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Acute pacing of the left ventricle is associated with largest hemodynamic improvement in PATH-CHF heart failure patients
Journal of Cardiac Failure Vol. 4 No. 3 Suppl. 1 1998
34
Clinical Trials/Heart Failure 126
125 T r e a t m e n t of I d i o p a t h i c Dilated C a r d i o m y o p a t h y b y l g G
Immunoadsorption Johannes MiJller, Gerd W a l l u k a t 1, Michael Dandel, H e i d r u n Bieda, Susanne Spiegelsberger, Manfred Hummel, Roland Hetzer, G e r m a n H e a r t Institute Berlin, Berlin, Germany; 1Max Delbr/ick Center, Berlin, G e r m a n y A causative therapy of idiopathic dilated cardiomyopathy (IDC) is not known. In 70% of pafients with IDC a pathological level of auto-antibodies directed against cardiac I]L-adrenoceptors(AAB) can be fotmd. We wanted to evaluate whether immmtmoadsorptian has a positive effect on cardiac function and dimension, i.e. left ventriculur ejection fraction (EF) and "left ventricular internal diameter in diastole (LVIDd). Thirty-four patients with IDC were derided into two groups (I,(2) of 17 patients eacK Both groups were not statistically different regarding the followingparameters: age, sex, NYHA class, EF, LVIDd, level of AAB arid drug therapy regarding cardiac insufficiency. After study recruitment all patients who were not on B-blocker medication received these additionally. After synchrodisafion of both groups, group I received irmnunoadsorption whereas group C was not treated. Two patients ont of group C were transplanted two and five months, respectively, after recruitment. The table shows the results one year after inlmunoadsorption as compared to the data at the begilming of the study. at l h e t i m e o f r e c r u i t m e n t E F [%1 group I
L~Dd
lmm]
alter one year
AAB [L~
E F [%1
LVIDd [mm]
AAB [LU]
38 • 8
64 i 6
not detectable 5 ± 1.0
22±3
75~7
6.0±1.4
24±3
76~6
4.7~1.0
(n-17) group C
25~-6
73:k7
(n=17)
(n=ls)
0~=ts)
P- v a l u e s
P <0.0001
P < O.00O3
(n-is) P
Imnmnoadsorption led to a significant improvement of cardiac function and dimension. AAB directed against cardiac Bx-receptors seem to be a suitable parameter to assessthe success of immunoadsurption. The reason why the cardiac function o.fthe control group also improved may be due to the positive effect of the B-blockertherapy.
Comparison of Patient's and Physician's Points of View on Quality of Life in Case of Congestive Heart Failure A n d r e a Gallina, Giuseppe Giacomarra, Antonio Previti, Marco Bobbio. Universitary Division of Cardiology - Molinette Hospital, Turin (Italy)
Although there is an increasing interest of physicians and investigators on the evaluation of quality of life, very few data are available on the physician's and patient's point of view. Our population includes 37 patients, 94.6% male and 54% with congestive heart failure. The patients, with stable congestive heart failure, before the visit and after 15 days filled in the Minnesota Living with Heart Failure Questionnaire (MQ) and the SF36 Questionnaire (SF) and performed a Six Minute Walk Test (6W). During both visits the same questionnaires were filled in by the cardiologist, blinded about the patient's answers. Between the first and the second visit, patients remained clinically stable and they did not need any therapy adjustment. In the follow-up visit after 15 days, patients did not show variation in the 6W (from 365 _+ 104 to 352 + 99 minutes) in total MQ score (from 39.8+ 23.5 to 38.4 + 20.2), and in physical activity estimated with SF (from 20.8 + 4.4 to 22.1 _+4.0), demonstrating a real clinical stability. The ~valuation of MQ by the physician was lower (more optimistic) than the one by the patients, either for the first (35.2_+ 21.6 vs 39.8 + 23.5; p = 0.034), or for the second evaluation (33.6 + 18.6 vs 38.4 + 20.3; p = 0.018). Physical activity evaluation with SF was not statistically significative between patients and physicians. in conclusion, as demonstrated in other pathologies, also in case of congestive heart failure, there is a trend by physicians to underestimate patient's symptoms. For those reason patients complain that often physicians pay poor attention to the severity their symptoms.
127
128
H i g h Diuretic Doses are Associated w i t h S u d d e n Death in Patients w i t h A d v a n c e d Heart Failure: The PRAISE Trial Gerald W. Neuberg, Chris M. O'Connor, Alan B. Miller, Robert N. Belkin, Peter E. Carson, Anne B. Cropp, David Frid, Regi Nye, Milton L. Pressler, John H. Wertheimer, Milton Packer for the PRAISE Investigators. Columbia University, N e w York, NY
Acute Pacing of the Left Ventricle is Associated w i t h Largest H e m o d y n a m i c I m p r o v e m e n t in PATH-CHF Heart Failure Patients Angelo Auricchio, Christoph Stellbrink, Michael Block, H e l m u t Klein (PATH-CHF Study Group, Div. Card., U. Hosp., Magdeburg, Germany); A n d r e w Kramer, Jiang Ding, Rod Salo, Bruce Tockman, Thierry Pochet, Julio Spinelli (CHF Res., Guidant/CPI, St. Paul, MN)
Diuretics are often necessary to correct and prevent fluid overload in patients with chronic CHF, but their effect on long-term outcome is unknown. The Prospective Amlodipine Survival Evaluation (PRAISE) enrolled 1153 patients with L V ejection fi'aetion < 30% and Class IIIb-IV CHF despite background therapy with digoxin, diuretics and ACE inhibitors. Almost all patients received a loop diuretic, with initial daily doses o f 10-480 nag o f furosemide (n=1038) and 0.5-12 nag ofbumetalfide (n=86). Over a median o f 14 months, there were 413 deaths (190 on amlodipine, 223 on placebo). We evaluated the relation o f background drug doses ("high" vs. ' l o w " dose = above vs. below median) and other baseline variables to cause-specific mortality as judged by the Endpoints Committee. By proportional hazards regression, high diuretic dose was an independent predictor o f sudden death (P=0.023) and total mortality (P--O.012), but not o f pump failure death. L o w ACE inhibitor dose was an independent predictor of pump failure death (p-M3.001 ) and total mortality (P=0.04), but not o f sudden death. Digoxin dose was not an independent predictor of mortality. The benefit of high ACE inhibitor dose is consistent with results o f randomized trials. The mortality risk associated with high diuretic dose does not prove causality, but could relate to known side effects (i.e. neurohormonal activation and electrolyte depletion). The selective risk of sudden death (but not other eanses of death) is suggestive o f a direct effect of diuretics and requires prospective study.
The role of pacing site and AV delay for treatment of congestive heart failure (CHF) with pacing is uncertain. We compared the effects of right (RV), left (LV), and right plus left (BV) ventricular pacing at different AV delays on the actlte hemodynamic function of CHF patients. Methods. Twenty-five pts in the PATH-CHF study (NYHA Class III/IV in sinus rhythm with QRS duration > 120ms) were tested at implant while catheterized with Millar micromanometers in the LV and aorta. Pts were acutely paced in VDD mode at RV, LV, or BV sites with 5 AV delays normalized by PR interval while max LV +dP/dt and aortic pulse pressure (PP) percentage changes from baseline were recorded during brief pacing/no-pacing sequences. Results. The LV +dP/dt or PP averaged over all AV delays increased significantly from baseline (p<.00t paired ttest) in 20/25 pts with LV or BV pacing and in 14/25 pts with RV pacing. Group means (+SE) of LV +dP/dt and PP plotted in the figures by pacing site varied significantly with AV delay (ANOVA p<.0001). Both parameters increased significantly more with BV and LV pacing compared to RV pacing, while LV +dP/dt increased more with LV than BV pacing (ANOVA/Tukey, p<.01), bat PP increases were statistically similar for LV and BV pacing.
o
zs a0 r, m ~,la r (%ot PR- sore n}
10o
0
2s a~ rs aVee~sy(~ orP~- 70ms)
1o0
Conclusions. Pacing site and AV delay combine to determine hemodynamic efficacy of acute pacing for CHF pts. LV pacing alone or in combination with RV pacing is associated with the largest improvements in PATH-CHF patients.
34
Clinical Trials/Heart Failure 126
125 T r e a t m e n t of I d i o p a t h i c Dilated C a r d i o m y o p a t h y b y l g G
Immunoadsorption Johannes MiJller, Gerd W a l l u k a t 1, Michael Dandel, H e i d r u n Bieda, Susanne Spiegelsberger, Manfred Hummel, Roland Hetzer, G e r m a n H e a r t Institute Berlin, Berlin, Germany; 1Max Delbr/ick Center, Berlin, G e r m a n y A causative therapy of idiopathic dilated cardiomyopathy (IDC) is not known. In 70% of pafients with IDC a pathological level of auto-antibodies directed against cardiac I]L-adrenoceptors(AAB) can be fotmd. We wanted to evaluate whether immmtmoadsorptian has a positive effect on cardiac function and dimension, i.e. left ventriculur ejection fraction (EF) and "left ventricular internal diameter in diastole (LVIDd). Thirty-four patients with IDC were derided into two groups (I,(2) of 17 patients eacK Both groups were not statistically different regarding the followingparameters: age, sex, NYHA class, EF, LVIDd, level of AAB arid drug therapy regarding cardiac insufficiency. After study recruitment all patients who were not on B-blocker medication received these additionally. After synchrodisafion of both groups, group I received irmnunoadsorption whereas group C was not treated. Two patients ont of group C were transplanted two and five months, respectively, after recruitment. The table shows the results one year after inlmunoadsorption as compared to the data at the begilming of the study. at l h e t i m e o f r e c r u i t m e n t E F [%1 group I
L~Dd
lmm]
alter one year
AAB [L~
E F [%1
LVIDd [mm]
AAB [LU]
38 • 8
64 i 6
not detectable 5 ± 1.0
22±3
75~7
6.0±1.4
24±3
76~6
4.7~1.0
(n-17) group C
25~-6
73:k7
(n=17)
(n=ls)
0~=ts)
P- v a l u e s
P <0.0001
P < O.00O3
(n-is) P
Imnmnoadsorption led to a significant improvement of cardiac function and dimension. AAB directed against cardiac Bx-receptors seem to be a suitable parameter to assessthe success of immunoadsurption. The reason why the cardiac function o.fthe control group also improved may be due to the positive effect of the B-blockertherapy.
Comparison of Patient's and Physician's Points of View on Quality of Life in Case of Congestive Heart Failure A n d r e a Gallina, Giuseppe Giacomarra, Antonio Previti, Marco Bobbio. Universitary Division of Cardiology - Molinette Hospital, Turin (Italy)
Although there is an increasing interest of physicians and investigators on the evaluation of quality of life, very few data are available on the physician's and patient's point of view. Our population includes 37 patients, 94.6% male and 54% with congestive heart failure. The patients, with stable congestive heart failure, before the visit and after 15 days filled in the Minnesota Living with Heart Failure Questionnaire (MQ) and the SF36 Questionnaire (SF) and performed a Six Minute Walk Test (6W). During both visits the same questionnaires were filled in by the cardiologist, blinded about the patient's answers. Between the first and the second visit, patients remained clinically stable and they did not need any therapy adjustment. In the follow-up visit after 15 days, patients did not show variation in the 6W (from 365 _+ 104 to 352 + 99 minutes) in total MQ score (from 39.8+ 23.5 to 38.4 + 20.2), and in physical activity estimated with SF (from 20.8 + 4.4 to 22.1 _+4.0), demonstrating a real clinical stability. The ~valuation of MQ by the physician was lower (more optimistic) than the one by the patients, either for the first (35.2_+ 21.6 vs 39.8 + 23.5; p = 0.034), or for the second evaluation (33.6 + 18.6 vs 38.4 + 20.3; p = 0.018). Physical activity evaluation with SF was not statistically significative between patients and physicians. in conclusion, as demonstrated in other pathologies, also in case of congestive heart failure, there is a trend by physicians to underestimate patient's symptoms. For those reason patients complain that often physicians pay poor attention to the severity their symptoms.
127
128
H i g h Diuretic Doses are Associated w i t h S u d d e n Death in Patients w i t h A d v a n c e d Heart Failure: The PRAISE Trial Gerald W. Neuberg, Chris M. O'Connor, Alan B. Miller, Robert N. Belkin, Peter E. Carson, Anne B. Cropp, David Frid, Regi Nye, Milton L. Pressler, John H. Wertheimer, Milton Packer for the PRAISE Investigators. Columbia University, N e w York, NY
Acute Pacing of the Left Ventricle is Associated w i t h Largest H e m o d y n a m i c I m p r o v e m e n t in PATH-CHF Heart Failure Patients Angelo Auricchio, Christoph Stellbrink, Michael Block, H e l m u t Klein (PATH-CHF Study Group, Div. Card., U. Hosp., Magdeburg, Germany); A n d r e w Kramer, Jiang Ding, Rod Salo, Bruce Tockman, Thierry Pochet, Julio Spinelli (CHF Res., Guidant/CPI, St. Paul, MN)
Diuretics are often necessary to correct and prevent fluid overload in patients with chronic CHF, but their effect on long-term outcome is unknown. The Prospective Amlodipine Survival Evaluation (PRAISE) enrolled 1153 patients with L V ejection fi'aetion < 30% and Class IIIb-IV CHF despite background therapy with digoxin, diuretics and ACE inhibitors. Almost all patients received a loop diuretic, with initial daily doses o f 10-480 nag o f furosemide (n=1038) and 0.5-12 nag ofbumetalfide (n=86). Over a median o f 14 months, there were 413 deaths (190 on amlodipine, 223 on placebo). We evaluated the relation o f background drug doses ("high" vs. ' l o w " dose = above vs. below median) and other baseline variables to cause-specific mortality as judged by the Endpoints Committee. By proportional hazards regression, high diuretic dose was an independent predictor o f sudden death (P=0.023) and total mortality (P--O.012), but not o f pump failure death. L o w ACE inhibitor dose was an independent predictor of pump failure death (p-M3.001 ) and total mortality (P=0.04), but not o f sudden death. Digoxin dose was not an independent predictor of mortality. The benefit of high ACE inhibitor dose is consistent with results o f randomized trials. The mortality risk associated with high diuretic dose does not prove causality, but could relate to known side effects (i.e. neurohormonal activation and electrolyte depletion). The selective risk of sudden death (but not other eanses of death) is suggestive o f a direct effect of diuretics and requires prospective study.
The role of pacing site and AV delay for treatment of congestive heart failure (CHF) with pacing is uncertain. We compared the effects of right (RV), left (LV), and right plus left (BV) ventricular pacing at different AV delays on the actlte hemodynamic function of CHF patients. Methods. Twenty-five pts in the PATH-CHF study (NYHA Class III/IV in sinus rhythm with QRS duration > 120ms) were tested at implant while catheterized with Millar micromanometers in the LV and aorta. Pts were acutely paced in VDD mode at RV, LV, or BV sites with 5 AV delays normalized by PR interval while max LV +dP/dt and aortic pulse pressure (PP) percentage changes from baseline were recorded during brief pacing/no-pacing sequences. Results. The LV +dP/dt or PP averaged over all AV delays increased significantly from baseline (p<.00t paired ttest) in 20/25 pts with LV or BV pacing and in 14/25 pts with RV pacing. Group means (+SE) of LV +dP/dt and PP plotted in the figures by pacing site varied significantly with AV delay (ANOVA p<.0001). Both parameters increased significantly more with BV and LV pacing compared to RV pacing, while LV +dP/dt increased more with LV than BV pacing (ANOVA/Tukey, p<.01), bat PP increases were statistically similar for LV and BV pacing.
o
zs a0 r, m ~,la r (%ot PR- sore n}
10o
0
2s a~ rs aVee~sy(~ orP~- 70ms)
1o0
Conclusions. Pacing site and AV delay combine to determine hemodynamic efficacy of acute pacing for CHF pts. LV pacing alone or in combination with RV pacing is associated with the largest improvements in PATH-CHF patients.