Renin-angiotensin-aldosterone system stimulation in different stages of heart failure with reduced ejection fraction

Abstract

238 Poster Session 2 between proBNP and EF, the non-significant correlation between the absolute levels of CgA fragments and EF suggests that the evaluation of CgA and its fragments could be an independent and complementary marker to proBNP, as it is probably released through pathophysiological mechanisms which are different from other well-known mechanical and neuro-humoral phenomena involved in heart failure onset and progression. P1022 Subclinical hypothyroidism(SCH) as a risk factor in elderly patients with chronic heart failure(CHF)-still a challenge for clinical practice Background: Subclinical hypothyroidism (SCH), defined as an isolated elevation of thyroid-stimulating hormone (TSH) levels (>5.0mIU/L) with a normal free thyroxine (fT4) level, became a common disorder, with a strong impact on the cardiovascular diseases outcome. The prevalence of SCH is relatively high, ranging from 4% to 20% in the adult population, more often in women and elderly people. Purpose: This study was undertaken to assess the prevalence of SCH in elderly with chronic heart failure (CHF) and the relationship between SCH and clinical, bioumoral, echocardiographic and echovascular parameters. Methods: Data were collected on 874 patients, aged >65 years (mean age 73 years), women 63%, admitted to our hospital with the clinical syndrome of CHF. The New York Heart Association (NYHA) heart failure classification on admission was: 62% of patients had class IV, 25% had class III criteria and 13% met class II. Exclusion criteria were: known previous thyroid diseases, amiodarone therapy, atrial flutter and fibrillation. Among the analyzed cases, 52% had heart failure (HF) resulting from coronary artery disease,11% had HF attributable to valve disease, 9% had a dilated cardiomyopathy and 28% had HF as a result of arterial hypertension. In each patient measurement of ejection fraction (EF) was performed by the quantitative 2D(biplane Simpson) method and all cases underwent pulsed-wave Doppler examination of mitral inflow for diastolic evaluation, as well as carotid artery intima-media thickness measurements. Based on TSH level, patients were divided into two groups: group I, with SCH and CHF (10.8%), comprised 94 cases and group II, without SCH (89.2%), comprised 780 cases. The correlations were performed using Student's t-test.Results. Patients in group I were, compared with those in group II, older, more often women, had higher body mass index, higher prevalence of diabetes, higher systolic blood pressure, higher levels of serum lipids and higher serum creatinine values(p < 0.05). The CHF and SCH were associated more frequently with class III and IV NYHA and with a lower EF, compared with group with normal TSH(p < 0.001). Also, patients in group I had a higher index of intima-media thickness of carotid artery and more atheroma plaques "at risk". Conclusions: The presence of SCH (10.8% in our study) was associated for sure with a worse status of patients in CHF, but SCH could represent a potentially modifiable risk factor. The current determination of TSH threshold levels for the treatment of SCH remained a clinical controversy and the decision to treat or not to treat a SCH patient with CHF is still a challenge for clinician, in the light of known risk of hormonal replacement therapy. P1023 Mid-regional pro atrial natrieutic peptide predicts increase in cardiac output during submaximal exercise in patients with heart failure. Background: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is produced and secreted from the atria as a result of atrial distention in heart failure (HF). The association between MR-proANP and invasive hemodynamic parameters during exercise in patients with HF is unknown. Purpose: The purpose was to investigate the association of MR-proANP and invasive hemodynamic measures during submaximal exercise. Methods: Patients with chronic HF with a left ventricular ejection fraction (LVEF) <45 % performed a submaximal exercise test on a supine exercise bike. The individual submaximal exercise level was determined as 50 % of the maximal workload during maximal exercise testing one week prior. All patients underwent right heart catheterization with measurement of invasive hemodynamic parameters at rest and during submaximal exercise. Blood levels of MR-proANP were measured at rest and during exercise. MR-proANP was logtransformed for analyses. Results: A total of 18 patients (89 % male) were included (mean age 53 ± 12, mean LVEF 23 ± 8 %, mean VO2max 18 ± 5 l/kg/min, mean submaximal workload was 52 ± 18 Watts). Pulmonary capillary wedge pressure (PCWP) increased from rest (15 ± 8 mmHg) to submaximal exercise: (34 ± 11 mmHg) (p < 0.05). The increase in cardiac index (CI) from rest to submaximal exercise was 2.3 ± 0.5 L/min to 4.0 ± 1.3 L/min (p < 0.05). Levels of MR-proANP also increased from rest to submaximal exercise: 180 ± 114 pmol/L vs. 238 ± 142 pmol/L (p < 0.05). There was an inverse correlation between resting log(MR-proANP) and increase in cardiac index (CI) from rest to submaximal exercise (r2 = 0.41, p = 0.004). Log(MR-proANP) was also correlated with resting pulmonary capillary pressure (PCWP) (r2 = 0.37, p = 0.007), but there was no association between log(MR-proANP) and PCWP during peak exercise (p = 0.09). Increase in CO during exercise was also associated with resting PCWP (P = 0.005). NT-proBNP was not associated with CI or PCWP at rest or during exercise in this study (p>0.05). Conclusion: A low blood level of MR-proANP predicts a greater increase in cardiac output during submaximal exercise in patients with chronic HF. In systolic HF, MR-proANP is a predictor of resting PCWP, and hereby further predicts cardiac reserve during submaximal exercise. Association: Cardiac Index and MR-proANP P1024 Renin-angiotensin-aldosterone system stimulation in different stages of heart failure with reduced ejection fraction Background: Renin-angiotensin-aldosterone system (RAAS) stimulation in heart failure (HF) with reduced ejection fraction (HFREF) is detrimental through cardiac remodeling and water/salt retention. Cardiac function, hemodynamic alterations and HF therapies influence RAAS hormones. Aims: This study aims to describe RAAS activation during different stages of HFREF and assesses their prognostic role. Methods and Results: In 72 acute decompensated HFREF patients (ADHF), 78 stable chronic HFREF patients and 53 patients with HF with normalized ejection fraction (HFNEF), venous blood samples and hemodynamic parameters were obtained. Subjects were prospectively followed up to 30 months. RAAS hormones (plasma renin activity (PRA) and serum aldosterone) are significantly lower in ADHF compared to stable HFREF and HFNEF patients (all p < 0,05) (Table 1). Volume status, blood pressure and HF medication seem to play an important role (all p < 0,05). High PRA levels are associated with worse outcome in acute ADHF, which does not hold true in stable HFREF or HFNEF (Figure 1). There is a trend to lower PRA levels in HNEF patients compared to stable HFREF (p=0,06, not presented in table) which could not be accounted for by medication use or hemodynamic factors between these two groups. Conclusion: High RAAS activity in stable HFREF and HFNEF patients is not associated with worse outcome in contrast to patients with ADHF. During acute decom-pensation the RAAS system remains appropriate responsive and is downregulated. In HFNEF patients RAAS activity declines possibly due to the reversal of cardiac abnormalities.