The angiotensin converting enzyme 2 (ACE2) is a recently identified member of the renin-angiotensin-aldosterone system (RAAS), which has the ability to cleavage the angiotensin II. During systolic heart failure (SHF), rising levels of serum ACE2 were observed simultaneously to worsening of left ventricular function. In this prospective study, it has been proposed to analyze the activation of RAAS through the ACE levels in patients with SHF, before the resynchronization therapy and during the long-term treatment induced reverse remodeling. Left ventricular end-diastolic diameter and systolic ventricular function was characterized by ejection fraction (EF) measured by echocardiography. The serum ACE2 activity was determined by fluorescence intensity measurements using microplate reader.

A remarkable elevation of ACE2 activity was present in SHF patients (those who receiving standard medical therapy), compared to the hypertensive group with preserved left ventricular EF (31.45±2.09 U, n=79 vs 21.44±0.903 U, n=200; p<0.0001). In hypertensive subjects with good ventricular function the ACE2 activity was significantly higher in men than in women (27.30±1.58 U, n=93 vs 16.35±0.67 U, n=107; p<0.0001), among heart failure patients were not difference between genders (r²=0.036; p=0.130). Even in the case of well preserved left ventricular function the lower EF values had higher ACE2 activity (r²=0.113; p<0.0001, n=183). In serious left ventricular dysfunction, parallel to worsening of EF nearly linear rising of ACE2 activity was observed (r²=0.142; p=0.0007,n=78). The same nearly linear correlation was measured between ACE2 levels and proBNP – a biomarker of SHF – levels (r²=0.13; p=0.0024, n=68). After 6 months treatment for heart failure patients with biventricular pacemakers the left ventricular end-diastolic diameter significantly decreased (r²=0.278; p=0.0007, n=37) and the ejection fraction improved (r²=0.58; p<0.0001, n=36) to correspond with the process of the reverse remodeling. At the same time with these positive changes we found a significant reduction in the serum ACE2 activity (r²=0.2012; p=0.0047, n=37). In the clinical parameters were a significant difference after 3 months (EF: p<0.0001, n=17; EDD: p=0,00018, n=21), while in the level of the ACE2 we can be noted a general decrease, that only becomes significant after 6 months (p=0.049, n=21).

The results-therapy resulted improvement in echocardiographic parameters in parallel with reduced ACE2 activity -suggest the compensational role of ACE2 in the progression of human heart failure.