Univerzita Karlova 1. lékařská fakulta Studijní program: Doktorské studium biomedicíny 1. LF UK Studijní obor: Oborová rada Fyziologie a patofyziologie člověka MUDr. Gabriela Dostálová Disertační práce Vybrané aspekty akutního infarktu myokardu u mladých nemocných Specifics of Acute Myocardial Infarction in Young Adults Školitelé: prof. MUDr. A. Linhart, DrSc., doc. MUDr. D. Karetová, CSc. Praha 2017 Abstract Coronary heart disease is the leading cause of death in adults in the western world. Myocardial infarction can represent the lethal manifestation of coronary heart disease leading to sudden cardiac death. Although myocardial infarction mainly occurs in patients older than 45 years, the young population can be affected as well. Despite the relatively low incidence of myocardial infarction in the young population, the mortality rates and long-term disability make acute myocardial infarction in young patients an important clinical issue. Consequences of myocardial infraction usually have great impact on the young patient's psychology, ability to work and the overall quality of life. The management of young myocardial infarction patients should differ at least slightly from the older ones. Young patients usually have a different risk factor profile, clinical presentation, and prognosis in comparison with...

Introduction: Acute coronary syndromes (ACS) belong to cardiovascular diseases and contribute significantly to mortality, morbidity and disability in developed countries. Therefore the aim of current therapy is to reduce the risk of subsequent complications, including early death, and to increase patients' quality of life. For successful therapy it is necessary to follow regimen and dietary principles which are along with pharmacotherapy an integral part of treatment. Therefore sufficient knowledge of these principles by patients is a basic precondition for their successful treatment. Objectives: The aim of the diploma thesis was to assess dietary and regime knowledge in patients diagnosed with ACS. The specific objectives were: to determine an effect of sex or previous education on the knowledge; to describe patients' dietary habits; to specify their knowledge of nutrition; and to identify which knowledge is the most deficient. Methods: The research was carried out as a questionnaire survey. The questionnaire was compiled directly for the purposes of this thesis and was approved by the VFN Ethics Committee for use in inpatient wards at II. and III. internal clinics and at the Coronary unit of II. internal clinics of VFN. A total of 80 patients diagnosed with ACS were included in the study....

Introdução: Alguns autores estudaram o valor prognóstico do eletrocardiograma inicial na sobrevida em longo prazo dos pacientes com síndrome coronariana aguda sem supradesnivelamento do segmento ST. O valor prognóstico de outros traçados eletrocardiográficos na fase intra-hospitalar do tratamento foi menos estudado. Objetivos: Avaliar o papel no prognóstico clínico dos registros eletrocardiográficos obtidos durante o evento índice dos participantes do estudo Estratégia de Registro de Insuficiência Coronariana (ERICO) com síndrome coronariana aguda sem supradesnivelamento do segmento ST. Métodos: Foram analisados e classificados, de acordo com o Código de Minnesota, os traçados eletrocardiográficos intra-hospitalares de 634 participantes do estudo ERICO com síndrome coronariana aguda sem supradesnivelamento do segmento ST, no período de fevereiro de 2009 a dezembro de 2013. Foram classificados como alterados os traçados eletrocardiográficos com infradesnivelamento do segmento ST > 1mm e/ou com onda T negativa > 1mm. Foram construídos modelos de regressão de Cox brutos e ajustados, para estudar se o padrão eletrocardiográfico foi um preditor independente de desfechos clínicos (morte por qualquer causa, morte por causa cardiovascular, morte por infarto agudo do miocárdio, e desfecho combinado de morte por infarto do miocárdio ou novo infarto do miocárdio não fatal). Resultados: A mediana de seguimento foi de 3 anos. Encontramos uma tendência não significativa para a associação entre a presença de alteração de segmento ST no eletrocardiograma inicial com o desfecho combinado de morte por infarto do miocárdio ou novo infarto do miocárdio não fatal [Hazard Ratio (HR) ajustado: 1,64, intervalo de confiança de 95% (IC 95%): 1,00-2,70, p = 0,052]. Encontramos um risco significativamente maior de morte por infarto do miocárdio em indivíduos com alterações do segmento ST no eletrocardiograma final (HR ajustado: 2,04; IC 95%: 1,06-3,92). Os indivíduos com alterações do segmento ST em qualquer traçado durante o evento índice apresentaram risco significativamente maior para desfecho combinado de morte por infarto do miocárdio ou novo infarto do miocárdio não fatal (HR ajustado: 1,71; IC 95%: 1,04-2,79). Quando as alterações de onda T foram incluídas na classificação dos traçados, não houve associação significativa com o prognóstico a longo prazo. Conclusões: Encontramos associações significativas entre as alterações de segmento ST e pior prognóstico em longo prazo. A avaliação sequencial dos traçados eletrocardiográficos durante o evento índice parece adicionar informação prognóstica ao ECG inicial / Introduction: Some authors have studied the prognostic value of initial electrocardiogram in long-term survival of patients with a non-ST-segment elevation acute coronary syndrome (NSTE-ACS). The prognostic value of other in-hospital electrocardiographic tracings has been less studied. Objectives: To describe the association between electrocardiogram abnormalities (in ST-segment and T wave) during the index event and outcomes in patients with NSTE ACS in the Strategy of Registry of Acute Coronary Syndrome (ERICO) cohort. Methods: We analyzed and classified, according to the Minnesota Code, in-hospital ECG tracings of 634 ERICO participants with NSTE-ACS, from February 2009 to December 2013. We considered as altered electrocardiographic tracings with ST-segment depression > 1 mm and / or negative T wave > 1 mm. We built crude and adjusted Cox regression models to study if ECG pattern was an independent predictor for clinical outcomes (death from any cause, death from cardiovascular causes, death from acute myocardial infarction, and combined outcome of fatal or new nonfatal myocardial infarction). Results: Median follow-up was 3 years. We found a trend for the association between initial ECG tracing and the combined outcome of fatal or new nonfatal myocardial infarction [Hazard Ratio (HR) adjusted: 1,64, confidence interval 95% (95% CI): 1,00-2,70, p = 0,052]. We found a significantly higher risk of death due myocardial infarction in patients with ST-segment abnormalities in the final ECG tracing (adjusted HR: 2,04; 95% CI: 1,06 to 3,92). Individuals with ST-segment abnormalities in any tracing had significant higher risk for fatal or new nonfatal myocardial infarction (adjusted HR: 1,71; 95% CI: 1,04 2,79). When the T wave changes were included in the classification, there was no significant association with long-term prognosis. Conclusions: We found significant associations between ECG patterns and worse long-term prognosis. Sequential evaluation of electrocardiographic tracings during the index event seems to add prognostic information to the initial ECG

INTRODUÇÃO: O Infarto agudo do miocárdio (IAM) é infrequente em indivíduos jovens (<45 anos) e está associado à história familiar precoce de doença cardiovascular.OBJETIVO: O presente estudo descreveu o perfil sócio-demográfico e os fatores de risco cardiovascular de indivíduos com diagnóstico de IAM < 45 anos de idade e seus familiares de primeiro grau. Avaliou-se também a relação de parâmetros clínico-laboratoriais de acordo com a extensão angiográfica da doença arterial coronária (DAC) dos casos índices (doença uniarterial vs. multiarterial) e dos seus respectivos familiares.MÉTODOS: Estudo transversal realizado de novembro de 2010 a janeiro de 2015 em hospital terciário em Fortaleza, Ceará. Foram incluídos 103 casos índices e 166 familiares de primeiro grau que não apresentavam suspeita de hipercolesterolemia familiar. Estes foram comparados com 111 indivíduos assintomáticos e sem história familiar de DAC pareados para sexo e idade. Foram avaliados os parâmetros clínicos e laboratoriais dos 3 grupos. Os dados foram estudados por análises uni e multivariadas. RESULTADOS:O grupo casos apresentou maior prevalência de tabagismo (57,3 vs. 28,6%, p < 0,001), diabete melito tipo 2 - DM2 (43,4 vs. 19,5%, p < 0,001) e hipertensão arterial sistêmica - HAS (42,7 vs. 19%, p < 0,001) quando comparado aos familiares pareados para sexo e idade. Da mesma forma, os casos, quando comparados ao grupo controle, apresentaram, além destes fatores, concentrações mais elevadas de triglicerídeos (192 ± 75 vs. 140±74mg/dL, p < 0,001), menores concentrações de HDL-c (36 ± 12 vs. 48 ± 14mg/dL, p < 0,001) e uma maior prevalência de síndrome metabólica -SM (82,2 vs. 36%, p<0,001). Observou-se que 50,5% dos casos tinham acometimento multiarterial. Após análise multivariada, a HAS (p=0,030) e o DM2 (p=0,028) associaram-se de forma independente à DAC multiarterial. Quando comparados ao grupo controle, os familiares apresentaram maior prevalência de tabagismo (29,5 vs. 6,3%, p < 0,001), DM2 (19,9 vs. 1,8%, p < 0,001), pré-diabetes (40,4 vs. 27%, p < 0,024) e SM (64,7 vs. 36% p < 0,001). Foram observadas aindaconcentrações mais baixas de HDL-c (39±10 vs. 48 ± 14mg/dL, p < 0,001), valores mais elevados de triglicerídeos (179 ± 71 vs. 140 ± 74mg/dL, p = 0,002), LDL-c (122±37 vs. 113±36mg/dL, p = 0,031) e colesterol não-HDL (157 ± 43 vs. 141 ± 41mg/dL, p = 0,004) nos familiares. Não houve diferenças entre familiares e controles quanto ao IMC (p=0,051). Os familiares também apresentaram maior prevalência do risco calculado como alto/intermediário de acordo com o escore de Framingham (82,7 vs. 2,6%, p < 0,001) em relação aos controles. Os valores de TSH foram maiores, mesmo dentro do valor de referência do método, no grupo de casos (2,6 ± 1,6 vs. 1,9 ± 1,0 mUI/L, p < 0,001) e familiare (2,4±1,6 vs. 1,9 ± 1,0 mUI/L, p=0,002) em relação aos controles. CONCLUSÃO: Evidenciou-seelevada prevalência de fatores de risco cardiovascular, principalmente a SM, dislipidemia aterogênica, DM2, HAS e tabagismo em casos e familiares de primeiro grau de indivíduos com IAM < 45 anos. A HAS e o DM2 associaram-se à maior extensão angiográfica da DAC / BACKGROUND: The acute myocardial infarction (AMI) is uncommon in young individuals ( < 45 years), and is associated with premature family history of cardiovascular disease. OBJECTIVE: This study described the socio-demographic and cardiovascular risk factors of both subjects with AMI < 45 years of age and their first-degree relatives. The association of clinical and laboratory parameters with the angiographic extension of coronary artery disease (CAD) of index cases (single-vessel vs. multivessel disease) and in their respective relatives was also evaluated. METHODS: Cross-sectional study conducted from November 2010 to January 2015 in a tertiary hospital in Fortaleza, Ceara. One hundred and three index cases and 166 first-degree relatives without suspicion of familial hypercholesterolemia were included. These were compared with 111 asymptomatic individuals without family history of CAD matched for sex and age. Clinical and laboratory parameters of the 3 groups were evaluated. Associations were tested by univariate and multivariate analysis. RESULTS: AMI cases presented a higher prevalence of smoking (57.3% vs. 28.6%, p < 0.001), type 2 diabetes mellitus -DM2 (43.4 vs. 19.5%, p < 0.001), and hypertension (42.7 vs. 19%, p < 0.001) when compared to relatives matched for sex and age. Likewise cases, when compared to controls showed in addition higher triglycerides (192 ± 75mg/dL vs. 140 ± 74mg/dL, p < 0.001), lower HDL-C (36 ± 12mg/dL vs. 48±14mg/dL, p < 0.001), and a greater prevalence of the metabolic syndrome-MS (82.2% vs. 36%, p < 0.001). Multivessel disease was found in 50.5% of cases. After multivariate analysis, hypertension (p=0.030), and DM2 (p=0.028) were independently associated with multivessel disease. First-degree relatives showed a greater prevalence of smoking (29.5% vs. 6.3%, p < 0.001), DM2 (19.9% vs. 1.8%, p < 0.001), pre-diabetes (40.4 % vs. 27%, p < 0.024) and MS (64.7% vs. 36%, p < 0.001), when compared to controls. Lower HDL-c (39±10mg/dL vs. 48 ± 14mg/dL, p < 0.001), higher triglycerides (179±71mg/dL vs. 140±74mg/dL, p=0.002), higher LDL-C (122 ± 37mg/dL vs. 113 ± 36mg/dL, p=0.031) and non-HDL cholesterol (157 ± 43 vs. 141±41mg/dL, p=0.004) were found in relatives than controls. There was no difference in BMI (p=0.051) between the groups. Relatives also showed a higher prevalence of high/intermediate calculated coronary heart disease risk according to the Framingham risk score (82.7% vs. 2.6%, p < 0.001). TSH levels even within the reference value method were higher in AMI patients (2.6 ± 1.6mUI/mL, p < 0.001) and relatives (2.4 ± 1.6mUI/mL, p=0.002) in comparison with controls 1.9±1.0mUI/mL). CONCLUSION: A high prevalence of risk factors mainly MS, atherogenic dyslipidemia, type 2 DM, hypertension and smoking were encountered in cases and first-degree relatives of individuals with AMI < 45 years. Hypertension and DM2 were associated with greater angiographic extent of coronary artery disease

<p>In patients with diabetes mellitus (DM), acute myocardial infarction (AMI) is a major cause of death. We have studied two populations with respect to the relationship between DM or related glucometabolic disturbances and AMI.</p><p>In the first population, the prevalence of DM and the importance of the glycaemic state for the long-term prognosis in non-diabetic patients were investigated in patients with AMI admitted to the Coronary Care Unite at Västerås Central Hospital.</p><p>In the second population, the prevalence of impaired glucose tolerance (IGT), DM and other metabolic abnormalities was investigated in patients with AMI and without known DM admitted to the Coronary Care Units at Västerås and Karolinska Hospital, Stockholm.</p><p>21% of the patients with AMI had previously known DM and 4% had newly detected DM if diagnosis is based upon fasting blood glucose (F-BG). The glycemic state, measured as HbA1c, at a 5.5 years follow-up was a risk factor for re-infarction and/or death in non-diabetic patients after AMI.</p><p>If an oral glucose tolerance test (OGTT) is performed, 40-45% of all patients with AMI have DM and in addition about 30% have IGT. Both an OGTT and a single post-challenge blood glucose value after 60 minutes performed at hospital discharge, were independent predictors of IGT or DM at follow-up. Insulin resistance, measured by homeostatic model assessment (HOMA-IR), decreased during hospital stay, with no further decrease from hospital discharge to follow-up.</p><p>In summary, the studies in this dissertation have revealed an unexpectedly high prevalence of abnormal glucose tolerance in patients with AMI. The glycaemic state, reflected by HbA1c, in non-diabetic patients after AMI has an impact on the long-term prognosis. Consequently, in all patients with AMI, HbA1c and casual blood glucose should be measured at admission and, at least, F-BG at hospital discharge.</p>

<p>We evaluated, in patients with ST-elevation myocardial infarction (STEMI) treated with thrombolytics, admission Troponin T (tnT), ST-segment resolution and admission N-terminal pro-brain natriuretic peptide (NT-proBNP) for early risk stratification as well as time delays and outcome in real life patients according to prehospital or in-hospital thrombolytic treatment. Also, baseline characteristics, treatments and outcome in patients enrolled in the ASSENT-2 trial in Sweden and in patients not enrolled were evaluated. </p><p>TnT (n=881) and NT-proBNP (n=782) on admission and ST-resolution at 60 minutes (n=516) in patients from the ASSENT-2 and ASSENT-PLUS trials were analysed. Elevated levels of NT-proBNP and tnT on admission were both independently related to one-year mortality. However, when adding information on ST-resolution (</≥50%) 60 minutes after initiation of thrombolytic treatment, tnT no longer contributed independently to mortality prediction. High and low risk patients were best identified by a combination of NT-proBNP and ST-resolution at 60 minutes.</p><p>We investigated consecutive STEMI patients included in the RIKS-HIA registry between 2001 and 2004, if they were ambulance transported and had received prehospital (n=1690) or in-hospital (n=3685) thrombolytic treatment. Prehospital diagnosis and thrombolysis reduced the time to thrombolysis by almost one hour, were associated with better left ventricular function and fewer complications and reduced the adjusted one-year mortality by 30% compared with in-hospital thrombolysis. </p><p>Prospective data from the RIKS-HIA registry on STEMI patients treated with thrombolytics were linked to data on trial participants in the ASSENT-2 trial of thrombolytic agents and used for direct comparisons. Patients treated with thrombolytics and not enrolled in a clinical trial at trial hospitals (n=2048) had higher risk characteristics, more early complications and twice as high adjusted one-year mortality compared to those enrolled (n=729). One major reason for the difference in outcome appeared to be the selection of less critically ill patients to the trial.</p>

In patients with diabetes mellitus (DM), acute myocardial infarction (AMI) is a major cause of death. We have studied two populations with respect to the relationship between DM or related glucometabolic disturbances and AMI. In the first population, the prevalence of DM and the importance of the glycaemic state for the long-term prognosis in non-diabetic patients were investigated in patients with AMI admitted to the Coronary Care Unite at Västerås Central Hospital. In the second population, the prevalence of impaired glucose tolerance (IGT), DM and other metabolic abnormalities was investigated in patients with AMI and without known DM admitted to the Coronary Care Units at Västerås and Karolinska Hospital, Stockholm. 21% of the patients with AMI had previously known DM and 4% had newly detected DM if diagnosis is based upon fasting blood glucose (F-BG). The glycemic state, measured as HbA1c, at a 5.5 years follow-up was a risk factor for re-infarction and/or death in non-diabetic patients after AMI. If an oral glucose tolerance test (OGTT) is performed, 40-45% of all patients with AMI have DM and in addition about 30% have IGT. Both an OGTT and a single post-challenge blood glucose value after 60 minutes performed at hospital discharge, were independent predictors of IGT or DM at follow-up. Insulin resistance, measured by homeostatic model assessment (HOMA-IR), decreased during hospital stay, with no further decrease from hospital discharge to follow-up. In summary, the studies in this dissertation have revealed an unexpectedly high prevalence of abnormal glucose tolerance in patients with AMI. The glycaemic state, reflected by HbA1c, in non-diabetic patients after AMI has an impact on the long-term prognosis. Consequently, in all patients with AMI, HbA1c and casual blood glucose should be measured at admission and, at least, F-BG at hospital discharge.

We evaluated, in patients with ST-elevation myocardial infarction (STEMI) treated with thrombolytics, admission Troponin T (tnT), ST-segment resolution and admission N-terminal pro-brain natriuretic peptide (NT-proBNP) for early risk stratification as well as time delays and outcome in real life patients according to prehospital or in-hospital thrombolytic treatment. Also, baseline characteristics, treatments and outcome in patients enrolled in the ASSENT-2 trial in Sweden and in patients not enrolled were evaluated. TnT (n=881) and NT-proBNP (n=782) on admission and ST-resolution at 60 minutes (n=516) in patients from the ASSENT-2 and ASSENT-PLUS trials were analysed. Elevated levels of NT-proBNP and tnT on admission were both independently related to one-year mortality. However, when adding information on ST-resolution (&lt;/≥50%) 60 minutes after initiation of thrombolytic treatment, tnT no longer contributed independently to mortality prediction. High and low risk patients were best identified by a combination of NT-proBNP and ST-resolution at 60 minutes. We investigated consecutive STEMI patients included in the RIKS-HIA registry between 2001 and 2004, if they were ambulance transported and had received prehospital (n=1690) or in-hospital (n=3685) thrombolytic treatment. Prehospital diagnosis and thrombolysis reduced the time to thrombolysis by almost one hour, were associated with better left ventricular function and fewer complications and reduced the adjusted one-year mortality by 30% compared with in-hospital thrombolysis. Prospective data from the RIKS-HIA registry on STEMI patients treated with thrombolytics were linked to data on trial participants in the ASSENT-2 trial of thrombolytic agents and used for direct comparisons. Patients treated with thrombolytics and not enrolled in a clinical trial at trial hospitals (n=2048) had higher risk characteristics, more early complications and twice as high adjusted one-year mortality compared to those enrolled (n=729). One major reason for the difference in outcome appeared to be the selection of less critically ill patients to the trial.

科学研究費補助金 研究種目:一般研究(B) 課題番号:06454236 研究代表者:豊嶋 英明 研究期間:1994-1995年度

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