Abstract 19808: Characterization of Myocardial and Serum Levels of Phosphodiesterase 9A in Patients With Heart Failure - Relation to Left Atrial Size and Right Ventricular Function
Aims: Heart failure with preserved ejection fraction (HFPEF) remains a major diagnostic and therapeutic challenge in clinical cardiology. Intense research currently aims to identify mediators relevant to the pathophysiology of HFPEF. Recently, phosphodiesterase 9A (PDE9A) has been discovered as a promising cardioprotective enzyme in hypertrophic heart disease in mice. However, a comprehensive characterization of myocardial and serum levels of PDE9A in patients with heart failure is missing.
Methods: Endomyocardial biopsies from both ventricles and blood samples were obtained from patients with HFPEF and left ventricular hypertrophy (n=18), heart failure with reduced ejection fraction (HFREF, n=22), inflammatory cardiomyopathy (iCMP, n=24) and healthy subjects (n=5). Patients underwent cardiac magnetic resonance and echocardiography imaging. Endomyocardial PDE9A mRNA and protein levels were characterized by RT-PCR and immunohistochemistry, respectively. Furthermore, a western blotting technique was established to identify and compare for the first time PDE9A serum levels in humans.
Results: Whereas endomyocardial PDE9A was expressed at low levels in healthy subjects, patients with iCMP and HFREF displayed elevated PDE9A expression on endomyocardial biopsy. Patients with HFPEF presented a 2.1-fold increase in endomyocardial PDE9A expression when compared to patients with HFREF (P<0.01). Notably, with a new established protocol we were able to detect circulating PDE9A in human serum. Again, serum levels of PDE9A were elevated in patients with HFPEF as compared to HFREF and iCMP (4.5- vs. 2.8- and 2.4-fold as compared to healthy subjects, respectively, P<0.01). Interestingly, patients with endomyocardial PDE9A expression above median demonstrated increased left atrial size and reduced tricuspid annular plane systolic excursion (TAPSE) on echocardiography.
Conclusion: The present study demonstrates for the first time that endomyocardial and serum levels of PDE9A are particularly increased in patients with HFPEF. Levels of PDE9A are associated with left atrial size as a marker of diastolic burden and right ventricular function. PDE9A may serve as a potential novel diagnostic marker and therapeutic target in HFPEF.
Author Disclosures: C. Besler: None. K. Rommel: None. A. Burkert: None. M. von Roeder: None. A. Linke: None. G. Schuler: None. V. Adams: None. P. Lurz: None.
- © 2016 by American Heart Association, Inc.