Transcript Laboratory diagnostics in cardiology Biomarkers

Laboratory diagnostics in cardiology
Biomarkers
Robert Halmosi MD, PhD
1st Dept. of Medicine, University of Pécs
2016
I. CHD, stable angina pectoris
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Identification of risk factors and checking their adequate
treatment, or the side effects of drug treatment
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Plasma glucose
HgbA1c (glycosylated Hgb)
Triglyceride
Total cholesterol
HDL-cholesterol
LDL-cholesterol
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measurement
Friedewald-formula:
LDL-cholesterol = total cholesterol – HDL-cholesterol – triglyceride/2,2
ApoA↓, ApoB↑, Lp(a)↑
Uric acid
BUN, Creatinine (renal failure?)
Hematology - anemia? (e.g.: sec. angina)
Platelet aggregation test (effectivity of antiplatelet therapy?)
AST, ALT, CK (side effect of statin treatment?)
Platelet aggregation test result of a non-treated
patient
Normal value or individual target value?
Normal value or individual target value?
Ten year risk of fatal CVD in high-risk regions of Europe
II. Acute coronary syndrome
 Necroenzymes (at the admission of patient and 3-6 hours later):
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CK
CK-MB
AST
LDH
Troponin I
Troponin T
Myoglobin
 Other laboratory parameters:
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CRP
Ions
Hematology (white blood cell count, hgb)
Platelet aggregation test
PTR/INR
aPTT, fibrinogen
 Creatine-kinase (CK)
– Normal value <200 U/l
– Elevated serum activity:
1. Myocardial disorders
- AMI
- Myocarditis
2. Skeletal muscle disorders
- Duchenne muscular dystrophy
- Polymyositis
- Dermatomyositis
3. Injury of skeletal muscles
- Trauma
- im. injection
- hypothermia
– Isoenzymes:
- MM – skeletal muscle
- MB – heart muscle
- BB – CNS
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CK-MB:
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Myocardial isoenzyme of CK
Normal value:
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< 25 U/l
≤ 6 % of total CK activity (if total CK-activity is > 200 U/l)
AMI: first rise after 4 hours, peak after 24 hours, return to
normal after 2-3 days
AST
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Normal value:
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< 44 U/l
Liver, heart, skeletal muscle.
Elevated serum activity:
1. Liver diseases
2. AMI (first rise after 6-8 hours, peak after 36-48 hours, returns to
normal after 4-6 days)
3. Skeletal muscle disorders (dystrophies)
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LDH: Lactate dehydrogenase
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Normal value:
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< 450 U/l
5 isoenzymes
LDH1 is the myocardial isoenzyme
First rise after AMI: 8-24 hours, peak after AMI: 3-6 days,
return to normal: 7-14 days.
Myoglobin
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Large amount in heart and skeletal muscle
Normal value:
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<70 μg/l
– Elevated plasma level:
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AMI (first rise after 2 hours, peak after 6-8 hours, return to normal
after 1-2 days)
Skeletal muscle disorders, trauma
Sensitive and early biomarker for AMI, but it is not specific!
 Cardiac troponins !!!
– High sensitive Troponin I (hs-cTnI) and Troponin T (hs-cTnT)
 Normal value: <14 ng/l
 Lab and bedside test
– cTn-s are specific for myocardial damage
– Elevated plasma level:
1. AMI (first rise after 3-4 hours, peak after 24 hours,
return to normal after 7-14 days)
2. False positivity (not due to ACS):
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Contusion of heart or heart injury (e.g. operation, ablation, resuscitation)
Myocarditis
Severe heart failure
Pulmonary embolism, severe pulmonary hypertension
Cerebrovascular events (stroke, subarachnoid hemorrhage)
End-stage renal failure
Extensive burn injury
Patients with critical conditions (MOF, sepsis, respiratory failure)
Extensive physical activity
The use of hs-cTns in the diagnosis of NSTEMI
Types and laboratory diagnostics of AMI
 I. AMI due to primary coronary event (plaque erosion, rupture or fissure)
– Troponin level is >14 ng/l
 II. Secondary AMI caused by elevated O2 demand or decreased O2 supply
(coronary spasm, anaemia, pulmonary embolism, arrhythmia)
– Troponin level is >14 ng/l
 III. Sudden cardiac death
– Troponin level is not diagnostic!!!
 IV. a. AMI due to PCI
– Troponin level is >5x higher than normal value
b. AMI caused by in stent thrombosis
 V. AMI due to CABG surgery
– Troponin level is >10x higher than normal value
 Myocardial reinfarction
– Clinical signs of an ACS several days after an AMI
– Determination of necroenzyme (troponin or CK-MB) levels/activities immediately
and after 3-6 hours.
– In the 2nd sample the levels/activities are at least 20 % higher than in the 1st sample
Time-course of cardiac necroenzymes
High troponin ≠ ACS
III. Heart failure
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Etiology:
– CV risk factors (ischemic DCM?)
– TSH (thyrotoxicosis?, hypothyroidism?)
– gammaGT, AST/ALT ratio, platelet… (alcohol abuse?)
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Diff. dg.
– Leg edema:
 Liver diseases (total protein, albumin, pseudocholinesterase, PTR/INR, AST, ALT, bilirubin)
 Renal diseases (Na, K, BUN, creatinine, creatinine-clearence, urine analysis, 24-hour urine analysisproteinuria)
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COPD (arterial blood gases)
Pneumonia (white blood cell count, CRP)
Pulmonary embolism (D-dimer, arterial blood gases)
Anemia (Hgb)
ACS (necroenzymes)
Secondary organ failures due to heart failure:
– Liver: PTR/INR, AST, ALT, bi
– Kidney: Na, K, BUN, creatinine
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Side effects of diuretic treatment (Na, K, BUN, creat, uric acid)
Arterial blood gases
Natriuretic peptides:
– BNP
– NT pro-BNP
NATRIURETIC PEPTIDES
BNP reflects better myocardial disease then ANP does.
NT pro-BNP (which is the stable form of BNP) is also used
•for the diagnosis of heart failure (distinguishing the causes of dyspnoe)
•to follow the effectivity of therapy
•to judge the prognosis
Therapeutic usage: recombinant human BNP (nesiritid) inreases natriuresis, diuresis
and the cardiac output and improves clinical status.
BNP or NT-proBNP
BNP
NT-proBNP
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FDA - 2002
120 minutes half-life
6-10 x greater level
Better in diastolic HF
Diagnostic during nesiritide
infusion
 Prognostic marker
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FDA - 2000
18 minutes half-life
Better in renal failure
Prognostic marker
Good correlation
Relative diagnostic contribution of tools
Algorythm for the use of BNP testing
European Heart Journal (28) 2007.
Caveats to BNP interpretation
Caveats to BNP interpretation
Pulmonary diseases
Morrison LK, et al. J American Coll of Card. 2002;39(2):202-209.
BNP - Prognosis
 599 breathless patients treated in the emergency department.
 At 1 year, 91 patients (15.2%) had died. Median NT-proBNP
concentrations at presentation among decedents were significantly
higher than those of survivors (3277 vs 299 pg/mL; P<.001).
 NT-proBNP concentration greater than 986 pg/mL at presentation
was the single strongest predictor of death at 1 year (HR, 2.88).
Arch Intern Med. 2006;166:315-320
BNP level is a good marker of left
ventricular (LV) dysfunction and a
strong marker to predict morbidity and
mortality in patients with chronic heart
failure (HF).
A novel biomarker in heart failure – Galectin-3
Key Characteristics of Galectin-3 and Natriuretic
Peptides
Biology
Related approved
indications for use
Effect of
decompensation
Stability over time
Response to HF
treatments
Galectin-3
Natriuretic Peptides
Mediator of cardiac fibrosis
and adverse remodeling
Released in response to
myocardial stretch
Aid in prognosis
Aid in risk stratification
Not affected
Marked response
Stable once elevated
Highly variable
No effect from common HF
Generally reduce NP levels
medications
IV. Valvular diseases/Patient with arteficial valve
 Coagulation parameters (PTR/INR)
– Anticoagulation monitoring in every 4-6 weeks!
– Disease of a native valve: OAC is not necessary, only in the case of:
– Mitral stenosis+AF/embolisation or MS+SR, if there is embolisation in the
patient’s history, or the atria are big, or the stenosis is very severe
 INR target value: 2,0-3,0
– Bioprosthetic valve/valvuloplasty (for 3 months OAC, INR 2,0-3,0; then
aspirin)
– Patients with mechanical valve
 INR target value: 2,0-3,0 in aortic position
 INR target value: 2,5-3,5 in mitral position;
or in aortic position+high thromboembolic risk
 INR target value: 2,5-3,5 + aspirin:
- if there was embolisation in the patient’s history, despite of appropriate
anticoagulant treatment
 INR target value: 3,0-3,5 + aspirin: after mechanical valve thrombosis (aortic
position)
 INR target value: 3,5-4,5 + aspirin: after mechanical valve thrombosis (mitral
position)
 Hemolysis:
– Mild haemolysis can be seen in all patients with arteficial valve
– Severe hemolysis: paravalvular leak!!!
– Laboratory parameters:
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Hematology (anemia?)
Bilirubin
LDH
Haptoglobin
– Binding of free hemoglobin
– Normal value: 0.5-2 g/l
– Haptoglobin level decreases in the case of hemolysis
 Infective endocarditis:
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Anemia (70-90%)
Leukocytosis is not characteristic (20-30 %)
ESR and CRP are high (90%)
Proteinuria (mild or moderate), microscopic hematuria (60 %)
RF is also elevated (after several weeks)
Blood culture!!!
V. Pulmonary embolism
 D-dimer
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Break-down product of fibrin
Normal value??? (100→500)
500 ng/ml cut off value: sensitivity 97 %, specificity 45 %
Low value rules out PE
False positivity
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Inflammation
Neoplasms
Trauma (haematoma)
Intravascular coagulation and fibrinolysis (atrial fibrillation)
Hepatic cirrhosis
Arterial blood gases (hypoxemia+hypocapnia)
PTR/INR
Fibrinogen, aPTT, TT (checking the treatment – Na-heparin, thrombolysis)
Troponin, BNP
– Prognostic markers
– Therapy: Troponin and/or BNP elevation or right ventricular dysfunction →
thrombolysis (IIb indication)
VI. Rhythm disorders
 Etiology:
– TSH
– Digoxin level (0.5-0.9 mg/l)
– K
 Treatment (can we perform the cardioversion?)
– PTR/INR
– Na, K
VII. Hypertension
1. Routine laboratory tests
- blood glucose
- lipids (total cholesterol, HDL-cholesterol, TG)
- uric acid
- creatinine
- Na, K
- blood count
- urine stick/urinary sediment
2. Recommended laboratory tests
- CRP
- microalbuminuria
- quantitative proteinuria, if urine stick is positive
 3. Secondary hypertension
- renal parerenchymal HT:
- renal function
- urine tests (proteinuria, RBC in urine)
- primary hyperaldosteronism:
- hypopotassemia
- metabolic alkalosis
- plasma aldosteron/renin ratio is high
- Cushing’s syndrome:
- high plasma cortisol level at night or in the morning
- plasma cortisol level is not repressed by dexamethason in the morning
- Pheochromocytoma:
- plasma catecholamine
- 24-hour urine collection (catecholamins)