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Statins shorten QTc interval without affecting plasma BNP levels in patients with advanced heart failure
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Abstracts
79 SUCCESSFUL IMPLEMENTATION OF HEART FAILURE SELF MANAGEMENT TOOLS IMPROVES SURVIVAL J.A. Hall,1,2 K.D. Rasmusson,1,2 T.K. French,1 A.G. Kfoury,1,2 L.C. Hofmann,1 D.G. Renlund,1,2,3 1Heart Failure Prevention and Treatment Program, LDS Hospital, Salt Lake City, UT; 2UTAH Cardiac Transplant Program, LDS Hospital, Salt Lake City, UT; 3 Division of Cardiology, University of Utah Health Science Center, Salt Lake City, UT Background: In 2002, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) mandated that hospitalized heart failure (HF) patients (pts) receive self-management instruction (SMI) before discharge. SMI was implemented in a 20-hospital, non-profit, integrated health care system and tracked by an electronic data system. We hypothesized that hospital-based SMI could be implemented successfully leading to improved outcomes. Methods: An SMI tool called MAWDS© was developed that focused on HF instructions and monitoring of pt medications, activity, weight, diet, symptoms and when to call a provider for assistance. Providers and nurses were trained on the use of the tool, then nurses began formal SMI and tool delivery to hospitalized HF pts. Results: 745 pts who had documented formal MAWDS© instruction and a comparison cohort of 1,041 pts without documented SMI of any kind were tracked for 2 years after discharge. After adjustments for age, length of stay, severity of illness, and gender, a survival benefit was observed (p⫽0.0002, RR⫽0.66) in pts that received MAWDS©based SMI.
The Journal of Heart and Lung Transplantation February 2005
either therapy with eight grams of n-3 fatty acids (Group A; n⫽7) or placebo (Group B; n⫽7) for 18 weeks. Fifty-seven percent of the study population was cachectic by anthropometric assessment. TNFalpha and interleukin-1 (IL-1) production were measured by radioimmunoassay following endotoxin stimulation of peripheralblood mononuclear cells. Results: Placebo treated patients demonstrated a 44% rise in TNFalpha (1.28 pg/ml to 1.84 pg/ml; p⫽0.07) and no significant change in IL-1 (0.68 pg/ml to 0.78 pg/ml) production during the study period. However, supplementation with n-3 fatty acids resulted in a 59% reduction in TNFalpha (1.64 pg/ml to 0.68 pg/ml; p⫽0.02) and a 39% decrease in IL-1 (1.98 pg/ml to 1.21 pg/ml; p⫽0.09) production. There was also a strong inverse correlation found between change in TNFalpha production and change in percent body fat (r ⫽ ⫺0.6; p⫽ 0.02).
Conclusion: Fish oils (n-3 fatty acids) exert anti-inflammatory effects in severe heart failure by decreasing TNFalpha production. This modulation of TNFalpha with fish oils is associated with changes in body composition, which may have important therapeutic implications in the setting of late stage heart failure. 81 Conclusion: Implementing a program that addresses the SMI mandate from JCAHO is a challenge to hospital systems. However, it appears to improve survival in pts discharged after an HF hospitalization. Success factors may include: designing an effective HF SMI tool, educating providers and staff, setting reasonable goals for implementation, and developing a tracking system to monitor documented HF education.
80 FISH OILS IMPROVE BODY COMPOSITION IN CARDIAC CACHEXIA BY THEIR ANTI-INFLAMMATORY EFFECTS R.V. Milani,1 M.R. Mehra,1 H.O. Ventura,1 C.J. Lavie,1 P.A. Uber,1 R.L. Scott,1 M.H. Park,1 1Cardiomyopathy and Heart Transplantation, Ochsner Clinic Foundation, New Orleans, LA Background: TNFalpha is implicated to play an important role in heart failure with resultant cardiac cachexia. N-3 fatty acids have been shown to reduce production of TNFalpha in healthy subjects; however, their potential impact in a clinical syndrome where TNFalpha is presumed to play a pathophysiologic role has not been previously investigated. Methods: Fourteen patients with stable severe heart failure (NYHA III-IV, LVEF 0.17) were enrolled in a randomized, double-blind trial to
STATINS SHORTEN QTC INTERVAL WITHOUT AFFECTING PLASMA BNP LEVELS IN PATIENTS WITH ADVANCED HEART FAILURE B. Vrtovec,1 R. Okrajsek,1 A. Golicnik,1 M. Ferjan,1 P.V. Juarez,2 B. Radovancevic,2 1Division of Cardiology, Ljubljana University Medical Center, Ljubljana, Slovenia; 2Transplant Research, Texas Heart Institute, Houston, TX Background: QTc interval and BNP levels predict outcomes of patients with heart failure (HF). Since statin therapy appears to improve survival in HF, we analyzed the effect of statins on QTc interval and BNP levels in these patients. Methods: A prospective randomized trial included 80 patients with advanced HF (NYHA 3 or 4), low LVEF (⬍30%), and plasma cholesterol ⬎5 mmol/l. Forty patients underwent statin therapy (atorvastatin 10 mg/day) (statin group); the remaining 40 patients served as controls. We measured QTc interval and BNP levels at baseline and at 3 months. QT interval was determined by averaging 3 consecutive beats in ECG leads II and V4, and corrected with the Bazett formula. Results: Overall 3-month mortality was 5% (3% in the statin group vs. 8% in the controls, P⫽0.30). The groups did not differ in age (66⫾16 years in the statin group vs. 68⫾8 years in the controls, P⫽0.52), male gender (56% vs. 51%, P⫽0.66), ischemic etiology (56% vs. 68%, P⫽0.32), or LVEF (24.0⫾4.9% vs. 24.2⫾3.9%, P⫽0.88). At baseline,
The Journal of Heart and Lung Transplantation Volume 24, Number 2S
QTc interval was similar in both groups (450⫾30 msec in the statin group vs. 446 ⫾ 27 msec in controls, P⫽0.59). After 3 months, QTc interval decreased in the statin group (436⫾29 msec, P⫽0.0003), but not in controls (450⫾25 msec). QTc interval shortening with statin therapy was more pronounced in patients with a baseline QTc interval ⬎440 msec (from 470⫾21 msec at baseline to 450⫾26 msec at 3 months, P⫽0.0001), and in patients with non-ischemic HF (from 452⫾32 msec at baseline to 435⫾28 at 3 months, P⫽0.004). BNP levels at baseline were comparable in both groups (713⫾303 pg/ml in statin group vs. 791⫾271 pg/ml in controls, P⫽0.25) and remained unchanged after 3 months (695⫾340 pg/ml vs. 809⫾331 pg/ml, P⫽0.13). Conclusions: Statins shorten QTc interval, but do not change BNP levels in advanced HF. Statin therapy may be of particular benefit to patients with non-ischemic HF and a prolonged QTc interval. 82 IN THE LONG TERM HEART TRANSPLANTATION PROVIDES ADDITIONAL BENEFIT IN TRANSPLANT CANDIDATES WITH UPTITRATED ACE-INHIBITOR- AND -BLOCKER-THERAPY B. Meyer,1 D. Moertl,1 M. Huelsmann,1 R. Pacher,1 R. Berger,1 1 Department of Cardiology, Medical University of Vienna, Vienna, Austria Background: We recently demonstrated that in heart transplantation (HTx) candidates who tolerate uptitration of ACE-inhibitors and -blockers, HTx does not seem to provide additional survival benefit in the short term (2 years). The aim of this study was to compare the outcome of these HTx candidates (treated with combined ACE-I and -blockers) with patients post HTx in the long-term. Methods: Three hundred and eighteen patients (NYHA class III or IV, LVEF 16⫾7%, cardiac index 2.2L/min. m2 at time of referral) were treated with digitalis, loop diuretics, maximally uptitrated RAASantagonists, and -blockers (as tolerated), and intravenous support (if needed). Patients were retrospectively stratified according to their medical therapy 3 months after referral into those receiving -blockers plus ACE-I (Group A, n⫽126), ACE-I (Group B, n⫽135), ACE-I plus intravenous support (Group C, n⫽57). Patients who underwent HTx within 3 years after study-start formed Group D (n⫽70). During an observation period of six to nine years outcome was documented. Results: One hundred and fifteen patients (36%) survived without HTX, 89 patients (28%) underwent HTx, and 114 patients (36%) died. In Group A 65 patients (52%) survived without HTX, 18 patients (14%) underwent HTx, and 43 patients (34%) died. In Group D 17 patients (21%) died after HTx. Using the endpoint death or HTx in Group A and death in Group D, Kaplan Meier analysis revealed a significant difference between groups in favour of Group D (p⬍0.005). Using the endpoint death in Group A (excluding patients who underwent HTx) and Group D, Kaplan Meier demonstrated a clear trend between groups in favour of Group D (p⫽0.07). Conclusion: Not in the short term (2 years) but in the long term (⬎6 years) HTx seems to provide additional survival benefit in HTx candidates who tolerate uptitration of ACE-I and -blockers. 83 SHOULD UNOS STATUS 2 PATIENTS BE TRANSPLANTED? N.R. Shah,1 G.A. Ewald,2 D.A. Horstmanshof,2 E.M. Geltman,2 S.L. Moorhead,2 N. Moazami,1 1Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO; 2Cardiology, Washington University School of Medicine, St. Louis, MO Introduction: With recent improvements in medical and device therapy, the benefit of cardiac transplantation for UNOS status 2 patients has been questioned. To date, no randomized trial has been performed to compare transplantation versus contemporary medical therapy.
Abstracts
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Methods: Between January, 1996 and December, 2003, 203 patients were listed at our institution for heart transplantation as UNOS status 2. We performed a retrospective review to determine outcomes in these patients. Results: Demographics of this cohort revealed a mean age of 52 years, female gender in 28%, and ischemic etiology in 48%. 81 (40%) patients had an AICD. A total of 66 (33%) patients had to be upgraded in their UNOS status (24 to status 1, 8 to status 1A, 37 to status 1B), with 9 requiring a VAD. 95 (47%) patients received an allograft at a mean time of 303 days on the waiting list. 45 (22%) patients died while waiting for a suitable allograft at a mean time of 397 days. 26 (13%) patients were removed from the waiting list due to improved condition at a mean time of 1112 days. The remaining patients continue to wait for a transplant or have been removed from consideration due to concomitant illness. Survival at 1- and 3-years post listing was 94% and 87% respectively for transplanted patients compared to 81% and 57% for non-transplanted patients. (p⬍0.01). Conclusion: A significant number of patients originally listed for heart transplantation as status 2 are upgraded in UNOS status or die while on the waiting list. Early and mid-term survival is significantly better with transplantation. Identification of variables associated with deterioration versus stability in status 2 patients may allow better risk stratification in the future; however, at this point, transplantation offers the best outcome. 84 HLA-DR MATCHING IMPROVES SURVIVAL AFTER HEART TRANSPLANTATION-IS IT TIME TO CHANGE ALLOCATION POLICIES? I. Kaczmarek,1 P. Landwehr,1 J. Groetzner,1 B. Meiser,1 U. Peter,1 B. Reichart,1 1Cardiac Surgery, LMU Munich, Grosshadern University Hospital, Munich, Germany Background: HLA matching has improved outcome in kidney transplantation but is not considered in current allocation policies in heart transplantation. This study analyses the impact of HLA matching on long-term outcome after heart transplantation. Methods: The records of 240 consecutive heart transplant recipients (1995–2003, mean age 51.8 ⫾ 11.7 years, mean follow-up 5.9 ⫾ 1.8 years) were analyzed retrospectively. According to the renal allocation policy HLA mismatches (MM) on the loci HLA-A, HLA-B and
Abstracts
79 SUCCESSFUL IMPLEMENTATION OF HEART FAILURE SELF MANAGEMENT TOOLS IMPROVES SURVIVAL J.A. Hall,1,2 K.D. Rasmusson,1,2 T.K. French,1 A.G. Kfoury,1,2 L.C. Hofmann,1 D.G. Renlund,1,2,3 1Heart Failure Prevention and Treatment Program, LDS Hospital, Salt Lake City, UT; 2UTAH Cardiac Transplant Program, LDS Hospital, Salt Lake City, UT; 3 Division of Cardiology, University of Utah Health Science Center, Salt Lake City, UT Background: In 2002, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) mandated that hospitalized heart failure (HF) patients (pts) receive self-management instruction (SMI) before discharge. SMI was implemented in a 20-hospital, non-profit, integrated health care system and tracked by an electronic data system. We hypothesized that hospital-based SMI could be implemented successfully leading to improved outcomes. Methods: An SMI tool called MAWDS© was developed that focused on HF instructions and monitoring of pt medications, activity, weight, diet, symptoms and when to call a provider for assistance. Providers and nurses were trained on the use of the tool, then nurses began formal SMI and tool delivery to hospitalized HF pts. Results: 745 pts who had documented formal MAWDS© instruction and a comparison cohort of 1,041 pts without documented SMI of any kind were tracked for 2 years after discharge. After adjustments for age, length of stay, severity of illness, and gender, a survival benefit was observed (p⫽0.0002, RR⫽0.66) in pts that received MAWDS©based SMI.
The Journal of Heart and Lung Transplantation February 2005
either therapy with eight grams of n-3 fatty acids (Group A; n⫽7) or placebo (Group B; n⫽7) for 18 weeks. Fifty-seven percent of the study population was cachectic by anthropometric assessment. TNFalpha and interleukin-1 (IL-1) production were measured by radioimmunoassay following endotoxin stimulation of peripheralblood mononuclear cells. Results: Placebo treated patients demonstrated a 44% rise in TNFalpha (1.28 pg/ml to 1.84 pg/ml; p⫽0.07) and no significant change in IL-1 (0.68 pg/ml to 0.78 pg/ml) production during the study period. However, supplementation with n-3 fatty acids resulted in a 59% reduction in TNFalpha (1.64 pg/ml to 0.68 pg/ml; p⫽0.02) and a 39% decrease in IL-1 (1.98 pg/ml to 1.21 pg/ml; p⫽0.09) production. There was also a strong inverse correlation found between change in TNFalpha production and change in percent body fat (r ⫽ ⫺0.6; p⫽ 0.02).
Conclusion: Fish oils (n-3 fatty acids) exert anti-inflammatory effects in severe heart failure by decreasing TNFalpha production. This modulation of TNFalpha with fish oils is associated with changes in body composition, which may have important therapeutic implications in the setting of late stage heart failure. 81 Conclusion: Implementing a program that addresses the SMI mandate from JCAHO is a challenge to hospital systems. However, it appears to improve survival in pts discharged after an HF hospitalization. Success factors may include: designing an effective HF SMI tool, educating providers and staff, setting reasonable goals for implementation, and developing a tracking system to monitor documented HF education.
80 FISH OILS IMPROVE BODY COMPOSITION IN CARDIAC CACHEXIA BY THEIR ANTI-INFLAMMATORY EFFECTS R.V. Milani,1 M.R. Mehra,1 H.O. Ventura,1 C.J. Lavie,1 P.A. Uber,1 R.L. Scott,1 M.H. Park,1 1Cardiomyopathy and Heart Transplantation, Ochsner Clinic Foundation, New Orleans, LA Background: TNFalpha is implicated to play an important role in heart failure with resultant cardiac cachexia. N-3 fatty acids have been shown to reduce production of TNFalpha in healthy subjects; however, their potential impact in a clinical syndrome where TNFalpha is presumed to play a pathophysiologic role has not been previously investigated. Methods: Fourteen patients with stable severe heart failure (NYHA III-IV, LVEF 0.17) were enrolled in a randomized, double-blind trial to
STATINS SHORTEN QTC INTERVAL WITHOUT AFFECTING PLASMA BNP LEVELS IN PATIENTS WITH ADVANCED HEART FAILURE B. Vrtovec,1 R. Okrajsek,1 A. Golicnik,1 M. Ferjan,1 P.V. Juarez,2 B. Radovancevic,2 1Division of Cardiology, Ljubljana University Medical Center, Ljubljana, Slovenia; 2Transplant Research, Texas Heart Institute, Houston, TX Background: QTc interval and BNP levels predict outcomes of patients with heart failure (HF). Since statin therapy appears to improve survival in HF, we analyzed the effect of statins on QTc interval and BNP levels in these patients. Methods: A prospective randomized trial included 80 patients with advanced HF (NYHA 3 or 4), low LVEF (⬍30%), and plasma cholesterol ⬎5 mmol/l. Forty patients underwent statin therapy (atorvastatin 10 mg/day) (statin group); the remaining 40 patients served as controls. We measured QTc interval and BNP levels at baseline and at 3 months. QT interval was determined by averaging 3 consecutive beats in ECG leads II and V4, and corrected with the Bazett formula. Results: Overall 3-month mortality was 5% (3% in the statin group vs. 8% in the controls, P⫽0.30). The groups did not differ in age (66⫾16 years in the statin group vs. 68⫾8 years in the controls, P⫽0.52), male gender (56% vs. 51%, P⫽0.66), ischemic etiology (56% vs. 68%, P⫽0.32), or LVEF (24.0⫾4.9% vs. 24.2⫾3.9%, P⫽0.88). At baseline,
The Journal of Heart and Lung Transplantation Volume 24, Number 2S
QTc interval was similar in both groups (450⫾30 msec in the statin group vs. 446 ⫾ 27 msec in controls, P⫽0.59). After 3 months, QTc interval decreased in the statin group (436⫾29 msec, P⫽0.0003), but not in controls (450⫾25 msec). QTc interval shortening with statin therapy was more pronounced in patients with a baseline QTc interval ⬎440 msec (from 470⫾21 msec at baseline to 450⫾26 msec at 3 months, P⫽0.0001), and in patients with non-ischemic HF (from 452⫾32 msec at baseline to 435⫾28 at 3 months, P⫽0.004). BNP levels at baseline were comparable in both groups (713⫾303 pg/ml in statin group vs. 791⫾271 pg/ml in controls, P⫽0.25) and remained unchanged after 3 months (695⫾340 pg/ml vs. 809⫾331 pg/ml, P⫽0.13). Conclusions: Statins shorten QTc interval, but do not change BNP levels in advanced HF. Statin therapy may be of particular benefit to patients with non-ischemic HF and a prolonged QTc interval. 82 IN THE LONG TERM HEART TRANSPLANTATION PROVIDES ADDITIONAL BENEFIT IN TRANSPLANT CANDIDATES WITH UPTITRATED ACE-INHIBITOR- AND -BLOCKER-THERAPY B. Meyer,1 D. Moertl,1 M. Huelsmann,1 R. Pacher,1 R. Berger,1 1 Department of Cardiology, Medical University of Vienna, Vienna, Austria Background: We recently demonstrated that in heart transplantation (HTx) candidates who tolerate uptitration of ACE-inhibitors and -blockers, HTx does not seem to provide additional survival benefit in the short term (2 years). The aim of this study was to compare the outcome of these HTx candidates (treated with combined ACE-I and -blockers) with patients post HTx in the long-term. Methods: Three hundred and eighteen patients (NYHA class III or IV, LVEF 16⫾7%, cardiac index 2.2L/min. m2 at time of referral) were treated with digitalis, loop diuretics, maximally uptitrated RAASantagonists, and -blockers (as tolerated), and intravenous support (if needed). Patients were retrospectively stratified according to their medical therapy 3 months after referral into those receiving -blockers plus ACE-I (Group A, n⫽126), ACE-I (Group B, n⫽135), ACE-I plus intravenous support (Group C, n⫽57). Patients who underwent HTx within 3 years after study-start formed Group D (n⫽70). During an observation period of six to nine years outcome was documented. Results: One hundred and fifteen patients (36%) survived without HTX, 89 patients (28%) underwent HTx, and 114 patients (36%) died. In Group A 65 patients (52%) survived without HTX, 18 patients (14%) underwent HTx, and 43 patients (34%) died. In Group D 17 patients (21%) died after HTx. Using the endpoint death or HTx in Group A and death in Group D, Kaplan Meier analysis revealed a significant difference between groups in favour of Group D (p⬍0.005). Using the endpoint death in Group A (excluding patients who underwent HTx) and Group D, Kaplan Meier demonstrated a clear trend between groups in favour of Group D (p⫽0.07). Conclusion: Not in the short term (2 years) but in the long term (⬎6 years) HTx seems to provide additional survival benefit in HTx candidates who tolerate uptitration of ACE-I and -blockers. 83 SHOULD UNOS STATUS 2 PATIENTS BE TRANSPLANTED? N.R. Shah,1 G.A. Ewald,2 D.A. Horstmanshof,2 E.M. Geltman,2 S.L. Moorhead,2 N. Moazami,1 1Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO; 2Cardiology, Washington University School of Medicine, St. Louis, MO Introduction: With recent improvements in medical and device therapy, the benefit of cardiac transplantation for UNOS status 2 patients has been questioned. To date, no randomized trial has been performed to compare transplantation versus contemporary medical therapy.
Abstracts
S69
Methods: Between January, 1996 and December, 2003, 203 patients were listed at our institution for heart transplantation as UNOS status 2. We performed a retrospective review to determine outcomes in these patients. Results: Demographics of this cohort revealed a mean age of 52 years, female gender in 28%, and ischemic etiology in 48%. 81 (40%) patients had an AICD. A total of 66 (33%) patients had to be upgraded in their UNOS status (24 to status 1, 8 to status 1A, 37 to status 1B), with 9 requiring a VAD. 95 (47%) patients received an allograft at a mean time of 303 days on the waiting list. 45 (22%) patients died while waiting for a suitable allograft at a mean time of 397 days. 26 (13%) patients were removed from the waiting list due to improved condition at a mean time of 1112 days. The remaining patients continue to wait for a transplant or have been removed from consideration due to concomitant illness. Survival at 1- and 3-years post listing was 94% and 87% respectively for transplanted patients compared to 81% and 57% for non-transplanted patients. (p⬍0.01). Conclusion: A significant number of patients originally listed for heart transplantation as status 2 are upgraded in UNOS status or die while on the waiting list. Early and mid-term survival is significantly better with transplantation. Identification of variables associated with deterioration versus stability in status 2 patients may allow better risk stratification in the future; however, at this point, transplantation offers the best outcome. 84 HLA-DR MATCHING IMPROVES SURVIVAL AFTER HEART TRANSPLANTATION-IS IT TIME TO CHANGE ALLOCATION POLICIES? I. Kaczmarek,1 P. Landwehr,1 J. Groetzner,1 B. Meiser,1 U. Peter,1 B. Reichart,1 1Cardiac Surgery, LMU Munich, Grosshadern University Hospital, Munich, Germany Background: HLA matching has improved outcome in kidney transplantation but is not considered in current allocation policies in heart transplantation. This study analyses the impact of HLA matching on long-term outcome after heart transplantation. Methods: The records of 240 consecutive heart transplant recipients (1995–2003, mean age 51.8 ⫾ 11.7 years, mean follow-up 5.9 ⫾ 1.8 years) were analyzed retrospectively. According to the renal allocation policy HLA mismatches (MM) on the loci HLA-A, HLA-B and