Measurement of Endothelial Function and Cardiac Output: New Methods

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