New diagnostic tools for left ventricular hypertrophy: biomolecular and echocardiographic techniques

Background: Left ventricular hypertrophy (LVH) is related to different physiological and pathological conditions, as athlete's heart, systemic arterial hypertension, aortic stenosis and hypertrophic cardiomyopathy. The secondary cardiac structural and hemodynamic changes, referred as the “obesity cardiomyopathy” when these alterations result in congestive heart failure, comprise an increase in left ventricular wall thickness, mass and diameters, with systolic and diastolic dysfunction. MicroRNAs are small non-coding RNAs that regulate gene expression by inhibiting RNA translation. In myocardial tissue, microRNAs are involved in modulating phenomena such as cardiomyocyte (CM) hypertrophy, excitation-contraction coupling, and apoptosis; moreover, non-CM-specific microRNAs regulate myocardial vascularization and fibrosis. Recently, the possibility that circulating microRNAs may be biomarkers of cardiovascular disease has been raised, but studies are lacking. Objective: We aimed to evaluate LVH by molecular and imaging techniques. LVH was assessed in morbid obese patients, before and after sleeve gastrectomy by 2D Doppler and TDI echocardiography (TTE), included speckle tracking imaging. Moreover, we aimed to determine whether microRNAs involved in myocardial remodeling were increased in the peripheral blood of patients with hypertrophic cardiomyopathy (HCM); and if any significantly increased microRNA correlated with the degree of left ventricular hypertrophy evaluated by TTE and cardiac magnetic resonance. Methods: Sixteen obese patients (46.4±10.3y, 4 males) underwent a complete cardiac evaluation including color Doppler/TDI TTE preoperatively and 16 months (range 12-18) after bariatric surgery. Fifty-six HCM patients were characterized with conventional TTE and cardiac magnetic resonance. MicroRNA expression was measured in peripheral plasma by reverse transcription and amplification of extracted RNA. The levels of circulating microRNA were compared with those in a control group made up of thirty-one blood donors. Results: Echocardiographic data showed a significant reduction in interventricular septum, posterior wall thickness (from 11.3±1.8 to 9.4±2.1mm, from 10.4±1.7 to 8.6±1.9mm, respectively, p<0.01 both) and in left ventricular mass, absolute value and indexed by height (from 222.41±78.2 to 172.75±66.3g, p<0.05, from 55.9±14.3 to 43.8±17.2g/m2.7, p<0.001 both). Antihypertensive drugs intake was significantly reduced (p<0.05), such as the 10-year Framingham risk score (from 14.2±9.3% to 8.3±9.5%, p=0.003). Among those assessed, 12 microRNAs (miR-27, miR-199-5p, miR-26, miR-145, miR-133a, miR-143, miR-199-3p, miR-126-3p, miR-29, miR-155, miR-30, and miR-21) were significantly increased in the plasma of HCM patients. However, only miR-199-5p, miR-27, and miR-29 correlated with hypertrophy. Conclusions: Our data suggest that LVH is significantly ameliorated after bariatric surgery, with a global cardiovascular risk reduction as demonstrated by the 10-year Framingham risk score. Moreover, cardiac remodeling determines a massive release of microRNAs into the bloodstream of HCM patients.