Measurement of Endothelial Function and Cardiac Output: New Methods

Study Overview
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Brief Summary
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The main purpose of this study is to analyse test-retest-reliability of functional quantification of endothelial dysfunction through puls-amplitude-tonometry in patients with heart failure with preserved/reduced ejection fraction, pulmonary hypertension, arterial hypertension and diabetic nephropathy. In the same group, test-retest-reliability of circulating endothelial cells as well as test-retest reliability of non invasive cardiac output Monitoring will be observed and analysed.

Official Title
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Pilot Study: Analysis of Endothelial Function Through Circulating Endothelial Cells and Puls-amplitude-tonometry and of Non-invasive Measurement of Cardiac Output on Exertion in Patients With Heart Failure, Pulmonary Hypertension, Arterial Hypertension and Diabetic Nephropathy

Conditions
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Heart Failure, Hypertension, Pulmonary, Hypertension, Diabetic Nephropathies

Intervention / Treatment
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* Device: Endo-PAT
* Device: NICOM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically stable for the last 4 weeks (not for HFrEF: 7 days) Signed consent form HFpEF: Baseline-Echocardiography: hospitalization <= 12 months with diagnosis heart failure and E/E' > 8 or E' < 8 cm/s or BNP >= 100pg/ml or NT-proBNP >= 300pg/ml in the last 6 months or LAVI > 28 ml/m² and E/E' > 8 or E' < 8cm/s or PAPsys > 40mmHg and E/E' > 8 or E' < 8 cm/s Possibility to take part in cardiac stress test Heart failure NYHA I-III Sinus rhythm Max. O2-uptake on exertion < 20ml/kgBW/min HFrEF HFrEF due to ischemic or non-ischemic reasons NYHA I-III Individually optimized and stable pharmacological therapy (including beta-blocker, ACE-Inhibitor, AT1-antagonist, aldosterone-antagonist) EF <=45%, Simpson Biplan PH NICE-Classification 2013 I/II PAH >= 25 mmHg Precapillary PAH: Wedge-pressure <= 15 mmHg, CO normal or low Postcapillary PAH: Wedge-pressure >= 15 mmHg, CO normal or low Diabetic nephropathy: Diabetes mellitus Type 2 with oral or Insulin therapy and one or more of the following: Diabetic nephropathy has been diagnosed before (anamnesis) Macroalbuminuria: Urine Albumine/Creatinine-ratio > 300mg/g Creatinine (>34mg/mmol) in 2 out of 3 tests of Urine in the morning and GFR <90ml/min/1.73m² (CKD-EPI) Microalbuminuria: 30-300mg/g Creatinine (>=3.4 mg/mmol but <34mg/mmol) tested as above and GFR < 90 ml/min/1.73m² and diabetic retinopathy AH: Hypertension diagnosed at least 6 months except structural heart disease: EF > 55% and no sign of HFpEF No symptoms of coronary heart disease Possibility to take part in cardiac stress test Stable pharmacologic therapy of Hypertension for at least 4 weeks Systolic blood pressure <140 mmHG during Screening Exclusion Criteria: Patient incapable of contracting Angina pectoris > CCS II Coronary Intervention in the last 4 weeks or scheduled Intervention/Bypass Myocardial infarction in the last 3 months Stroke in the last 3 months Valvular heart disease > II° Cardiomyopathy due to Infiltrate/hypertrophic obstruction (e.g. HOCM, Amyloidosis) Congenital complex heart disease Active myocarditis Significant lung disease Significant Cardiac dysrhythmia Scheduled changes in medication during time of study (Scheduled) heart transplant Cardiac resynchronisation therapy over the last three months ICD/Pacemaker-implant in the last 4 weeks Uncontrolled Hyper/Hypotension (>180mmHg, <95mmHg) Patient taking part in Rehabilitation program Diagnosed Malignant disease or disease with life expectancy < 1 year Anemia with Hb<10mg/dl Untreated significant thyroid disease HFpEF, Hypertension and PH: Patient incapable of cardiac stress test (e.g. because of orthopedic Problems) Significant changes in cardiovascular Status over the two weeks of study Instable cardiopulmonary Status over the last four weeks HFrEF: I.v. Treatment with inotropic drug or diuretic in the last 7 days before Screening Myocardial infarction in the last 4 weeks

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HFpEF<br>patients with heart failure with preserved ejection fraction | Device: Endo-PAT<br>* Analysis of endothelial function through pulse-amplitude-tonometry<br>Device: NICOM<br>* Non-invasive measurement of cardiac output<br>|
| HFrEF<br>patients with heart failure with reduced ejection fraction | Device: Endo-PAT<br>* Analysis of endothelial function through pulse-amplitude-tonometry<br>|
| AH<br>patients with hypertension | Device: Endo-PAT<br>* Analysis of endothelial function through pulse-amplitude-tonometry<br>Device: NICOM<br>* Non-invasive measurement of cardiac output<br>|
| Nephropathy<br>patients with diabetic nephropathy | Device: Endo-PAT<br>* Analysis of endothelial function through pulse-amplitude-tonometry<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test-retest-reliability EndoPAT |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test-retest-reliability circulating endothelial cells |  | 2 weeks | 
| Test-retest-reliability NICOM |  | 2 weeks | 
| Correlation: Cardiac Output on exertion and cardiopulmonary exercise test and 6 Minute Walking test |  | 2 weeks | 
| Correlation: circulating endothelial cells and EndoPAT and endothelial function | will include the molecular diagnostic of circulating endothelial cells | 2 weeks | 
| Variability of biomarkers of myocardiac remodelling and of cardiorenal syndrome |  | 2 weeks | 
| Correlation cardiac Output on exertion and echocardiography in HFpEF |  | 2 weeks | 
| Clinical feasibility of circulating endothelial cells and EndoPAT |  | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EndoPAT, NICOM, circulating endothelial cells