Alterations in the expression of genes related to contractile function and hypertrophy of the left ventricle in chronically paced patients from the right ventricular apex

Aim Long-term right ventricular apical (RVA) pacing may lead to left ventricular (LV) remodelling and heart failure. This study assessed changes in the expression of genes regulating LV contractile function and hypertrophy, after permanent RVA pacing and investigated whether such changes proceed or even predict LV remodelling. Methods and results We enrolled 52 consecutive patients (age 79.1+/-7.7 years, 34 males) who underwent pacemaker implantation for bra-dycardic indications: Group A, 24 individuals with atrioventricular conduction disturbances and group B, 28 patients with sinus node disease. In group A, peripheral blood mRNA levels of gene sarcoplasmic reticulum calcium ATPase decreased at 3, 6, and 12 months' follow-up, while alpha-myosin heavy chain (MHC) decreased and beta-MHC increased until 6 months follow-up. In this group, 25% of patients demonstrated significant LV remodelling. At 4 years, LV end-systolic diameter increased from 29.67+/-3.39 mm at baseline to 35.38+/-4.22 mm, LV end-diastolic diameter increased from 50+/-4.95 to 56.71+/-5.52 mm, and ejection fraction declined from 63.04+/-10.22 to 52.83+/-10.81%. Early alterations in gene expression were associated with a deterioration in LV function and geometry that became apparent months later. In group B, echocardiographic indexes and mRNA levels of the evaluated genes demonstrated no statistically significant changes. Conclusions Permanent RVA pacing in patients with preserved ejection fraction is associated with alterations in the expression of genes regulating LV contractile function and hypertrophy, measured in the peripheral blood. These alterations are traceable at an early stage, before echocardiographic changes are apparent and are associated with LV remodelling that becomes evident in the long term.