Clinical trial NCT02299960: Measurement of Endothelial Function and Cardiac Output: New Methods
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure
Hypertension, Pulmonary
Hypertension
Diabetic Nephropathies
Keywords: EndoPAT
NICOM
circulating endothelial cells
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Bayer
name: Health Twist GmbH
First posted: 2014-11-24
Enrollment: 101
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients suffering from the conditions stated above

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Test-retest-reliability EndoPAT
timeFrame: 2 weeks
Secondary outcomes:
measure: Test-retest-reliability circulating endothelial cells
timeFrame: 2 weeks
measure: Test-retest-reliability NICOM
timeFrame: 2 weeks
measure: Correlation: Cardiac Output on exertion and cardiopulmonary exercise test and 6 Minute Walking test
timeFrame: 2 weeks
measure: Correlation: circulating endothelial cells and EndoPAT and endothelial function
timeFrame: 2 weeks
measure: Variability of biomarkers of myocardiac remodelling and of cardiorenal syndrome
timeFrame: 2 weeks
measure: Correlation cardiac Output on exertion and echocardiography in HFpEF
timeFrame: 2 weeks
measure: Clinical feasibility of circulating endothelial cells and EndoPAT
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin
Study officials:
affiliation: Charite Universitaetsmedizin Berlin
name: Hans-Dirk Duengen, PD Dr. med.
role: STUDY_CHAIR
References:
citation: Weisrock F, Fritschka M, Beckmann S, Litmeier S, Wagner J, Tahirovic E, Radenovic S, Zelenak C, Hashemi D, Busjahn A, Krahn T, Pieske B, Dinh W, Dungen HD. Reliability of peripheral arterial tonometry in patients with heart failure, diabetic nephropathy and arterial hypertension. Vasc Med. 2017 Aug;22(4):292-300. doi: 10.1177/1358863X17706752. Epub 2017 May 30.