Tissue Doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenicrabbit model of human hypertrophic cardiomyopathy

Background-Hypertrophic cardiomyopathy (HCM) is diagnosed clinically by the presence of left ventricular hypertrophy (LVH). However, LVH is absent in a significant number of genotype-positive patients. Because myocyte dysfunc tion and disarray are the primary abnormalities in HCM, we reasoned that ti ssue Doppler imaging could identify contraction and relaxation abnormalitie s, irrespective of hypertrophy, in a transgenic rabbit model of human HCM. Methods and Results-M-mode, 2D, Doppler echocardiography and tissue Doppler imaging were performed in nontransgenic (n=24), wild-type beta-myosin heav y chain-arginine(403) (n=14), and mutant beta-myosin heavy chain-glutamic a cid(403) (n=24) transgenic rabbits. Mean septal thicknesses were 2.0+/-0.3, 2.0+/-0.25, and 2.75+/-0.3 mm in the 3 groups, respectively (P=0.001). LVH was absent in 9 of the 24 mutant rabbits. Left ventricular dimensions, sys tolic function, heart rate, mitral inflow velocities, and time intervals we re similar in the groups. However, the difference between atrial reversal a nd transmitral A wave duration was increased in the mutant rabbits (P<0.001 ). More importantly, systolic and early diastolic tissue Doppler velocities were significantly lower in all mutant rabbits (7.45+/-2.2 versus 10.8+/-2 .3 cm/s in nontransgenic and 9.0+/-0.76 cm/s in wild-type; P<0.001), includ ing the 9 without LVH. A systolic velocity <8.5 cm/s had an 86% sensitivity and 100% specificity in identifying the mutant transgenic rabbits. Conclusions-Myocardial contraction and relaxation were reduced in the mutan t beta-myosin heavy chain-glutamic acid(403) transgenic rabbit model of hum an HCM, irrespective of the presence or absence of LVH. In addition, tissue Doppler imaging is more sensitive than conventional echocardiography for H CM screening.