Systemic Inflammation and Progression of Atherosclerosis in HIV Patients Underwent Noninvasive and Invasive Multimodality Imaging
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 1,000
- 试验地点
- 2
- 主要终点
- Number of participants with major adverse cardiac events that are related to plaque burden
研究概览
简要总结
In a prospective multi-center observational study, 200 HIV-infected patients treated with antiretroviral treatment (ART) and who suffered from coronary artery disease (CAD) will be enrolled. Blood samples for biological parameters will be collected with all participants: lipid profile and markers of systemic inflammation specific for HIV-infection (lipopolysaccharide-binding protein; cytokines: IL-1β, IL-6, IL-8, IL-10, TNF -α, INF-γ, INF-α; procalcitonin; inflammatory hsCRP).
All of them will undergo functional testing (Echo, CMR both at rest and stress if necessary) and invasive imaging with QCA, FFR, QFR, OCT, IVUS, VH-IVUS, NIRS.
Patients will be treated according to the current and previous recommendations. Both medical treatment and percutaneous transluminal coronary angioplasty (PTCA) with or without stenting will be done.
Collected data will be analyzed: correlation between ART, blood test results, coronary angiography results, including performed PTCA, history of myocardial infarctions, and other cardiovascular events.
The follow-up period will achieve 12 months prospectively with collected clinical events and imaging outcomes which will be determined at the baseline and 12-month follow-up.
The independent ethics expertise will be provided by the Central Clinical Hospital of the Russian Academy of Sciences (Moscow, Russia). The monitoring of the clinical data with imaging will be provided by The Ethics Board of Central Clinical Hospital of the Russian Academy of Sciences.
详细描述
HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is one of the world's most serious health and development challenges. Approximately 38 million people live with HIV, and tens of millions of people have died of AIDS-related causes since the beginning of the epidemic.
However, with increasing access to effective HIV prevention, diagnosis, treatment, and care, including opportunistic infections, HIV infection has transformed from an irreversible terminal illness to chronic disease. Unfortunately, increased life expectancy has increased the risk of other chronic diseases such as cardiovascular diseases (CVD). Actually, CVD has become the most common cause of death in HIV-infected individuals. The risk of myocardial infarction and coronary atherosclerosis prevalence is nearly twice as high in people living with HIV than in the general population. Statins are effective primary prevention for CAD events; however, there are no specific statin use guidelines in HIV. Besides, there is not enough information about systemic inflammation markers and their correlation with atherosclerosis severity.
Nowadays, using invasive imaging, including quantitative coronary angiography with or without further percutaneous coronary intervention, optical coherence tomography/ OCT, intravascular ultrasound/ IVUS, VH-IVUS, near-infrared spectroscopy/ NIRS, cardiovascular events can be predicted and prevented.
In a prospective multicenter observational study, 200 HIV-infected patients treated with antiretroviral treatment (ART) and who suffered from coronary artery disease (CAD) will be enrolled. Blood samples for biological parameters will be collected with all participants: lipid profile and markers of systemic inflammation specific for HIV-infection (lipopolysaccharide-binding protein; cytokines: IL-1β, IL-6, IL-8, IL-10, TNF -α, INF-γ, INF-α; procalcitonin; inflammatory hsCRP).
All of them will undergo functional testing (Echo, CMR both at rest and stress if necessary) and invasive imaging with QCA (Quantitative Coronary Angiography), FFR (Fractional Flow Reserve), QFR (Quantitative Flow Reserve), OCT (Optical Coherence Tomography), IVUS (Intravascular Ultrasound), VH-IVUS (Virtual Histology - IVUS), NIRS (Near Infrared Spectroscopy).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •all HIV-positive patients with chronic coronary syndrome or angina equivalent consistent with the manifestation of the stable coronary artery disease (in accordance with the 2019 Guidelines on Chronic Coronary Syndromes);
- •patients who underwent CCTA (index procedure) with or without further PCI;
- •age above 21 years old;
- •patients must receive antiretroviral medications (in accordance to the 2019 HIV Russian National Guidelines; EACS Guidelines 2020);
- •lesions may be either de novo or restenotic;
- •patient must have one or two-vessel disease in a native coronary vessel requiring or not requiring PCI without indications for immediate bypass surgery with any SYNTAX score;
- •successful uncomplicated PCI could be performed in the culprit vessels and all culprit lesions, but there should be no events or complications between the procedures of PCI in the past and 6 months prior to admission to the Chest Pain Center
- •the non-culprit vessel should have no flow-limiting lesions (diameter stenosis <39%, but any plaque burden) and must be available for imaging.The non-culprit vessel must be considered safe for imaging evaluation;
排除标准
- •any acute comorbidities;
- •patient has had a documented ST-elevation acute myocardial infarction within the 24 hours prior to admission to the Chest Pain Center;
- •unprotected left main lesion location;
- •culprit lesion is located within or distal to an arterial or saphenous vein graft;
- •untreated significant coronary lesion with a >50-75% diameter stenosis remaining in the culprit vessel after the planned intervention (branch stenosis is permitted);
- •lesion or vessel contains visible thrombus within the imaging procedure;
- •patient has an additional lesion that requires intervention within 180 days after the initial hospitalization;
- •any diameter stenosis more than 75% in the non-culprit vessel;
- •indications for immediate bypass surgery within one year of enrollment with the SYNTAX above 34 (multi-vessel disease requiring intervention in all three major coronary arteries);
- •creatinine >150 mmol/L;
- •need for dialysis;
- •severe endocrine disorders (diabetes is permitted) including pre-existing thyroid diseases;
- •decompensated hypotension or heart failure requiring intubation, inotropes,intravenous diuretics, or intra-aortic balloon counterpulsation;
- •patient has a known hypersensitivity, allergy, or contraindication to any of the following: aspirin, heparin, clopidogrel, and ticlopidine, or to contrast that cannot be adequately pre-medicated;
- •presence of cardiac implants;
- •presence of cardiogenic shock;
- •patient has a known left ventricular ejection fraction <39%;
- •refractory ventricular arrhythmia;
- •acute conduction system disease requiring a pacemaker;
- •patient has had a recent PCI (last 6 months prior to admission to the Chest Pain Center) unless the patient is undergoing a staged procedure for dual vessel treatment
- •prior participation in this study or patient is currently enrolled in another investigational use device, imaging, or drug study that has not been reached its primary endpoint;
- •mental diseases, inability for cooperation;
- •pregnancy;
- •stroke or CVA;
- •gastrointestinal bleeding.
结局指标
主要结局
Number of participants with major adverse cardiac events that are related to plaque burden
时间窗: At 12 months after the baseline imaging procedure
The composite of cardiac death, cardiac arrest, myocardial infarction, acute coronary syndrome, revascularization by coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI), or rehospitalization for angina for patients with both culprit- and non-culprit-lesion-related events. Event rates will be determined at: hospital, at 12months.
Diagnostic value of systemic inflammation markers for risk stratification
时间窗: At 12 months after the blood testing and the baseline imaging procedure
To determine prognostic value of systemic inflammation markers (LBP, Lipopolysaccharide binding protein, μg/mL; cytokines: IL-1β, pg/mL; IL-6, pg/mL; IL-8, pg/mL; IL-10, pg/mL; TNF-α, pg/mL; INF-γ, pg/mL; INF-α, pg/mL; procalcitonin, pg/L; inflammatory hsCRP, mg/L) to predict cardiovascular events in patients with HIV.
Invasive assessment of fractional flow reserve for risk stratification
时间窗: At 12 months after the baseline imaging procedure
To determine the prognostic value of FFR (fractional flow reserve) when below 0.75-0.80 in comparison with the relevant invasive results of QCA (quantitative coronary angiography), QFR (quantitative flow reserve), OCT (optical coherence tomography), IVUS (intravascular ultrasound), VH-IVUS (virtual histology IVUS), NIRS (near-infrared spectroscopy) handled with the expert-level postprocessing software for predicting cardiac death and nonfatal myocardial infarction.
Change of per cent of plaque burden from baseline to follow-up as assessed by QCA
时间窗: At 12 months after the baseline imaging procedure
Plaque burden for both culprit and non-culprit lesions will be calculated as a lesion volume (vessel volume-lumen volume)/lumen volume x 1 00. The progression of atherosclerosis and plaque composition in patients receiving different antiretroviral medications will be quantitatively characterized by the parameters of the lesions. The imaging data will be handled with the expert-level post-processing software.
次要结局
- Change of complexity of coronary artery disease from baseline to follow-up as assessed by SYNTAX score II(At 12 months after the baseline imaging procedure)
- Number of participants with encephalopathy(At 12 months after the baseline imaging procedure)
- Number of chest pain patients with non-obstructive coronary artery disease(At 12 months after the baseline imaging procedure)
- Change of serologic marker of inflammation CRP from baseline to follow-up(At 12 months after the baseline imaging procedure)
- Change of complexity of coronary artery disease from baseline to follow-up as assessed by Leaman Coronary Score(At 12 months after the baseline imaging procedure)
- Change of complexity of coronary artery disease from baseline to follow-up as assessed by SYNTAX score I(At 12 months after the baseline imaging procedure)
- Change of fractional flow reserve (FFR) from baseline to follow-up that are related to the progress of atherosclerosis(At 12 months after the baseline imaging procedure)
- Number of participants with procedural success(At 12 months after the baseline imaging procedure)
- Number of chest pain patients without coronary artery disease(At 12 months after the baseline imaging procedure)