Orientador: Mauro Pedrine Santamaria / Coorientador: João Manoel Theotonio dos Santos / Banca: Maria Aparecida Neves Jardini / Banca: Germano Emilio Conceição Souza / Resumo: A doença arterial coronária (DAC), assim como a doença periodontal (PD) são patologias muito prevalentes e apresentam vias em comum na sua fisiopatologia que é a inflamação crônica. A angioplastia coronária percutânea com implante de stent se estabeleceu como a principal forma de revascularização miocárdica no tratamento da DAC porém cerca de 16% a 44% dos pacientes podem evoluir com reestenose do stent. Se a doença periodontal, pelo seu estado inflamatório sistêmico crônico estaria contribuindo para um aumento nas taxas de reestenose de stents convencionais não está definido e não é uma rotina na prática clínica a avaliação da cavidade oral antes de um procedimento de angioplastia coronária. O objetivo primário do estudo foi avaliar a correlação entre a doença periodontal com a incidência de reestenose do stent, enquanto os objetivos secundários foram avaliar a prevalência da doença periodontal, o número de dentes, o grau de perda óssea e finalmente a gravidade da doença periodontal na população do estudo. Para isto realizamos um estudo pioneiro, retrospectivo, caso controle e em um único centro no período de janeiro de 2016 a fevereiro de 2018. Foram analisados 1685 exames de cinecoronariografia dos quais 283 apresentavam imagem de stent com e sem reestenose sendo incluídos 49 pacientes separados entre o grupo caso, com reestenose (n=15) e o grupo controle, sem reestenose (n=34). Excluímos os pacientes portadores de Diabetes Mellitus (DM) não controlados, portadores de sten... (Resumo completo, clicar acesso eletrônico abaixo) / ABSTRACT: Coronary artery disease (CAD), as well as periodontal disease (PD) are very prevalent pathologies and present common pathways in their pathophysiology which is chronic inflammation. Percutaneous coronary angioplasty with stent implantation has been established as the main form of myocardial revascularization in the treatment of CAD but about 16% to 44% of patients may evolve with stent restenosis. If periodontal disease, because of its chronic systemic inflammatory state would be contributing to an increase in the rates of restenosis of conventional stents is not defined and it is not a routine in clinical practice to evaluate the oral cavity before a coronary angioplasty procedure. The primary objective of the study was to evaluate the correlation between periodontal disease and the incidence of stent restenosis, while the secondary objectives were to evaluate the prevalence of periodontal disease, number of teeth, degree of bone loss and finally severity of periodontal disease in the study population. For this, we conducted a pioneering, retrospective, case control and single-center study from January 2016 to February 2018. We analyzed 1685 coronary angiography exams, of which 283 presented stent imaging with and without restenosis and 49 patients were separated between the case group, with restenosis (n = 15) and the control group, without restenosis (n = 34). We excluded patients with uncontrolled diabetes mellitus (DM), those with stents of the pharmacological type or those with restenosis from stents implanted more than two years ago. For statistical analysis, the chi-square test in the qualitative variables, ANOVA test for quantitative variables, Odds Ratio calculation and Equality of Two Proportions test were used to compare the restenosis groups with the distribution of the type of periodontal disease. We found no statistically significant ...(Complete abstract click electronic access below) / Mestre

<p>Coronary artery bypass graft (CABG) surgery is a common treatment for patients with coronary artery disease. A potential complication of CABG is myocardial ischemia or infarction. In this thesis, a method - based on laser Doppler flowmetry (LDF) - for detection of intra- and postoperative ischemia by myocardial perfusion monitoring is evaluated.</p><p>LDF is sensitive to motion artifacts. In previous studies, a method for reduction of motion artifacts when measuring on the beating heart has been developed. By using the ECG as a reference, the perfusion signal is measured in intervals during the cardiac cycle where the cardiac motion is at a minimum, thus minimizing the artifacts in the perfusion signal.</p><p>The aim of this thesis was to investigate the possibilities to use the ECG-triggered laser Doppler system for continuous monitoring of myocardial perfusion in humans during and after CABG surgery. Two studies were performed. In the first study, changes in myocardial perfusion during CABG surgery were investigated (n = 13), while the second study focused on postoperative measurements (n = 13). In addition, an ECG-triggering method was implemented and evaluated.</p><p>It was found that the large variations in myocardial perfusion during CABG surgery could be monitored with the ECG-triggered laser Doppler system. Furthermore, a perfusion signal of good quality could be registered postoperatively from the closed chest in ten out of thirteen patients. In eight out of ten patients, a proper signal was obtained also the following morning, i.e., about 20 hours after probe insertion. The results show that respiration and blood pressure can have an influence on the perfusion signal.</p><p>In conclusion, the results indicate that the method is able to detect fluctuations in myocardial perfusion under favourable circumstances. However, high heart rate, abnormal cardiac motion, improper probe attachment and limitations in the ECG-triggering method may result in variations in the perfusion signal that are not related to tissue perfusion.</p> / <p>Varje år utförs omkring 4500 kranskärlsoperationer i Sverige. En allvarlig komplikation som kan uppstå efter operationen är otillräcklig blodförsörjning till hjärtmuskeln. Den här licentiatavhandlingen handlar om utveckling och utvärdering av en metod, baserad på laserdopplerteknik, för att kunna upptäcka nedsatt blodperfusion i hjärtmuskeln på ett tidigt stadium.</p><p>Laserdopplertekniken är känslig för rörelsestörningar. I tidigare studier har en metod för reducering av rörelsestörningar vid mätning på slående hjärta tagits fram. Med EKG:t som referens mäts blodperfusionen i de faser under hjärtcykeln då hjärtats rörelse är som minst, vilket minskar bidraget av rörelsestörningar i blodperfusionssignalen.</p><p>I den här avhandlingen undersöks om metoden kan användas för kontinuerlig övervakning av hjärtmuskelns blodperfusion på patienter under och efter hjärtoperationer. Två studier har genomförts: en där hjärtmuskelns perfusion mättes i olika faser under kranskärlsoperationer och en där mätproben lades in i hjärtmuskeln under operationen och mätningar gjordes under det första dygnet efter operationen.</p><p>Det visade sig vara möjligt att följa förändringar i hjärtmuskelns blodperfusion under operation. Det var även möjligt att registrera en perfusionssignal av god kvalitet efter operationen då bröstkorgen var stängd. Hos åtta av tio patienter erhölls en bra signal även morgonen efter operationen, dvs. ca 20 timmar efter att proben lades in. Resultaten visar också att andning och blodtryck kan ha en påverkan på blodperfusionssignalen.</p><p>Slutsatsen av arbetet är att det går att se variationer i hjärtmuskelns blodperfusion med EKG-triggad laserdoppler under vissa förutsättningar. Signalen är dock i många fall svårtolkad på grund av att t ex hög hjärtfrekvens, onormal hjärtväggsrörelse eller ändrad probposition sannolikt kan ge variationer i perfusionssignalen som inte är relaterade till blodflödesförändringar.</p> / Report code: LIU-TEK-LIC-2007:35.

<p>Kvantifisering av hjertets muskelfunksjon med tøyning og tøyningshastighet målt med ultralyd for vurdering av koronar sykdom.</p><p>Automatisert metode versus manuell ved akutt hjerteinfarkt og ultralyd stress test.</p><p>Vanligvis måles hjertets muskelfunksjon med ultralyd, en mye brukt metode for å diagnostisere hjertesykdommer. Vurderingen av muskelfunksjonen baserer seg i dag på en subjektiv visuell gradering av bevegelsen av hjertemuskelen, og dette krever erfaring. En ny automatisert diagnostisk ultralydsmetode basert på måling av hastigheten i hjertemuskelen gir et kvantitativt mål på muskelens tøyning og sammentrekning. Den nye metoden gir ny og mer detaljert informasjon om hjertets funksjon og om pasientens prognose enn vanlig ultralydsvurdering.</p><p>Den nye metoden er mer presis ved oppfølgning etter hjerteinfarkt. Et hjerteinfarkt gir nedsatt bevegelse av muskelen og måles med den nye metoden som nedsatt hastighet som muskelen forkortes med. Små forandringer i den skadde hjertemuskelen, ikke alltid synlige for øyet, kan mer nøyaktig følges over tid med den nye metoden. Utbredelsen av hjerteinfarktet kan også vurderes mer nøyaktig.</p><p>Det samme gjelder når angina vurderes under belastning. Når en pasient ikke kan sykle eller gå på tredemølle brukes en medisinsk belastningstest. Ved å belaste hjertet med et medikament som øker hjertemuskelens arbeid samtidig med en ultralydundersøkelse, kan vi oppdage redusert blodforsyningsreserve i hjertet. Stresstesten hjelper til med å vurdere om en trang blodåre bør åpnes etter et hjerteinfarkt, og til å vurdere pasienters risiko for hjertekomplikasjoner før en større operasjon. Den nye metoden gir i tillegg mer informasjon om den langsiktige prognosen sammenlignet med den gamle metoden. Vi har funnet at den nye ultralydsmetoden er mer presis (gir større diagnostisk treffsikkerhet i diagnostikk av koronarsykdom) sammenlignet med den gamle.</p><p>Måling av sammentrekningshastigheter i hjertemuskelen ble utviklet og testet på Institutt for sirkulasjon og bildediagnostikk ved NTNU av Andreas Heimdal og Asbjørn Støylen i 1998. Metoden trengte teknisk videreutvikling og testing i et større pasientmateriale. Metoden har ikke fått stor utbredelse på sykehusene pga støyfylte kurver og tidskrevende analyser, men med denne automatiserte metoden blir brukervennligheten større som muliggjør klinisk bruk.</p> / Paper I and II preprinted with kind permission of Elsevier, sciencedirect.com

<p>The purpose of this study was to investigate the presence of arterial insufficiency in patients undergoing CABG surgery and whether arterial insufficiency is a risk factor for postoperative wound infections in the harvesting leg. Patients who had CABG surgery were enrolled consecutively. A total of 144 patients participated in the study. During their hospital stay demographic data was recorded, as well as pre-, intra-, and postoperative tests and risk factors. The patients answered a questionnaire regarding postoperative wound infections 30 days after surgery patients answered a questionnaire regarding infections. The known and potential risk factors that were recorded were BMI, HB, tobacco usage, diagnosed diabetes, hyperglycemia, duration of surgery, the lowest temperature during surgery and clinical or subclinical arterial insufficiency. The result showed that 34% had postoperative wound infections in the harvesting leg and 26 patients had an ABI (Ankel Brachial Index) indicating arterial insufficiency. There was no significant relationship between ABI and postoperative wound infections in the lower extremity in the total study group (p = 0.36) nor among men (p = 0.92). There was a significant correlation between ABI and postoperative wound infections in the lower extremity (p = 0.02) among women. The conclusion is that arterial insufficiency is more prevalent in women. The relationship between postoperative infections of the lower limbs and arterial insufficiency was significant for the participating women, but not in the total group nor among the men.</p>

<p>In patients with unstable coronary artery disease, this study evaluated the degree of inflammation and coagulation activity, relations to myocardial cell damage, prognosis, and influences of randomisation to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor (n=904), or unfractionated heparin (n=305). </p><p>Anticoagulant treatment effects were evaluated with aPT time. In inogatran treated patients with aPT times ≥ 44 s (median), the 7-days event rate - death, myocardial infarction or refractory angina – was 11.6 %, compared to 6.6 % with aPT times < 44 s (p=0.01). Higher aPT times was related to improved outcome during heparin treatment.</p><p>Markers of inflammation, i.e. fibrinogen and C-reactive protein (CRP), and coagulation, i.e. prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), soluble fibrin (SF) and D-dimer were analysed in serial samples (n=320). High fibrinogen, F1+2 and D-dimer levels persisted at 30 days. Patients with myocardial damage, detected by elevated troponin, had higher levels of all markers except TAT.</p><p>Ischemic events occurred at 30 days in 17 % of patients with high (pre-treatment top tertile) and 8.5 % of patients with lower fibrinogen levels (p=0.03), while high CRP levels only were related to increased mortality. At 30 days, patients with high compared to low pre-treatment levels of TAT or SF had 40 % lower event rate. Patients with early decreased compared to raised F1+2 or TAT levels during treatment had 50 % lower 30-days event rate (p<0.05). </p><p>Conclusions: The aPT time is an inappropriate indicator of antithrombotic efficacy. The raise in fibrinogen in the acute phase is sustained, and indicates risk of thrombosis and new ischemic events. The pronounced CRP elevation is transient, but associated with increased mortality. Higher coagulation activity may identify patients with a thrombotic condition as the major cause of instability, who are best responders to anticoagulant therapy. However, reactivation of coagulation activity with raised risk of ischemic events is a concern at cessation of treatment.</p>

Today, invasive coronary angiography is still the gold standard to perform the diagnosis of coronary artery disease. But it is an invasive procedure that carries non negligible morbidity (1.5%) and mortality (0.15%), and results in high costs. Less invasive and more cost-effective techniques are highly desirable. Over the past 15 years, substantial advances have been made in non-invasive cardiac imaging. In the first part of this work, we prospectively evaluated the diagnostic accuracy of 40-slice multidetector CT (MDCT) to detect coronary artery disease prior to cardiac valve surgery in 82 patients. On a per-patient basis, MDCT correctly identified 14/15 patients with (sensitivity 93%) and 60/67 patients without coronary disease (specificity 90%). Performing invasive angiography only in case of abnormal CT might have avoided invasive angiography in 60/82 (73%) patients without coronary disease. Thus, MDCT could be potentially useful in the preoperative evaluation of such patients, allowing to avoid systematic cardiac catheterization in a large number of patients. Magnetic resonance coronary angiography (MRCA) has also emerged as a promising alternative due to the lack of ionizing radiation and absence of iodinated contrast injection. Therefore, we compared diagnostic accuracy of whole-heart MRCA and MDCT, against QCA, to identify >50% stenosis basis in 77 patients. WH-MRCA acquisition failed in a high number of patients. This was caused by an unstable breathing pattern or drift of the diaphragm position. Because of higher success rate, MDCT had higher diagnostic accuracy than WH-MRCA to detect coronary stenosis. Thus MDCT is superior to WH-MRCA, however WH-MRCA can perform as well as CT in interpretable segments with adequate image quality. In the second part of this work, to evaluate whether MDCT and cardiac magnetic resonance (cMR) might allow simultaneous assessment of aortic valve area (AVA), we compared measurements of AVA by MDCT to cMR, transesophageal and transthoracic echocardiography. AVA by MDCT and cMR correlated highly with AVA by other techniques. In our study, we compared 3 planimetric approaches to AVA calculated by the continuity equation using TTE. We did observe excellent correlations between planimetric and continuity equation-derived AVA, but all 3 planimetric measures were found to overestimate continuity equation AVA. A potential explanation for this observation could be that we measure different aortic valve orifices. Indeed planimetric techniques measure the true dimensions of the anatomical orifice, whereas the continuity equation measures the "effective" orifice area. The ability of MDCT and cMR to accurately assess aortic valve area at the time of non-invasive coronary imaging, places these techniques in a strong position for the comprehensive assessment of such patients. However, despite these good results, it must nonetheless be emphasized that to be acceptable in daily clinical practice, a strategy in which invasive coronary angiography would not be performed systematically but rather selectively in only a subset of patients, requires a perfect sensitivity for disease detection in individual patients. Unfortunately, the present work shows that MDCT and WH-MRCA have not yet reached such a level of accuracy. Finally, these tests are not a substitute for other imaging techniques in all cardiovascular conditions. Unlike an echocardiogram machine, the MRI and MDCT scanners cannot be brought to the bedside of an acutely ill patient.

In patients with unstable coronary artery disease, this study evaluated the degree of inflammation and coagulation activity, relations to myocardial cell damage, prognosis, and influences of randomisation to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor (n=904), or unfractionated heparin (n=305). Anticoagulant treatment effects were evaluated with aPT time. In inogatran treated patients with aPT times ≥ 44 s (median), the 7-days event rate - death, myocardial infarction or refractory angina – was 11.6 %, compared to 6.6 % with aPT times &lt; 44 s (p=0.01). Higher aPT times was related to improved outcome during heparin treatment. Markers of inflammation, i.e. fibrinogen and C-reactive protein (CRP), and coagulation, i.e. prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), soluble fibrin (SF) and D-dimer were analysed in serial samples (n=320). High fibrinogen, F1+2 and D-dimer levels persisted at 30 days. Patients with myocardial damage, detected by elevated troponin, had higher levels of all markers except TAT. Ischemic events occurred at 30 days in 17 % of patients with high (pre-treatment top tertile) and 8.5 % of patients with lower fibrinogen levels (p=0.03), while high CRP levels only were related to increased mortality. At 30 days, patients with high compared to low pre-treatment levels of TAT or SF had 40 % lower event rate. Patients with early decreased compared to raised F1+2 or TAT levels during treatment had 50 % lower 30-days event rate (p&lt;0.05). Conclusions: The aPT time is an inappropriate indicator of antithrombotic efficacy. The raise in fibrinogen in the acute phase is sustained, and indicates risk of thrombosis and new ischemic events. The pronounced CRP elevation is transient, but associated with increased mortality. Higher coagulation activity may identify patients with a thrombotic condition as the major cause of instability, who are best responders to anticoagulant therapy. However, reactivation of coagulation activity with raised risk of ischemic events is a concern at cessation of treatment.

Kvantifisering av hjertets muskelfunksjon med tøyning og tøyningshastighet målt med ultralyd for vurdering av koronar sykdom. Automatisert metode versus manuell ved akutt hjerteinfarkt og ultralyd stress test. Vanligvis måles hjertets muskelfunksjon med ultralyd, en mye brukt metode for å diagnostisere hjertesykdommer. Vurderingen av muskelfunksjonen baserer seg i dag på en subjektiv visuell gradering av bevegelsen av hjertemuskelen, og dette krever erfaring. En ny automatisert diagnostisk ultralydsmetode basert på måling av hastigheten i hjertemuskelen gir et kvantitativt mål på muskelens tøyning og sammentrekning. Den nye metoden gir ny og mer detaljert informasjon om hjertets funksjon og om pasientens prognose enn vanlig ultralydsvurdering. Den nye metoden er mer presis ved oppfølgning etter hjerteinfarkt. Et hjerteinfarkt gir nedsatt bevegelse av muskelen og måles med den nye metoden som nedsatt hastighet som muskelen forkortes med. Små forandringer i den skadde hjertemuskelen, ikke alltid synlige for øyet, kan mer nøyaktig følges over tid med den nye metoden. Utbredelsen av hjerteinfarktet kan også vurderes mer nøyaktig. Det samme gjelder når angina vurderes under belastning. Når en pasient ikke kan sykle eller gå på tredemølle brukes en medisinsk belastningstest. Ved å belaste hjertet med et medikament som øker hjertemuskelens arbeid samtidig med en ultralydundersøkelse, kan vi oppdage redusert blodforsyningsreserve i hjertet. Stresstesten hjelper til med å vurdere om en trang blodåre bør åpnes etter et hjerteinfarkt, og til å vurdere pasienters risiko for hjertekomplikasjoner før en større operasjon. Den nye metoden gir i tillegg mer informasjon om den langsiktige prognosen sammenlignet med den gamle metoden. Vi har funnet at den nye ultralydsmetoden er mer presis (gir større diagnostisk treffsikkerhet i diagnostikk av koronarsykdom) sammenlignet med den gamle. Måling av sammentrekningshastigheter i hjertemuskelen ble utviklet og testet på Institutt for sirkulasjon og bildediagnostikk ved NTNU av Andreas Heimdal og Asbjørn Støylen i 1998. Metoden trengte teknisk videreutvikling og testing i et større pasientmateriale. Metoden har ikke fått stor utbredelse på sykehusene pga støyfylte kurver og tidskrevende analyser, men med denne automatiserte metoden blir brukervennligheten større som muliggjør klinisk bruk. / Paper I and II preprinted with kind permission of Elsevier, sciencedirect.com

Angiogenic cell therapy is currently being developed as a treatment for coronary artery disease (CAD); however, endothelial dysfunction (ED), commonly found in patients with CAD, impairs the ability for revascularization to occur. We hypothesized that culture on a collagen matrix will improve survival and function of circulating progenitor cells (CPCs) isolated from a mouse model of ED. Overall, ED decreased the expression of endothelial markers in CPCs and impaired their function, compared to normal mice. Culture of CPCs from ED mice on collagen was able to increase cell marker expression, and improve migration and adhesion potential, compared to CPCs on fibronectin. Nitric oxide production was reduced for CPCs on collagen for the ED group; however, CPCs on collagen had better viability under conditions of serum deprivation and hypoxia, compared to fibronectin. This study suggests that a collagen matrix may improve the function of therapeutic CPCs that have been exposed to ED.

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