BIO-2-HEART: Identification of Biomarkers in T2DM and Heart Failure

Официальное название

BIO-2-HEART Study (Identifying New BIOmarkers in Patients With Type 2 Diabetes Mellitus and HEArt Failure Receiving Cardiac Resynchronization Therapy Device Implantation)

Обзор

The primary aim of the current study is a better understanding of the role of Type 2 Diabetes Mellitus (T2DM) in heart failure and, in particular, changes in cardiac metabolism, which may contribute to heart failure. Various biomarkers in the coronary artery blood, as well as in the arterial and peripheral venous blood, are to be identified for this purpose. Included are patients with and without T2DM and with or without heart failure (HFpEF, HFmrEF, HFrEF), who have a clinically indicated and guidance-appropriate Cardiac Resynchronisation Therapy (CRT) implantation or pulmonary vein ablation/electrophysiological examination. Not all patients currently benefit from the implantation of a CRT system (so-called non-responder). Despite narrow inclusion criteria, these "non-responders" cannot be unmasked in advance of the implantation. A further aim of this study is to identify biomarkers, which can be determined in advance of implantation to differentiate between responders and non-responders.

Подробное описание

The primary aim of the current study is a better understanding of the role of Type 2 Diabetes Mellitus (T2DM) in heart failure and, in particular, changes in cardiac metabolism, which may contribute to heart failure. Various biomarkers in the coronary artery blood, as well as in the arterial and peripheral venous blood, are to be identified for this purpose. Included are patients with and without T2DM, who have a clinically indicated and guidance-appropriate Cardiac Resynchronisation Therapy (CRT) implantation due to their cardiac insufficiency and patients who have a clinically indicated electrophysiological examination (EPU) or pulmonary vein ablation (PVI).

Not all patients currently benefit from the implantation of a CRT system (so-called non-responder). Despite narrow inclusion criteria, these "non-responders" cannot be unmasked in advance of the implantation. Thus, a further aim of this study is to identify biomarkers, which can be determined in advance of implantation to differentiate between responders and non-responders.

Patient selection is based on the previously defined inclusion and exclusion criteria. The patient is informed by the physician and gives written consent to participate in the study. Prior to the implantation of the CRT system/the electrophysiological examination(EPU)/pulmonary vein ablation(PVI), the patient first responds to a study-related questionnaire and performs a 6-minute walk test.

Afterwards the clinically indicated, elective CRT implantation/EPU/PVI is performed by experienced physicians of the Medical Clinic I. Routinely, an arterial pressure catheter for invasive blood pressure monitoring (usually arteria radialis) is inserted. In addition, 2 peripheral venous accesses are established. The system of the CRT system is carried out via a small pectoral section. The cardiac probes are inserted into the heart via the subclavian vein. First, the probe is implanted in the right ventricle and, if necessary, a probe is placed in the right atrium. For EPU/PVI a femoral vein acsess is established.

To establish the coronary sinus (CS) probe, the intubation of the coronary sinus is performed by means of a guide catheter, which can be used to take blood samples. After intubation of the coronary sinus, the coronary artery blood is taken from the guide catheter for the study as well as arterially via the underlying pressure catheter as well as peripheral venous over a horizontal venous catheter. During EPU/PVI the coronary sinus has also to be intubated due to the ablation protocol. The blood sampling does not take more than 1-2 minutes.

The surgery is then terminated as planned and postoperative care is performed according to the standard operation procedure (SOP) of the Medical Clinic I. Within the framework of a control visit routinely performed in the Medical Clinic I , an echocardiographic follow-up of heart failure, a history assessment and a laboratory-based blood analysis are performed 6 months after CRT implantation. In the context of this visit peripheral venous blood is collected again for the study. In addition, the 6-minute walk test is performed once more and the patient receives the same questionnaire again.

Laboratory routine blood analysis is performed in the central laboratory of the University Hospital of Aachen and is independent of the study. The analysis measures standard parameters such as electrolytes, blood count, retention parameters, glucose, HbA1c, liver values, N-terminal Brain Natriuretic Peptide (NT-pro-BNP) etc. .

A blood gas analysis of the study blood is performed out first. The remaining blood is processed and stored at -80 ° C, so-called "biobank", for further biomarker analysis, e.g. metabolite analysis, peptides/proteins and RNA.

Вмешательства

• Диагностический тест 6-minute walk test
  The 6-minute walk test is a functional test established in the clinic to assess the performance of a patient. The patient walks continuously for 6 minutes without interruption as far as possible. Breaks, speed changes and running are allowed. Test is performed prior the intervention and 6 months after the intervention.
• Диагностический тест Study specific questionnaire
  Study specific questionnaire The questionnaire is performed prior and 6 months after the intervention.
• Процедура Blood collection
  Blood collection during surgery: * coronary sinus * arterial * peripheral venous Blood collection 6 months after surgery: \- peripheral venous

Первичные конечные точки

• Oxygen partial pressure (pO2) [mmHg] [Срок оценки: Directly prior to the CRT-implantation]
• Oxygen partial pressure (pO2) [mmHg] [Срок оценки: 6 months after CRT-implantation]
• Carbon dioxide partial pressure (pCO2) [mmHg] [Срок оценки: Directly prior to the CRT-implantation]
• Carbon dioxide partial pressure (pCO2) [mmHg] [Срок оценки: 6 months after CRT-implantation]
• potential of hydrogen (pH) value [-] [Срок оценки: Directly prior to the CRT-implantation]
• potential of hydrogen (pH) value [-] [Срок оценки: 6 months after CRT-implantation]
• Base excess [mmol] [Срок оценки: Directly prior to the CRT-implantation]
• Base excess [mmol] [Срок оценки: 6 months after CRT-implantation]
• Lactate [mmol/l] [Срок оценки: Directly prior to the CRT-implantation]
• Lactate [mmol/l] [Срок оценки: 6 months after CRT-implantation]

Критерии участия

Критерии включения

• guideline-appropriate clinical indication for CRT implantation/electrophysiologial examination/pulmonary vein ablation
• age of majority
• written declaration of consent
• persons who are able to work and mentally able to follow the instructions of the study staff
• free access routes

Критерии исключения

• anemia Hb <8 mg / dl
• patients with acute infectious disease (e.g. pneumonia)
• non-intubatable coronary sinus
• patients who do not have access to the subclavian vein (e.g. thrombosis of the subclavian vein or superior vena cava)
• patients with idiopathic hypertrophic, restrictive or constrictive cardiomyopathy, or heart failure due to a known inflammatory or infiltrating disease (e.g. amyloidosis, sarcoidosis) or a constrictive disease
• patients with heart failure by sepsis
• persons with acute myocardial ischaemia, e.g. by angina pectoris or ECG changes under load
• patients with acute coronary syndrome are not implanted in the past 3 months
• patients who were hospitalized during the last month due to heart failure and who had to be treated intravenously with diuretics or inotropic substances
• patients with mechanical aortic valve or tricuspid valve
• patients with heart transplant.
• patients with acute liver or renal failure
• pregnant and lactating women
• patients placed under an official or judicial order in an institution
• patients who are in a dependency or employment relationship with the sponsor or auditor
• taking an investigational medicinal product 30 days before the start of the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Германия · 1 центр

• University Hospital RWTH Aachen — Aachen

Публикации

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• Truong QA, Januzzi JL, Szymonifka J, Thai WE, Wai B, Lavender Z, Sharma U, Sandoval RM, Grunau ZS, Basnet S, Babatunde A, Ajijola OA, Min JK, Singh JP. Coronary sinus biomarker sampling compared to peripheral venous blood for predicting outcomes in patients with severe heart failure undergoing cardiac resynchronization therapy: the BIOCRT study. Heart Rhythm. 2014 Dec;11(12):2167-75. doi: 10.1016/ PMID 25014756
• Costello-Boerrigter LC, Lapp H, Boerrigter G, Lerman A, Bufe A, Macheret F, Heublein DM, Larue C, Burnett JC Jr. Secretion of prohormone of B-type natriuretic peptide, proBNP1-108, is increased in heart failure. JACC Heart Fail. 2013 Jun;1(3):207-12. doi: 10.1016/j.jchf.2013.03.001. Epub 2013 Jun 3. PMID 24621871

Идентификаторы

NCT: NCT03323216 · 16-132

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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