Introduction: The biomechanics of contraction changes with advancing age both in diastole and in systole. Such changes contribute to the development of heart failure with a preserved ejection fraction in the elderly. Left ventricular (LV) twist is the circumferential motion of the apex with respect to the base of the heart and has an important role in LV ejection and filling. We examined the biomechanics of age-related changes in LV twist by determining a broad spectrum of LV rotation parameters in different age groups, using speckle tracking echocardiography (STE). Formation glucose-dependent cross-links of collagen, termed advanced glycation end products (AGEs) can accumulate with age and increase myocardial stiffness. The purpose of this study was to investigate the changes in LV twist in relation with glycation and a marker of replicative senescence such as telomere length.
Methods: 2-D speckle tracking analysis was performed on 194 healthy non-obese volunteers aged 40 to 88 years without history of cardiovascular disease, diabetes, regular use of medication and significant deviations by 12-lead electrocardiogram. LV rotation parameters, systolic twist were measured using off-line analysis program QLAB (Advanced Ultrasound Quantification Software Release 8.1.2 (Philips). In 29 subjects (15%) image quality was insufficient for STE analysis. Methylglyoxal (MG) is a byproduct of glucose metabolism and an inducer of AGEs. Concentration of MG in serum was determined using HPLC with UV detector. Telomere length was measured in leukocyte (LTL) by real-time quantitative polymerase chain reaction.
Results: The subjects were 68.04±6.57 years old, 36% were men. With increasing age, apical rotation (P<0.05), time to apical rotation (P<0.05) and twist (P<0.001) increased, whereas basal rotation (P<0.01), time to basal rotation (P<0.01), and rotational deformation delay (defined as the difference of time to basal rotation and apical rotation) (P<0.05) decreased. LTL was associated with age (β=-0.026, P=0.015), LV systolic twist (r=-0.761, P=0.03) and apical rotation (r=-0.690, P=0.002). MG was related with age (r=0.866, p<0.001). In multivariate regression MG was associated with LV twist (β=0.518, P=0.03), apical (β=0.128, P=0.005) and basal (β=-0.136, P=0.001) rotation. Increased MG was observed in 85% of people with increased LV twist and apical rotation, and in 78% of people with decreased basal rotation. Older subjects with higher MG and shorter telomeres length had more pronounced changes in the biomechanics of LV twist.
Conclusions: Our findings suggest that age-related increase of LV twist, apical rotation and decrease of basal rotation are associated with accumulation AGEs, significant contributing factors in heart aging. Changes in these parameters of STE are related to marker of replicative senescence – shortening of telomere length.