Table 2.

The differential diagnosis of valvular abnormalities resembling non-bacterial thrombotic endocarditis

Clinical characteristics	NBTEa	Papillary fibroelastomab	Lambl's excrescenceb	IE	Toxic valvulopathy c	Rheumatic HDd	Myxoma
Incidence	Rare	85% of valvular tumours	Rare	Common	Rare	Common	30% of cardiac tumours
		8% of cardiac tumours					Rarely on valves
Age of the patient	Elderly (50–80 years)	Elderly (60–80 years)	Elderly (60–70 years)	Elderly (50–70 years)	Mostly elderly	All ages	Middle aged (30–60 years)
Sex predilection		M = F		M > V (2:1)			F > M (2:1)
Predisposing conditions/agents	Hypercoagulability	Hypercoagulability	Unknown	Bacteraemia	Endocrine tumour	Previous infection	Possible familial
	Endothelial damage	Endothelial damage	Hypercoagulability?	Endothelial damage	Serotonin-like drugs#	S. pyogenes	Mostly unknown
	Immune complexes	Possible oncogenic (KRAS)	Endothelial damage?		Endothelial damage	Auto-immune reaction
	Hypoxia
Fever	No	No	No	Yes	No	No	No
Cardiac murmur	Rare	Possible	No	Often	Rare	Often	Possible
Laboratory markers of infection	Possible	No	No	Yes	Possible	No	No
Blood cultures	Negative	Negative	Negative	Positive	Negative	Negative	Negative
Echocardiographic features
Shape	Verrucous, friable	Round, oval, often stalked	Thin and long	Verrucous, irregular	Nodular	Nodular, verrucous	Round, oval
	Rounded	Frond-like, sea-anemone	Filifom strands		Irregularly shaped		Cluster of grapes
	Broad based	Stippling along edges					Irregular or smooth
Mobility	Moderately mobile	Often mobile	Hypermobile	Often mobile	Immobile	Immobile	Mobile
Penduncated	No	Often (50%)	Yes	No	No	No	Often
Homogeneity	Homogenous	Homogenous	Homogenous	Homogenous	Homogenous	Homogenous	Non-homogenous
Size/length	Mostly < 3–4 mm	1–2 cm	Thin (<1 mm)	Variable	<1 mm	<1 mm	4–8 cm
	Maximum 1 cm	Range 0.2–4.6	Long (upto 1–2 cm)	Upto several cm			Range 2–12
Preferred side of the heart	Left	Left	Left	Left	Right	Left	Left
Preferred cardiac valve	Mitral>aortic	Aortic>mitral	Aortic>pulmonic	–	Tricuspid>pulmonic	Mitral>aortic	—
Location to the valve	Mostly upstream	Mostly downstream	Mostly upstream	Mostly upstream	Mostly downstream	—	Downstream
Location on the valve	Anywhere on valve	Anywhere on valve	Along closure lines	Anywhere	Entire leaflet	Starting at the tip	—
Valvular involvement	Thickening, fibrosis	Minimal at base	None	Thickening	Diffuse thickening	Thickening, calcification	Minimal at base
				Abces, perforation	Immobility	Domed appearance
						Valvular fusion
Valvular regurgitation	Possible	Rare	No	Often	Very often	Often	Possible
Histological composition	Platelets, fibrin	Avascular	Avascular	Micro-organisms	Fibroblasts	Granulomatous lesions	Vascularized
	Granulation tissue	Fibro-elastic tissue	Fibro-elastic tissue	Platelets, fibrin	Smooth muscle cells	Macrophages	Myxoid matrix
	Neovascularization	Endothelial layer	Endothelial layer	Neutrophils			Collagen, calcified
Embolic events	Frequent (>30%)	Frequent (33%)	Considered possible	Often (∼10%)	No	No	Frequent (>30%)
Association with stroke	Yes	Yes	Yes	Yes	No	No	Yes

^aAlthough arguably different in aetiology, marantic (also known as terminal or cachectic endocarditis; and notably due to carcinomatosis), and Libman–Sacks (also known as atypical verrucous endocarditis; notably due to SLE and APS) are considered indistinguishable by echocardiography and histology.

^bVarious authors consider papillary fibroelastoma's to be giant Lambl's excrescences.

^cIncluding carcinoid Syndrome (also known as Hedinger syndrome), in which case an endocrine tumour releases high levels of seretonin/tryptophan resulting in endothelial damage/inflammation, and carcinoid-like syndrome or diet-drug valvulopathy, in which case high serotonin levels are caused by diet and/or drugs, e.g.: ergotamin, methylsergide, pergolide, fenfluramine-phentermine, methylenedioxymethamphatamine (MDMA). NB: Carcinoid(-like) syndrome mainly involves the right heart due to inactivation of serotonin-related metabolites in the lungs (although the left side of the heart might be involved in case of right–left shunting or pulmonary metastases).

^dRheumatic heart disease, also known as typical verrucous endocarditis.

F, female; IE, infective endocarditis; M, male.