59 Carvedilol does not worsen depressive symptoms and cognitive function in very elderly patients with heart failure. A pilot study

Abstract

S PRESENTED IN PLENARY SESSIONS SESSION WG HF: THERAPEUTIC RESPONSE IN CHRONIC HEART FAILURE. ARE THERE DIFFERENCES? 59 Carvedilol does not worsen depressive symptoms and cognitive function in very elderly patients with heart failure. A pilot study G. Pulignano1, J. Vlasic2, G. Minardi2, M.S. Fera2, D. Del Sindaco3, M. Pugliese2, L. De Lio2, E. Carmenini2, A. Mazza2, E. Giovannini2 1Rome, Italy; 2S. Camillo Hospital, I Cardiology Unit, Rome, Italy; 3IRCCS I.N.R.C.A., Cardiology Unit, Rome, Italy Aim: Depression is a relatively common condition among pts with heart failure (HF) and is associated with a poor outcome. Betablocker (BB) treatment has been demonstrated by several trials to reduce mortality, however, few data are available on BB safety in the elderly and these pts are usually underprescribed BB because their perceived side effects. Aim of this observational study was to prospectively assess the impact of Carvedilol (C) treatment to depressive symptoms and cognitive function in very elderly HF pts. Methods: Fifty-three consecutive pts aged >70 yrs (mean 78.3±6.6, range 70-94, 41.5% women, mean NYHA class 2.7±0.7) with stable HF and systolic dysfunction (mean EF% 29.9±8) were prospectively studied in a specialized HF clinic. Depressive symptoms were assessed by means of the 15-item Geriatric Depression Scale (GDS). We defined clinically relevant a score≥6. Emotional status was also assessed by means of the Emotional Dimension score of the Minnesota LHFQ (MED). Cognitive status and functional capability in activities of daily living (ADL) were assessed by means of Folstein MMSE (MMSE) and Katz ADL scale. Results: At baseline, contraindications to C were present in 20 pts (37,7%, Conventional Treatment (ConvT)). In the remaining 33 (62.3%) C was started (CT) using standard uptitration schedule. No significant differences were found between the 2 groups in age, gender, BMI, NYHA class, EF%, ischemic etiology, atrial fibrillation, serum sodium and creatinine, comorbidity, drug treatment. A GDS >/=6 was present in 41.9% of pts. No baseline differences were found in mean GDS (6.87±5.1 vs 4.86±2.8*), MMSE (23±5.5 vs 27.1±2.6*), ADL (5.88±1.0 vs 6.69±0.55*), and MED (10.2±7.4 vs 7.7±5.9*) scores (*=pns). At a mean 206±47 days f-up, 28(68.3%) of the 43 surviving pts were still on CT (mean dose 15.3±8 mg). C was discontinued in 1 pt because of worsening HF (tolerability 97%). Considering only survived pts, no significant differences were found between the 2 groups in GDS, MMSE, ADL and MED scores either at baseline or f-up and GDS≥6 was present in 34% of CT pts at baseline and 33.3% at f-up (p=ns). F-up HR and SBP were 68.5±10 b/m and 123±22 mmHg in CT pts vs 78.6±26 and 130±20 in ConvT pts (p=0.095 and p=ns). NYHA class was 2.1±0.57 vs 3.0±0,63 (p<0,0001). Conclusions: This study suggests that: 1) depression is common in elderly HF pts; 2) Carvedilol does not worsen depressive symptoms and does not adversely affect cognitive and functional status; 3) Carvedilol is well tolerated in eligible elderly pts when treatment is carefully monitored. SESSION ISHR: NEW PARTNERS OF POTASSIUM CHANNELS 63 SAP-97 promotes hKv1.5 compartmentation to lipid rafts and interaction with beta-subunit: consequences on currents properties A. Maguy1, D. Godreau1, P. Ratajczak2, C. Heymes2, R. Vranckx1, S. Hatem1 1INSERM U460, Paris, France; 2INSERM U572, PARIS, France Rational:The scaffolding protein SAP-97 is abundantly expressed in human atrial myocardium where it binds to the hKv1.5 channel that underlie an important repolarising K+ current of these cells. Aim: To determine how SAP-97 regulates the functional expression of hKv1.5 channel. Method: CHO cells were transiently transfected with pIRES-2-EGFP plasmid containing hKv1.5 and SAP-97 cDNA obtained by RT-PCR. Currents were recorded with patch-clamp technique in whole cell configuration. To study lipid raft and cytoskeleton cells were incubated for 2 hours with 2% beta-cyclodextrin and 18 hours with 50μM colchicine respectively. Proteins interaction were studied by co-immunoprecipitation. Results: In addition to the up-regulation of hKv1.5 currents (275%), and the leftward shift of its activation curve (V1/2 = 1.919 mV vs 19.73 mV in hKv1.5 vs hKv1.5/SAP-97), SAP-97 caused a fast C-type inactivation of the current (Tau-fast: 2523±458 vs 1409±261 in hKv1.5 vs hKv1.5/SAP-97). The percentage of cells with a current showing a fast inactivation increased with the reduction of the hKv1.5 cDNA concentration: 73.58% with 0.01μg vs 12.5% with 0.1 μg of hKv1.5 cDNA. When lipid rafts were altered by beta-cyclodextrin or when cytoskeleton was disrupted by colchicine, none of hKv1.5-SAP97 currents showed inactivation. SAP-97 co-immunoprecipitated with both caveolin-1alpha (vice-versa) and the endogenous beta-2.1 subunit known to inactivate hKv1.5 channel. Conclusion: SAP-97 regulates the compartmentation of hKv1.5 channel to lipid rafts probably promoting the interaction between hKv1.5 channel and endogenous beta-subunits responsible of the inactivation of the