Heart Failure Pts Research Articles

Abstract 1597: Safety and Efficacy of Inhaled Iloprost Via a Disposable Nebulizer in Heart Failure Patients With Elevated Pulmonary Vascular Resistance

Background : Pulmonary vascular resistance (PVR) is routinely measured in patients (pts) being evaluated for a heart transplant. Pts with a high PVR are often treated with a milrinone or intravenous vasodilator “challenge” to establish that the PVR is not “fixed”. However, all current agents have dose-limiting side effects such as arrhythmias and hypotension. Inhaled iloprost would be an option but it is given with a costly adaptive aerosol delivery device. In addition, the efficacy and safety of this drug in left heart failure is poorly studied. Methods : 10 adult heart failure pts who were found to have a PVR of greater than 200 dyne-sec on routine right heart catheterization were enrolled. 50 micrograms (mcg) of iloprost was inhaled while in the catheterization laboratory using a disposable nebulizer and outflow filter, over 10 minutes. Hemodynamics were monitored at baseline, following drug inhalation, and 20 minutes later. Results : The average age of the patients (6 male, 4 female) was 64.8 ± 8.9 years. The mean left ventricular ejection fraction was 20.6 ± 8.6 %. The mean creatinine clearance (Cockroft-Gault) was 48.7 ± 18.9 ml/hr. The mean arterial pressure (MAP), pulmonary artery systolic (PAS), PA diastolic (PAD), PCWP, transpulmonic gradient (TPG), cardiac output (CO), and PVR at baseline, 10 minutes and 20 minutes post-inhalation are detailed below. Iloprost significantly reduced PAS, TPG and PVR without changes in MAP, PAD, PCWP or CO. These effects remained significant at study completion as well. There were no adverse events noted. Conclusion : Iloprost inhalation was well tolerated in heart failure patients undergoing right heart catheterization. Inhalation of 50 mcg of iloprost via a simple hospital nebulizer was associated with safe, rapid, and significant declines in indices of pulmonary vascular tone, without affecting cardiac output or PCWP. Further investigation of this novel use of iloprost is warranted. Results

Differential Response to Ultrafiltration and Intravenous Diuretics in Decompensated Heart Failure Patients with Preserved Versus Reduced Systolic Function

Background: Over 40% of heart failure(HF) pts hospitalized for volume overload (VO) have preserved systolic function (HFNEF). The Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD) trial showed that among 200 HF pts with VO (63 ± 15 yrs, 69% male, 71% LVEF ≤ 40%) the ultrafiltration (UF) group, compared to the intravenous diuretic group (Standard Care-SC), had greater net fluid loss (p = .001) at 48 h after randomization and fewer re-hospitalization at 90 days (p = .037).

Does Hospital Length of Stay for Heart Failure Influence Compliance with Performance Measures?

Introduction: Early discharge (dc) may contribute to under-treatment during heart failure (HF) hospitalizations. Objective: To evaluate the relationship between length of stay (LOS) and quality of care (QOC) indicators in patients (pts) hospitalized with HF. Methods: Get with the Guidelines (GWTG) employs a collaborative model of care and a web-based Pt Management Tool™ (Outcome, Cambridge, MA). Baseline data for HF pts who survived to dc was recorded for 36,078 admissions at 209 sites from 1/05 – 9/06.

Factors Affecting Early Mortality in Patients Receiving Ventricular Assist Devices as Bridge to Transplant

Ventricular assist devices (VAD) are effective bridges to transplantation in patients (pts) with severe heart failure (HF) yet early post-implant mortality remains a problem. We performed this study to identify factors that predict post-implant 60-day mortality. Methods: Pre-implant clinical data were reviewed for consecutive adult HF pts receiving VADs as bridges to transplantation. Logistic regression analyses were performed to identify risk factors for post-implant 60-day mortality. Groups were created based on the number of multivariate risk factors, and mortality rates for these groups were calculated.

Medication Assistance Program and Intensive Patient Education Reduces Heart Failure Hospitalizations in Rural Eastern North Carolina

Objectives: Many heart failure (HF) hospitalizations are due to patients (pts) inability to afford medications or poor understanding of self-care plans. The aim of this study was to evaluate whether intensive education with provision of medicines to under-insured or low-income HF pts would reduce hospitalizations and healthcare costs associated with decompensated HF. Methods: Thirty-eight pts contracted to meet with a PharmD monthly for medications, counseling, and assessment of adherence to prescribed medical regimen that was provided free of charge.

The Value of an Advanced Practice Nurse-Led Heart Failure Clinic as Demonstrated by Improvements in Kansas City Cardiomyopathy Questionnaire Scores

Background: It is often difficult to measure the benefits of innovative changes in healthcare delivery. Beyond merely quantifying improved adherence to heart failure (HF) guidelines, we sought to define the merits of an advanced practice nurse (APN)-led HF clinic from the perspective of patient (pt)-centered outcomes. Methods: NYHA class 2-4 HF pts referred to an APN-led HF clinic completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) at the time of enrollment and 3 months later. Results: 124 pts (64% Caucasians; 35% African Americans; 39% women; mean age 65.1 ± 15.1 yrs; mean LVEF 29.9 ± 10.4%) completed 2 KCCQs.

Compliance with Once Daily Controlled Release vs Twice Daily Immediate Release Carvedilol in Patients with Heart Failure: The CASPER Trial

Background: Once daily (QD) vs twice daily (BID) dosing may increase compliance, thereby increasing effective daily dosage. The CASPER Trial was designed to measure differential compliance, quality of life (QOL) and satisfaction with medication in chronic heart failure (HF) patients taking BID carvedilol immediate release (Carv IR) vs bioequivalent QD Carv controlled release (CR). Methods: HF pts with LV EF < 40% on > 2 mos stable Carv IR BID were randomized to either group A: staying on Carv IR BID double blind, group B: switched to equivalent dose carv CR in AM and placebo in PM, double blind, or Group C: switched to open label equivalent dose carv CR QD.

Anemia in Advanced Heart Failure Is Due to Iron Deficiency and Malnutrition and It Is Associated with Worse Prognosis

Objective: This study sought to investigate the incidence of anemia and its possible impact on mortality in a population with extremely advanced heart failure (HF). Methods: We studied 343 patients (pts) with advanced HF (NYHA class III/IV, mean age 51.8 years, male 72.3% male), hospitalized for compensation and followed after discharge. Pts were submitted to clinical, laboratory and echocardiographyc evaluation. Iron and transderin dosage were performed in a group of 91 pts. Pts were divided into two groups: anemic (hemoglobin = < 12 g%) and non-anemic. These groups were compared through Mann-Whitney U-test for the continuous variables and qui-square test for the categorical variables. Mortality was analyzed stratifying the population in intervals of 1 g of Hb. Results: During hospitalization this extremely ill population presented a mortality of 53.6% in the first year of follow-up. Anemia was detected in 72 (20.9%) pts. In the comparison of the 2 groups, anemic pts were more lean (57.9 vs 63.3 kg; p = 0.027), presented lower albumin levels (3.28 vs 3.61 mg/dl; p = 0.001), with no difference in the degree of cardiac compromise and renal function (1.5 vs 1.5 mg/dl). Anemic pts had lower iron plasmatic levels (30.9 vs 63.9 mg/dl; p < 0.001), with no difference in transferrin levels. During the follow-up pts with Hb between 12 and 13 g% presented the lower mortality. The presence of anemia or polyglobulia was associated with greater mortality. Hb levels of 10.5 g% stratify significantly the population in those with better and worse prognosis. Conclusions: The presence of anemia in HF pts was associated with worse prognosis. Anemic pts had more frequently malnutrition and iron deficiency. The degree of left ventricular dysfunction and renal insufficiency did not show any correlation with the presence of anemia.

AB7-4: Biventricular pacing allows maintenance of sinus rhythm in patients with persistent atrial fibrillation

Bivententricular (BiV) pacing improves heart failure (HF) symptoms and survival in patients (pts) with left ventricular (LV) ejection fraction ≤35%, NYHA Class 3 or 4 HF, and QRS duration >120 ms. AF is common in HF pts. BiV pacing has been found to be more effective in pts in sinus rhythm (SR) vs. atrial fibrillation (AF). Many pts referred for BiV pacing have persistent AF, and attempts to restore sinus rhythm have been abandoned. We placed an atrial lead and attempted cardioversion in pts with persistent AF referred for BiV pacing.

Cardiac resynchronisation therapy in sinus rythm heart failure patients using a vdd lead

Purpose of study Single-lead VDD pacing has shown a reduction in operating time and complications compared to the DDD mode. The objective of our study was to evaluate in sinus rhythm (SR) heart failure pts the interest and limits of a simplified CRT procedure with 2 leads, one VDD and one left ventricle (LV). Methods used Over a 1-year period (May 2002-May 2003), 8 consecutive heart failure pts (1/3 of CRT during the period) in SR, received CRT by the implant of a Medtronic InSync 8042 pacemaker with a Medtronic 5038 VDD lead and an LV lead chosen after per-operative coronary sinus angiography. Summary of results The 8 pts (average age 68±9 years, 5 male) were NYHA class III (3 pts) or IV (5 pts) ; the ejection fraction was 25±3 %. Six pts were primo-implants; 2 pts had VDD pacemakers for 3-7 years, upgraded by the addition of an LV lead. A right approach was used for the 2 upgraded pts and a left approach for the 6 others. There was 1 sub-clavian venous puncture for each implanted lead. The VDD lead was positioned at the right ventricular (RV) apex; sensing (p = 1,9±1,3 mV, R= 17±5,4 mV) and RV threshold (0,5±0,2 V) values were deemed satisfactory. All 8 LV leads were Medtronic 4193 placed in LV lateral veins. Mean implant duration was 133±27 mn versus 147±37 mn for a 3-lead CRT. No implant-related complication occured. 1 pt died of non-cardiac causes at M8; after an average 25 (19-31) months of follow-up, 7 pts are still living, 2 in NYHA class III, 5 in class II. Conclusion In heart failure patients without sinus dysfunction, 2-lead CRT with one VDD lead is achievable. With good atrial sensing, the procedure is simplified thus sparing venous capital and reducing implantation times in these fragile patients.

Right ventricular apical pacing in patients with previous left bundle brunch block

The aim of the study was to compare the functional effects of right ventricular apical pacing (RVAP) with spontaneous ventricular activation in heart failure patients with and without LBBB. Methods 12 patients (mean age 65 ± 9, 5 women, NYHA 2–3, DDD pacemakers implanted for brady-arrythmias) devided in two group. Group I consisted of 6 heart failure patients with LBBB. Group II consisted of 6 heart failure patients without LBBB. Age, gender, NYHA class, pacemaker indication, RR interval, AV delay, diagnosis, LV size were similiar in the two groups. All patients underwent Echo Doppler examination before and after 29±4 days of continuous RVAP. The following parametars were measured: electromechanical delay (EMD) – the time from ventricular spike during RVAP or the onset of QRS to the onset of contraction of the last activated LV segment (posterior wall); Interventricular contraction delay (IVCD) – as the time between onset of aortic and pulmonary flow; LV diastolic filling duration, preejection time and ejection time. Results Group I: RVAP was associated with no significant difference in QRS width (148±24 vs 139±31ms, NS), significant shortening of EMD (170±11 vs 179±22ms, p 0.05), significant longer EMD (129±14 vs 98±10 ms, p<0.05), significant longer IVCD (61±20 vs 17±8ms p<0.01); LV filling time was shorter (324±61 vs 357±61 ms, p<0.05). Preejection time and ejection time showed no significant difference. Conclusion RVAP can reduce the degree of LV asynchrony in heart failure pts with LBBB, while in heart failure pts without LBBB, RVAP worsening LV perfomance and induced higher degree of interventricular desynchronization. In pts with reduced LV function the RVAP should be minimal or CRT should be considered.

Long-term outcome of heart failure patients treated with cardiac resynchronization therapy: A comparison between diabetic and non-diabetic patients

Background: Cardiac resynchronization therapy (CRT) is able to improve symptoms, functional capacity and prognosis of patients (pts) with advanced heart failure (HF). Data on long-term outcome of diabetic (D) and non-diabetic (ND) advanced HF pts treated with CRT are still lacking.

Fluid accumulation status trial (FAST)

Introduction: Pts with severe heart failure (HF) on optimal drug and CRTD therapy are still at risk of decomp. and thoracic fluid overload (F/O) events, thus the assessment of cardiopulmonary hemodynamics and thoracic fluid are routinely required. The ability of an implantable device to continuously monitor fluid status could be a valuable adjunct to existing tools used to assess the status of HF pts.

Synchronized biventricular pacing after av node ablation in CHF patients

Background atrioventricular junctional (AVJ) ablation with PM implantation has been shown to improve quality of life (QoL) in selected patients(pts) with drug resistant atrial fibrillation (AF). However,after the procedure,some pts worsen because of asinchronous ventricular stimulation. History during the last 9 years,among 1986 pts who referred to our Institution for AF, 28 pts underwent ablate and pace procedure by right ventricular single lead.The long term follow up(FU) of 36 months demonstrated an improvement of QoL in all but 4 pts who developed a progressive, irreversible heart failure. Methods from january 2001 to july 2002, 12 consecutive pts (6F,6M of mean age of 70.2 years) with dilated cardiomyopathy and chronic, non controlled high rate AF, were recruited. Eight pts had chronic persistant AF and 4 pts had chronic paroxismal AF. After AVJ ablation, a biventricular device was implanted : Medtronic Insync in 9 pts and Insync biventricular ICD in 3 pts. The NYHA functional class, the QRS duration, the mean heart rate, left ventricular ejection fraction (LVEF) and LV end diastolic dyameter (LVEDD) by 2D echocardiography, 6 minutes walking test(6'WT), the score of Minnesota questionnaire and the score of palpitation symptoms were evaluated at baseline and at 1, 3, 6 and 12 months FU in every pts. Results the mean FU was 7.2+/− 4 months.The results have been quite terrific as shown as follow. One pt,3 months after the procedure, in spite of wide clinical improvements, died suddenly on ecg Holter monitoring that demonstrated a ventricular fibrillation as the cause of death. In pts with paoxismal AF, a trend of reduction of numbers and duration of episodes of AF was observed. View this table: Conclusions these results demonstrated that the AVJ ablation combined with biventricular pacing is an effective tecnique to improve QoL in AF in congestive heart failure pts, mostly by relief of symptoms of palpitations and by means of the resinchronization therapy. The clinical results are not correlated to the QRS duration and to the LVEDD.Also the number of episodes of paroxismal AF seems to be lowered by the resnchronization therapy.However, life threatening ventricular arrhythmias have to be considered in pts without previous episodes.

All-cause mortality and heart failure hospitalization event rates observed with cardiac resynchronization therapy with defibrillation in NYHA class I/II heart failure

Introduction: Previous studies of cardiac resynchronization therapy with defibrillation (CRT-D) have focused on the treatment of heart failure (HF) in patients (pts) with moderate to severe HF (ModSev HF, NYHA Class III/IV) with relatively little focus on mild HF (Mild HF, NYHA Class I/II). The event rates of all-cause mortality (ACM) and HF hospitalization (HFH) of CRT-D recipients with Mild HF is expected to be less than that for ModSev HF, but these have not been previously quantified in this pt population. Methods: The CONTAK CD study database was analyzed retrospectively for ACM and HFH. All pts were indicated for a defibrillator, had QRS=120 ms, and were NYHA II-IV at the time of enrollment. Following a 30-day post-implant recovery period, pts were randomized to CRT or No CRT. Pts were stratified into two populations (Mild HF and ModSev HF) and HFH was analyzed over a six-month period and ACM over a two-year period. The hazard ratio (HR) was calculated for each to determine the risk of that event associated with each cohort. Results: Of 490 pts randomized, 263 (54%) were in Mild HF and 227 (46%) were in ModSev HF. HFH events were reported in 21 (8%) Mild HF pts and 50 (22%) ModSev HF pts during six months of follow-up. ACM was reported in 89 (34%) Mild HF pts and 125 (55%) ModSev pts during two years of follow-up. Both event rates were significantly lower in Mild HF as quantified in the table below. Conclusions: When compared to studies of NYHA Class III/IV pts, heart failure hospitalization and all-cause mortality rates are significantly lower in NYHA Class I/II pts by approximately 50-60%. Future trials of CRT-D in Mild HF pts using these outcomes as endpoints will likely require larger sample sizes and/or longer follow-up durations than those used in ModSev HF in order to demonstrate clinically meaningful improvements.All-cause Mortality Event RateHF Hospitalization Event RateTimeClass I/IIClass III/IVClass I/IIClass III/IV6 months1%9%11%25%1 year3%19%N/AN/A2 years11%31%N/AN/AHazard Ratio0.47 [95% CI (0.35.63), p<0.0001]0.41 [95% CI (0.25, 0.63), p<0.01]

The effect of glycemic control on heart failure severity in diabetics

Introduction: Glycosylated hemoglobin (Hb A1c) is an index of metabolic control in diabetes (D). Recent studies suggest that poor glycemic control in diabetic patients (pts) indicated by elevated Hb A1c levels (>7.0%) may be associated with increased risk of heart failure (HF). Our goal was to investigate the association between Hb A1c level and severity of HF in advanced HF pts with D. Methods: Among 180 pts referred for cardiac transplantation, 35 consecutive patients with advanced HF and D underwent evaluation with serum glucose, serum creatinine, Hb A1c, B-type natriuretic peptide (BNP), cardiopulmonary exercise testing and right heart catheterizaton. Pts were divided into two groups based on Hb A1c7% (Group A, mean Hb A1c=5.9±0.8) and Hb A1c >7% (Group B, mean Hb A1c=10.1±2.4). Results:∗Parameter (mean value)Hb A1c ≤7% (Group A: n=19)Hb A1c >7% (Group B: n=16)p valueAge (years)53.9±13.149.6±13.30.34Gender (male %)79690.70NYHA Class2.9±0.83.9±0.90.43Peak Oxygen Consumption (V02) ml/kg/minute16.2±2.214.5±3.40.25BNP (pg/ml)399.6±281.1754.8±696.40.05∗Pulmonary capillary wedge (PCW) pressure (mm Hg)22.2±8.026.2±8.50.24Glucose (mg/dl)141±75217±1190.03∗Creatinine (mg/dl)1.4±0.51.4±0.40.88BMI26.5±7.927.9±6.30.57% on Insulin9130.09∗p ≤ 0.05 Conclusion: BNP level was significantly elevated in diabetic pts with Hb A1c >7% (Group B). Glucose level was significantly higher in Group B. In Group B pts compared to Group A there was also a trend towards increased severity of symptoms demonstrated by worse NYHA class, lower peak VO2 and higher PCW pressure. Poor glycemic control in HF pts appears to have negative impact on functional capacity and severity of symptoms. Persistent glucose intolerance as shown by elevated Hb A1c>7% may be contributing to increased fluid retention reflected by higher PCW pressure and significantly higher BNP level in Group B compared to Group A pts. The effect of improved glycemic control on clinical outcomes such as frequency of hospitalization and survival in advanced HF pts with D deserves further study.

Treatment patterns in patients with heart failure and anemia: is there a bias?

Anemia in heart failure (HF) patients (pts), defined as hemoglobin (Hb)<12 g/dL, is often sub-optimally evaluated and inconsistently treated. In an effort to define Health Care Providers (HCP) awareness and quantitate perceived thresholds for anemia treatment in HF pts, approximately 300 surveys that addressed the treatment patterns for patients with heart failure, anemia and other conditions were distributed during the 7th Annual Scientific Meeting of the Heart Failure Society of America in September 2003. A total of 155 surveys were completed, with a response rate 52%. HCP consisted of 102 physicians (66%) and 53 advanced practice professionals (34%). The survey contained 21 questions of which 10 were specific to the importance of anemia in HF pts. The survey queried the threshold of blood transfusion as well as the initiation and comfort level of utilizing an erythropoietic agent (EPO). As anemia may be associated with cancer and its treatment, the survey also addressed the extent of the HCP willingness to provide cardiovascular intervention to cancer pts. Results: Anemia was perceived as important or very important in 137 (88%) of respondents. With regard to prescribing an EPO agent, 117 (78%) were comfortable or very comfortable. The blood transfusion threshold was Hb≤8 g/dL in 102 (67%) and the EPO agent threshold was Hb≤10 g/dL in 88 (57%) of respondents. The majority of HCP were comfortable prescribing transfusions (n=89, 57%), EPO agent (n=109, 70%) and/or iron therapy (n=133, 85%). HCP believed anemia occurred in HF pts more than 11% of the time (n=123,79%), and 124 (80%) perceived anemia was important for prognosis. However, only 101 (65%) of HCP check Hb routinely. HPC who perceived anemia as very important and were comfortable prescribing an EPO agent were more likely to check Hb and initiate an EPO agent at higher Hb levels (p<0.01). Surprisingly, HCP are reluctant to utilize cardiac intervention according to treatment guidelines in eligible cancer pts. Furthermore HPC who are comfortable prescribing an EPO agent were more likely to adhere to these guidelines (p<0.01). Conclusions: The majority of HCP perceived anemia in heart failure as important, and were comfortable prescribing an EPO agent. However, greater than 30% seldom or never check hemoglobin. HPC who are comfortable prescribing an EPO agent were more likely to check hemoglobin and initiate EPO therapy. Patients with cancer as a comorbidity may not be treated with cardiac intervention using the same rigor as the guidelines suggest.

Device-Based Intra-Thoracic Impedance Correlates with Fluid Status and Provides Automated Prediction of CHF Hospitalization

Introduction: 65% of current ICD and all CRT patients (pts) suffer from heart failure (HF). New trial data suggests a large number of new HF pts may also benefit from ICD therapies. Many pts have repeated hospitalizations due to fluid overload. There is a significant clinical need for implantable devices to also offer ambulatory diagnostic information to help guide HF medical therapies and reduce hospitalization. The MIDHeFT study investigated the ability of intra-thoracic impedance (Z) from the implanted device to monitor pulmonary fluid overload and predict CHF admission. Methods: Thirty-three HF pts in NYHA functional class III-IV were implanted with a special pacemaker in the left pectoral region and an ICD lead in the right ventricle (RV). Z was measured between the RV electrodes and the pacemaker case. During HF hospitalizations, pulmonary capillary wedge pressure (PCWP) and fluid status were carefully measured. The emergency room (ER) records were reviewed for self-reported onset time of worsening HF symptoms prior to ER visit. Retrospectively, an automated algorithm to detect impending admission from changes in Z was developed and performance was evaluated. Results: During a mean follow-up of 20±8.4 months, 11 pts had a total of 26 hospitalizations for worsening HF and with available Z data, including 25 due to congestion and one due to dehydration. In all congestive episodes, Z gradually decreased before admission, over a mean duration of 13.5±8.1 days (p<0.0001) and with a mean reduction of 11.4±5.9% (p<0.0001). For the 19 admissions with available symptom onset data, the decline in Z also preceded the symptom onset by a mean lead-time of 11.2±7.9 days (p<0.0001). During hospitalization, Z correlated with PCWP and volume status with r=−0.61 (p<0.001) and r=−0.70 (p<0.001), respectively. Using a single threshold for all pts, the algorithm detected 76% of the eligible congestive admissions with a median of 17 days of early warning. One false warning occurred for every 322 days of pt monitoring. During 3 days before the admission due to dehydration, Z increased 8%. Conclusions: Intra-thoracic impedance from the implanted device correlates well with PCWP and fluid status, and predicts CHF hospitalization with a high sensitivity and low false alarm rate. When combined with ways to notify patients and/or clinicians, an “early warning” system may allow early initiation of medical therapy and prevent ER visits and HF hospitalizations.

An embolic event contributes to death in 2/3 of patients with idiopathic dilated cardiomyopathy in end stage heart failure

Background: Patients (pts) with idiopathic dilated cardiomyopathy (IDC) and end stage heart failure have a worse prognosis with high mortality. Embolic events (EE) could contribute to this poor prognosis. Objective: To clarify the importance of EE in the evolution of pts with IDC, we analyzed the data from necropsies of heart failure pts who died at the hospital during ten years. Methods: Between 1990 and 1999, 3847 necropsies were performed and 118 pts had IDC. The pts' mean age was 41.8 years and 74 (62.7%) were male.

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

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