Cardiac Troponin Mutations and Restrictive Cardiomyopathy

Table 1

Clinical data were collected from in vivo and/or ex vivo human and transgenic mice hearts containing the RCM-associated mutation. The diagnosis of RCM was given on the basis of echocardiographic, electrocardiographic, and/or cardiac catheterization examination. The maximal wall thickness (MWT) was measured from the septal or free wall (or both). In vitro data were collected from skinned cardiac muscle preparations reconstituted with the mutant or expressed as a transgene product. The maximal force and ATPase generating capabilities (max force/ATPase) were tested in high [Ca²⁺]; whereas the ability of the muscle to relax or inhibit the ATPase activity (relax/inhibit) was measured in low [Ca²⁺]. ∆pCa₅₀, –log[Ca²⁺]_free at which 50% of the maximal response occurs (– or + denotes an increase or decrease in the Ca²⁺ sensitivity, resp.). BA: both atria; DP: diastolic pressure; E/A: ratio of early diastolic filling [E] to atrial filling [A]; EF: ejection fraction; IF: impaired filling; IRT: intraventricular or isovolumic relaxation time; LV: left ventricle; LVOTO: LV outflow tract obstruction; SCD: sudden cardiac death; ND: not determined.

Protein	Mutation	ex and in vivo properties					In vitro effects			Ref.
		MWT range (mm)	Diastolic	Systolic	Enlarged	SCD	∆pCa50	Max Force/ATPase	Relax/inhibition	In/ex vivo	In vitro
TnT	∆E96	normal	IF, ↑ DP, ↑ E/A	↓ EF	LV, BA	unclear	+0.43	no ∆ or ↑	↓	[33]	[38]
	E136K	normal	IF, ↓ IRT, ↑ DP, ↑ E/A	Preserved	BA	unclear	ND	ND	ND	[37]
TnI	L144Q, R145W	≤15	IF, ↓ IRT, ↑ DP, ↑ E/A, LVOTO	Preserved	LV, BA	yes	+0-0.30	↓ or ↑	↓	[35, 39]	[40–43]
	A171T	≤14	IF, ↓ IRT, ↑ E/A	Preserved	LV, BA	no	+0.14-0.30	↓	↓	[35]	[40–42]
	K178E	≤15	IF, ↓ IRT, ↑ E/A	Preserved	LV, BA	no	+0.15-0.47	↓	↓	[35, 37]	[40–42]
	D190H/G	15–17	IF, ↓ IRT, ↑ E/A	Preserved	LV, BA	yes	+0.17-0.30	no ∆	↓	[35]	[40, 42, 44]
	R192H	10–17	IF, ↓ IRT, ↑ E/A	Preserved	LV, BA	yes	+0.28-0.36	↓	↓	[35, 45]	[40, 41, 44, 46]
	R204H	11–13	IF, ↑ DP	Preserved	BA	yes	ND	ND	ND	[47]
	E177 fs X209	normal	IF, ↓ IRT, ↑ DP, ↑ E/A	Preserved	BA	unclear	ND	ND	ND	[37]
	D168 fs X176	10–11	IF, ↓ IRT, ↑ DP, ↑ E/A	Preserved	BA	yes	ND	ND	ND	[36]