INTRODUCTION

Heart Failure : A Costly Deadly Disorder

Paradigma baru Gagal Jantung
 Gagal Jantung
Jalan Akhir bersama bagi berbagai penyakit kardiovaskuler

• Iskemia koroner
• hipertensi
• kardiomiopat
Gagal
• Penyakit katup jantung
• Kongenital
Jantung
• Penyakit genetk

Drexler H, et al . Molecular Mechanism in Heart Failure. JAAC 2006;

8(9):56-66
 Definitons
“A biomarker is a substance used as an indicator
of a biologic state. It is a characteristic that is
objectively measured and evaluated as an
indicator of normal biologic processes,
pathogenic processes, or pharmacologic
responses to a therapeutic intervention.”
(NIH Working Group 2001)

“Cardiac biomarkers are substances released

from heart muscle when it is damaged as a result
of myocardial infarction.”

Note: As will be discussed, it has been shown that cardiac markers

can be released from cardiac tissue as a result of damage from
processes other than MI
Heart Failure, a major and growing public health problem, appears to
result not only from cardiac overload or injury but also from a complex
interplay among : genetic, neurohormonal, inflammatory, and biochemical
changes acting on cardiac myocytes, the cardiac interstitium, or both.

An increasing number of enzymes, hormones, biologic substances, and

other markers of cardiac stress and malfunction, as well as myocyte injury
— collectively referred to as biomarkers — appear to have growing clinical
importance.
Although biomarkers include genetic variants, clinical images, physiological
tests, and tissue-specimen biopsies, this review focuses on biomarkers
derived from the blood or urine other than serum levels of hemoglobin,
electrolytes, liver enzymes, and creatinine, which are routinely determined
as part of clinical care.

Morrow & de Lemos: 3 criteria a biomarker should fulfill to be useful

clinically. First, accurate, repeated measurements must be available to
the clinician at a reasonable cost and with short turnaround times;
second, the biomarker must provide information that is not already
available from a careful clinical assessment; and finally, knowing the
measured level should aid in medical decision making
Morrow & de Lemos: Criteria Biomarker
 CLASSIFICATION of
BIOMARKERS in HEART FAILURE
 Biomarkers in Heart Failure
1. Inflammation*†‡
C-reactive protein
Tumor necrosis factor α
Fas (APO-1/CD-95); CD-40L
Interleukins 1, 6, and 18

2. Oxidative stress*†§
Oxidized low-density lipoproteins
Myeloperoxidase
Urinary biopyrrins
Urinary and plasma isoprostanes
Plasma malondialdehyde
Extracellular-matrix remodeling*†§

3. Matrix metalloproteinases
Tissue inhibitors of metalloproteinases
Collagen propeptides
Propeptide procollagen type I
Plasma procollagen type III
4. Neurohormones*†§
Norepinephrine
Renin
Angiotensin II
Aldosterone
Arginine vasopressin
Endothelin

5. Myocyte injury*†§
Cardiac-specific troponins I and T
Myosin light-chain kinase I
Heart-type fatty-acid protein
Creatine kinase MB fraction

6. Myocyte stress†‡§¶
B-type natriuretic peptide (BNP)
N-terminal pro–brain natriuretic peptide (NT-proBNP)
Midregional fragment of proadrenomedullin
ST2
7. New biomarkers†
Chromogranin
Galectin 3
Osteoprotegerin
Adiponectin
Growth Differentiation Factor 15 (GDF-15)

* Biomarkers in this category aid in elucidating the pathogenesis

of heart failure.

† Biomarkers in this category provide prognostic information

and enhance risk stratification.

‡ Biomarkers in this category can be used to identify subjects

at risk for heart failure.

§ Biomarkers in this category are potential targets of therapy.

¶ Biomarkers in this category are useful in the diagnosis of

heart failure and in monitoring therapy.
A.Mark Richards

Heart Failure Clin 5

(2009) 463–470
Biomarkers and diagnostics in heart failure
Hanna K. Gaggin, James L. Januzzi Jr.
Biochimica et Biophysica Acta 1832 (2013) 2442–2450
Gambar 2.4. Struktur gen dan protein BNP33
Gambar 2.4. Struktur gen dan protein BNP33
Receiver operating characteristic (ROC) Plot (AUC)
TPR vs FPR
Kaplan-Meier Survival Plot