modern biological markers in cardiology and internal medicine · 2019-11-11 · assoc.prof. pd...

Assoc.Prof. PD Dr.med.univ. Michael Lichtenauer, PhD Paracelsus Medical University Salzburg Department of Internal Medicine II, Cardiology

Modern Biological Markers in cardiology and internal medicine

https://de.123rf.com/photo_47545295_herzerkrankungen-klappenerkrankungen-aneurysma-koronare-herzkrankheit-herzrhythmusst%C3%B6rungen-herz-failtu.html

N Engl J Med 2012; 366:2333-2338

Epidemiology

en.wikipedia.org/wiki/Myocardial_infarction Journal of Applied Physiology Published 1 June 2007 Vol. 102 no. 6, 2104-2111 DOI: 10.1152/japplphysiol.00033.2007 http://nyheartfailure.com/heart-failure

Novel Biomarkers in Cardiology

Front. Immunol., 24 April 2017 | https://doi.org/10.3389/fimmu.2017.00475


The ST2 (Suppression of tumorigenicity 2) and Interleukin-33 system

Cardiovasc Res. 2010 Sep 1;87(4):769-77.

ST2 Regulation

Salzburg 2016

Cardiovasc Res. 2010 Sep 1;87(4):769-77.

ST2 Regulation

Cardiomyocytes Lung alveolar cells

Int. J. Mol. Sci. 2017, 18(4), 783; https://doi.org/10.3390/ijms18040783

ST2 Regulation

Cardiomyocytes

https://doi.org/10.3390/ijms18040783

Salzburg 2016

Journal of the American College of Cardiology Volume 70, Issue 19, November 2017 DOI: 10.1016/j.jacc.2017.09.031

ST2 Regulation in Heart Failure

https://en.wikipedia.org/wiki/Heart-type_fatty_acid_binding_protein https://commons.wikimedia.org/wiki/File:Cardiac_Muscle.png https://www.clinlabint.com/detail/clinical-laboratory/heart-fabp-fabp3-elisa/


H-FABP, Heart-type fatty acid binding protein

https://en.wikipedia.org/wiki/Heart-type_fatty_acid_binding_protein https://commons.wikimedia.org/wiki/File:Cardiac_Muscle.png https://www.clinlabint.com/detail/clinical-laboratory/heart-fabp-fabp3-elisa/


suPAR, soluble urokinase-type plasminogen activator receptor

Canadian Journal of CardiologyVolume 31, Issue 10, October 2015, Pages 1293-1302


suPAR, soluble urokinase-type plasminogen activator receptor

GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational ProspectiveRamu Adela, Sanjay Kumar BanerjeePublished in Journal of diabetes research 2015DOI:10.1155/2015/490842


GDF-15, Growth-differentiation factor 15

Cytokine & Growth Factor ReviewsVolume 26, Issue 3, June 2015, Pages 329-346


IGFBP-2, Insulin-like growth factor-binding protein 2

en.wikipedia.org/wiki/Myocardial_infarction Journal of Applied Physiology Published 1 June 2007 Vol. 102 no. 6, 2104-2111 DOI: 10.1152/japplphysiol.00033.2007 http://nyheartfailure.com/heart-failure

Novel Biomarkers in Myocardial Infarction

Eur J Clin Invest. 2017 Sep;47(9):638-648.


61 Patients with STEMI 57 Patients with NSTEMI 76 Controls (same age, sex,…)

sST2

Control

STEMI

NSTEMI

0

5000

10000

15000

20000

25000*** ***

pg

/ml

suPAR

Control

STEMI

NSTEMI

0

2000

4000

6000

*** ***

pg

/ml

GDF-15

Control

STEMI

NSTEMI

0

500

1000

1500

*****

pg

/ml

H-FABP

Control

STEMI

NSTEMI

0

5

10

15

20

******

ng

/ml

ELISA

https://commons.wikimedia.org/wiki/File:Heart_attack-NIH.gif Circulation. 2004 May 11;109(18):2186-90


ST2 and Prognosis

Circulation. 2004 May 11;109(18):2186-90


ST2 and Prognosis

Novel Biomarkers in Heart Failure

JACC: Heart Failure Volume 5, Issue 4, April 2017 DOI: 10.1016/j.jchf.2017.01.008

Biomarkers in Heart Failure


no HF

NYHA I + II

NYHA III + IV

0

10000

20000

30000 **

sS

T2 (

pg

/ml)

no HF

NYHA I + II

NYHA III + IV

0

1000

2000

3000

4000

5000 *

GD

F-1

5 (

pg

/ml)

no HF

NYHA I + II

NYHA III + IV

0

5000

10000

15000 ***

su

PA

R (

pg

/ml)

no HF

NYHA I + II

NYHA III + IV

0

5

10

15

20

***

**H

-FA

BP

(n

g/m

l)


Fibrosis


with preserved Ejection Fraction

https://www.labmedica.com/clinical-chemistry/articles/294773150/cv-biomarkers-associated-with-incident-heart-failure.html



Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction July 2017 Frontiers in Endocrinology



Control

ICM

DCM

HFpEF

0

5000

10000

15000

< 0.0001

< 0.0001

0.0001

0.0006

sS

T2 (

pg

/ml)

Control

ICM

DCM

HFpEF

0

500

1000

1500

0.0039

0.0249

0.0001

GD

F-1

5 (

pg

/ml)

Control

ICM

DCM

HFpEF

0

1

2

3

4

5

< 0.0001

< 0.0001

< 0.0001

< 0.0001

H-F

AB

P (

ng

/ml)

Control

ICM

DCM

HFpEF

0

2000

4000

6000< 0.0001

< 0.0001

0.0038

0.0055

su

PA

R (

pg

/ml)

ICM=ischaemic cardiomyopathy, reduced

EF

DCM=dilative cardiomyopathy, reduced

EF

HFpEF=heart failure with preserved EF


Influences of concomitant medication

Ivabradine


Influences of concomitant medication

baseline

3 month

s

6 month

s

0

2000

4000

6000

8000

sS

T2 (

pg

/ml)

baseline

3 month

s

6 month

s

0

500

1000

1500

2000

0.0215

GD

F-1

5 (

pg

/ml)

baseline

3 month

s

6 month

s

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0 0.0151

H-F

AB

P (

ng

/ml)

Degenerative Aortic Valve Stenosis

- Prevalence 3% > 75 years

- Degeneration of the valve (reduction of the orifice area from 3-4 cm2 to <1 cm2)

- Without treatment 2 year mortality is 50%

- Typical symptoms are angina pectoris, dyspnea and syncopy

https://de.wikipedia.org/wiki/Erworbene_Aortenklappenstenose https://de.wikipedia.org/wiki/Aortenklappe https://emedicine.medscape.com/article/150638-overview

Therapeutic options

- Surgical aortic valve replacement (SAVR)

https://www.ukr.de/kliniken-institute/innere-medizin-2/Medizinische_Leistungen/Zentrum_f__r_interventionelle_Aortenklappentherapie/TAVI/index.php https://www.heart-valve-surgery.com/heart-surgery-blog/2010/11/24/heart-valve-replacement-failure-aortic/ https://health.clevelandclinic.org/heart-valve-problems-is-repair-or-replacement-best-for-you/

- percutaneous aortic valve replacement (TAVR or TAVI: Transcatheter Aortic Valve Implantation)

- Medical therapy (diuretics)

Novel Biomarkers in TAVI patients

Novel Cardiovascular Biomarkers

in Renal Disease

https://commons.wikimedia.org/wiki/File:Peripheral_Arterial_Disease.gif


in Peripheral Artery Disease


in Peripheral Artery Disease

Patient characteristics 67-year old female patient

Case Report

was admitted to the Department of Gastroenterology and Hepatology for diagnistic assessment of tumor mass in the liver

presented also signs of right heart failure (ankle edema, aszites), NYHA III

the patient was transferred to the Department of Cardiology for diuretic therapy/re-compensation and further diagnostic work-up

Clinical Status: slightly cyanotic, arrhythmic pulse/atrial fibrillation, systolic heart murmur, slight aszites, lower extremity edema

Transthoracic Echocardiography

massive right atrial dilatation (volume 202 ml), slightly reduced right ventricular function (TAPSE 15 mm), and a large coaptation defect of the tricuspid valve leaflets (23 mm), slighty reduced to normal systolic left ventricular function moderate to severe mitral valve regurgitation, severe tricuspid valve regurgitation

Ebsteins anomaly? Post-inflammatory remodelling?

MRI Exam

Neuroendocrine tumour? Carcinoid?

Further Laboratory Tests

Serum Serotonin: 1248 µg/l (normal range: 117-194 µg/l)

Urinary 5-hydroxyindoleacetic acid: 87 mg/24h (normal range: 2-9 mg/24h) Chromogranin A: 486 U/l (normal range: <34 U/l)

Diagnosis: Carcinoid Syndrom with cardiac involvement

Source: uptodate.com

Dopa-PET-CT

neoplasm in the terminal ileum as primary tumor with three metastases in the liver and metastases in the mesenterial lymph nodes

Further course

To confirm the diagnosis, an ultrasound-guided biopsy of one liver metastasis was performed and a neuroendocrine tumor. The patient underwent Tricuspid valve replacement (Edwards St. Jude Epic, 33mm bioprosthesis) and mitral valve reconstruction (Edwards Physio Ring, 30mm). Two months later, the patient was transferred to the general surgery department and a right hemicolectomy, a cholecystectomy and a bi-segment resection of segment VI and VII of the liver was performed.

Novel Biomarkers other Conditions

Short term exercise


Diavolezza, Switzerland, 2978 meters above sea level


Parabolic Flight Microgravity


Parabolic Flight Microgravity

Baseline

1 hour afte

r flig

ht

24 hour afte

r flig

ht

0

1000

2000

3000

4000 **

***

sS

T2 (

pg

/ml)

Baseline

1 hour afte

r flig

ht

24 hour afte

r flig

ht

0.0

0.5

1.0

1.5

2.0

H-F

AB

P (

ng

/ml)

Baseline

1 hour afte

r flig

ht

24 hour afte

r flig

ht

0

100

200

300

400

500 *

**

GD

F-1

5 (

pg

/ml)

Baseline

1 hour afte

r flig

ht

24 hour afte

r flig

ht

0

500

1000

1500

2000**

su

PA

R (

pg

/ml)

Conclusion

Biomarkers for Cardiovascular

Disease

(sub-clinical) Myocardial

Injury/Ischemia

H-FABP

Inflammation Fibrosis

Hemodynamic Stress

Ventricular Remodeling

ST2

uPAR GDF-15

Physical Exercise

Conclusion

Circulation. 2013 Oct 15;128(16):e240-327.

Troponins

ST2, Galectin-3

Thank you!

Special thanks to: Dr. Bernhard Wernly, Dr. Attila Kiss, Vera Paar, Prof. Uta C. Hoppe, Prof. Bruno Podesser, Dr. Hackl

modern biological markers in cardiology and internal medicine · 2019-11-11 · assoc.prof. pd...

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