RESUMO
BACKGROUND: Growing evidence supports physiology-guided revascularization, with Fractional Flow Reserve (FFR) the most commonly used invasive measure of coronary blood flow impairment at the time of diagnostic angiography. Recently, there has been growing interest in stenosis severity indices measured at rest, such as Instantaneous Wave Free Ratio (iFR) and the ratio of distal coronary to aortic pressure at rest (resting Pd/Pa). Their reliability may, theoretically, be more susceptible to changes in microvascular tone and coronary flow. This study aimed to assess variability of resting coronary flow with normal catheter laboratory stimuli. METHODS: Simultaneous intracoronary pressure (Pd) and Doppler Average Peak Flow Velocity (APV) recordings were made at rest and following the verbal warning preceding an intravenous adenosine infusion. RESULTS: 72 patients undergoing elective angiography were recruited (mean age 62â¯years, 52.7% male) with a wide range of coronary artery disease severity (FFR 0.86⯱â¯0.09). Average peak flow velocity varied significantly between measurements at rest and just prior to commencement of adenosine, with a mean variation of 10.2% (17.82⯱â¯9.41â¯cm/s vs. 19.63⯱â¯10.44â¯cm/s, pâ¯<â¯0.001) with an accompanying significant drop in microvascular resistance (6.27⯱â¯2.73â¯mmâ¯Hg·cm-1·s-1 vs. 5.8⯱â¯2.92â¯mmâ¯Hg·cm-1·s-1, pâ¯<â¯0.001). These changes occurred without significant change in systemic hemodynamic measures. Whilst there was a trend for an associated change in the resting indices, Pd/Pa and iFR, this was statistically and clinically not significant (0.92⯱â¯0.08 vs. 0.92⯱â¯0.08, pâ¯=â¯0.110; and 0.90⯱â¯0.11 vs. 0.89⯱â¯0.12, pâ¯=â¯0.073). CONCLUSION: Resting coronary flow and microvascular resistance vary significantly with normal catheter laboratory stimuli, such as simple warnings. The clinical impact of these observed changes on indices of stenosis severity, particularly those measured at rest, needs further assessment within larger cohorts.
Assuntos
Cateterismo Cardíaco , Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico , Vasos Coronários/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico , Adenosina/administração & dosagem , Idoso , Velocidade do Fluxo Sanguíneo , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/fisiopatologia , Feminino , Humanos , Hiperemia/fisiopatologia , Masculino , Microcirculação , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Descanso , Índice de Gravidade de Doença , Estresse Psicológico/fisiopatologia , Resistência Vascular , Vasodilatadores/administração & dosagemAssuntos
Ponte de Artéria Coronária , Vasos Coronários , Infarto do Miocárdio , Intervenção Coronária Percutânea , Complicações Pós-Operatórias , Medição de Risco/métodos , Ponte de Artéria Coronária/métodos , Ponte de Artéria Coronária/mortalidade , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Humanos , Multimorbidade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Administração dos Cuidados ao Paciente/métodos , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/mortalidade , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Projetos de Pesquisa , Fatores de Risco , Função Ventricular EsquerdaRESUMO
BACKGROUND: There is emerging evidence of the central role of neutrophils in both atherosclerotic plaque formation and rupture. Patients with lower neutrophil counts following acute coronary syndromes tend to have a greater coronary flow reserve, which is a strong predictor of long-term cardiovascular health. But so far, no data are available regarding the impact of neutrophil inhibition on cardiovascular clinical or surrogate endpoints. Therefore, the aim of this study is to investigate the effects of AZD5069, a cysteine-X-cysteine chemokine receptor 2 (CXCR2) inhibitor, on coronary flow reserve and coronary structure and function in patients with coronary artery disease. METHODS/DESIGN: Ninety subjects with coronary artery disease undergoing percutaneous coronary intervention will be included in this investigator-driven, randomised, placebo-controlled, double-blind, phase IIa, single-centre study. Participants will be randomised to receive either AZD5069 (40 mg) administered orally twice daily or placebo for 24 weeks. Change in coronary flow reserve as determined by 13N-ammonia positron emission tomography-computed tomography will be the primary outcome. Change in the inflammatory component of coronary plaque structure and the backward expansion wave, an invasive coronary physiological measure of diastolic function, will be assessed as secondary outcomes. DISCUSSION: Cardiovascular surrogate parameters, such as coronary flow reserve, may provide insights into the potential mechanisms of the cardiovascular effects of CXCR2 inhibitors. Currently, ongoing trials do not specifically focus on neutrophil function as a target of intervention, and we therefore believe that our study will contribute to a better understanding of the role of neutrophil-mediated inflammation in coronary artery disease. TRIAL REGISTRATION: EudraCT, 2016-000775-24 . Registered on 22 July 2016. International Standard Randomised Controlled Trial Number, ISRCTN48328178 . Registered on 25 February 2016.