Risk stratification of patients with atrial fibrillation: Biomarkers and other future perspectives

Table 1 Explaining the CHADS₂ and CHA₂DS₂-VASc risk scores

Risk score	Risk factor	Risk score	Risk factor
C	Congestive heart failure	C	Congestive heart failure (or left ventricular systolic dysfunction)
H	Hypertension	H	Hypertension
A	Age ≥ 75 yr	A2	Age 65 to 74 yr
			Age ≥ 75 yr1
D	Diabetes mellitus	D	Diabetes mellitus
S2	Stroke or transient ischemic attack1	S2	Stroke or transient ischemic attack1
		VASc	Previous myocardial infarction, peripheral arterial disease or aortic plaque
			Female

All variables are assigned one point, when present, except those marked with (¹), which receive two points. Subjects with a CHADS₂ score of 0 (low risk) should be placed under antiplatelet therapy, those with a score of 1 (intermediate risk) can either undergo oral anticoagulation or antiplatelet therapy and the remaining (high risk) have clear benefit with oral anticoagulation, unless contraindicated. Using the CHA₂DS₂-VASc score, individuals with a score of zero (truly low risk) should be placed under no treatment (preferably) or, as an option, medicated with an antiplatelet agent. Intermediate risk individuals (score of 1) should be placed under oral anticoagulation (preferably) or antiplatelet agents (as an alternative). The remaining patients (score ≥ 2) should be anticoagulated.

Table 2 Clinical risk stratification scores for patients with atrial fibrillation: pros and cons

In favour

Very simple to understand

Easy to use

Solid evidence supporting the use of these classifications

Patients classified as low risk according to the CHA2DS2-VASc score are truly low risk (annual risk of events 0%)

Against

Limited capability to detect patients at risk of thromboembolism

Patients with a high thromboembolic risk are also bound to present a high bleeding risk

Patients classified as high risk present no additional benefit when treated more aggressively

Individuals classified as low risk with the CHADS2 score are not truly low risk: 19% risk at ten years

According to the CHA2DS2-VASc score, almost all individuals should be placed under oral anticoagulation (only 8.4% of subjects were classified as having a score of 0 in the validation cohort of this score[5]) and, even in the highest risk score, with a CHA2DS2-VASc score of 9, most patients experienced no events after 5 and 10 yr of follow-up

Table 3 Biomarkers associated with thromboembolism in atrial fibrillation

cTnI and NT-proBNP[11]	cTnI and NT-proBNP were independently associated with the rate of stroke
	Both markers were also associated with vascular mortality
	Only cTnI was associated with bleeding risk
	cTnI and NT-proBNP added prognostic information to the CHADS2 and CHA2DS2-VASc scores
CRP and IL-6[17]	CRP and IL-6 have been associated with an increased risk of vascular death and cardiovascular events
	IL-6 levels were predictive of stroke and major bleeding
D-dimers[16,18]	D-dimers are independently associated with the risk of stroke and cardiovascular death
	Raised D-dimer levels were associated with major bleeding

cTnI: Cardiac troponin I; NT-proBNP: N-terminal prohormone of brain natriuretic peptide; CRP: C reactive protein; IL–6: Interleukin-6.

Table 4 Echocardiographic parameters associated with thromboembolism in atrial fibrillation

Transthoracic echocardiogram	Left ventricle systolic dysfunction has long been known to be associated with thromboembolism in atrial fibrillation and is currently used in the CHA2DS2-VASc score[4]
	Left atrial diameter was shown to be associated with thromboembolism in old studies. Nowadays, diameter is not considered an appropriate way of assessing left atrial size[21]
	Left atrial area and volume have been shown to be associated with the presence of left atrial appendage thrombus and other markers of left atrial stasis[22]. Studies concerning hard clinical endpoints are still lacking[23]
	Left atrial deformation assessment (strain and strain rate) holds promise in this field, since it translates changes in atrial kinetics and function
Transesophageal echocardiogram	Left atrial appendage thrombus, spontaneous echocardiographic contrast and low flow velocities in the left atrial appendage have been associated with a high risk of thromboembolic events and an adverse prognosis[22]
	The invasive nature of this technique makes it inadequate for wide usage in AF patients