Search

β-myosin heavy chain mutations are the most frequently identified basis for hypertrophic cardiomyopathy (HCM). A transgenic mouse model (αMHC(403)) has been extensively used to study various mechanistic aspects of HCM. There is general skepticism whether mouse and human disease features are similar. Herein we compare morphologic and functional characteristics, and disease evolution, in a transgenic mouse and a single family with a MHC mutation. Ten male αMHC(403) transgenic mice (at t-5 weeks, -12 weeks, and -24 weeks) and 10 HCM patients from the same family with a β-myosin heavy chain mutation were enrolled. Morphometric, conventional echocardiographic, tissue Doppler and strain analytic characteristics of transgenic mice and HCM patients were assessed. Ten male transgenic mice (αMHC(403)) were examined at ages -5 weeks, -12 weeks, and -24 weeks. In the transgenic mice, aging was associated with a significant increase in septal (0.59±0.06 vs. 0.64±0.05 vs. 0.69±0.11 mm, P<0.01) and anterior wall thickness (0.58±0.1 vs. 0.62±0.07 vs. 0.80±0.16 mm, P<0.001), which was coincident with a significant decrease in circumferential strain (-22%±4% vs. -20%±3% vs. -19%±3%, P=0.03), global longitudinal strain (-19%±3% vs. -17%±2% vs. -16%±3%, P=0.001) and E/A ratio (1.9±0.3 vs. 1.7±0.3 vs. 1.4±0.3, P=0.01). The HCM patients were classified into 1st generation (n=6; mean age 53±6 years), and 2nd generation (n=4; mean age 32±8 years). Septal thickness (2.2±0.9 vs. 1.4±0.1 cm, P<0.05), left atrial (LA) volume (62±16 vs. 41±5 mL, P=0.03), E/A ratio (0.77±0.21 vs. 1.1±0.1, P=0.01), E/e' ratio (25±10 vs. 12±2, P=0.03), global left ventricular (LV) strain (-14%±3% vs. -20%±3%, P=0.01) and global LV early diastolic strain rate (0.76±0.17 s(-1) vs. 1.3±0.2 s-1, P=0.01) were significantly worse in the older generation. In β-myosin heavy chain mutations, transgenic mice and humans have similar progression in morphologic and functional abnormalities. The αMHC(403) transgenic mouse model closely recapitulates human disease.

The prevalence of rheumatic diseases was studied in representative subsamples by interview (n = 134), and by physical (n = 89) and radiographic (n = 81) examination in a representative sample of 79-year-olds in Göteborg, Sweden. The prevalence of rheumatoid arthritis (3-8 ARA criteria) was 10%. Radiographic osteoarthritis (OA) was diagnosed in wrists and/or finger joints of 65% of the probands and in knee joints of 14%. The first metacarpophalangeal (MCP I) joint was more frequently involved in males than in females (p less than 0.05). In females palpable enlargement of distal (DIP) and proximal interphalangeal finger joints correlated (p less than 0.01) to radiographic OA. The degree of heavy work in previous occupations was correlated to radiographic OA of DIP II-V in females (p less than 0.05 and of MCP I in males (p less than 0.05) but not to radiographic or clinical OA in knee joints. Symptoms of OA were reported by 6.1% in the knee and in 4.5% in hip joints. The prevalence of chondrocalcinosis averaged 15% (23% of females and 6% of males). Chondrocalcinosis of the hands occurred in 21% of females but in no males. The prevalence of hyperuricemia was 15% (women 6%, men 29%), and gouty arthritis was found in one woman.