom intervencijom bez uporabe ishemijskog postkondicioniranja. METODE. U istraživanju je sudjelovalo 100 pacijenata s akutnim infarktom miokarda – STEMI i šećernom bolesti tipa 2, podijeljenih u dvije skupine: 50 ispitanika, prosječne dobi od 60 godina, liječeni ishemijskim postkondicioniranjem u toku primarne perkutane koronarne intervencije, te 50 ispitanika, prosječne dobi od 60 godina, liječeni primarnom perkutanom koronarnom intervencijom bez primjene ishemijskog postkondicioniranja. Uključni kriteriji za ulazak pacijenata u istraživanje bili su sljedeći. Pacijenti koji su uključeni u istraživanje morali su biti liječeni inzulinskom terapijom najmanje godinu dana prije ulaska u istraživanje. Vrijeme proteklo od početka simptoma do početka primarne perkutane koronarne intervencije kod svih pacijenata uključenih u istraživanje trebalo je biti < 120 min, prema preporukama ACC/AHA. Svim pacijentima na target leziju postavljen je „drug–eluting stent“ – stent obložen lijekom (Cypher stent). Isključeni kriteriji za ulazak pacijenata u istraživanje bili su: ranije preboljeli infarkt miokarda, urađeni CABG, ranije srčane dekompenzacije (odnosno pacijenti s NYHA III, IV), te pacijenti kojima se zbog ozbiljnosti koronarografskog nalaza odmah pristupa aortokoronarnom premoštenju – CABG. Tijekom prve hospitalizacije vršila se analiza podataka: anamnestički se ispitala terapija prije hospitalizacije, a za procjenu rizika kardiovaskularnih incidenata kod obje grupe pacijenata koristio se TIMI risk score. Koronarografski nalaz bodovao se prema Sintax scoreu. Bilježio se biohumoralni porast enzima (troponin, CK-MB), na način da se mjerio inicijalni troponin i CK-MB, zatim nakon 24 sata, te svaki drugi dan do 7.-og dana hospitalizacije. Ehokardiografskim pregledom utvrdila se EF (prema Simpsonu) i WMSI, te su se zabilježili kardijalni incidenti nastali za vrijeme hospitalizacije pacijenta (poremećaji ritma – VF, VT, rana restenoza stenta, dekompenzacija ...). Follow up bio je nakon godinu dana kada se kontrolnim ehokardiografskim pregledom utvrdila EF i WMSI. Anamnestičkim pregledom utvrdilo se postojane dotadašnjih eventualnih kardijalnih incidenata, te se uradio ergometrijski test kojim se objektiviziralo postojanje postinfarktne angine pectoris REZULTATI: Mjerene su vrijednosti kretanja troponina od dana kada se dogodio infarkt miokarda do 7.-og dana nakon infarkta. Nije bilo statistički značajne razlike između vrijednosti troponina između dvije grupe ispitanika. U istraživanju je postojala je znakovita statistička razlika u vrijednostima troponina 4.-og dana nakon infarkta. Ispitanici u kontrolnoj skupini imali su veće vrijednosti u odnosu na ispitanike u ispitivanoj skupini. Zatim, prikazane su vrijednosti kreatin kinaze izoenzima MB, također od dana kada se dogodio infarkt miokarda do 7.-og dana nakon infarkta. Također, nije bilo razlike između kontrolne i ispitivane skupine ispitanika. U istraživanju nije dokazana razlika u vrijednostima u EF i WMSI među skupinama. Ukupni broj komplikacija do sedmog dana nakon infarkta miokarda nije se razlikovao između ispitanika u kontrolnoj i ispitivanoj skupini. Nije bilo razlike u učestalosti aritmija unutar sedam dana od infarkta miokarda između skupina ispitanika, u učestalosti stenoze unutar sedam dana od infarkta miokarda između skupina ispitanika, kao ni znakovite razlike u dekompenzaciji srca unutar sedam dana od infarkta miokarda u odnosu na ispitanike u kontrolnoj skupini. Smrtnog ishoda u kontrolnoj skupini ispitanika nije bilo, dok su u ispitivanoj skupini dva ispitanika umrla. Poslije godinu dana, na kontrolnom pregledu, nije pokazana znakovita razlika u ejekcijskoj frakciji i WMSI između skupina ispitanika. Pronađena je statistički znakovita negativna povezanost TIMI risk zbroja i ejekcijske frakcije pri infarktu miokarda (rs = - 0,262; P = 0,009). Što je TIMI risk zbroj bio veći, to je vrijednost ejekcijske frakcije bila manja. Slična povezanost pokazana je za Sintax zbroj i ejekcijsku frakciju pri infarktu miokarda (rs = - 0,318; P = 0,001), odnosno kontrolnom pregledu (rs = - 0,293; P = 0,004). Analizirajući komplikacije pri kontrolnom pregledu ustanovljeno je da nije bilo ponovljenog infarkta miokarda (tablica 16.). Nije pokazana razlika u učestalosti ponovne stenoze krvnih žila srca između ispitanika u ispitivanoj i kontrolnoj skupini pri kontrolnom pregledu, te nije bilo razlike u ishodu ergometrije pri kontrolnom pregledu između ispitanika u ispitivanoj u usporedbi s ispitanicima u kontrolnoj skupini.

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