1. The role of biomarkers in the diagnosis of cardiac dysfunction and heart failure in the elderly: time for a paradigm shift?
Dr. Bert Vaes

2. Case: George, 84 years old
George, 84 years, married, living at home

3. Case: George - Background: Ex-smoker (40 package years till 1992)
COPD stage II-III
Osteoarthritis with a knee prosthesis (2003)
Hypercholesterolemia
Peripheral arterial disease with ilio-femoral bypass surgery (1992)
- Medication Clopidogrel, ramipril 5mg, simvastatin, paracetamol,
inhaled CS and β mimetics
- Symptoms Dyspnea and fatigue when marching up a stairs, nocturnal dyspnea, loss of appetite
- Clinical ex Fine bilateral crepitations on lung auscultation,
systolic cardiac murmur (intensity 2/6)
- Lab results Haemoglobin 12.4mg/dL, creat 1.1mg/dL
(MDRD 63mL/min)

4. Are the patient’s symptoms caused by heart failure?
The research question
Are the patient’s symptoms caused by heart failure?
“The very essence of cardiovascular medicine is the recognition of early heart failure”
Sir Thomas Lewis, 1933

5. Definition of heart failure
ESC Heart Failure guidelines 2005
ESC Heart Failure guidelines 2008

6. HFrEF versus HFpEF?
Difference between systolic and diastolic dysfunction (HFPEF)
 two separate syndromes? Based on functional, structural and molecular biological arguments
 single syndrome? 2 phenotypes at the end of the spectrum

7. HFrEF versus HFpEF?
ESC guidelines 2012

8. Heart failure staging

9. Problems in the very elderly
High burden of multimorbidity
2. Polypharmacy  BELFRAIL: 85% one or more cardiac (possibly symptom reducing) medication

10. Problems in the very elderly
Cardinal symptoms of HF are very prevalent in subjects aged 80 and older1
4. Low specificity of signs and symptoms in elderly patients2
5. No accurate signs and symptoms for cardiac dysfunction or HF in the elderly, especially for detection of the early stages3
1Vaes et al. Int J Cardiol 2012;155: , 2Fonseca et al. Eur J Heart Fail 2004;6: ,
3Morgan et al. BMJ 1999;318:

12. NPR-C/ endopeptidase / renal
Natriuretic peptides: the ‘ultimate’ biochemical test for heart failure?
Differences between BNP and NT-proBNP
BNP
NT-proBNP
Half-life
20’
120’
Clearance
NPR-C/ endopeptidase / renal
Renal +++
Increase with age +
+++
Stability
4-24h
>72h
Variability (significant changes)
+++ (>130%)
++ (>90%)
Also explain NP are not just used as a diagnostic test, but are also used as prognostic markers, therapeutic agents and indicators to guide treatment of patients with heart failure.
Wu et al. Eur J Heart Fail 2004;6:355-8

13. Natriuretic peptides: a marker of pancardiac disease in old age
 marker of pancardiac disease1 Cardiovascular continuum of Braunwald and Dzau2
1Struthers A et al. Eur Heart J 2007;28: , 2Dzau E, Braunwald E. Am Heart J 1991;121:

14. BELFRAIL study
Vaes B et al. BMC Geriatr. 2010; 10:39.

15. Prevalence of cardiac dysfunction
1Int J Card 2012;155: , 2JAMA 2003;289: , 3Heart 2006;92: , 4Lancet 2006;368:

16. Prevalence of cardiac dysfunction
In the Western World 1-2% of the adult population
>70j  >10%!
BELFRAIL study (≥80j)
- According to GP  30% chronic HF
- Cardiac dysfunction  19.3%
°LVEF≤50%
°severe diastolic dysfunction
°valvular heart disease
- 55% had symptoms of heart failure
- 85% received cardiovascular medication
°49% diuretics
°42% B-blockers
°42% ACE-I of sartans

17. The added value of NP
What is the diagnostic value of background variables, anamnesis and clinical examination
2. What is the added value of natriuretic peptides for the diagnosis of
heart failure / severe cardiac dysfunction

18. The added value of NP The clinical model
Table 3. The diagnostic accuracy of anamnesis and clinical examination for severe CD or new-onset heart failure
BELFRAIL1
Oudejans et al2
Kelder et al3 n
567
206
721
Mean age (±SD)
85 ± 4
82 ± 6
71 ± 12
Women (n,%)
358 (63)
144 (70)
466 (65)
Reference standard
Severe CD
New-onset HF
C statistic clinical model (95% CI)
0.79 (0.74 – 0.85)
0.75 (0.69 – 0.82)
0.83
1Am J Cardiol 2013;111: , 2Eur J Heart Fail 2011;13: , 3Circulation 2011;124;

19. The added value of NP The clinical + model
Subjects without CAF or PM
Table 7. The diagnostic accuracy of anamnesis and clinical examination for severe CD or new-onset heart failure
BELFRAIL1
Oudejans et al2
Kelder et al3 n
567
206
721
Mean age (±SD)
85 ± 4
82 ± 6
71 ± 12
Women (n,%)
358 (63)
144 (70)
466 (65)
Reference standard
Severe CD
New-onset HF
C statistic clinical model (95% CI)
0.79 (0.74 – 0.85)
0.75 (0.69 – 0.82)
0.83
C statistic clinical + NP
0.81 (0.75 – 0.87)
0.92 (0.88 – 0.95)
0.86
C statistic clinical +ECG
0.80 (0.74 – 0.85)
0.79 (0.73 – 0.85)
0.84
1Am J Cardiol 2013;111: , 2Eur J Heart Fail 2011;13: , 3Circulation 2011;124;

20. Case evaluation
ESC guidelines 2012

21. Case evaluation Oudejans et al. Eur J Heart Fail 2011;13:518-527
Kelder et al. Circulation 2011;124;

22. Case evaluation: George
NT-proBNP  1612pg/mL
ESC guidelines: echocardiography is needed
Oudejans  56 points  echocardiography
Kelder  92 points  HF> 80% likelihood
Echocardiography: dilated left ventricle, LVEF 20%, mitral regurgitation 2/4 and diastolic relaxation disturbance

23. Case: Maria 88 years old

24. Case: Maria
Background: Osteoarthritis with bilateral knee prosthesis (1999, )
Hypertension and diabetes type II
Chronic renal insufficiency
Colon cancer (surgery and chemo) 1995
Chronic atrial fibrillation
- Medication Ace-I, β blocker, diuretics, coumarine, insuline, paracetamol
- Symptoms Severe fatigue and oedema LE, no dyspnea
- Clinical ex Oedema LE, obese, HJR+, systolic cardiac murmur (3/6), BP 170/70mmHg, HR 82/min
- Lab results Haemoglobin 10.6mg/dL, creat 1.9mg/dL
(MDRD 25mL/min)

25. Case evaluation: Maria
NT-proBNP = 1514pg/mL
ESC  Echocardiography is needed
Oudejans  echocardiography
Kelder  Heart failure > 80% likelihood
Echocardiography: LVEF 62%, left atrium dilated, moderate aortic stenosis

26. Conclusions A high prevalence of cardiac dysfunction
High diagnostic accuracy of history, anamnesis and clinical examination
Natriuretic peptides
 disease specific markers, despite ↑ burden of multimorbidity
 markers of pancardiac disease
 Impact of confounders on test performance (CAVE renal function, atrial fibrillation)
 “rule-out” test and “rule-in” test
 could be used as a prognostic marker in the very old

27. No limits, just edges (Jackson Pollock)