Download Indezine Template

Troponin Elevation in ICUbeyond Myocardial Infarction
Dr. TH De Klerk
Critical Care
Definition
• Biomarker is a characteristic that is objectively
measured and evaluated as an indicator of
normal biological processes, pathogenic
processes or pharmaco-dynamic response to a
therapeutic intervention.
• Fit-for- purpose paradigm:
Exploration- Research
Demonstration- Diagnosis
Characterization- Prognosis
Surrogacy- Surrogate clinical end-points
Background
• Troponin complex consist of I, C and T
subunits, that mediates actin and myosin
coupling. The troponin I and T isoforms
are specific to the myocardium.
• Two storage forms: cytosolic and
myofibrillar. The concentration is 35X
higher in the myofibril.
• Therefore a marker of myocardial damagedoesn’t tell about mechanism of injury. Eg.
Can be inflammatory rather than
ischaemic.
Myocardial Infarction
• Definition: Myocardial cell death due to
prolonged ischaemia.
• 2012-Third consensus definition.
• The diagnosis rests on three pillars:
a) Clinical setting- symptom recognition in
ICU unreliable.
b) Raised biomarkers- levels and false
positives.
c) New electrocardiographic,
echocardiographic or angiographic
evidence consistent with ischaemia.
• Need 2 or more for diagnosis.
Clinical Classification of Myocardial
Infarction
• Type 1- Spontaneous coronary event.
Either plaque rupture, erosion, fissure, etc.
• Type 2- Supply-Demand Mismatch.
Anemia, tachycardia, hypo- orhypertension, etc.
• Type 3- Unexpected cardiac death with
electrocardiographic, echocardiographic,
angiographic or autopsy findings indicative
of myocardial ischaemia.
• Type 4 a- PCI-related b- Stent thrombosis
• Type 5 CABG related
Troponin levels and false positives.
• Troponin rise or fall with at least one value above
99th percentile upper reference limit. CV< 10%.
• The troponin level in myocardial infarction
predicts extent of infarct, risk for complications,
morbidity, mortality and length of stay.
• The troponin level outside setting of myocardial
infarction independently predicts severity of
illness, mortality, duration of ventilation, as well
as length of ICU stay.
• Troponin release without necrosis- increased
myocyte membrane permeability of cytosolic
content. This still correlates with myocardial
depression, mostly fully reversible.
Non-Ischaemic Conditions with Raised
Troponins
•
•
•
•
•
•
•
•
•
•
Myocarditis
Cardiac contusion
Burns
Pulmonary embolism
Aortic dissection
Heart failure
Sepsis
Acute neurological disease
Cardiotoxic drugs
Renal failure
Myocardial Oxygen Supply
• Supply determined by magnitude of coronary flow
and oxygen carrying capacity.
• Oxygen carrrying capacity influenced by anaemia,
hypoxia and Hb-O2 affinity.
• Coronary blood flow determined by
a) Metabolic control- adenosine, K+, CO2, lactate and
pH.
b) Autoregulation: Myogenic and neurogenic factors.
c) Extravascular compressive forces-intramyocardial.
d) Diastolic phase of cardiac cycle
e) Humural factors: angiotensin, nitric oxide, etc.
f) Neural control- autonomic innervation.
Myocardial Oxygen Demand
• Heart rate
• Contractility
• Systolic wall tension: proportional to
systolic ventricular pressure x radius/
ventricular wall thickness.
Common conditions in ICU with
Troponin leaks
• Tachycardia- severe and especially dysrhythmias.
Atrial fibrillation with raised tropononins predict risk
for embolism much better than CHA2DS2-VASc
score.
• Direct trauma- minority of patients with troponin
elevation develop significant complications such as
hypotension, dysrhythmias, etc.
• Burns- >25% Total body surface area.
• Chronic hypertension with left ventricular
hypertrophy- demand increase with left ventricular
mass, coronary flow reserve decrease due
microcirculatory remodelling.
• Heart failure- Increased strain: Volume and/or
pressure overload. Myocyte death: Inflammation,
apoptosis and catecholamine toxicity.
Common conditions in ICU with
Troponin leaks
• Pulmonary and pulmonary vascular
disease- including ARDS: Severe right
heart strain.
• Acute central nervous system injury eg.
Trauma, stroke, etc. Autonomic
imbalance- Sympathetic hyperactivity.
• Renal failure-endothelial dysfunction,
impaired excretion, left ventricular
hypertrophy, loss cardiac myocyte
membrane integrity.
Troponins and Sepsis
• Direct injury: Endotoxin, inflammation, etc.
• Indirect: Supply-demand mismatch.
• Septic cardiomyopathy: Reversible systolic and/or
diastolic dysfunction.
• Genetic factors- iNOS deficiency.
• Calcium channel dysregulation- decrease L-type
receptors.
• Nitric Oxide- myocardial depression via
mitochondrial dysfunction.
• Cytokine- “MDF”- TNF-alpha, IL-1, IL-6.
• Toll-like receptor activation- negative inotropic.
• Endothelin-1- myocardial apoptosis.
• No evidence suggestive of microthrombosis
Troponins and Sepsis
Metabolic alterations:
• Maldistribution of coronary blood flow with
unchanged global myocardial blood flow.
• Inhibition of cytochrome C oxidase, with myocardial
oxygen depletion.
• Reactive oxygen species causes impaired
myocardial contraction.
• Autonomic dysregulation, decreased receptor
density, catecholamine myocyte toxicity.
• Myocardial infiltration –immune cells with
subsequent necrosis and apoptosis.
Troponins and sepsis
• 44% of patients with septic shock- diastolic
dysfunction.
• 24% both systolic and diastolic dysfunction.
• Septic shock often accompanied by ARDS with
hypoxic pulmonary vasoconstriction with reversible
pulmonary hypertension.
• Troponin elevation in sepsis correlates best with
echocardiographic parameters of left ventricular
diastolic dysfunction and right ventricular dilatation.
These parameters as well as troponin elevations
seems to be the best independent cardiac predictors of
mortality in sepsis.
Treatment of troponin elevations
in sepsis
• Fluid therapy remains cornerstone to restore
euvolemic state.
• Dobutamine used in the setting of decreased
cardiac output. High dose >10mcg/kg/min
cardiotoxic.
• Calcium channel sensitizers- Levosimendan.
• Beta blockers in septic shock- 2013 JAMA RCT
with Esmolol titrated to heart rate 80-95/min,
decrease mortality.
• Role of statins in myocardial dysfunction unknown.
• Aspirin reasonable- if no contra-indications.
Utility of Troponin Elevations in Peri-operative
Period in Non-cardiac Surgery
• Most commonly used cardiac risk evaluating tool in
the peri-operative period is the Revised Cardiac
Risk Index (Lee index).
• Pre-operative hs-Troponin substantially improves
risk stratification when added to this index.
• Hs-Troponin elevation was shown to be the
strongest independent risk predictor for serious
peri-operative cardiac events.
• Currently a class 1A recommendation by European
Society of Cardiology guidelines.
References
•
•
•
•
Antonucci E, Fiaccardori E, Donadello K, Taccone FS,
Tranchi F, Scoletta S. Myocardial depression in sepsis:
From pathogenesis to clinical manifestations and
treatment. J of Crit Care 2014;29:500-511.
Ventetuolo CE, Levy MM. Cardiac Biomarkers in the
Critically Ill. Crit Care Clin 2011;27:327-343.
Landesberg G, Jaffe As, Gilon D, Levin PD, Goodman S,
Abu-Baih A, et al. Troponin Elevation on Severe Sepsis
and Septic Shock: The Role of Left Ventricular Diastolic
Dysfunction and Right Ventricular Dilatation. Crit Care
Med 2014;42:790-800.
Weber M, Luchner A, Manfred S, Mueller C, Liebetrau C,
Schlitt A, et al. Incremental value of high-sensitivity
troponin T in addition to the revised cardiac index for
peri-operative risk stratification in non-cardiac surgery.
Eur Heart J 2013;34:853-862.