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Heart disease is a major cause of morbidity and mortality in the United States with coronary artery disease (CAD) representing more than half of all cardiovascular events. Stable patients presenting with symptoms suggestive of CAD are likely to undergo either an exercise ECG and/or imaging study as a first line diagnostic assessment. A cardiopulmonary exercise test (CPX) is an ECG stress test plus ventilatory gas analysis. Recently CPX has been used to detect exercise-induced myocardial ischemia suggestive of underlying CAD. Currently there are a number of diagnostic tests available for the identification of CAD with the most widely used being exercise ECG, myocardial perfusion imaging (MPI) and cardiac catheterization. Exercise ECG, although inexpensive, has a number of well-recognized limitations, including low sensitivity resulting in false positive results. MPI and catheterization are more accurate but also more invasive and expensive. It appears that CPX may improve the diagnostic accuracy of exercise ECG in a cost effective manner.

Os pacientes portadores de afecções ateroscleróticas das artérias coronárias, que necessitam tratamento odontológico sob anestesia local com vasoconstritor, constituem um grupo especial de manejo por múltiplos aspectos. Trata-se de doença que pode apresentar, nestas circunstâncias, complicações com potencial de gravidade como: arritmias, angina instável e até mesmo infarto agudo do miocárdio. O cirurgião-dentista diante destes riscos deve conhecer as soluções anestésicas, bem como as interações medicamentosas e eventuais repercussões cardiovasculares. Objetivos: avaliar a ocorrência das seguintes variáveis detectoras de isquemia miocárdica durante ou após o tratamento odontológico:1) alterações do segmento ST avaliadas pelo sistema Holter; hipocontratilidade do ventrículo esquerdo pela Doppler-ecocardiografia e elevação dos marcadores bioquímicos; 2) precordialgia, arritmias e insuficiência mitral. Métodos: Os pacientes coronariopatas eram submetidos à exodontia sob anestesia local com ou sem vasoconstritor, divididos em dois grupos (sorteio por envelope). Em todos praticava-se monitoração eletrocardiográfica com Holter por 24 horas; Doppler-ecocardiograma antes e após intervenção odontológica e dosavam-se os marcadores bioquímicos antes e 24 horas após a exodontia (CKMB massa, CKMB atividade e troponina T). Aferia-se, também, a freqüência cardíaca e a pressão arterial nas fases pré, pós-anestesia e pós-exodontia. A Doppler-ecocardiografia avaliava a contratilidade segmentar do ventrículo esquerdo e a eventual ocorrência de insuficiência mitral. Resultados: 54 pacientes com doença coronária comprovada por cinecoronariografia e com indicação de extração dentária foram incluídos no estudo, no período de maio de 2004 a maio de 2005. Os casos foram divididos em dois grupos: grupo I com 27 pacientes tratados sob anestesia local com vasoconstritor e grupo II, 27 casos sem vasoconstritor. A média das idades no grupo I foi 58 (DP 7,98) anos e no grupo II de 55 anos (DP 8,57); 59,3 por cento eram do sexo masculino no grupo I e 66,7 por cento no grupo II; 66,6 por cento apresentaram infarto do miocárdio prévio com ou sem supradesnivelamento do segmento ST no grupo I e 77,7 por cento no grupo II. No grupo I a média de dentes extraídos foi de 1,6 dentes por paciente (DP 0,96) e 1,8 dentes por paciente (DP 1,21) no grupo II e a média de tubetes anestésicos por paciente no grupo I foi 1,5 tubetes (DP 0,87) e 1,8 tubetes (DP 0,79) no grupo II. Três pacientes do grupo I apresentaram depressão do segmento ST (1,0 mm), durante a aplicação da anestesia, e em nenhum deles verificou-se presença de isquemia avaliada pelos outros métodos; dois outros pacientes do mesmo grupo I tiveram elevação da CKMB massa. No estudo não se observou ocorrência ou agravamento de hipocontratilidade segmentar do ventrículo esquerdo, precordialgia, arritmias ou insuficiência mitral. Conclusão: Exodontia praticada sob uso de anestesia com epinefrina 1:100.000 não implica em riscos isquêmicos adicionais, uma vez que realizada com boa técnica anestésica e manutenção do tratamento farmacológico prescrito pelo cardiologista / Background: Patients with coronary artery disease, needing odontological treatment under local anesthesia with vasoconstrictor agents, comprised a special group to manage because of multiple aspects. In this situation, cardiovascular disease can be presented with serious complications, such as: arrhythmias, unstable angina and even acute myocardial infarction. The dental practioner facing these controversies must know the anesthesical solutions, drug interactions and possible cardiovascular repercussions. Objectives: To evaluate the occurrence of myocardial ischemic parameters during or after the odontological treatment such as: 1) ST-segment changes evaluated by Holter system, left ventricular hypocontractility by Doppler-echocardiography and serium biomarkers elevation; 2) angina pectoris, arrhythmias and mitral insufficiency. Methods: The coronary patients were submitted to dental extractions under local anesthesia with or without vasoconstrictor and were divided into two groups according to randomization. All patients were monitor with Holter throughout 24 hours; Doppler-echocardiograms were done before and after odontological interventions and the biochemical markers were measured before and 24 hours after the dental extractions (CKMB mass, CKMB activity and Troponin T). Besides that, cardiac rate and blood pressure were also measured pre and post-anesthesia and post-dental extractions. The Doppler-echocardiograms were done to evaluate the left ventricular contractility and possible mitral insufficiency. Results: Between May 2004 and May 2005, fifty-four patients with coronary artery disease and with indication for dental extraction were included in this study. Patients were equally divided into two groups: 27 patients treated with local anesthesia with vasoconstrictor (group I) and 27 patients without vasoconstrictor (group II). The mean age of group I was 58 years old (SD 7.98) and of group 2 was 55 years old (SD 8.57); male gender was 59.3 per cent in group I and 66.7 per cent in group II; 66.6 per cent had previous myocardial infarction with or without ST elevation in group I and 77.7 per cent in group II. In group I the mean dental extraction was 1.6 teeth per patient (SD 0.96) and 1.8 teeth per patient (SD 1.21) in group II. The mean number of anesthesic tubes per patient were 1.5 tubes (SD 0.87) and 1.8 tubes (SD 0.79) for groups I and II, respectively. Three patients from group I had ST-segment depression (1.0 mm) during the anesthesia application, and in none of these patients were observed any other ischemic method. Two other patients from group I had CKMB mass elevation. In none of the patients was observed left ventricular hypocontractility, angina pectoris, arrhythmias or mitral insufficiency. Conclusions: The dental extraction performed under the use of anesthesia with epinephrine 1:100,000 do not cause additional ischemical risks, since it is done with good anesthesical technique and maintenance of the pharmacological treatment prescribed by the cardiologist

Hjärtrehabilitering är ett program som ger bästa möjliga medicinska, fysiska och psykiska förutsättningar för patienter som har drabbats av kranskärlssjukdom, Den förbättrar livskvaliteten hos dessa patienter till en optimal individuell funktionsnivå. Syftet med denna studie var att belysa upplevelser av hjärtrehabilitering hos patienter med kranskärlssjukdom. En litteraturöversikt baserad på elva artiklar, tio av kvalitativ och en kvantitativ design hämtade från tre databaser Cinahl Complete, PubMed och PsycINFO. Artiklarna granskades enligt Friberg (2017) och därefter sammanställdes resultat i form av fyra tema. Vid analysen av de valda artiklarna har fyra huvudteman inklusive några underteman identifierats: Psykologiska upplevelser av hjärtrehabiliteringen. Upplevelser av stöd och motivation. Upplevelser av sjuksköterskans roll. Upplevelser av förhinder att delta i hjärtrehabilitering. Resultatet från denna litteraturöversikt har diskuterats utifrån Dorothea Orems egenvårdsteori. Patienterna hade en positiv inställning till hjärtrehabilitering men de flesta upplevde förhinder i någon form. Brist på information kan förbättras genom att vårdpersonalen har rätt kunskap och ger stöd. För att underlätta svårigheter av livsstilsförändringar kan sjuksköterskan använda motiverande samtal utifrån patientens individuella behov för att utveckla egenvårdskapaciteten hos patienten. / Cardio rehabilitation is a programme which provides best possible medical, physical and mental conditions for patients who have suffered from cardiovascular disease. It improves quality of life for these patients to an optimal individual functioning level. The aim of this study was to highlight experiences from cardiac rehabilitation of patients with coronary artery disease. This study was carried out by a literature review method. Eleven articles, ten of qualitatative and of quantitative design identified in three databases: Cinahl Complete, PubMed och PsycINFO. Articles were reviewed according to Friberg (2017) and then the result was compiled in the form of four themes. In the analysis of the selected articles, four main themes, including some sub-themes, have been identified: Phsycological experiences of cardiac rehabilitation, Experiences of support and motivation, Experiences of nurses’ role and Experiences facing difficulties attending cardic rehabilitation program. Results from this literature review have been discussed related to Dorothea Orem's self-care theory. The patients had a positive attitude towards cardiac rehabilitation but most experienced some form of obstruction. Lack of information can be improved by the health care professions having the right knowledge and providing support. In order to facilitate difficulties in lifestyle changes, the nurse can use motivational talks based on the patient's individual need to develop self-care capacity in the patient.

Introdução: A interação entre os anticoagulantes e a agregabilidade plaquetária é complexa. Dados laboratoriais prévios mostraram que a dabigatrana aumenta a excreção urinária de metabólito do tromboxano, indicando efeito de ativação de plaquetas. Posteriormente, dados do estudo RELY sugeriram que a dabigatrana 150mg poderia aumentar o risco de infarto do miocárdio em pacientes com fibrilação atrial. Objetivos: Comparar a influência da Dabigatrana e Enoxaparina na agregabilidade plaquetária. Métodos: Estudo prospectivo, intervencionista, realizado em pacientes com doença arterial coronariana (DAC) crônica em uso de aspirina em baixas doses. Os indivíduos foram inicialmente designados para dabigatrana 150mg, 2x/dia, por 5 dias, seguido por um período de washout de 30 dias e depois para exoxaparina 1mg/kg, 2x/dia, por um período adicional de 5 dias. Os testes de função plaquetária foram realizados no início e após cada fase de intervenção, usando agregometria de sangue total p (MEA) (objetivo primário), ELISA para determinação quantitativa de tromboxano B2 (TXB2), Verify Now Aspirin e testes de coagulação (objetivos secundários). Resultados: Em comparação com os valores basais, a dabigatrana aumentou a agregabilidade plaquetária avaliada pelo teste MEA-ASPI (+5U ± 24,1), enquanto a enoxaparina diminuiu a agregabilidade plaquetária (-6U ± 22,2), p=0,012 para a comparação entre os grupos ). O mesmo padrão foi observado usando o ensaio TXB2 (+2pg/mL para dabigatrana, -13pg/mL para enoxaparina, p = 0,011). Não houve diferenças significativas entre os dois grupos em relação aos demais testes. Individualmente, a enoxaparina diminuiu significativamente a agregabilidade plaquetária por TXB2 [33 (16,5 - 95)pg/mL vs. 20 (10-52) pg/mL, respectivamente, p = 0,026), mas não foram observadas diferenças significativas individuais com a dabigatrana em relação aos valores basais. Conclusões: Em relação à agregabilidade plaquetária, há um efeito oposto significativo da dabigatrana (aumento) em comparação com a enoxaparina (diminuição). Individualmente, foi observada uma diminuição significativa na agregabilidade plaquetária apenas com a enoxaparina, quando comparada com valores basais / Background: The interaction between anticoagulants and platelet aggregation is complex. Previous laboratory data have shown that dabigatran increases urinary thromboxane metabolite excretion, indicating platelet-activating effect. Thereafter, data from RELY trial suggested that dabigatran 150mg could enhance the risk of myocardial infarction in atrial fibrillation patients. Objectives: To compare the influence of Dabigatran and Enoxaparin on platelet aggregation. Methods: Prospective, interventional study conducted in chronic coronary artery disease (CAD) patients taking low-dose aspirin. Subjects were assigned initially to dabigatran 150mg bid for 5 days followed by a washout period of 30 days and then to exoxaparin 1mg/kg bid for an additional 5 days period. Platelet function tests were performed at baseline and after each intervention phase using multiple electrode aggregometry (MEA) (primary endpoint), ELISA for plasma quantitative determination of thromboxane B2, Verify Now Aspirin and coagulation tests as secondary endpoints. Results: In comparison with the baseline values, dabigatran increased platelet aggregation evaluated by MEAASPI test (+5U ± 24.1), whereas enoxaparin decreased platelet aggregation (- 6U± 22.2), p=0.012 for the comparison between the groups). The same pattern was observed using theTxB2 assay (+2pg/mL for dabigatran, -13pg/mL for enoxaparin, p=0.011). There were no significant differences between both groups regarding the VerifyNow Aspirin or the other platelet function and coagulation tests utilized. Individually, enoxaparin significantly decreased platelet aggregation by TXB2 [33 (16,5 - 95) pg/mL vs. 20 (10-52) pg/mL, respectivamente, p = 0.026) but no significant differences were observed with dabigatran when individually compared to baseline. Conclusions: Regarding platelet aggregation, there is a significant opposite effect of dabigatran (increase) in comparison with enoxaparin (decrease). Individually, a significant decrease in platelet aggrebability was observed with enoxaparin, but no significant differences were observed with dabigatran

Dynamic contrast enhanced (DCE) cardiac magnetic resonance imaging (MRI) is well-established as a non-invasive method for qualitatively detecting obstructive coronary artery disease (CAD) which can impair myocardial blood flow and may result in myocardial infarction. Mathematical modelling of cardiac DCE-MRI data can provide quantitative assessment of myocardial blood flow. Quantitative assessment of myocardial blood flow may have merit in further stratification of patients with obstructive CAD and to improve the diagnosis and prognostication of the disease in the clinical setting. This thesis investigates the development of a quantitative analysis protocol for cardiac DCE-MRI data. In the first study presented in this thesis, Fermi and distributed parameter (DP) modelling are compared in single bolus versus dual bolus analysis. For model-based myocardial blood flow quantification, the convolution of a model with the arterial input function (i.e. contrast agent concentration-time curve extracted from the left ventricular cavity) is fitted to the tissue contrast agent concentration-time curve. In contrast to dual bolus DCE-MRI protocols, single bolus protocols reduce patient discomfort and acquisition protocol duration/complexity but, are prone to arterial input function saturation caused in the left ventricular cavity by the high concentration of contrast agent during bolus passage. Saturation effects can degrade the accuracy of quantification using Fermi modelling. The analysis presented in this study showed that DP modelling is less dependent on arterial input function saturation than Fermi modelling in eight healthy volunteers. In a pilot cohort of five patients, DP modelling detected for the first time reduced myocardial blood flow in all stenotic vessels versus standard clinical assessments. In the second study, it was investigated whether first-pass DP modelling can give accurate myocardial blood flow, against ideal values generated by numerical simulations. Unlike Fermi modelling which is convolved with only the first-pass range of the arterial input function, DP modelling is convolved with the entire contrast agent concentration-time course. In noisy and/or dual bolus data, it can be particularly challenging to identify the end point of the first-pass in the arterial input function. This study demonstrated that contrary to Fermi modelling, myocardial blood flow analysis using DP modelling does not depend on the number of time points used for fitting. Furthermore, this data suggests that DP modelling can reduce the quantitative variability caused by subjectivity in selection of the first-pass range in cardiac MR data. This in turn may help to facilitate the development of more automated software algorithms for myocardial blood flow quantification. In the third study, Fermi and DP modelling were compared against invasive clinical assessments and visual MR estimates, to assess their diagnostic ability in detecting obstructive CAD. A single bolus DCE-MRI protocol was implemented in twentyfour patients. In per vessel analysis, DP modelling reached superior sensitivity and negative predictive value in detecting obstructive CAD compared to Fermi modelling and visual estimates. In per patient analysis, DP modelling reached the highest sensitivity and negative predictive value in detecting obstructive CAD. These studies show that DP modelling analysis of cardiac single bolus DCE-MRI data can provide important functional information and can establish haemodynamic biomarkers to non-invasively improve the diagnosis and prognostication of obstructive CAD.

Introdução. Em pacientes com doença arterial coronária (DAC) estável, não está claro se os efeitos da redução do colesterol sobre a inflamação, agregação plaquetária e células endoteliais progenitoras (CEPs) diferem entre duas estratégias hipolipemiantes: ezetimiba associada à sinvastatina em dose moderada e sinvastatina isolada em dose elevada. Objetivo. Avaliar os efeitos de sinvastatina em dose elevada comparada a ezetimiba associado à sinvastatina em dose moderada sobre a inflamação, agregação plaquetária e CEPs. Métodos e Resultados. Pacientes com DAC estável (n=83, 63 ± 9 anos, 48 homens), em uso de sinvastatina 20 mg, foram randomizados para tratamento com sinvastatina 80 mg (S80) ou ezetimiba 10 mg/sinvastatina 20 mg (E10/S20), por seis semanas. O perfil metabólico e lipídico, a proteína C-reativa (PCR), molécula de adesão intercelular solúvel (sICAM)-1, proteína quimiotática de monócitos (MCP)-1, interleucinas (IL) -1, -6 e -10, glicoproteína CD-40 ligante solúvel (sCD-40L), LDL oxidado (LDLox), células endoteliais progenitoras (CEPs) e a agregação plaquetária pelo platelet function analyzer (PFA)-100 foram avaliados antes e após o tratamento. Os níveis basais de lipídios, marcadores inflamatórios, CEPs e PFA-100 foram similares em ambos os grupos. Após o tratamento com S80 e E10/S20, ambos os grupos apresentaram: (1) Redução significante e similar de LDL-C (-23 + 30% vs -29 + 13%, respectivamente; p=0,46), Apo-B (-22 + 15% vs -18 + 17%, respectivamente; p=0,22) e LDLox (-18 + 47% vs -15 + 33%, respectivamente; p=0,65); (2) Redução modesta, similar e não significativa de PCR (-16% [IIQ: -42 - 7] vs -11% [IIQ= -37 26], respectivamente; p= 0,3). Nenhuma alteração significante foi encontrada nos marcadores inflamatórios restantes ou nas CEPs. (3) O PFA-100 elevou-se significativamente com E10/S20, mas não com S80 (27 + 43% vs 8 + 33%, respectivamente; p=0,02). Conclusão. Nossos dados demonstram que em pacientes com DAC estável: (1) Tanto S80 como E10/S20 são igualmente eficientes na redução de LDL-C e apresentam efeitos anti-inflamatórios semelhantes; (2) E10/S20 apresentou efeito antiagregante plaquetário mais eficiente do que S80. Portanto, apesar de apresentarem efeitos hipolipemiantes e anti-inflamatórios semelhantes, E10/S20 promoveu maior efeito pleiotrópico antiagregante plaquetário do que S80, a despeito da dose quatro vezes menor de estatina na combinação. Novos estudos são necessários para elucidar os efeitos antiplaquetários da ezetimiba / Background. Among patients with stable coronary artery disease (CAD), it is not clear if the effects of cholesterol reduction on inflammation, platelet aggregation and endothelial progenitor cells (EPCs) differ between combined ezetimibe plus moderate-dose simvastatin and high-dose simvastatin alone. Objective. We sought to test the effects of a higher simvastatin dosage compared with combined treatment with ezetimibe plus a moderate simvastatin dose, on inflammation, platelet aggregation and EPCs. Methods and Results. CAD patients (n=83, 63 ± 9 years, 48 men), on simvastatin 20 mg, were randomly allocated to receive the combination ezetimibe 10 mg/simvastatin 20 mg (E10/S20) or simvastatin 80 mg (S80), for 6 weeks. Lipid profile, inflammatory markers (C-reactive protein [CRP], interleukin -1, -6 and -10, monocyte chemotactic protein (MCP)-1, soluble intercellular adhesion molecule (sICAM)-1, soluble CD-40 ligand [sCD-40L] and oxidized LDL [oxLDL]), platelet aggregation (platelet function analyzer [PFA]-100) and EPCs were determined before and after treatment. Baseline lipids, inflammatory markers and PFA-100 were similar in both groups. After treatment, S80 and E10/S20 patients presented: (1) significant and similar reductions on LDL-C (-23 + 30% vs -29 + 13%, respectively; p=0.46), Apo-B (-22 + 15% vs -18 + 17%, respectively; p=0.22) and oxLDL (-18 + 47% vs -15 + 33%, respectively; p=0.65), and (2) modest lowering on CRP (-16% [IIQ: - 42 - 7] vs -11% [IIQ= -37 26], respectively; p= 0.3). No significant changes were denoted among other inflammatory markers or EPCs. (3) PFA-100 increased significantly with E10/S20 but not with S80 (27 + 43% vs 8 + 33%, p=0.02). Conclusions. These data show that among stable CAD patients: (1) both E10/S20 and S80 are equally effective in reducing LDL-C, and have similar anti-inflammatory effects. (2) E10/S20 is more effective than S80 in inhibiting platelet aggregation. Thus, despite similar lipid lowering and antiinflammatory effects, and a dose four times less of simvastatin, E10/S20 induced a greater pleiotropic platelet inhibition than S80. The potentially favorable antiplatelet effects of E10/S20 merit further study

Introdução. A necessidade de melhorar a acurácia do teste de esforço determinou o desenvolvimento de escores, cuja aplicabilidade já foi amplamente reconhecida. Objetivo. Avaliação prognóstica do coronariopata estável por meio de um novo escore simplificado ao ser comparado com o escore de Hubbard. Métodos. Um novo escore foi aplicado em 372 coronariopatas bi ou triarteriais, 71,8% homens com idade média de 59,5+9,07 anos, randomizados para angioplastia, revascularização cirúrgica e tratamento clínico, com seguimento de cinco anos. O óbito cardiovascular foi o desfecho primário. O infarto do miocárdio não-fatal, e o óbito e re-intervenção formaram o desfecho combinado secundário. O escore baseou-se em uma equação previamente validada, resultante da soma de um ponto para: gênero masculino, história de infarto, angina, diabetes, uso de insulina e ainda um ponto para cada década de vida a partir dos 40 anos. Para o teste positivo foi adicionado um ponto. Resultados. Ocorreram 36 óbitos (10 no grupo angioplastia, 15 no grupo revascularização e 11 no grupo clínico), p=0,61. Observou-se 93 eventos combinados: 37 no grupo angioplastia, 23 no grupo revascularização e 33 no grupo clínico (p=0,058). Duzentos e quarenta e sete pacientes apresentaram escore clínico 5 pontos e 216 pacientes 6 pontos. O valor de corte >5 ou >6 pontos identificou maior risco, com p=0,015 e p=0,012, respectivamente. A curva de sobrevida mostrou uma incidência de óbito após a randomização diferente daquela com escore 6 pontos (p=0,07), e uma incidência de eventos combinados diferente entre pacientes com escore <6 e 6 pontos (p=0,02). Conclusão. O novo escore demonstrou consistência na avaliação prognóstica do coronariopata estável multiarterial / Introduction. The need to improve the exercise testing accuracy, lead the development of scores, which applicability were already widely recognized. Objective. Prognostic evaluation of stable coronary disease throughout a new simplified score. Methods. A new score was applied in 372 bi or triarterial coronary patients, 71,8% men mean age 59,5+9,07 years, randomized for percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG) and clinical treatment, with 5 years follow-up. Cardiovascular death was considered the primary outcome. Non-fatal myocardial infarction, death and re-intervention were considered the combined secondary outcome. The score was based on a previously validated equation, resulting from a sum of one point score for: male gender, infarction history, angina, diabetes, use of insulin and one point score for each decade of life after the age of 40 years. Positive exercise testing summed one additional point score. Results. There were 36 deaths (10 in the PCI group, 15 in the CABG group and 11 in the clinical group), p=0.61. There were 93 combined events: 37 in the PCI group, 23 in CABG group and 33 in the clinical group (p=0.058). Two hundred and forty-seven patients presented a clinical score 5 points and 216 patients 6 points. The cut-off point 5 or 6 identified an increased risk, p=0.015 and p=0.012, respectively. The survival curve showed a different death incidence after the randomization when the score reached 6 points or more (p=0.07), and a distinct incidence of combined events between the patients with points score <6 and 6 (p=0.02). Conclusion. The new score showed to be consistent in the prognostic evaluation of stable multivessel coronary artery disease

A disfunção endotelial é uma das possíveis causas relacionadas à taxa mais elevada de trombose após o implante da primeira geração de stents farmacológicos. Se a presença do polímero durável ou elevada dose de fármacos antiproliferativos, ou ambos, são responsáveis por este fenômeno não está definido. O Estudo VESTASYNC II comparou um novo stent farmacológico, com superfície revestida por uma camada porosa de hidroxiapatita e impregnado com baixa dose de sirolimus. (55?g - stent VestaSync®) com seu equivalente não farmacológico (Stent VestaCor® ). O Vestasync II é um estudo prospectivo, randomizado (2:1) e duplo-cego, que incluiu pacientes com lesões de novo em artérias nativas com extensão menor que 14mm, com diâmetro entre 3,0 e 3,5mm. Um subgrupo composto por 20 pacientes (10 em cada grupo) submeteu-se à avaliação da função endotelial, no seguimento angiográfico de oito meses. O objetivo primário foi a comparação da vasomotricidade após o implante de stents com a mesma plataforma, com e sem eluição de sirolimus, a fim de determinar o real impacto de baixa dose do sirolimus na função endotelial. O desfecho de eficácia foi a perda luminal tardia e o porcentual de obstrução intra-stent. A avaliação da função endothelial foi realizada através da estimulação atrial com marcapasso (20ppm acima da frequência cardiaca basal até alcançar 150ppm) e o diâmetro luminal foi mensurado nas extremidades proximal e distal do stent e em um segmento controle, em estágios diferentes (repouso, sucessivas fases do estímulo e após a infusão intracoronária de nitroglicerina). A eficácia deste novo dispositivo foi confirmada por angiografia coronária quantitativa (perda luminal tardia VestaSync = 0,39 mm vs. 0,78 mm, p=0,005) e ultrassom intravascular (% obstrução VestaSync 9,3% vs. 17,6%, p= 0,005). Houve variação negativa no diâmetro luminal, entre o repouso e o estímulo máximo, nas bordas proximal (10%) e distal (8%). Entre os segmentos controles esta variação não alcançou 3%. A eluição de dose baixa do sirolimus não parece interferir na função endotelial, oito meses após o implante do stent sem polímero revestido com hidroxiapatita. / Endothelium dysfunction is among the possible causes related to higher thrombosis rates after first generation drug-eluting stents implant. Whether the presence of durable polymer or high anti-proliferative drug dose, or both, can be responsible for this phenomenon is not clear. The VESTASYNC II trial compared a novel polymer-free drug-eluting stent with a nanothinmicroporous hydroxyapatite surface coating impregnated with a low-dose of sirolimus (55?g-VestaSyncTM stent) to a bare-metal equivalent also coated with a nanothin-microporous hydroxyapatite surface (VestaCorTM stent). This is a randomized (2:1), double-blinded trial which enrolled patients with single de novo lesions in native coronary arteries from 3.0 to 3.5mm diameter and less than 14mm in length. A subset of 20 patients (10 from each group) underwent to endothelial function assessment at eight-month angiographic follow-up. The primary objective was to compare the vasomotricity after implantation of stents with the same platform, with and without drug elution, to determine the real impact of low-dose sirolimus release in endothelial function. Efficacy endpoint was in-stent late loss and % of stent obstruction. Endothelial function was assessed with atrial pacemaker stimulation (20 ppm over basal cardiac frequency until reach 150 ppm) and the lumen diameter was measured at 5 mm of proximal and distal stent edges and in a control segment, in different stages (at rest, at successive phases of stimulli and after nitroglycerin intracoronary infusion). The efficacy of this new device was confirmed by means of quantitative coronary angiography (late loss VestaSync = 0.39 mm vs. 0.78 mm, p=0.005) and intravascular ultrasound (% obstruction VestaSync 9.3% vs. 17.6%, p= 0.005). There was a negative variation in luminal diameter between basal and maximum stimulli in proximal (10%) and distal (8%) edges of both groups. Among control segments this variation did not reach 3%. The elution of low-dose of sirolimus does not seem to interfere in endothelial function 8 months after polymer-free hydroxyapatite coating stent implantation.

Cardiovascular diseases (CVD) remain the most common cause of death in the United States. Additionally, peripheral artery disease affects thousands of people each year. A major underlying cause of these diseases is the occlusion of the coronary or peripheral arteries due to arteriosclerosis. To overcome this, a number of vascular interventions have been developed including angioplasty, stenting, endarterectomies and bypass grafts. Although all of these methods are capable of restoring blood flow to the distal organ after occlusion, they are all plagued by unacceptably high restenosis rates. While the biological reactions that occur as a result of each of these methods differ, the initiating factor of both the primary atherosclerosis and subsequent failure of vascular interventions appears to be intimal hyperplasia (IH). Intimal hyperplasia is most simply defined as the expansion of multiple layers of cells internally to the internal elastic lamina of the blood vessel. This excessive cellular growth leads to arterial stenosis, plaque formation and inflammatory reactions. Despite extensive research the underlying factors that cause IH remain unclear. A quantity of research to date has implicated endothelial cell mechanosensation as the mechanism by which IH is initiated with evidence positively correlating wall shear stress with IH. Others, however, have demonstrated that changes in the stresses applied to the wall in vitro can modulate IH independent of hemodynamic shear stress. Thus, relations between wall tensile stress and IH in vivo may shed light on the underlying mechanisms of IH. Since noninvasive measurement of wall tensile stress in vivo is difficult, it is most feasible to measure oscillatory wall strain which is intimately related to wall tensile stress through the mechanical properties of the arterial wall. In this dissertation, we hypothesize that reductions in oscillatory wall strain precede the formation of intimal hyperplasia in a murine model. To test our hypothesis, we first developed a novel, high spatial and temporal resolution method to measure oscillatory wall strains in the murine common carotid artery. We validated this method both in vitro using an arterial phantom and in vivo using a murine model of abdominal aortic aneurysms. To assess relationships between strain and IH, we applied our strain measurement technique to a recently developed mouse model of IH. In this model, a suture is used to create a focal stenosis and reduce flow through the common carotid artery by 85%; resulting in proximal IH formation. Using this approach, we identified a relationship between oscillatory strain reductions and IH. Subsequent analysis demonstrated that early reductions in mechanical strain just 4 days after focal stenosis creation correlate with IH formation nearly 1 month later. Since IH is not expected to form by day 4 in this model, we went on to assess changes in gross vascular morphology at day 4. We discovered that, although strains are significantly reduced by day 4, no significant IH can be observed, suggesting that changes in wall structure are resulting in strain reductions. At day 4 post-op, we observed cellular proliferation and leukocyte recruitment to the wall without intimal hyperplasia. These studies suggest that early reductions in mechanical strain may be an important predictor of IH formation. Clinically, this relation could be important for the development of novel techniques for predicting IH formation before it becomes hemodynamically significant.