The objective is to assess whether myocardial microvascular perfusion and myocardial energy metabolism is impaired in HFpEF patients. Additionally we will evaluate whether endothelial dysfunction is associated with diminished myocardial perfusion (e…
ID
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Aandoening
he prevalence of heart failure (HF) continues to rise exponentially worldwide, solely to be attributed to an increase in HFpEF (Heart Failure with preserved Ejection Fraction). HF can be split evenly into HFpEF, formerly classified as diastolic heart failure, and HFrEF (HF with reduced ejection fraction) formerly classified as systolic heart failure. In the Netherlands, approximately 70.000 patients suffer from HFpEF. HFpEF, is characterized by an increased stiffness of the heart, and is associated with multiple comorbidities, such as diabetes, hypertension and obesity. However, HFpEF is more than just a complication of these comorbidities, and consequently requires more than just treatment of these comorbidities. Typical heart failure medications, proven to be successful in HFrEF, such as ace inhibitors and beta-blockers have failed to improve quality of life or survival in HFpEF patients. Currently, no evidence-based treatment can be offered for HFpEF, resulting in poor quality of life, enormous costs and bad outcome. Therefore, a better understanding of the underlying pathophysiology is essential in order to find a treatment for these patients.
Low-grade inflammation, caused by multiple comorbidities is suggested to play a central role in HFpEF. It is thought that low-grade inflammation causes endothelial dysfunction, which is shown to be present in these patients. Additionally, our previous research demonstrated the inability of HFpEF patients to increase myocardial oxygen delivery during exercise. We therefore hypothesize that endothelial dysfunction results in coronary microvascular dysfunction, diminished myocardial perfusion and impaired cardiac metabolism.
Ondersteuning
Health Foundation Limburg
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
-Impaired perfusion (assessed using CMR): assess if myocardial perfusion is diminished in HFpEF compared to controls assessed by CMR.
Achtergrond van het onderzoek
The prevalence of heart failure (HF) continues to rise exponentially worldwide, solely to be attributed to an increase in HFpEF (Heart Failure with preserved Ejection Fraction). HF can be split evenly into HFpEF, formerly classified as diastolic heart failure, and HFrEF (HF with reduced ejection fraction) formerly classified as systolic heart failure. In the Netherlands, approximately 70.000 patients suffer from HFpEF. HFpEF, is characterized by an increased stiffness of the heart, and is associated with multiple comorbidities, such as diabetes, hypertension and obesity. However, HFpEF is more than just a complication of these comorbidities, and consequently requires more than just treatment of these comorbidities. Typical heart failure medications, proven to be successful in HFrEF, such as ace inhibitors and beta-blockers have failed to improve quality of life or survival in HFpEF patients. Currently, no evidence-based treatment can be offered for HFpEF, resulting in poor quality of life, enormous costs and bad outcome. Therefore, a better understanding of the underlying pathophysiology is essential in order to find a treatment for these patients.
Low-grade inflammation, caused by multiple comorbidities is suggested to play a central role in HFpEF. It is thought that low-grade inflammation causes endothelial dysfunction, which is shown to be present in these patients. Additionally, our previous research demonstrated the inability of HFpEF patients to increase myocardial oxygen delivery during exercise. We therefore hypothesize that endothelial dysfunction results in coronary microvascular dysfunction, diminished myocardial perfusion and impaired cardiac metabolism.
Doel van het onderzoek
The objective is to assess whether myocardial microvascular perfusion and myocardial energy metabolism is impaired in HFpEF patients. Additionally we will evaluate whether endothelial dysfunction is associated with diminished myocardial perfusion (e.g. coronary microvascular dysfunction) and impaired myocardial metabolism.
Onderzoeksopzet
This case control cohort study will assess the endothelial function, myocardial perfusion and myocardial metabolism of 72 patients ;48 diagnosed with HFpEF (24 of them with Diabetes Mellitus) and 24 controls with hypertension.
Measurements will be performed based on standard study protocols (for details see methods section).
Study design: case control cohort study
Group I: HFpEF patients
Group II: controls with hypertension
Duration: 2 separate days for HFpEF patients and 3 separate days for control patients. No treatment intervention or follow-up.
HFpEF patients (these patients already had the standard HFpEF screening tests)
Day 1
-Cardiac MRI (CMR)
-Glycocalyx thickness measurement
-Heat-induced skin hyperaemic response
Day 2
-MR spectroscopy
Control patients
Day 1 Clinical assessment (standard clinical care for HFPEF patients)
-Echocardiography
-Holter
-6MWT
-Lung function test
-Exercise test
-ApneaLink
-QoL questionnaires
-Lab
Day 2
-Cardiac MRI (CMR)
-Glycocalyx thickness measurement
-Heat-induced skin hyperaemic response
Day 3
-MR spectroscopy
Onderzoeksproduct en/of interventie
1. Cradiac MRI and MR spectroscopy
-Cardiac MRI: Myocardial fibrosis, assessed using T1 mapping, appears to be linked to myocardial dysfunction in a multitude of non-ischemic cardiomyopathies. Accurate non-invasive quantitation of this extra-cellular matrix has the potential for widespread clinical benefit in both diagnosis and guiding therapeutic intervention. T1 mapping is a cardiac magnetic resonance (CMR) imaging technique, which shows early clinical promise particularly in the setting of diffuse fibrosis.
-MR spectroscopy: Cardiac MRS enables the study of in vivo changes in cardiac metabolism. Several metabolites can be measured but phosphocreatine (PCr) and adenosine triphosphate (ATP) have been shown to be altered in heart failure patients.
Phan et al. showed in a small study that patients with HFpEF have a reduced cardiac energetic reserve (creatine phosphate/adenosine triphosphate ratio) compared to controls (1.57+/-0.52 vs. 2.14+/- 0.63; p=0.003). We will try to confirm these data and analyse a correlation between energy metabolism and myocardial perfusion and endothelial dysfunction.
2.Glycocalyx thickness measurement is a
non-invasive, endothelial function measurement method. This method has no contra-indications or adverse effects.
3.Heat-induced skin hyperaemic response, is a non-invasive, endothelial function measurement method. This method has no contraindications or adverse effects. The warm electrodes (warmth until 44° C) are not painful and just a slight local warmth can be felt.
Publiek
Arantxa Barandiaran
Maastricht University Medical Centre, Department of Cardiology
Maastricht 6202 AZ
The Netherlands
+31(0)43-3871148
arbaraiz.2@gmail.com
Wetenschappelijk
Arantxa Barandiaran
Maastricht University Medical Centre, Department of Cardiology
Maastricht 6202 AZ
The Netherlands
+31(0)43-3871148
arbaraiz.2@gmail.com
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. All patients • Age > 50 • Estimated glomerular filtration reserve (eGFR) >30 ml/min • Body weight<130kg 1.1. HFpEF group 1.1.1 All HFPEF patients •Diagnosis of HFpEF, requires three conditions to be satisfied, as stated in the ESC guidelines: (1) symptoms or signs of heart failure (2) normal or only mildly reduced LV ejection fraction in a non-dilated LV (LVEF>= 50%) (3) relevant structural heart disease (LV hypertrophy/LA enlargement) and/or diastolic dysfunction. •Current BP < 160/90 •Estimated glomerular filtration reserve (eGFR) >30 ml/min 1.1.2 HFPEF with Diabetes Mellitus •Inclusion criteria as mentioned above and Diabetes Mellitus: oDiabetes Mellitus is diagnosed as history of diabetes and use of anti-diabetic medication or fasting plasma glucose ≥ 7.0 mmol/L or 2h-post load glucose ≥ 11.1 mmol/l. 1.2 Hypertensive control patients •No coronary artery disease (CAD; coronary stenosis>70% or history of CABG) •No heart failure •Estimated glomerular filtration rate (eGFR) > 30 ml/min •Preserved left ventricular ejection fraction (LVEF) (>= 50%) on echocardiography •No left ventricular hypertrophy (lateral and septal left ventricular wall =<10mm) •No left atrium enlargement •No diastolic dysfunction type 2 or 3 •Blood pressure >140/90 mmHg or use of anti-hypertensive therapy •Normal cardiac structure and function on echocardiography
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
A potential subject who meets any of the following criteria will be excluded from participation in this study: - Age < 50 years - Life expectancy of <1 year (malignancy etc.) - Contraindication for CMR • ODIN protocol: • “Uitvoering van MRI onderzoek bij patiënten met een cardiaal implanteerbaar elektronisch device (CIED), waaronder een pacemaker en ICD” • ODIN protocol: • “Voorbereiding klinische patiënten voor MRI onderzoek” • Metallic implant (vascularclip, neuro-stimulator, cochlearimplant) • Pacemaker or implantable cardiac defibrillator(ICD) • Claustrophobia • Persistent or chronic atrial fibrillation - Contraindication to adenosine: • High degree atrio-ventricular block (2nd or 3rd degree) • Severe asthma bronchial • Chronic obstructive pulmonary disease Gold ≥ III • Concomitant use of dipyridamole (Persantin) • Long QT syndrome (congenital) - Contraindication to gadolinium (Dihydroxy- hydroxymethylpropyl- tetraazacyclododecane-triacetic acid (butrol) - Gadovist ® ) • Severe renal impairment (Glomerular filtration rate (GFR) < 30 ml/min/1.73m2
Opzet
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL6428 |
| NTR-old | NTR6605 |
| CCMO | NL57468.068.16 |
| OMON | NL-OMON47584 |