Table 2.
Phenotypes and possible pathogeneses of sarcomere gene–related cardiomyopathiesa
| DCM | HCM | RCM | |
|---|---|---|---|
| ↓Contractility | ↑(or↓?) Contractility | ↑Ca2+ sensitivity | ↑Ca2+ sensitivity |
| Volume overload | Pressure overload | ↓Relaxation | ↓Relaxation |
| Hypertrophy (eccentric) | Hypertrophy (asymmetric) | No hypertrophy No compensation |
|
| ↓Myocardial stiffness | ↑Myocardial stiffness | ||
| ↑N2BA/N2B; ↑SLsl | ↓N2BA/N2B; ↓SLsl | ||
| Loss of myofibrils | Ischemia, loss of myofibrils, fibrosis | ||
| ↓Relaxation | OFT obstruction | ||
a
Possible primary defects are underlined. The most important compensatory effects are in boldfaced. Possible secondary effects are italicized. Note that the primary defect for titin mutations may be myocardial stiffness or N2BA/N2B ratio.
Abbreviations: DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; N2BA and N2B, long and short cardiac isoforms of titin, respectively; OFT, outflow tract; RCM, restrictive cardiomyopathy; SLsl, slack sarcomere length.