Thèses sur le sujet « Acute coronary sindrome »

Background: To investigate in patients with non ST-segment elevation acute coronary syndrome (NSTE-ACS) the prevalence and the features of optical coherence tomography (OCT)-detected macrophages accumulation (MA) in culprit plaques (CP) as compared to non culprit plaques (NCP). Methods: The study is a post-hoc analysis of a prospective study aimed at evaluating the relationship between aortic inflammation as assessed by 18F-Fluorodeoxyglucose-positron emission tomography and features of coronary plaque vulnerability as assessed by OCT. We enrolled 32 patients with first NSTE-ACS that successfully underwent 3-vessel OCT. Results: The median age was 65 (54-72) years and 27 patients (84%) were male. CPs were clinically defined. MAs were defined as signal-rich, distinct, or confluent punctuate regions that exceed the intensity of background speckle noise. Their prevalence was 4.2 per patients and MAs were more likely found in CP than NCP (84% vs. 61%, p=0.015). MA had also a higher circumferential extension in CP and the risk for CP associated with macrophages extension was higher (OR = 4.42; 95CI;2.54-9.15, p<0.001) than that associated with the mere presence of MA (OR=3.36; 95%CI;1.30-8.66, p=0.012). CP with thrombus had a lower distance between MA and the luminal surface than CP with no thrombus (0.06 vs. 0.1 mm; p=0.04). Conclusions: In patients with NSTE-ACS, MAs are more likely present in CP where they disclose also a greater extension compared to those observed in NCP. The distance between MA and the luminal surface is lower in thrombotic CP than that in non thrombotic CP.

L'infarto miocardico in assenza di coronaropatia ostruttiva (MINOCA) è definito dall'evidenza di infarto miocardico acuto spontaneo e dalla documentazione angiografica di stenosi coronariche <50%. Negli ultimi anni, sono stati fatti grandi progressi nei campi dell'epidemiologia, patofisiologia, diagnosi, stima della prognosi e terapia di questa condizione. Finora, tuttavia, la definizione di MINOCA è piuttosto eterogenea in quanto condizioni specifiche come la miocardite e la sindrome di Takotsubo sono state spesso incluse, generando così risultati contrastanti. Questa tesi di dottorato si articola in quattro parti: parte I, Introduzione; parte II, Caratteristiche e prognosi; parte III, MINOCA e morte cardiaca improvvisa; parte IV, MINOCA e terapia farmacologica. Lo scopo di questo lavoro è di valutare alcuni degli aspetti più controversi relativi a questa condizione, in particolare per quanto riguarda la prognosi e la terapia farmacologica per i pazienti affetti da MINOCA.
Myocardial infarction and non-obstructed coronary arteries (MINOCA) is defined by the evidence of a spontaneous acute myocardial infarction and angiographic documentation of coronary stenosis <50% in any potential infarct related artery, after having excluded clinically overt causes for the acute presentation. The introduction of this new concept was meant to fill a gap in knowledge and to encourage discovery of putative pathophysiological mechanisms. In recent years, great advances have been made in the fields of epidemiology, pathophysiology, diagnosis, prognosis estimation and therapeutics of this condition. So far, however, the definition of MINOCA is rather heterogeneous as specific cardiac conditions such as myocarditis and Takotsubo syndrome are included thus generating conflicting results. This doctoral dissertation is divided in four sections: part I, Introduction; part II, Characteristics and Prognosis; part III, MINOCA and Sudden Cardiac Death; part IV, MINOCA and Pharmacological Therapy. The aim of this work is to assess some controversial aspect of this condition, in particular with regards to the prognosis and pharmacological therapy for patients affected by MINOCA.

Introducción: El consumo recreacional de cocaína ha aumentado en los últimos años en Europa, siendo España uno de los principales países consumidores de cocaína. La cocaína tiene múltiples efectos sobre el sistema cardiovascular, entre ellos ser desencadenante de un Síndrome Coronario Agudo (SCA). Método: Estudio observacional prospectivo, entre 2001 y 2014, en pacientes con SCA menores de 50 años que ingresaban en la unidad coronaria. Se realizó una anamnesis específica del consumo de cocaína y una determinación de los metabolitos de cocaína en orina. Nuestra hipótesis de trabajo fue “El consumo reciente de cocaína asociado a un síndrome coronario agudo (SCA-ACC) tiene un impacto pronóstico deletéreo a corto y largo plazo respecto al SCA no debido a cocaína”. Se definió el SCA-ACC en aquellos pacientes con SCA y determinación positiva de metabolitos de cocaína en orina o consumo reciente de cocaína por anamnesis. Resultados: Se incluyeron 1002 pacientes menores de 50 años con SCA. El 15.1% reconocían haber consumido cocaína alguna vez en su vida (el 41.7% eran exconsumidores, el 33.1% eran consumidores ocasionales y el 25.2% eran consumidores habituales de cocaína). Observamos un incremento en la prevalencia de consumo de cocaína des del 6.6% en 2002 hasta un pico del 21.7% y 20.5% en 2008 y 2009. Obtuvimos una determinación de metabolitos en orina en 864 pacientes (86.2%), siendo positiva en 52 (6%). Presentaban un SCA-ACC 59 pacientes (6.8%). Los pacientes con antecedentes de consumo de cocaína presentaban un mayor consumo de tóxicos además de cocaína como el tabaco, el alcohol y las otras drogas. En los pacientes con SCA-ACC observamos una mayor frecuencia de presentación como SCA con elevación del segmento ST (SCAEST). Los pacientes con SCA-ACC recibieron menos tratamiento con betabloqueantes en la fase aguda (40.7 contra 78.1%, p<0.001) y también al alta (59.6 contra 84.2%, p<0.001). Sin diferencias en los tratamientos de reperfusión realizados a los pacientes con SCAEST, únicamente una menor utilización de stents farmacoactivos (17.6 contra 34.5%, p=0.043). Durante la fase hospitalaria los SCA-ACC presentaron mayores complicaciones hospitalarias como la taquicardia ventricular (16.9 contra 4.7%, p<0.001), shock cardiogénico (6.8 contra 2.2%,p=0.032) y trastorno agudo de la conducción intraventricular (6.8 contra 1.5%,p=0.004) y una tendencia a mayor mortalidad hospitalaria (3.4 contra 1.0,p=0.097). El seguimiento realizado al 92.4% de los pacientes (mediana de 2381 días) observamos una mayor mortalidad en los pacientes con SCA-ACC (12.3 contra 5%,p=0.020) y también mortalidad cardiaca (7 contra 1.2%,p<0.001). El evento combinado de muerte, infarto o revascularización (MACE) también fue superior en SCA-ACC (35.1 contra 18.8%,p=0.003). El análisis multivariado de supervivencia por Coxx ajustado por la clasificación de killip y el tratamiento al alta presentó una HR de 2.126 ([IC 0.926-4.881],p=0.075) para mortalidad global, 4.038 ([IC 1.151-14.168],p=0.029) para mortalidad cardiaca y 2.015 ([IC 1.247-3.255],p=0.004) para MACE. Conclusiones: El tratamiento administrado en los pacientes con SCA-ACC es diferente al SCA-NACC, utilizando una menor proporción de fármacos betabloqueantes, así como de stents liberadores de fármaco en los procedimientos de intervencionismo coronario. Los pacientes con SCA-ACC tienen una peor evolución al seguimiento que los pacientes con SCA-NACC con una mayor incidencia de trombosis del stent, una mayor mortalidad (global y especialmente la de causa cardiaca) y tienen mayores eventos isquémicos, principalmente el infarto de miocardio. En nuestro medio se confirma nuestra hipótesis y los pacientes con síndrome coronario agudo asociado al consumo reciente de cocaína presentan un peor pronostico hospitalario con mayor numero de complicaciones hospitalarias y un peor pronostico a largo plazo con mayor mortalidad y infarto de miocardio al seguimiento.
Background: Recreational cocaine consumption in European countries has increased in recent years, and Spain is one of the main cocaine-using country in Europe. Cocaine has several effects on the cardiovascular system, being a trigger for Acute Coronary Syndrome (ACS). Methods: A prospective observational study was conducted between 2001 and 2014 in patients admitted to our coronary unit younger than 50 years old who suffered from an ACS. A detailed history of cocaine use and a determination of the metabolites of cocaine in urine were performed. Our working hypothesis was "Recent cocaine use associated with an acute coronary syndrome (ACS-ACC) has a deleterious short- and long-term prognostic impact on ACS not due to cocaine." Recent cocaine use associated with ACS (ACS-ACC) was defined as positive determination of cocaine metabolites in urine or admitting recent cocaine consumption prior to admission in the anamnesis in those patients who suffered an ACS. Results: 1002 patients younger than 50 years with ACS were included. 15.1% reported having consumed cocaine at least once in their lifetime (41.7% were former users, 33.1% occasional users and 25.2% current users). We observed an increase in prevalence of cocaine use from 6.6% in 2002 to a peak of 21.7% and 20.5% in 2008 and 2009. Determination of metabolites was obtained in 864 patients (86.2%), being positive in 52 (6%). A total of 59 patients (6.8%) presented a ACS-ACC. Patients with a history of cocaine use had a higher consumption of other substances, such as tobacco, alcohol, and other. Higher frequency of ACS with ST segment elevation was observed in cocaine users. The group of patients with ACS-ACC received less treatment with beta-blockers in the acute phase (40.7 vs 78.1%, p<0.001) and also at discharge (59.6 vs 84.2%, p<0.001). Differences in reperfusion treatments for patients with ACS-ACS were not observed in spite of a lower lower use of drug-eluting stents (17.6 vs 34.5%, p=0.043). During hospitalization, patients with ACS-ACC presented higher complications such as ventricular tachycardia (16.9 vs 4.7%, p<0.001), cardiogenic shock (6.8% vs 2.2%, p=0.032) and acute intraventricular conduction abnormalities (6.8 vs 1.5%,p=0.004) as well as a trend towards a higher hospital mortality (3.4 vs 1.0, p=0.097). Higher mortality in patients with ACS-ACC was observed (12.3% vs 5%, p=0.020) and also cardiac mortality (7% vs. 1.2%, p<0.001). The combined event of death, infarction or revascularization (MACE) was also higher in ACS-ACC (35.1 vs 18.8%, p = 0.003). Coxx survival multivariate analysis adjusted for killip classification and treatment at discharge showed a HR of 2.126 ([IC 0.926-4.881], p = 0.075) for overall mortality, 4,038 ([1,151-14,168], p = 0.029) for cardiac mortality and 2.015 ([1.247-3.255], p=0.004) for MACE. Conclusions: The treatment given in patients with ACS-ACC differs from patients with ACS-NACC, with lower proportion of beta-blocking drugs being used during admission and at discharge as well as a higher implantation of drug-eluting stents in coronary intervention procedures. Patients with ACS-ACC have a worse outcome at follow-up than patients with ACS-NACC with more incidence of stent thrombosis, higher mortality (overall and especially cardiac cause) and higher ischemic events, mainly miocardial infarction. Our hypothesis is confirmed in our setting, and patients with acute coronary syndrome associated with recent cocaine use have worse hospital prognosis with greater number of hospital complications, worse long-term prognosis with higher mortality and myocardial infarction at follow-up.

Orientadores: Roberta Cunha Matheus Rodrigues, Maria Cecilia Bueno Jayme Gallani
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Historical Background. “Angina pectoris” has been known since in ancient Egyptian time. Ebers Papyrus (1500 BC) wrote in a passage ".... If you examine a man for heart disease, he complains of pain in the arm, chest and part of the heart ....". This is the beginning of the long journey that takes us to the 1912 description of the myocardial infarction by coronary thrombosis by James Herrick, the 1962 subsequent birth of the first coronary care unit by Desmond Julian and finally in 1981 to the most modern Chest Pain Unit. Research continues to evaluate new aspects that could lead to the discovery of new strategies to reduce mortality rate of this disease. Background and aims. Preinfarction angina (defined as angina onset within 24 hours from the myocardial infarction) gives protection to the myocardium by reducing infarct size, and limiting left ventricular remodeling. The purpose of this study was to evaluate patients with acute coronary syndrome with ST elevation, and in particular subgroups. We compared patients with preinfarction angina (API +) to those without preinfarction angina (API-) with regard to ventricular function, end-diastolic volume and in-hospital clinical outcome. All these patients are followed up for one year under echocardiography and clinical settings, in order to assess whether any protective effects that are present during the hospital stay persist after one year. Methods and results. We evaluated over a period of two years 448 consecutive patients admitted to the Coronary Care Unit for acute coronary syndrome with ST elevation. Regardless of treatment received, of these patients we analyzed in greater detail a homogeneous subgroup, which had a significant lesion on left anterior descending coronary artery. Of these patients we performed a clinical and echocardiographic follow-up to a year. This study excluded patients enrolled in other studies. Our population was divided as follows: 112 patients, representing 25%, had suffered preinfarction angina (API +) within 24 hours from myocardial infarction, the remaining 336 (75%) had had no angina in the last 24 hours (API-). The two groups compared (API + versus API-) showed no significant differences in age, sex, risk factors (hypertension, high cholesterol, diabetes, family history of coronary artery disease, smoking). With regard to the treatment we found that the API + group had been treated more frequently with primary angioplasty compared to the API- group (88% vs 79%, p = 0.025). With regard to the in-hospital outcome group API+ compared to API- had a significantly reduced length of stay (9 ± 4 days vs 11 ± 9 days, p = 0.004), lower presence of arrhythmias (20% vs 32%, p = 0.015 ), less presence of heart failure (6% vs 14%, p = 0.035) and with regard to data echocardiography: ventricular function was better in group API + (ejection fraction 51 ± 7 % vs 48 ± 9%, p = 0.003) in correspondence to a lower end-diastolic volume (58 ± 11 ml/m2 vs 62 ± 17 ml/m2, p = 0.005) In a one year clinic follow up the number of admissions in other departments was significantly reduced (15% vs 25% p= 0.04) in the group API+, there is no statistical difference regarding the other parameters evaluated between outcome and preinfarction angina even if they are suggestive of a better prognosis in presence of the latter (one year survival 98% in API+ vs 93% in API-). So, considering the well known benefits of revascularization with primary angioplasty and thinking that they may cover the benefits of preinfarction angina, we evaluated a very homogeneous subgroup of 277 patients who had a critical lesion on the left anterior descending coronary artery. Of these, 30% was API +, while the remaining 70% were API-. There were no significant differences with regard to clinical variables. There were no significant differences with regard to the treatment received, while confirming the data of better in-hospital prognosis of group API + compared to API- with reduced hospital stay (9 ± 4 days vs 13 ± 10 days, p = 0.01), a lower presence of arrhythmias (20% vs 32%, p = 0.03), less presence of heart failure (7% vs 17%, p = 0.029) and also with regard to echocardiography: ventricular function was greater in the API + (50 ± 8% vs 46 ± 9%, p = 0.00) at a lower end-diastolic volume (59 ± 12 ml/m2 vs 64 ± 18 ml/m2, p = 0.018). Survival at one year did not differ significantly in the two groups (API + 97% vs API- 94%), it remained an improved ejection fraction (52 ± 9 % vs 48 ± 9 %, p = 0.010) without significant differences in relation to the end-diastolic volume (67 ± 16 ml/m2 vs 69 ± 18 ml/m2). Preinfarction angina by multivariate analysis was an independent predictor of lower presence of arrhythmias (OR 0.48 with 95% CI 0.25-0.93, p = 0.03), fewer episodes of heart failure (OR 0.33 with 95% CI 0.12-0.91, p = 0.03) and reduced hospital stay (in-hospital decreased of -2.62 ± 1.21 days, p = 0.03). Concerning to the echocardiographic data obtained at the discharge preinfartion angina was also protective, with better ventricular function (higher left ventricular ejection fraction 3.21 ± 1.14%, p = 0.01), and reduced diastolic volume (decreased end diastolic volume -5.20 ± 2.26 ml/m2, p = 0.02). Multivariate analysis of the data obtained during the follow up has shown a better ventricular function also at the echocardiography performed at 1 year (2.96 ± 1.44, p = 0.03). At the clinical follow-up at one year we have seen that the presence of preinfarction angina has played a protective role with regard to new episodes of acute coronary syndrome (6 cases vs. 22, OR 0.27) and episodes of heart failure (0 cases vs 5). Conclusions. Preinfarction angina has a certain protective effect with regard to in-hospital outcome, as it is associated with a lower presence of arrhythmias, fewer episodes of heart failure and reduced hospitalization, API+ patients, in despite of equal treatment, also have better sistolic ventricular function with less volume than API- patient . At the echocardiography obtained during the follow up ventricular function is improved in the API + group and our data show a protective role of preinfarction angina even with regard to new episodes of acute coronary syndrome and new episodes of heart failure.
Premessa storica. Già al tempo degli egizi, nel papiro di Ebers (1500 a.C.) è riconoscibile la descrizione dell'angina pectoris da un passo che dice: “.... se esamini un uomo per malattia del cuore, egli si lamenta per dolore al braccio, al petto e ad una parte del cuore....”. Da qui ha inizio il lungo cammino che ci porterà alla descrizione dell’infarto nel 1912 da trombosi coronarica da parte di James Herrick, alla successiva nascita delle prime Unità coronariche nel 1962 per opera di Desmond Julian e le più moderne Chest Pain Unit nel 1981. La ricerca continua a valutare nuovi aspetti che possano portare al rinvenimento di nuove strategie per ridurre la mortalità causata da questa malattia. Background e obiettivi. L’angina preinfartuale (intesa come angina comparsa nelle 24 ore precedenti l’infarto miocardico acuto) conferisce una protezione al miocardio riducendo le dimensioni dell’infarto, e limitando il rimodellamento ventricolare sinistro. Lo scopo di questo studio è valutare i pazienti che si presentano con sindrome coronarica acuta con sopraslivellamento del tratto ST, e in particolare alcuni sottogruppi, confrontando i pazienti con angina pre-infartuale (API+) e quelli senza (API-) per quanto riguarda la funzione ventricolare, il volume telediastolico e gli outcome clinici intraospedalieri e a distanza di un anno, per poter valutare se gli eventuali effetti protettivi presenti durante la degenza si mantengano anche nel tempo. Metodi e risultati. Abbiamo valutato in un arco temporale di due anni 448 pazienti consecutivi ricoverati in Unità Coronarica per sindrome coronarica acuta con ST sopraslivellato (SCA ST sopra) indipendentemente dal trattamento ricevuto. Di questi abbiamo poi analizzato più approfonditamente un sottogruppo omogeneo, che presentava lesione emodinamicamente significativa su ramo discendente anteriore della coronaria sinistra. Di questi pazienti è stato eseguito un follow-up clinico ed ecocardiografico ad un anno. Sono stati esclusi dal presente lavoro pazienti arruolati per altri studi. La nostra popolazione risultava così suddivisa: 112 pazienti, corrispondenti al 25 %, avevano presentato angina pre-infartuale (API+) nelle 24 ore precedenti l’infarto miocardico, i restanti 336 (75 %) non avevano avuto episodi anginosi nelle ultime 24 ore (API-). I due gruppi confrontati ( API+ vs API-) fra di loro non hanno dimostrato differenze significative per quanto riguardava l’età, il sesso, i fattori di rischio (ipertensione arteriosa, ipercolesterolemia, diabete, familiarità per coronaropatia, fumo). I due gruppi sono stati confrontati per quanto riguarda il trattamento ed è risultato che il gruppo API+ era stato trattato più frequentemente con angioplastica primaria rispetto al gruppo API- (88% vs 79% con p=0.025). Per quanto riguarda l’outcome intraospedaliero nel gruppo API+ rispetto a quello API- è risultata significativamente ridotta la durata della degenza (9±4 giorni vs 11±9 giorni con p=0.004), la presenza di aritmie ( 20% vs 32% con p= 0.015), la presenza di scompenso (6% vs 14% con p=0.035) e per quanto riguarda i dati ecocardiografici: la funzione ventricolare era migliore nel gruppo API+ (frazione di eiezione 51±7% vs 48± 9% con p= 0.003) in corrispondenza di un minor volume telediastolico (58 ± 11 ml/m2 vs 62 ± 17 ml/m2 con p = 0.005). Nel follow up ad un anno è risultato significativamente ridotto il numero di ricoveri in altro reparto (15% vs 25% con p=0.04), non vi è significatività statistica per quanto riguarda gli altri parametri valutati tra outcome e angina pre IMA anche se sono suggestivi di una migliore prognosi nel caso di angina pre IMA (sopravvivenza ad un anno API+ 98% vs API- 93%). Considerando i noti vantaggi legati alla rivascolarizzazione con angioplastica primaria e pensando che questi potessero offuscare i vantaggi legati all’angina-preinfartuale, abbiamo valutato un sottogruppo particolarmente omogeneo di 277 pazienti che avevano come caratteristica una lesione critica su discendente anteriore. Di questi il 30% aveva presentato API+, mentre il restante 70% era API-. Anche in questo gruppo non vi erano differenze significative per quanto riguardava età, sesso, fattori di rischio associati (ipertensione arteriosa, diabete, ipercolesterolemia, familiarità per coronaropatia, fumo) e malattie concomitanti (insufficienza renale cronica, broncopneumopatia cronica ostruttiva). Non risultavano differenze significative per quanto riguarda il trattamento ricevuto, mentre si confermavano i dati di miglior prognosi intraospedialiera nel gruppo API+ rispetto a quello API- con ridotta degenza ospedaliera (9±4 giorni vs 13±10 giorni, con p=0.01), la presenza di aritmie ( 20% vs 32% con p= 0.03), la presenza di scompenso (7% vs 17% con p=0.029) e anche per quanto riguarda i dati ecocardiografici: la funzione ventricolare era maggiore nel gruppo API+ (frazione d’eiezione 50± 8% vs 46± 9% con p = 0.00) in corrispondenza di un minor volume telediastolico (59 ± 12 ml/m2 vs 64 ± 18 ml/m2 con p = 0.018). Nel follow up ad un anno la sopravvivenza non presentava differenze statisticamente significative nei due gruppi (API+ 97% vs API- 94%), mentre si manteneva una miglior frazione di eiezione (52± 9 % vs 48± 9 % con p = 0.010) senza differenze significative per quanto riguarda il volume telediastolico (67 ± 16 ml/m2 vs 69 ± 18 ml/m2). All’analisi multivariata l’angina pre-infartuale risultava predittore indipendente di minor presenza di aritmie (OR 0.48 con 95%CI 0.25-0.93, p=0.03), minori episodi di scompenso (OR 0.33 con 95%CI 0.12-0.91, p=0.03) e ridotta degenza (degenza ridotta di -2.62±1.21 giorni con p=0.03). Risultava protettiva anche per quanto riguarda i dati ecocardiografici ottenuti in dimissione con miglior funzione ventricolare (frazione di eiezione aumentata di 3.21±1.14 % con p=0.01), e minor volume telediastolico (volume telediastolico ridotto di -5.20±2.26 ml/m2 con p=0.02). L’analisi multivariata dei dati ottenuti nel follow up ha dimostrato come si mantenga predittore di migliore funzione ventricolare anche nell’ecocardiogramma eseguito ad 1 anno (frazione di eiezione aumentata 2.96±1.44 % con p=0.03). Per quanto riguarda il follow up clinico ad 1 anno abbiamo visto che la presenza di angina pre-infartuale ha svolto un ruolo protettivo per quanto riguarda nuovi episodi di sindrome coronarica acuta (6 casi vs 22, OR 0.27) e per episodi di scompenso cardiaco (0 casi vs 5). Conclusioni. L’angina pre-infartuale risulta avere un effetto protettivo certo per quanto riguarda l’outcome intraospedaliero, in quanto porta ad una minor presenza di aritmie, minori episodi di scompenso e minori giorni di degenza, inoltre i pazienti API+ hanno a parità di trattamento una migliore funzione ventricolare con minor volume telediastolico rispetto ai pazienti API-. Per quanto riguarda il follow up ad un anno la funzione ventricolare risulta migliore nel gruppo API+ e i nostri dati mostrano un ruolo protettivo dell’angina pre-infartuale anche per quanto riguarda nuovi episodi di sindrome coronarica acuta e nuovi episodi di scompenso.

Background: l’acido urico (AU) nei pazienti che si presentano con SCA è stato riconosciuto come fattore determinante la mortalità intra-ospedaliera. Inoltre esso è anche correlato con le complicanze intraospedaliere in termini di recidiva precoce di altri eventi cardiovascolari non fatali e altri outcome intermedi interpretabili come segni di decorso intra-ospedaliero complicato (l’utilizzo di contropulsatore aortico o di ventilazione non invasiva, un maggior tempo di degenza ed una maggior frequenza di sanguinamenti ma anche la presentazione con un quadro di scompenso cardiaco acuto o con FA all’ingresso in unità coronarica). Scopo dello studio: scopo principale del nostro studio è quello di valutare il ruolo dell’AU misurato in acuto come possibile determinante di mortalità intraospedaliera (outcome primario) e di complicanze durante la degenza (outcomes secondari). Scopo secondario è stato anche quello di individuare il miglior cut-off per tale associazione. Oltre all’individuazione di uno specifico cut-off è stata anche valutata la performance diagnostica, in termini di sensibilità e specificità, del cut-off classico oggi utilizzato per definire l’iperuricemia (> 6 mg/dL nelle femmine e 7 mg/dL nei maschi) e di un cut-off più basso individuato dalla letteratura più recente (5.26 mg/dL per le femmine e 5.49 mg/dL per i maschi). Metodi: Per fare questo sono stati analizzati i dati di 563 pazienti ricoverati presso l’Unità di Cure Intensive Cardiologiche (UCIC) dell’ospedale Niguarda Ca’ Granda. Gli outcome considerati sono la mortalità intraospedaliera per tutte le cause, il re-infarto, la trombosi intrastent, la nuova rivascolarizzazione non programmata, i sanguinamenti, gli stroke, la presentazione con scompenso cardiaco, la presentazione con FA, l’utilizzo di inotropi, contropulsatore aortico e ventilazione non invasiva, l’evidenza di coronaropatia trivasale alla coronarografia e la FE in ingresso ed in dimissione dall’UCIC. Risultati: i pazienti presentavano un’età media di 66.5 ± 12.3 anni, nel 79.2% dei casi erano maschi e nel 49.9% dei casi accedevano per STEMI. Con entrambi i cut-off i soggetti iperuricemici erano più anziani e presentavano più frequentemente FRCV e pregresso infarto miocardico. Essi morivano più frequentemente durante la degenza, giungevano al ricovero in FA o con scompenso cardiaco, presentavano con maggior frequenza coronaropatia trivasale ed utilizzavano più frequentemente contropulsatore aortico e NIV. Infine i valori di FE sia all’ingresso che in dimissione dall’UCIC erano più bassi rispetto al gruppo dei non iperuricemici. All’analisi multivariata l’AU resisteva come determinante significativo di tutti gli outcomes (esclusa la coronaropatia trivasale) in un modello contenente età, genere, precedente infarto miocardico, anamnesi positiva per ipertensione arteriosa, Charlson Comorbidity Index e creatinina. Entrambi i cut-off erano in grado di discriminare in modo statisticamente significativo l’incrementata mortalità dei pazienti iperuricemici anche se in entrambi i casi la performance in termini di Sensibilità (Sn) e Specificità (Sp) presentava alcuni problemi. Abbiamo infine provato ad individuare un cut-off ideale per questa specifica popolazione che è stato di 6.35 mg/dL con un’area sotto la curva complessiva di 0.772 e con una Sn ed una Sp di 70.3% ed 81.8%. Conclusioni: in conclusione AU risulta determinante indipendente della mortalità intraospedaliera per tutte le cause e di variabili indicative di peggior presentazione al momento dei ricovero (scompenso cardiaco, FA ed FE all'ingresso), di complicanze intra-ricovero (utilizzo di contropulsatore aortico e NIV) e di un peggior risultato sulla ripresa della funzione ventricolare sinistra (FE in dimissione). Ulteriori studi con valutazione longitudinale dell'andamento dell'AU sono necessari per chiarire definitivamente la direzionalità delle relazioni individuate.
Background: Uric acid (UA) has been related to in-hospital mortality in ACS patients. Furthermore, it has been related to early relapse of non-fatal cardiovascular events and to intermediate outcome such as use of intra-aortic balloon pump, noninvasive ventilation, longer inward stay, bleeding but also clinical presentation with AF or heart failure. Aim of the study: principal aim of our study was to evaluate the role of UA as a possible determinants of in-hospital mortality (primary outcome) and in hospital complications (secondary outcomes). Secondary aim was to identify the best cut-off and to evaluate diagnostic performance of already used cut-off (the classic one of > 6 mg/dL in female and 7 mg/dL in males, and a recently described one with 5.26 mg/dL in females and 5.49 mg/dL in males). Methods: we analyze data of 563 patients admitted for ACS at the Cardiological Intensive Care Unit of the Niguarda Ca’ Granda Hospital. We consider as outcome in-hospital mortality, inward myocardial infarction, instent thrombosys, bleeding, stroke, clinical presentation with heart failure of AF, inotropes, intra-aortic balloon pump and non-invasive ventilation uses during hospital stay, three vessels coronaric involvement at the coronary angiogram and EF both at admission and at discharge. Results: mean age was 66.5 ± 12.3 years, 79.2% of the patients were males and 49.9% of the ACS were STEMI. With both cut-off hyperuricemic subjects were older, with more prominent cardiovascular risk factor and previous myocardial infarction. Furthermore, they more frequently died during hospital stay, they present more frequently heart failure and AF as clinical presentation, have more commonly three vessels disease and use more frequently intra-aortic balloon pump and non-invasive ventilation. Finally, also EF at admission and discharge were lower in hyperuricemic patients. At multivariate analysis UA was a significant determinants of primary and secondary outcomes (except for three vessels coronaric disease) in a model with age, gender, previous myocardial infarction, arterial hypertension, Charlson Comorbidity Index and creatinine as covariates. Both cut-off can significantly discriminate in-hospital mortality but with only fair results in term of Sensibility (Sn) and Specificity (Sp). Finally, we identify 6.35 mg/dL as the best cut-off for this specific population with an area under the curve of 0.772, Sn 70.3% and Sp 81.8%. Conclusions: in conclusion UA was an independent determinants of in-hospital mortality and of variables suggestive of worst clinical presentation (heart failure, AF and admission EF), in-hospital complications (intra-aortic balloon pump and non-invasive ventilation uses) and worst recovery (discharge EF). Further study with longitudinal evaluation of UA during ACS are needed in order to better clarify directionality of detected relationship.

El síndrome coronario agudo (SCA) es la principal complicación de la cardiopatía isquémica y se produce como consecuencia de la inestabilización de las placas de aterosclerosis de las arterias coronarias. Se sabe que la inflamación juega un papel importante en todas las fases de la enfermedad aterosclerosa; en el inicio de la formación de la placa, en la progresión de la misma y es máxima en el momento de inestabilización y aparición del SCA. Los objetivos de esta tesis son analizar el papel e implicaciones clínicas de la anemia adquirida intrahospitalariamente y del déficit de hierro (DH) en pacientes con SCA y su posible relación con la inflamación. Para responder a estos objetivos se realizaron dos registros prospectivos de pacientes que ingresaron de manera consecutiva por un SCA en nuestro centro. Para el análisis de la anemia nosocomial se incluyeron 221 pacientes entre el 2009 y 2010 y para el análisis del DH se incluyeron, entre el 2012 y 2015, a otros 244. Se observó que la anemia nosocomial sin sangrado evidente sucede en el 25% de los pacientes con SCA, que su aparición se relaciona con un estado inflamatorio marcado indicado por valores de proteína C reactiva >3.1mg/dl y que es un predictor de morbi-mortalidad a largo plazo. Así mismo, también se observó que el DH se encuentra en más del 50% de los pacientes con SCA, que se relaciona con un estado inflamatorio marcado indicado por niveles elevados de Interleucina-6 y que su persistencia a los 30 días tras el evento coronario implica una peor capacidad funcional y una peor calidad de vida.
The Acute Coronary Syndrome (ACS) is the main complication of ischemic cardiovascular disease and it’s caused by Coronary atherosclerotic plaque instability. It is known than Inflammation plays a key role in all phases of atherosclerosis; at the beginning of plaque formation, in its progression and reaches maximum levels at the time of ACS onset. The objectives of the present thesis are to analyze the role and clinical implications of in-hospital acquired anemia and iron deficiency (ID) in patients with ACS and their possible relationship with inflammation. In order to respond to these objectives, we performed two prospective registries of patients consecutively admitted for an ACS in our center. For the first analysis, 221 patients were included between 2009 and 2010, and for the ID analysis 244 were included between 2012 and 2015. Nosocomial anemia was observed in 25% of patients with ACS and was a strong predictor of cardiovascular morbidity and mortality in the long-term follow-up. A > 3.1mg/dl value of C-reactive protein was highly predictive of developing nosocomial anemia. In the other hand, ID was registered in more than 50% of ACS patients; its presence was related to a marked inflammatory status indicated by high levels of Interleukin-6 and its persistence 30 days after the coronary event resulted in a poorer mid-term functional recovery, as measured by exercise capacity and quality of life.

Tirti pasirinktiniai 193 pacientai, gydyti Vilniaus universiteto ligoninės Santariškių klinikų Kardiologijos reanimacijos ir intensyviosios terapijos skyriuje. Tyrime buvo nagrinėjami vyresnio amžiaus pacientų ūminio koronarinio sindromo klinikinės eigos ypatumai, ligonių išgyvenamumo ryšys su klinikinės eigos ypatumais bei gydymo būdais. Tuo tikslu buvo išanalizuotas vyresnio amžiaus pacientų, patyrusių ūminį koronarinį sindromą, išgyvenamumas bei didžiųjų nepageidaujamų kardiovaskulinių įvykių dažnis per 3 metus nuo ūminio koronarinio sindromo pasireiškimo pradžios. Buvo įvertintas pacientų grupių homogeniškumas pagal amžiaus grupes, ūminio koronarinio sindromo formas bei GRACE riziką. Buvo palyginti pacientų, kuriems taikytas ir netaikytas invazinis gydymas, ūminio koronarinio sindromo klinikinės eigos bei išeičių ypatumai. Tyrime buvo įvertintos išgyvenamumo sąsajos su pacientų anamnezės, klinikinės eigos bei gydymo veiksniais, taip pat bei palyginti išgyvenę ir neišgyvenę pacientai, patyrę ūminį koronarinį sindromą pagal anamnezės, klinikinės eigos bei gydymo veiksnius priklausomai nuo invazinio ar neinvazinio gydymo taikymo. Tokiu būdu buvo ieškoma veiksnių, kurie skirtingai reikšmingi pacientų, gydytų invaziniu ir neinvaziniu būdu, išgyvenamumui.
193 consecutive patients older than 75 years with ACS were included in the study. Clinical process characteristics of acute coronary syndrome in elderly patients have been assessed in this study; the relation between patient survival and clinical process characteristics as well as treatment methods has been established. For this purpose the survival of elderly patients with acute coronary syndrome and, also, the frequency of MACE (major adverse cardiovascular events) during the 3 years after acute coronary syndrome has been analysed. The assessment of the patient group homogeneity according to the age group, acute coronary syndrome forms and GRACE risk has been performed. The analysis and comparison of the patients who received and those who did not receive invasive treatment, as well as the characteristics of their acute coronary syndrome clinical progress and outcomes have been presented in this study. The links between the patient survival and the factors of patient history, clinical progress and treatment have been established. The comparison of the patients with acute coronary syndrome who survived with the ones who did not survive based on the various factors of their history, clinical progress and treatment subject to the invasive or conservative treatment received has been provided. Thus, the study searched for the factors having various impacts on the patients survival depending on the treatment – invasive or conservative – received.

193 consecutive patients older than 75 years with ACS were included in the study. Clinical process characteristics of acute coronary syndrome in elderly patients have been assessed in this study; the relation between patient survival and clinical process characteristics as well as treatment methods has been established. For this purpose the survival of elderly patients with acute coronary syndrome and, also, the frequency of MACE (major adverse cardiovascular events) during the 3 years after acute coronary syndrome has been analysed. The assessment of the patient group homogeneity according to the age group, acute coronary syndrome forms and GRACE risk has been performed. The analysis and comparison of the patients who received and those who did not receive invasive treatment, as well as the characteristics of their acute coronary syndrome clinical progress and outcomes have been presented in this study. The links between the patient survival and the factors of patient history, clinical progress and treatment have been established. The comparison of the patients with acute coronary syndrome who survived with the ones who did not survive based on the various factors of their history, clinical progress and treatment subject to the invasive or conservative treatment received has been provided. Thus, the study searched for the factors having various impacts on the patients survival depending on the treatment – invasive or conservative – received.
Tirti pasirinktiniai 193 pacientai, gydyti Vilniaus universiteto ligoninės Santariškių klinikų Kardiologijos reanimacijos ir intensyviosios terapijos skyriuje. Tyrime buvo nagrinėjami vyresnio amžiaus pacientų ūminio koronarinio sindromo klinikinės eigos ypatumai, ligonių išgyvenamumo ryšys su klinikinės eigos ypatumais bei gydymo būdais. Tuo tikslu buvo išanalizuotas vyresnio amžiaus pacientų, patyrusių ūminį koronarinį sindromą, išgyvenamumas bei didžiųjų nepageidaujamų kardiovaskulinių įvykių dažnis per 3 metus nuo ūminio koronarinio sindromo pasireiškimo pradžios. Buvo įvertintas pacientų grupių homogeniškumas pagal amžiaus grupes, ūminio koronarinio sindromo formas bei GRACE riziką. Buvo palyginti pacientų, kuriems taikytas ir netaikytas invazinis gydymas, ūminio koronarinio sindromo klinikinės eigos bei išeičių ypatumai. Tyrime buvo įvertintos išgyvenamumo sąsajos su pacientų anamnezės, klinikinės eigos bei gydymo veiksniais, taip pat bei palyginti išgyvenę ir neišgyvenę pacientai, patyrę ūminį koronarinį sindromą pagal anamnezės, klinikinės eigos bei gydymo veiksnius priklausomai nuo invazinio ar neinvazinio gydymo taikymo. Tokiu būdu buvo ieškoma veiksnių, kurie skirtingai reikšmingi pacientų, gydytų invaziniu ir neinvaziniu būdu, išgyvenamumui.

Scopo: Il quadro clinico dei pazienti con sindrome coronaria acuta (SCA) può essere atipico, con enzimi miocardiospecifici normali ed elettrocardiogrammi non diagnostici. Una percentuale dei pazienti (2-8%) con SCA giunti in pronto soccorso, viene erroneamente dimessa. Spesso i pazienti con angina instabile (UA) o infarto miocardico senza sopraslivellamento del tratto ST (NSTEMI) possono presentare malattia coronarica multivasale o lesioni critiche dei rami principali prossimali; è importante quindi una stratificazione del rischio per la scelta del timing terapeutico ottimale. Scopo del nostro studio è stato quello di valutare il ruolo della TCMS nella stratificazione del rischio di questi pazienti, confrontando tale tecnica con un’analisi clinica, biochimica e di funzionalità miocardica. Materiali e Metodi: Sono stati arruolati nello studio 47 pazienti consecutivi (34 maschi, 13 femmine; età media 63.3 ± 11,6 anni) con NSTEMI (94%) o UA (6%). E’ stata effettuata una valutazione clinico-anamnestica, biochimica, elettrocardiografica ed ecocardiografica. Entro 12 ore dall’ingresso tutti i pazienti sono stati sottoposti ad esame TCMS 64-strati e suddivisi in monovasali, bivasali, trivasali, con patologia e del tronco comune e con stenosi < 50%. Successivamente tutti i pazienti sono stati sottoposti ad esame coronarografico. Risultati: La TCMS ha mostrato una sensibilità nell’identificare malattia coronarica del 97%, una specificità dell’83%, un valore predittivo negativo dell’83%, un valore predittivo positivo del 97% ed un’accuratezza diagnostica del 95%. Un solo paziente con malattia coronarica, con un’importante componente vasospastica, non è stato identificato alla TCMS. La concordanza della TCMS con l’esame coronarografico nell’identificazione di pazienti monovasali, bivasali, trivasali, con malattia del tronco comune e con stenosi < 50% è stata rispettivamente dell’83%, 81%, 82%, 78%, 80%. Nessuno dei parametri clinici, biochimici, elettrocardiografici ed ecocardiografici ha invece mostrato una correlazione con l’estensione della malattia coronarica. Il 58% delle lesioni culprit aveva una componente lipidica, l’11% calcifica, il 30% mista. La TCMS ha identificato la lesione culprit della SCA nell’86% dei casi (densità media della placca: 76 ± 41 HU, densità minima: 50,9 ± 29 HU) e il vaso responsabile nel 92%. Conclusioni: La TCMS è risultata affidabile nella stratificazione del rischio di pazienti con NSTEMI e UA, avendo correlato con l’estensione della malattia, avendo identificato i pazienti con malattia coronarica nel 97% dei casi e avendo identificato e caratterizzato la lesione responsabile. I dati clinici, elettrocardiografici, enzimatici ed ecocardiografici invece non si sono dimostrati utili strumenti nella stratificazione del rischio in tale gruppo di pazienti.
Rationale and Objectives: Clinical presentations in acute coronary syndrome (ACS) are sometimes atypical consisting in normal initial cardiac enzymes and nondiagnostic electrocardiogram. Previous studies have found that between 2% and 8% of patients with ACS who present to the emergency department are inappropriately discharged home. Unstable angina and non-ST elevation myocardial infarction (NSTEMI) patients have usually multivessel disease or proximal coronary vessel disease and a non invasive coronary evaluation could be useful for risk stratification and for an optimal therapeutic strategy timing. The aim of our study was to evaluate multislice computed tomography (MSCT) role in risk stratification of ACS without ST elevation, comparing this technique with a clinical, biochemical and echocardiographic analysis. Materials and Methods: Forty-seven consecutive patients (34 male, 13 female; mean age: 63.3 ± 11,6 years) admitted because of ACS [NSTEMI (94%), UA (6%)] were enrolled. All patients underwent a clinical, biochemical, electrocardiographic, echocardiographic evaluation. Sixty-four MSCT coronary angiography was performed in all patients within 12 hours of acute event. In a patient-based analysis all subjects were divided in 5 groups: 1-vessel, 2-vessels, 3-vessels, left main and non significant disease. Selective coronary angiography was performed within 12 hours after MSCT. Results: Sensitivity, specificity, negative predictive value, positive predictive value and accuracy of MSCT for detecting coronary artery disease (CAD) were 97%, 83%, 83%, 97% and 95%, respectively. Only one patient with CAD and a vasospastic component was non identified by MSCT. MSCT correlation with coronary angiography in the identification of 1-vessel, 2-vessels, 3-vessels, left main and non significant disease patients was respectively 83%, 81%, 82%, 78%, 80%. Clinical, biochemical, electrocardiographic, echocardiographic parameters were not able to correlate with CAD severity and extension. Culprit lesion composition was lipidic in 58% of cases, calcified in 11%, mixed in 30%. MSCT identified ACS culprit lesion in 86% of patients (mean plaque density 76 ± 41 HU, minimum plaque density 50,9 ± 29 HU) and culprit vessel in 92% of cases. Conclusions: In the majority of cases, MSCT definitively and non invasively establishes or excludes CAD as the cause of chest pain. Our results show that 64-slice CT is an accurate non invasive technique to detect CAD in NSTEMI/UA patients, useful for risk stratification, assessing CAD extension and culprit lesion composition. Clinical, biochemical, electrocardiographic, echocardiographic parameters resulted not useful in risk stratification in this group of patients.

Uvod: Kardiovaskularne bolesti predstavljaju vodeći uzrok obolevanja i umiranja savremenog čoveka i vodeći su javno-zdravstveni problem u svetu i kod nas. Brojna istraživanja sugerišu da se mediteranski način ishrane povezuje sa smanjenjem rizika za nastanak i razvoj kardiovaskularnih bolesti i drugih masovnih nezaraznih bolesti kao i smanjenjem stope ukupnog mortaliteta. Cilj istraživanja: Utvrditi stepen pridržavanja mediteranskom načinu ishrane kod obolelih od akutnog koronarnog sindroma i kod osoba sa utvrđenim rizikom za nastanak kardiovaskularnih bolesti, upotrebom validovanog skora mediteranske ishrane – MedDiet skora. Takođe, cilj istraživanja je bio da se utvrdi da li postoji značajna razlika u vrednostima biohemijskih i kliničkih faktora rizika za razvoj kardiovaskularnih bolesti između dve posmatrane grupe ispitanika, kao i da se odredi granična vrednost MedDiet skora između poželjnog i rizičnog načina ishrane za nastanak akutnog koronarnog sindroma. Metod: Istraživanje je sprovedeno kao analitička studija preseka na uzorku od 294 ispitanika (146 žena i 148 muškaraca), starosti od 30 do 82 godine. Istraživanje je sprovedeno u vremenskom periodu od 07.02.2016. godine do 16.03.2017. godine. Prvu grupu činili su ispitanici kod kojih je  dijagnostikovan akutni koronarni sindrom, koji su hospitalizovani u Institutu za kardiovaskularne bolesti Vojvodine u Sremskoj Kamenici, dok su drugu grupu činili ispitanici kod kojih je utvrđeno prisustvo najmanje jednog faktora rizika za nastanak kardiovaskularnih bolesti, bez klinički manifestne koronarne bolesti, koji su se javili na pregled u Savetovalište za pravilnu ishranu, Instituta za javno zdravlje Vojvodine u Novom Sadu. Kod svih učesnika u studiji izvršena su: antropometrijska merenja, merenje arterijskog krvnog pritiska, odgovarajuće biohemijske analize, EKG i anketiranje upotrebom posebno pripremljenog upitnika, u čijem sastavu se nalazio i MedDiet skor – validovan skor system za procenu stepena zastupljenosti mediteranskog načina ishrane kod pojedinca. Rezultati istraživanja: Srednja vrednost MedDiet skora ispitanika bez akutnog koronarnog sindroma bila je 27,48±6,59, dok je srednja vrednost MedDiet skora ispitanika sa akutnim koronarnim sindromom bila 20,53±4,01. Razlika srednjih vrednosti MedDiet skora između dve grupe ispitanika bila je statistički značajna (p=0,029). Ispitivanjem prediktivnih vrednosti pojedinih varijabli utvrđeno je da su MedDiet skor i glikemija našte odlični markeri za akutni koronarni sindrom (AUROC=0,815, p<0,0005 i AUROC=0,829, p<0,0005, respektivno). Rezultati istraživanja su pokazali da konzumiranje pojedinih namirnica iz kategorija definisanih MedDiet skorom (voće, povrće, živinsko meso i maslinovo ulje) može doprineti smanjenju rizika za nastanak akutnog koronarnog sindroma. Konzumiranje crvenog mesa i mesnih prerađevina povećava rizik od pojave akutnog koronarnog sindroma. Utvrđena granična vrednost MedDiet skora iznosila je 22,5. Vrednosti MedDiet skora ≤22,5 predstavljaju faktor rizika za nastanak akutnog koronarnog sindroma, dok vrednosti MedDiet skora >22,5 ukazuju na smanjen rizik za nastanak akutnog koronarnog sindroma. Multivarijantnom regresionom analizom pokazano je da na pojavu akutnog koronarnog sindroma utiču sledeći faktori rizika: godine starosti 1,063 (1,270-1,819), muški pol 4,071 (1,901-8,719), pušenje 3,067 (1,322-7,114), indeks telesne mase 0,902 (0,839-0,970), sistolni pritisak 1,020 (1,003-1,037), glikemija našte 1,520 (1,025-1,101) i MedDiet skor 0,783 (0,722-0,849). Zaključak: Akutni koronarni sindrom predstavlja značajan javno-zdravstveni problem odraslog stanovništva u Republici Srbiji na šta ukazuju visoke prevalencije u populaciji. Rezultati sprovedenog istraživanja pokazuju da je i diskretnim povećanjem unosa namirnica koje predstavljaju osnovu mediteranskog načina ishrane moguće postići značajne zdravstvene koristi. Ovi rezultati mogu predstavljati okvir za razvoj lokalnog skoring sistema ishrane prikladnog za nemediteransko područje, kao i modela za procenu rizika za nastanak akutnog koronarnog sindroma u našoj populaciji.
Introduction: Cardiovascular diseases are the leading cause of morbidity and mortality of a modern society and are major public health problem in our country and also worldwide. Numerous studies suggest that the Mediterranean diet is associated with a reduction in the risk of developing cardiovascular diseases and other non-communicable diseases, as well as reduction in the overall mortality rate. Aim: To determine the degree of Mediterranean diet complience in subjects with acute coronary syndrome and subjects with an established risk for developing cardiovascular diseases, using validated Mediterranean diet score - MedDiet. Also, the aim of the study was to determine whether there is a significant difference in the values of the  biochemical and clinical risk factors for the development of cardiovascular diseases between the two observed groups of subjects, and to determine the cut-off value of the MedDiet score between the favorable and unfavorable dietaty pattern for the development of acute coronary  syndrome. Method: The study was conducted as an analytical cross-sectional study with enrollment of 294 subjects (146 women and 148 men), 30 to 82 years of age. The research was conducted during the period from 02/07/2016 until 03/16/2017. The first group of subjects consisted of patients diagnosed with acute coronary syndrome who were hospitalized at the Institute for Cardiovascular Diseases Vojvodina in Sremska Kamenica. The second group was comprised of subjects with established at least one major risk factor for the development of cardiovascular diseases but without clinically manifest coronary artery disease, who came to the medical examination of the Counseling Center for Proper Nutrition, Institute of Public Health of Vojvodina in Novi Sad. Among all participants in the study the following examinations were conducted: anthropometric measurements, arterial blood pressure measurements, appropriate biochemical analysis, ECG and surveys using a specially prepared questionnaire, which included MedDiet score - validated score system for assessing the degree of compliance with Mediterranean dietary pattern among subjects. Results of the study: The average value of the MedDiet score among subjects without acute coronary syndrome was 27.48 ± 6.59, while the average value of MedDiet score among subjects with acute coronary syndrome was 20.53 ± 4.01. The difference in MedDiet average values between the two groups of subjects was statistically significant (p = 0.029). By examining the predictive values of individual variables, it was shown that MedDiet score and fasting blood sugar were excellent markers for acute coronary syndrome (AUROC = 0.815, p<0.0005 and AUROC = 0.829, p <0.0005, respectively). The results of the study showed that the consumption of certain foods in the categories defined by MedDiet score (fruits, vegetables, poultry, and olive oil) can contribute to reduction of the risk for developing acute coronary syndrome. On the other hand, consuming red meat and meat products increased the risk of acute coronary syndrome. The established cut-off value for MedDiet score was 22.5. MedDiet score ≤22.5 practicaly indicated greater risk for the development of acute coronary syndrome, while MedDiet score> 22.5 indicated reduced risk for the development of acute coronary syndrome. Multivariate regression analysis showed that acute coronary syndrome is affected by the following risk factors: age 1,063 (1,270-1,819), male gender 4,071 (1,901-8,719), smoking 3,067 (1,322-7,114), body mass index 0,902 (0.839-0.970 ), systolic blood pressure 1.020 (1.003-1.037), fasting blood sugar 1.520 (1.025-1.101) and MedDiet score 0.783 (0.722- 0.849). Conclusion: Acute coronary syndrome is a major public health problem in the adult population of the Republic of Serbia, as indicated by its high prevalence. The results of the conducted research show that discrete increase in food intakes of foods which represent the basis of the Mediterranean diet, can lead to significant health benefits. These results can represent a framework for the development of a local scoring system for a non-mediterranean area, and also for creation of risk assessment model for acute coronary syndrome in our population.

Uvod: U savremenom svetu koronarna arterijska bolest srca (KABS) je vodeći uzrok obolevanja i umiranja, a akutni koronarni sindrom (AKS) je jedna od njenih najčešćih i najopasnijih kliničkih manifestacija. Dijastolna disfunckija leve komore često prati KABS i mogući je doprinosni faktor za loš klinički tok i ishod. Postavlja se pitanje u kom obimu je dijastolna disfunkcija leve komore udružena sa koronarnom arterijskom bolešću i da li savremeni programi ambulantne sveobuhvatne kardijalne rehabilitacije (ASKR) imaju uticaja na bolju prognozu ove grupe kardioloških bolesnika. Uprkos širokoj primeni revaskularizacionih procedura u svakodnevnoj kardiološkoj praksi i brojnih studija koje su ukazale na pozitivne efekte programa SKR na funkcionalni status pacijenata nakon AKS, još uvek postoji mnogo kontroverzi o efektima fizičkog treninga, na srčanu funkciju i poboljšanje funkcionalnog kapaciteta kod pacijenata sa KABS i pridruženom dijastolnom disfunkcijom. Cilj istraživanja: bio je da ispita uticaj superviziranih vežbi fizičkim opterećenjem (VFO) u okviru programa ambulantne sveobuhvatne kardijalne rehabilitacije (ASKR), na dijastolnu disfunkciju leve komore (DDLK) i funkcionalni status pacijenata (FS), nakon AKS, rešenog perkutanom koronarnom intervencijom (PCI), kao i da li, s druge strane, prisustvo i stepen dijastolne disfunkcije na početku istraživanja, utiče na funkcionalni status i pojavu neželjenih kardijalnih događaja, kod ove grupe pacijenata u okviru programa ASKR i van njega  Materijal i metode: Istraživanjem je bilo obuhvaćeno ukupno 85 ispitanika, oba pola, starosti od 18-65 godina, koji su tokom indeksne hospitalizacije lečeni kao klinički dokazani AKS (APNS; NSTEMI; STEMI) i kod kojih je urađena neka od interventnih koronarnih procedura (pPCI; PCI; PTCA). Nakon 4 nedelje od otpusta sa hospitalizacije, zbog NSTEMI ili APNS, odnosno nakon 6 nedelja od otpusta sa hospitalizacije zbog STEMI, pacijenti sa EFLK ≥ 45%, bez značajnih valvularnih i drugih mana i sa nekim od poremećaja dijastolne funkcije, bili su kandidati za učešće u istraživanju. Svi ispitanici su podvrgavani „ulaznom“ehokardiografskom pregledu (EHO) u cilju procene sistolne funkcije i stepena dijastolne disfunkcije leve komore, kao i „ulaznom“ spiroergometrijskom testu (CPET) u cilju procene funkcionalnog statusa, na osnovu kojeg je vršena preskripcija vežbi fizičkim opterećenjem (VFO) u okviru programa ASKR. Program ASKR odvijao se u ukupnom trajanju od 12 nedelja, odnosno 36 pojedinačnih sesija VFO, 3 puta nedeljno u trajanju od po 30 minuta. Kontrolna grupa obuhvatila je grupu pacijenata koja nije živela u blizini IKVBV i koja nije bila u mogućnosti da dolazi redovno na VFO u sklopu ASKR. Njima je bilo pušteno na volju da na osnovu urađenog EHO pregleda i CPET, određuju stepen VFO po sopstvenom nahođenju, uz primenu optimalnog medikamentnog lečenja i ostalih mera sekundarne prevencije. Nakon 3 meseca obe grupe pacijenata bile su podrvrgnute novom –“izlaznom” ehokardiografskom i CPET pregledu u cilju komparacije sa rezultatima na početku istraživanja. Rezultati:Istraživanje je pokazalo da nakon 3 meseca superviziranog treninga VFO, u okviru programa ASKR, kod bolesnika nakon AKS, lečenih perkutanom koronarnom intervencijom, dolazi do poboljšanja stepena dijastolne disfunkcije leve komore, naročito kroz promene vrednosti ehokardiografskih parametara e’l i E/e’ l. U kontrolnoj grupi e’l se smanjio za (0,003 ± 0,025), a u osnovnoj se povećao za (0,011 ± 0,021). U kontrolnoj grupi e’l se nije značajno promenio (p = 0,515), a u osnovnoj grupi se značajno povećao (p < 0,0005). Na početku istraživanja u osnovnoj grupi e’l je bio (0,097 ± 0,027 m/sec), a na kraju (0,108 ± 0,031 m/sec). E/e’l se nije značajno promenio u kontrolnoj grupi (p = 0,226), a u osnovnoj grupi se značajno smanjio (p = 0,002). Na početku istraživanja u osnovnoj grupi E/e’l je bio (8,02 ± 2,98), a na kraju (6,97 ± 2,17). Takođe je utvrđeno da nakon 3 meseca superviziranog treninga u okviru programa ASKR, dolazi do poboljšanja funkcionalnog kapaciteta pacijenata sa KABS i dijastolnom disfunkcijom leve komore, kroz povećanje CPET parametara: peak VO2, VO2 predict i METs. U kontrolnoj grupi peak VO2 se smanjio za (1,79 ± 3,84), a u osnovnoj se povećao za (1,67 ± 4,29). U kontrolnoj grupi peak VO2 se značajno smanjio (p = 0,018), a u osnovnoj grupi se značajno povećao (p = 0,005).Na početku istraživanja u kontrolnoj grupi srednja vrednost peak VO2 iznosila je (23,01 ± 3,99 ml/kgTT/min), a u osnovnoj grupi je iznosila (23,15 ± 4,99 ml/kgTT/min). Na kraju istraživanja u osnovnoj grupi srednja vrednost peak VO2 iznosila (24,82 ± 5,77 ml/kgTT/min), dok je kod kontrolne grupe iznosila (21,21 ± 4,05 ml/kgTT/min). U kontrolnoj grupi ppVO2(%) se smanjio za (5,28 ± 14,39), a u ispitivanoj se povećao za (7,16 ± 18,51). U kontrolnoj grupi ppVO2(%) se nije značajno promenio (p = 0,058), dok se u osnovnoj grupi statistički značajno povećao (p = 0,005). Razlika srednjih vrednosti promena METs između osnovne i kontrolne grupe je bila statistički značajna (p < 0,0005). U kontrolnoj grupi METs se smanjio za (0,55 ± 1,12), a u osnovnoj se povećao za (0,58 ± 1,12). U kontrolnoj grupi METs se značajno smanjio (p = 0,013), a u osnovnoj grupi se značajno povećao (p < 0,0005). Zaključak: Program ambulantne sveobuhvatne kardijalne rehabilitacije, kod bolesnika nakon akutnog koronarnog sindroma, lečenih perkutanom koronarnom intervencijom, utiče na poboljšanje faktora rizika kardiovaskularnih bolesti, značajno utiče na poboljšanje stepena dijastolne disfunkcije leve komore i na poboljšanje funkcionalnog statusa pacijenata, u odnosu na početak istraživanja.
Background: In modern world, coronary artery disease (CAD) is one of the leading cause of morbidity and mortality, and acute coronary syndrome (ACS) is one of its most common and most dangerous clinical manifestations. Left ventricle diastolic dysfunction (LVDD) is often associated with CAD and is possibly a contributing factor for poor clinical course and outcome. The question arises as to the extent to which the left ventricle diastolic dysfunction is associated with CAD and whether modern ambulatory comprehensive cardiac rehabilitation programs (ACCR) have an impact on a better prognosis of this group of cardiac patients. Despite the wide use of revascularization procedures in everyday clinical practice and numerous trials that have indicated the positive effects of the ACCR on the functional status of patients after ACS, there is still much controversy about the effects of physical training, and its impact on cardiac function and the improvement of functional capacity in patients with CAD and associated diastolic dysfunction. Objective: to examine the influence of supervised physical training programe as a part of ambulatory comprehensive cardiac rehabilitation (ACCR), on diastolic dysfunction and the functional capacity of patients after ACS resolved by percutaneous coronary intervention (PCI), and whether, on the other hand, the presence and the degree of diastolic dysfunction at the beginning of the study, affects the functional capacity and occurrence of unwanted cardiac events (MACE), in this group of patients within the ACCR program and without it. Methods: The study include a total of 85 subjects, both sexes, ages 18-65, who were treated as clinically proven ACS during the index hospitalization and in which some of the interventional coronary procedures were performed (pPCI; PCI; PTCA). After 4 weeks of hospitalization due to NSTEMI or APNS, or after 6 weeks of hospitalization due to STEMI, patients with LVEF ≥ 45%, without significant valvular and other disorders and with some degree of lef ventricle diastolic dysfunction, were candidates for participation in the study. All patients were subjected to an initial, “entrance”, echocardiographic examination (ECHO) in order to evaluate the left ventricle systolic function and the degree of diastolic dysfunction, as well as the initial, “entrance”, spiroergometry test (CPET) in orther to asses the functional capacity. The ACCR program include a total duration of 12 weeks, or 36 individual exercise training sessions, 3 times a week, with the duration of 30 minutes. The control group included a group of patients who did not live near ICVDV and who was not able to come regularly to the exercise training sessions as a part of ACCR. They determine the degree of exercise trainig on their own will after they performed initial EHO and the CPET examination, using the optimal medical treatment and other secondary prevention measures. After 3 months, both groups of patients were subjected to a new, "exit", ECHO and CPET examinations in order to compare with the results at the start of the study. Results: The study showed that after 3 months of supervised exercise training program, as a part of the ACCR, in patients following ACS treated with percutaneous coronary intervention, there is an improvement in the degree of left ventricular diastolic dysfunction, especially through changes in the echocardiographic parameters e'l and E / e 'l . In the control group e'l decreased by (0,003 ± 0,025), and in the base group it increased by (0,011 ± 0,021). In the control group, e'l did not change significantly (p = 0,515), while in the base group significantly increased (p <0,0005). At the beginning of the study in the base group e'l was (0,097 ± 0,027 m/sec), and at the end (0,108 ± 0,031 m/sec). E / e'l did not change significantly in the control group (p = 0,226), and in the base group significantly decreased (p = 0,002). At the beginning of the study in the base group E / e'l was (8,02 ± 2,98), and at the end (6,97 ± 2,17). It has also been established that after 3 months of supervised training within the ACCR program, the functional capacity of patients with CAD and left ventricular diastolic dysfunction is improved, by increasing in peak VO2, VO2 predict and METs. In the control group, peak VO2 decreased by (1,79 ± 3,84), and in the base group it increased by (1,67 ± 4,29). In the control group, peak VO2 decreased significantly (p = 0,018) and significantly increased in the base group (p = 0,005). At the start of the study in the control group, the mean peak VO2 was (23,01 ± 3,99 ml/ kgTT / min), and in the base group it was (23,15 ± 4,99 ml / kgTT / min). At the end of the study in the base group, the mean peak VO2 was (24,82 ± 5,77 ml/ kgTT / min), while the control group was (21,21 ± 4,05 ml / kgTT / min). In the control group ppVO2 (%) it decreased by (5,28 ± 14,39), and in the examined it increased by (7,16 ± 18,51). The control group ppVO2 (%) did not significantly change (p = 0,058), while in the base group it increased significantly (p = 0,005). The difference in mean values of MET changes between base and control group was statistically significant (p <0,0005). In the control group METs decreased by (0,55 ± 1,12), and in the base group it increased by (0,58 ± 1,12). METs significantly decreased in the control group (p = 0,013), while in the base group significantly increased (p <0,0005). Conclusions: The program of ambulatory comprehensive cardiac rehabilitation in patients following acute coronary syndrome, treated with percutaneous coronary intervention, has an positive effect on the improvement of the risk factors for cardiovascular diseases, significantly influencing the improvement of the degree of left ventricle diastolic dysfunction and the improvement of the functional capacity of patients.

Moždani udar predstavlja drugi uzrok smrti u celom svetu i neurološku bolest sa najvećim stepenom invaliditeta. Za povoljan ishod moždanog udara veoma je važno sprečavanje i lečenje somatskih kompikacija (SK), pri čemu je njihova učestalost i značaj za oporavak pacijenata potcenjena, a uticaj na ishod moždanog udara zanemaren. Ciljevi istraživanja su bili da se utvrdi učestalost pacijenata sa somatskim komplikacijama u akutnoj fazi moždanog udara; zatim da se utvrdi učestalost svake pojedinačne somatske komplikacije: pneumonije, urinarnih infekcija, duboke venske tromboze, tromboembolije pluća, dijarealnog sindroma i akutnog koronarnog sindroma; zatim da se utvrde faktori rizika za nastanak svake pojedinačne SK, kao i da se utvrdi uticaj SK na ishod bolesti - iskazan kroz njihovu povezanost sa funkcionalnim statusom, dužinom hospitalizacije i mortalitetom pacijenata. Istraživanje je sprovedeno kao prospektivno i obuhvatilo je 403 pacijenta hospitalizovanih zbog akutnog moždanog udara na Klinici za neurologiju Kliničkog centra Vojvodine u periodu od godinu dana. Pacijenti su podeljeni u dve grupe, gde su prvu grupu sačinjavali pacijenti sa registrovanom jednom ili više somatskih komplikacija (n = 162), a drugu su činili pacijenti koji nisu imali somatske komplikacije (n = 241). Evaluacija pacijenata obuhvatila je registrovanje sociodemografskih karakteristika, ličnu i porodičnu anamnezu, karakteristike moždanog udara, neurološki status na prijemu i otpustu, funkcionalni status na prijemu i otpustu, laboratorijske analize krvi i urina na prijemu, vrstu i vreme nastanka pojedinačne somatske komplikacije, sve relevantne dijagnostičke metode za postavljenje dijagnoze i definisanje potencijalnih faktora rizika. Somatske komplikacije se češće javljaju kod starijih osoba, prosečne starosti 72,9 godina, kod osoba ženskog pola i kod pacijenata sa hemoragijskim moždanim udarom. Somatske komplikacije registrovane su kod 40,2% pacijenata, pri tome urinarnu infekciju imalo je 20,3% pacijenata, pneumoniju 16,3%, infarkt miokarda 4,7%, plućnu tromboemboliju 3,4%, duboku vensku trombozu 2,4% i dijarealni sindrom 2,9% pacijenata. Nezavisni prediktori pneumonije su disfagija, narušeno stanje svesti, hronična opstruktivna bolest pluća, mRS veći od 3. Prediktori urinarnih infekcija su: podatak o rekurentnim urinarnim infekcijama, ženski pol, starost preko 70 godina, mRS veći od 3 i NIHSS skor veći od 16. Kao nezavisni prediktori plućnog tromboembolizma dobijeni su duboka venska tromboza, narušeno stanje svesti i gojaznost, dok se jedinim nezavisnim prediktorom dijarealnog sindroma pokazala starost pacijenta preko 70 godina. Prediktori akutnog koronarnog sindroma su: starost veća od 70 godina i hemoragijski moždani udar. Pacijenti sa SK, na kraju hospitalnog lečenja imaju značajno lošiji funkcionalni status u odnosu na pacijente bez somatskih komplikacija. Somatske komplikacije statistički značajno produžavaju hospitalizaciju. Kod četvrtine pacijenata (25,9%) sa somatskim komplikacijama u akutnoj fazi moždanog udara registrovan je letalni ishod. Najveći procenat smrtnih ishoda kod pacijenata sa somatskim komplikacijama registrovan je kod pacijenata sa infarktom miokarda (63,2%), a najmanji kod pacijenata sa urinarnom infekcijom (18,3%).
Stroke is the second cause of death worldwide and neurological disease with the highest level of disability. For a favorable outcome of stroke, the prevention and treatment of somatic complications are of great importance, while their frequency and the importance of the recovery of patients are underestimated, and the influence on the outcome of stroke is neglected. The aims of the study were: to determine the frequency of patients with somatic complications in the acute phase of stroke; to determine the frequency of each somatic complication: pneumonia, urinary infections, deep venous thrombosis, lung thromboembolism, diarrheal syndrome, and acute coronary syndrome; to identify risk factors for the emergence of each somatic complication, as well as to determine the effect of those complications on the outcome of the disease - expressed through their association with the functional status, length of hospitalization and mortality of patients. The study was conducted as a prospective and included 403 patients hospitalized due to acute stroke at the Clinic for Neurology of the Clinical Center of Vojvodina for a period of one year. Patients were divided into two groups; the first group included patients with one or more somatic complications registered (n = 162), and the second group consisted of patients without any somatic complication (n = 241). Patient evaluation included registration of socio-demographic characteristics, personal and family history, stroke characteristics, neurological and functional status at the time of admission and discharge, laboratory analysis of blood and urine at admission, type and time of emergence of each somatic complication, all relevant diagnostic methods for setting diagnosis and defining potential risk factors. Somatic complications are more common in older people (the average age of 72.9 years) in females and in patients with hemorrhagic stroke. Somatic complications were reported in 40.2% of patients, 20.3% of patients had urinary infection, 16.3% pneumonia, 4.7% myocardial infarction, 3.4% pulmonary thromboembolism, deep venous thrombosis 2.4% and diarrheal syndrome 2.9% of patients. Independent predictors of pneumonia were dysphagia, impaired state of consciousness, chronic obstructive pulmonary disease, mRS higher than 3. Predictors of urinary infections were: data on recurrent urinary tract infections, female sex, age over 70 years, mRS higher than 3 and NIHSS score higher than 16. As independent predictors of pulmonary thromboembolism, deep venous thrombosis, impaired state of consciousness and obesity were obtained, while the only independent predictor of diarrheal syndrome proved to be the age of the patient over 70 years. Predictors of acute coronary syndrome were: age over 70 years and haemorrhagic stroke. Patients with somatic complications at the end of hospital treatment had significantly worse functional status compared to patients without somatic complications. Somatic complications statistically significantly prolong hospitalization. A quarter of patients (25.9%) with somatic complications in the acute phase of the stroke had a lethal outcome. The highest percentage of deaths in patients with somatic complications was registered in patients with myocardial infarction (63.2%) and the lowest was registered in patients with urinary tract infections (18.3%).

We sought to identify possible clinical and laboratory predictors of bleeding and ischaemic risk in a real-world population with concomitant atrial fibrillation and PCI, discharged from our cardiology ward with double antithrombotic therapy (DAT) or triple antithrombotic therapy (TAT). Nell'ambito della tesi sono stati ricercati predittori clinici o laboratoristi di eventi ischemici o emorragici in una popolazione di pazienti con storia di fibrillazione atriale, sottoposti ad angioplastica, e dimessi in duplice o triplice terapia antitrombotica.