The role of biomarkers in the diagnosis of cardiac

dysfunction and heart failure in the elderly: time for a

paradigm shift?

Dr. Bert Vaes

Case: George, 84 years old

George, 84 years, married, living at home

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)

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

Definition of heart failure

ESC Heart Failure guidelines 2005 ESC Heart Failure guidelines 2008

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

HFrEF versus HFpEF?

ESC guidelines 2012

Heart failure staging

1. High burden of multimorbidity

2. Polypharmacy BELFRAIL: 85% one or more cardiac (possibly symptom reducing) medication

Problems in the very elderly

Problems in the very elderly

3. 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;155:134-143, 2Fonseca et al. Eur J Heart Fail 2004;6:795-802, 3Morgan et al. BMJ 1999;318:368-372

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%)

Natriuretic peptides: the ‘ultimate’ biochemical test for heart failure?

Wu et al. Eur J Heart Fail 2004;6:355-8

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;28:1678-82, 2Dzau E, Braunwald E. Am Heart J 1991;121:1244-63.

BELFRAIL study

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

Prevalence of cardiac dysfunction

1Int J Card 2012;155:134-143, 2JAMA 2003;289:194-202, 3Heart 2006;92:1259-64, 4Lancet 2006;368:1005-11.

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

The added value of NP

1. 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

The added value of NPThe 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 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;111:1198-208, 2Eur J Heart Fail 2011;13:518-527, 3Circulation 2011;124;2865-2873

The added value of NPThe clinical + model

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 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;111:1198-208, 2Eur J Heart Fail 2011;13:518-527, 3Circulation 2011;124;2865-2873

Subjects without CAF or PM

Case evaluation

ESC guidelines 2012

Case evaluation

Oudejans et al. Eur J Heart Fail 2011;13:518-527Kelder et al. Circulation 2011;124;2865-2873

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

Case: Maria 88 years old

Case: Maria

Background: Osteoarthritis with bilateral knee prosthesis (1999, 2001)

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)

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

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

No limits, just edges (Jackson Pollock)