Diabetes Mellitus, Type 2, Heart Failure
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TEST6-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.
DIAGNOSTIC_TESTStudy specific questionnaire
Study specific questionnaire The questionnaire is performed prior and 6 months after the intervention.
PROCEDUREBlood collection
Blood collection during surgery: * coronary sinus * arterial * peripheral venous Blood collection 6 months after surgery: \- peripheral venous
Sponsors
RWTH Aachen University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. guideline-appropriate clinical indication for CRT implantation/electrophysiologial examination/pulmonary vein ablation 2. age of majority 3. written declaration of consent 4. persons who are able to work and mentally able to follow the instructions of the study staff 5. free access routes
Exclusion criteria
1. anemia Hb \<8 mg / dl 2. patients with acute infectious disease (e.g. pneumonia) 3. non-intubatable coronary sinus 4. patients who do not have access to the subclavian vein (e.g. thrombosis of the subclavian vein or superior vena cava) 5. 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 6. patients with heart failure by sepsis 7. persons with acute myocardial ischaemia, e.g. by angina pectoris or ECG changes under load 8. patients with acute coronary syndrome are not implanted in the past 3 months 9. patients who were hospitalized during the last month due to heart failure and who had to be treated intravenously with diuretics or inotropic substances 10. patients with mechanical aortic valve or tricuspid valve 11. patients with heart transplant. 12. patients with acute liver or renal failure 13. pregnant and lactating women 14. patients placed under an official or judicial order in an institution 15. patients who are in a dependency or employment relationship with the sponsor or auditor 16. taking an investigational medicinal product 30 days before the start of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oxygen partial pressure (pO2) [mmHg] | Directly prior to the CRT-implantation | Results of blood gas analysis: Oxygen partial pressure (pO2) \[mmHg\] |
| Carbon dioxide partial pressure (pCO2) [mmHg] | Directly prior to the CRT-implantation | Results of blood gas analysis: Carbon dioxide partial pressure (pCO2) \[mmHg\] |
| potential of hydrogen (pH) value [-] | Directly prior to the CRT-implantation | Results of blood gas analysis: pH value \[-\] |
| Base excess [mmol] | Directly prior to the CRT-implantation | Results of blood gas analysis: Base excess \[mmol\] |
| Lactate [mmol/l] | Directly prior to the CRT-implantation | Results of blood gas analysis: Lactate \[mmol/l\] |
| Glucose [mg/dl] | Directly prior to the CRT-implantation | Results of blood gas analysis: Glucose \[mg/dl\] |
| Electrolytes (K+, Na2+, Ca2+) [mmol/l] | Directly prior to the CRT-implantation | Results of blood gas analysis: Electrolytes (K+, Na2+, Ca2+) \[mmol/l\] |
| High-sensitive troponin T [µg/L] | Directly prior to the CRT-implantation | Markers of myocardial ischemia and heart failure: High-sensitive troponin T \[µg/L\] |
| Total creatine kinase [µg/L] | Directly prior to the CRT-implantation | Markers of myocardial ischemia and heart failure: Total creatine kinase \[µg/L\] |
| Creatinine kinase-myocardial band (CK-MB) [µg/L] | Directly prior to the CRT-implantation | Markers of myocardial ischemia and heart failure: Creatinine kinase-myocardial band (CK-MB) \[µg/L\] |
| Aspartate aminotransferase [µg/L] | Directly prior to the CRT-implantation | Markers of myocardial ischemia and heart failure: Aspartate aminotransferase \[µg/L\] |
| Lactate dehydrogenase [µg/L] | Directly prior to the CRT-implantation | Markers of myocardial ischemia and heart failure: Lactate dehydrogenase \[µg/L\] |
| N-terminal pro-B-type natriuretic peptide (NT-proBNP) [µg/L] | Directly prior to the CRT-implantation | Markers of myocardial ischemia and heart failure: N-terminal pro-B-type natriuretic peptide (NT-proBNP) \[µg/L\] |
| High-sensitive C-reactive protein (CRP) [µg/L] | Directly prior to the CRT-implantation | Cytokines and inflammation markers: High-sensitive C-reactive protein (CRP) \[µg/L\] |
| Procalcitonin (PCT) [µg/L] | Directly prior to the CRT-implantation | Cytokines and inflammation markers: Procalcitonin (PCT) \[µg/L\] |
| Interleukin 6 (IL-6) [µg/L] | Directly prior to the CRT-implantation | Cytokines and inflammation markers: Interleukin 6 (IL-6) \[µg/L\] |
Countries
Germany
Contacts
Primary ContactBen Kappel, MD PhD
Backup ContactChristina Kalvelage, M. Sc.
Outcome results
None listed