| Abstract |
Cardiac pacing is indisputably the only effective treatment for symptomatic bradycardia. However, right ventricular apical pacing has proven to induce electrical and mechanical dyssynchrony leading to asynchronous ventricular contraction, diastolic dysfunction, alterations in regional mechanical function and loading, myocardial perfusion and autonomic innervation and alterations in the expression of genes regulating myocardial contraction and hypertrophy. In a substantial percentage of paced patients the aforementioned adverse effects result in developing pacemaker induced cardiomyopathy (PICM), the incidence of which ranges from 3% annually to 26% after long-term follow up. Its prevalence depends on the interactions between numerous factors either patient-specific or pacing-related. Patient-specific factors comprise the presence of intrinsic AV and ventricular conduction disturbances, baseline atrial rhythm, left ventricular ejection fraction (EF), presence of heart failure (HF) and/or coronary artery disease (CAD) at the time of implantation. Pacing-related factors include the mode of pacing, site of ventricular lead, duration of paced QRS, percentage of ventricular pacing and duration of pacing.
Before birth, cardiac metabolism is based on carbohydrates for energy provision. However, post-natal energy substrate metabolism switches to fatty acid oxidation and to the expression of “adult” isoforms of metabolic enzymes and myocardial proteins. In conditions of hemodynamic or metabolic stress the post-natal heart returns to the so-called “fetal gene program” which includes the preference of carbohydrates over fatty acidsas substrates for evergy provision and an isoform switch of many proteins including metabolic enzymes and sarcomeric proteins.
We hypothesized that right ventricular apical pacing may induce alterations in the expression of myocardial genes that procede deterioration of myocardial function and geometry of the left ventricle. Therefore, the aim of our study was to assess early changes in the expression of certain genes related to contractile apparatus and excitation-contraction coupling proteins, in peripheral blood cells of patients with preserved left ventricular function, who underwent long-term right ventricular apical pacing.
We enrolled 52 consecutive patients with preserved ejection fraction who underwent pacemaker implantation for bradycardic indications. Group A consisted of 24 individuals with atrioventricular conduction disturbances and group B of 28 patients with sinus node disease. In group A, peripheral blood mRNA levels of the gene sarcoplasmic reticulum calciumATPase decreased at 3, 6, and 12 months’ follow-up, while a-myosin heavy chain (MHC) decreased and β-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.
According to the findings of our study, 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.
|
Search
