1. Καρδιακή ανεπάρκεια : Ο ρόλος των κλασικών και νεότερων βιοδεικτών
39ο Πανελλήνιο Καρδιολογικό Συνέδριο
Αθήνα Οκτωβρίου 2018
Καρδιακή ανεπάρκεια : Ο ρόλος των κλασικών και νεότερων βιοδεικτών
Αγάθη-Ρόζα Βρεττού
Επιμελήτρια Α´ Καρδιολογίας
Β´Πανεπιστημιακή Καρδιολογική Κλινική
ΠΓΝ Αττικόν

2. Disclosures
Nothing to disclose

3. Intern J of Cardiol 219 ;2016 :111–114

4. BNP Accuracy is 90% Negative predictive value=90%
Optimal cut-off point 100 pg/mL
1.0
BNP=50 pg/mL
0.8
BNP=80 pg/mL BNP=100 pg/mL
Positive predictive value=75%
0.6
BNP=125 pg/mL
0.4
BNP=150 pg/mL
Sensitivity
Final Diagnosis Heart Failure
Final Diagnosis NOT Heart Failure
BNP 100 pg/mL “Test positive”
673
227
BNP <100 pg/mL “Test negative” 71
Sensitivity
=90%
615
Specificity
=73%
0.2
Negative
0.0
predictive value=90%
0.0
0.2
0.4
0.6
0.8
1.0
1-Specificity
N Engl J Med. 2002;347:

5. Identifying the right patients for echocardiography
The use of NPs for rule-out heart failure in symptomatic patients in primary care
Identifying the right patients for echocardiography
< cut-off value
Patient presenting with symptoms suggestive of heart failure
Search for other explanation ?
“Rule out”
> cut-off value
Maisel A. ESC 2018
Referral to specialist

6. Assesment of Heart Failure Probability
Clinical History
Physical examination
ECG
All absent
≥1 present
Natriuretic peptides
NT –pro BNP >125pg/ml
BNP>35pg/ml
HF unlikely
Biomarkers not routinely done in clinical practice
ESC Guidelines 2016
Echocardiography

7. STOP-HF trial
Vs.
Routine care (n=677) Routine primary care Cardiology care PRN
BNP-directed care (n=697) Annual BNP check
If BNP >50 pg/ml at any time: cardiology consult, echo, nurse-coaching
1° Endpoint: LV systolic or diastolic dysfunction, or heart failure
2° Endpoints: Emergency hospitalization for arrhythmia, TIA, stroke, MI, PE/DVT, HF
JAMA. 2013;310(1):66-74.

8. JAMA 2013;310(1):66-74

10. Biomarkers for prevention

11. Biomarkers for Diagnosis

12. In high-risk patients with HFrEF, a strategy of NT-proBNP–
GUIDE IT
In high-risk patients with HFrEF, a strategy of NT-proBNP–
guided therapy was not more effective than a usual care strategy in improving outcomes

13. Biomarkers for Prognosis

14. Confounders of NP interpretation
Higher NP levels than expected
Lower NP levels than expected
Increasing age*
Obesity
ACS*
Flash pulmonary edema
Renal insufficiency
Pericarditis/Tamponade
RV dysfunction*
Genetic polymorphisms
Atrial fibrillation
“Burned-out” Cardiomyopathy
Pulmonary hypertension*
Pulmonary embolism*
Anemia/high output states*
Sepsis
Mitral Regurgiation*
* Delineates likely elevation from Ventricular stretch

15. High Sensitivity Troponin in Heart Failure

16. Mechanism of Cardiac Troponin Release in Heart Failure
J Am Coll Cardiol 2010;56:1071–8

17. Are they really false positives when the elevation gives you greater risk?
Chronic HF
Elevated in 50%
Acute HF
Elevated in >80%

18. Cardiac Troponin and outcome in Acute HF
N Engl J Med May 15;358(20):2117-2

19. Cardiac Troponin and outcome in Acute HF
N Engl J Med May 15;358(20):2117-2

20. Baseline hsTnT may identify patients with acute HF at very low risk
No CV deaths through day 180 were observed in patients with hsTnT levels<0.014mg/l despite highNT-pro BNP
Baseline hsTnT may identify patients with acute HF at very low risk
for CV mortality

22. A combination of Natriuretic Peptide and PCT can
A combination of Natriuretic Peptide and PCT can be used to better diagnose dyspneic
patients
Eur Journal of Heart Failure 2012;14: 278–286

23. ESC Heart Fail. 2017;4(3):

24. IMPACT EU –BIC-18: Procalcitonin-guided antibiotic therapy does not improve mortality in patients with shortness of breath and suspected AHF NCT
Terminated : At 75% patient completion overall mortality was much lower than expected and without significant difference at day 90. No chance to reach the primary endpoint.

25. sST2 soluble suppressor of Tumorigenicity 2
Arq Bras Cardiol. 2016; 106(2):

26. sST2 –solid cutpoints
>35ng/ml
RISK

27. lBMI ST2 not effected by lAge lSex
lEtiology of HF lAtrial Fibrillation lAnemia

28. The prognostic value of sST2 was not influenced by renal function
In a cohort of 879 heart failure patients ST2 did not show any correlation with renal function whereas NT-proBNP concentrations increased significantly with decreasing renal function
J Cardiac Fail 2013;19:768e775

30. independent of repeatedly measured
Repeated ST2 measurements appeared to be a strong predictor of outcome in patients with acute HF
independent of repeatedly measured
NT-pro BNP
J Am Coll Cardiol 2017;70:2378–88

31. sST2 is a predictor of all-cause CV death
JACC Heart
Fail 2017;5:284

32. Why ST-2 levels might be better than NP levels to follow patients
Natriuretic peptides
Much day to day variability of BNP- diuretic use, salt load from meals, time of blood draw.
“wet BNP” changes rapidly- which may justrepresent volume and not remodeling
Difficult to use with CKD
GUIDE IT negative
sST2
Little variability
Does not seem to be affected by volume as much
Not effected by CKD
ST-2 especially responsive to antifibrotic drugs like MRA and sacubitril–valsartan

33. sST2 unanswered issues Timing Frequency of testing
Earlier evaluation after hospitalization
Treatment escalation
Initiation/uptitration of antifibrotic drugs
Monitoring device ( Cardio-MEMS) Implantation?

34. Conclusions
Several biomarkers have emerged as adjunct tools to clinical decision making and CV imaging
Natriuretic peptides can be useful for
prevention of LV dysfunction
HF diagnosis in the ED setting
Improved risk stratification of HF patients
Cardiac Troponin may be considered for added risk stratification
sST2 as a marker of myocardial fibrosis may also be considered for added risk stratification and relevant therapeutic decision making

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