Impaired coronary and myocardial flow in severe aortic stenosis is associated with invreased apoptosis: a transthoracic Doppler and myocardial contrast echocardiography study

Leonarda Galiuto ^1*, Marzia Lotrionte ², Filippo Crea ³, Amedeo Anselmi ⁴, Giuseppe G.L. Biondi-Zoccai ⁵, Fabio De Giorgio ⁶, Alfonso Baldi ⁷, Feliciano Baldi ⁸, Gianfederico Possati ⁹, Mario Gaudino ¹⁰, George W Vetrovec ¹¹ and Antonio Abbate ¹¹

¹ Institute of Cardiology, Catholic University, Italy
² Institute of Cardiology, Rome, Italy
³ Institute of Cardiology Rome, Italy
⁴ Campus Biomedico Rome, Italy
⁵ Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy
⁶ Second University Napoli, Italy
⁷ Institute of Forensic Medicine Catholic University Rome, Italy
⁸ Institute of Forensic Medicine, Rome, Italy
⁹ Dept. of Cardiovascular Sciences, Rome, Italy
¹⁰ Dept of Cardiovascular Sciences, Rome, Italy
¹¹ Virginia Commonwealth University, United States

^* To whom correspondence should be addressed. E-mail: lgaliuto{at}rm.unicatt.it.

Accepted 12 May 2005

Abstract

Background: Aortic stenosis (AS) entails left ventricle (LV) pressure overload and it is associated with impaired coronary and myocardial flow. However, the mechanisms responsible for the transition to adverse remodelling and heart failure are only partially known. We hypothesized that impaired coronary and myocardial blood flow are linked with increased myocyte apoptosis, thus establishing a link between pressure overload and LV remodelling.

Methods and results: Peak diastolic coronary blood flow velocity (CBFV) was evaluated at transthoracic Doppler echocardiography (TDE), and signal intensity (SI) and the rate of SI rise (â) were measured at myocardial contrast echocardiography (MCE) in 11 patients with severe aortic stenosis and left ventricular hypertrophy. In the same patients, biopsies were obtained from the antero-lateral LV free wall during surgery and analysed for cardiomyocyte apoptosis. LV mass corrected CBFV values (CBFVi) were significantly lower in cases vs controls (0.100 cm*g/s[0.07-0.115] vs 0.130 cm*g/s[0.130-0.160], p=0.002). Similarly SI*â values were significantly lower in cases vs controls (11 1/s[8-66] vs 83 1/s[73-95], p=0.001). Apoptotic rate (AR) was increased in AS more than 100-fold vs controls (1.2%[0.8-1.4] vs. 0.01%[0.01-0.01], p<0.001) and inversely correlated with lower CBFVi and SI*â values (r=-0.77, p=0.001 for both).

Conclusions: Patients with severe AS and LV hypertrophy have impaired myocardial perfusion which is associated with enhanced cardiomyocyte apoptosis. Impaired myocardial perfusion, ensuing oxygen demand/supply imbalance, may, at least partially, be responsible for increased apoptosis and possible transition to heart failure, thus establishing a link between pressure overload, LV remodelling and heart failure.

Keywords: aortic stenosis, apoptosis, coronary flow reserve, myocardial contrast echocardiography, myocardial flow

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