Takotsubo cardiomyopathy: Pathophysiology and role of cardiac biomarkers in differential diagnosis

Table 1 Diagnostic clues for differentiating takotsubo cardiomyopathy and acute coronary syndrome

History	Stressful stimulus
	Female sex
	Age > 55 yr
	Neuropsychiatric conditions
EKG findings	Absence or paucity of reciprocal ST depression
	Widespread T wave inversion
	QTc prolongation
Laboratory findings	Catecholamine levels	Metanephrine, Normetanephrine
	Natriuretic peptides	BNP, NT-proBNP
	Myonecrosis markers	Myoglobin, CK-MB, Troponin I, Troponin T
	Others	Copeptin, sST2, soluble lectin like oxidized LDL receptor-1 (sLOX-1), IMA
Imaging	Echocardiogram	Reversible wall motion abnormalities > distribution of a epicardial coronary artery
		Reversible mitral regurgitation,
		Left ventricular outflow tract obstruction
	Coronary angiogram	Absence of ruptured plaque
		Diminished flow
		Coronary vasospasm
	SPECT	Reduced Thallium uptake
		Reduced fatty acid metabolism in BMIPP imaging
		Reduced myocardial MIBG uptake
	PET	Reverse metabolism perfusion mismatch
	CMR	T2 hyperintensity; lack of first pass hypoperfusion; LGE (may be seen if MRI done early)

sST2: Soluble suppression of tumorigenicity-2; sLOX-1: Soluble lectin like oxidized LDL receptor-1; IMA: Ischemic modified albumin; SPECT: Single photon emission computed tomography; BMIPP: β-Methyliodophenyl-pentadecanoic acid; MIBG: Metaiodobenzylguanidine; PET: Positron emission computed tomography; CMR: Cardiac Magnetic resonance imaging; LGE: Late gadolinium enhancement; MRI: Magnetic resonance imaging; LDL: Low-density lipoprotein; BNP: Brain natriuretic peptide.

Table 2 Natriuretic peptide/cardiac myonecrosis marker ratio in takotsubo cardiomyopathy and acute coronary syndrome

Ref.	Biomarker and time of collection	Takotsubo cardiomyopathy		Acute coronary syndrome
Frölich et al[36]	NT-proBNP (peak)	Cutoff NT-proBNP/TnT to differentiate TC and NSTEMI		Cutoff NT-proBNP/TnT to differentiate TC and STEMI
	TnT (peak)	5000		2889
Lahoti et al[37]	NT-proBNP (mean)	NT-proBNP/TnT		NT-proBNP/TnT (STEMI)
	TnT (peak)	5154 ± 1891.2		183 ± 128.9
Randhawa et al[38]	First simultaneous BNP and TnT	BNP/TnT	BNP/CKMB	BNP/TnT (AMI)	BNP/CKMB (AMI)
		1292 (443.4-2657.9)	28.44 (13.7-94.8)	226.9 (69.9-426.3)	3.63 (1.1-10.0)
Doyen et al[39]	BNP (admission)	BNP/TnI		BNP/TnI (NSTEMI)	BNP/TnI (STEMI)
	TnI (peak)	642 (331.8-1226.5)		184.5 (50.5-372.3)	7.5 (2.0-29.6)

BNP: Brain natriuretic peptide; NT-proBNP: N-terminal proBNP; TnT: Troponin T; TnI: Troponin I; NSTEMI: Non-ST elevation myocardial infarction; STEMI: ST elevation myocardial infarction; CKMB: Creatine kinase-MB fraction.