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Percutaneous mitral annuloplasty device reduces mitral regurgitation in experimental heart failure
The 7th Annual Scientific Meeting
•
HFSA
S43
Surgery, Transplantation, Devices 151
152
Survival in Heart Failure as Related to Maximal Oxygen Consumption Is “Shifted Upward” in the Beta Blocker Era Christine Lawless,1 Richard Cooper,2 Guichan Cao,2 Mirjana Vekich,2 Jeanne Nacpil2— 1 Cardiology, DuPage Medical Group, Winfield, IL; 2Epidemiology, Loyola University Medical Center, Maywood, IL
Percutaneous Mitral Annuloplasty Device Reduces Mitral Regurgitation in Experimental Heart Failure Calin V. Maniu,1 David G. Reuter,2 Margaret M. Redfield1—1Division of Cardiovascular Disease, Mayo Clinic and Foundation, Rochester, MN; 2Cardiac Dimensions, Inc., Kirkland, WA
Cardiopulmonary exercise testing (CPX) has been shown to be a useful tool in predicting outcomes and survival in heart failure patients in the transplant age group. Several studies have indicated that peak oxygen consumption (MVO2) less than 14ml/ kg/min is useful in determining timing of cardiac transplantation. This data was obtained prior to the beta blocker era. Since beta blockers improve survival, but do not have much effect on maximal oxygen consumption in heart failure, we hypothesized that beta blockers may shift the survival curve related to MVO2 upward, such that 14 ml/kg/min may no longer be predictive of a poor outcome. Thus this value may no longer be an appropriate cut-off for consideration for cardiac transplantation. To test this hypothesis, from a cohort of 2200 heart failure patients seen at our institution between 1993 and 2000, we analyzed the CPX results of 228 candidates for transplantation who were able to undergo testing, and achieve respiratory quotient (RER) greater than 1.00 ( mean age 52.2 ⫾ 12.6 yrs, 75% male, 46% ischemic cardiomyopathy, left ventricular ejection fraction 24 ⫾ 11%). Patients were divided according to whether they underwent CPX testing prior to the beta blocker era, (1993–1996), or after the beta blocker era (1997–2000). Results:
Background: Surgical mitral annuloplasty to decrease the degree of functional mitral regurgitation (MR) in patients with advanced heart failure (HF) may improve symptoms and possibly survival but is associated with perioperative morbidity and mortality. The current study objectives are to determine if percutaneous placement of an annuloplasty device in the coronary sinus will decrease the degree of MR associated with chronic experimental HF and to determine if placement has adverse hemodynamic effects. Methods and Results: Six dogs underwent rapid ventricular pacing for six weeks and developed severe left ventricular (LV) dysfunction and moderate MR. Dogs were studied with echocardiography and pressure volume analysis in the open-chest anesthetized state. LV function, LV volume and degree of MR were assessed at baseline and after reduction of annulus dimension by percutaneous placement of the annuloplasty device. The device was released and measurements repeated before and after device placement in the presence of phenylephrine (PE) infusion to increase the degree of MR. Percutaneous placement of the annuloplasty device resulted in a reduction of the mitral annulus diameter that was associated with a decrease in the degree of MR as assessed by the MR jet area to left atrial (LA) area ratio, in the absence and in the presence of phenylephrine infusion. Deployment of the device did not result in significant hemodynamically unfavorable consequences. Data are presented as mean ⫾ SEM. Conclusion: The present study provides “proof of principle” that deployment of a new percutaneous annuloplasty device results in reduction of functional MR associated with severe LV dysfunction.
Kaplan- Meier Survival (Death or Transplant)
Survival (%) 6 month 12 month 24 month
MVO2 ⱕ 14
MVO2 ⱕ 14
MVO2 ⬎ 14
MVO2 ⬎ 14
1993–1996 86% 69% 48%
1997–2000 90% 80% 65%*
1993–1996 98% 96% 86%
1997–2000 98% 96% 92%
*p less than 0.05 for beta blocker era vs non beta blocker era Conclusions: In the beta blocker era, MVO2 still appears to be a powerful predictor of survival. However, use of beta blockade shifts the survival curve upward, suggesting a new standard for MVO2 cut-off in determining survival in candidates for cardiac transplantation in the beta blocker era.
153 DeBakey VAD쑓 Performance Characteristics Edward R. Teitel,1 Robert J. Benkowski,1 Deborah Morley,1 George P. Noon,2 Michael DeBakey2—1MicroMed Technology, Inc., Houston, TX; 2Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX Since its introduction into clinical use in 1998, the 183 DeBakey VADs implanted in patients in Europe and the United States represent the largest experience for the new generation miniaturized left ventricular assist devices (LVAD). In Europe the device has earned the CE mark and in the U.S. the bridge to transplant feasibility trial is now complete with 65% of patients successfully bridged to transplant. (N ⫽ 30) The DeBakey VAD was run in mock loop simulations for 2 12 years to determine the durability of its bearings, which were analyzed by BAE Systems (formerly British Aerospace), and its flow performance envelope. Clinical report forms from the clinical trial patients were then analyzed to look at the actual physiology observed in patients with the device implanted. The front and rear zirconium/ruby bearings, after 212 years of continuous running, showed no appreciable wear, and analysis by BAE estimated the bearing’s durability to be at least 5 years. Of 150 pumps returned for analysis after explant, no bearings have failed and none have shown appreciable wear. To date, the longest supported patient is 470 days and he continues to do well on support. Although a continuous flow device, all the DeBakey VAD patients have achieved at least some degree of pulsatility within 2 weeks as seen on the pressure/flow waveforms as directly measured by its implanted dual channel ultrasound flow probe which is an integral part of the DeBakey VAD system. See Fig. 1. This pulsatility appears as the left ventricle recovers some function thereby modulating the ∆ P across the pump. The DeBakey VAD will deliver 10 l/min of flow at a ∆ P of 90 mm/Hg. See Fig. 2. CRF analysis shows that in patients with BSA ranging from 1.3 to 2.4 m2 the device delivers a mean CI
of 2.3 and a mean pump flow of 4.3 l/min which is stable across the entire BSA range and supports end organ function as measured by BUN, Cr, and total bilirubin. The mean flow is exclusive of any contribution the patient’s native heart may make through the aortic valve. Conclusion: The DeBakey VAD appears to be a durable new generation pump that delivers ample performance to unload the left ventricle and support end organ function, as evidenced by bench testing and patient data. Its durability and ability to deliver a wide spectrum of flow and levels of ventricular support may make it a versatile LVAD for multiple indications, e.g. bridge to recovery.
Peak LV pressure (mm Hg) LV minimum pressure (mm Hg) LV end-diastolic pressure (mm Hg) Mean LA pressure (mm Hg) ⫹dP/dt (mm Hg/sec) Tau (msec) LV end-diastolic volume (mL) LV ejection fraction (%) LV stroke volume (mL) Heart rate (bpm) Cardiac output (L/min)
Baseline
Device
PE
PE ⫹ Device
87.3 ⫾ 4.9
88.3 ⫾ 6.2
117.7 ⫾ 10.6*
118.6 ⫾ 11.2
4 ⫾ 0.8
3.2 ⫾ 1.2
11.3 ⫾ 2.5
10.1 ⫾ 2.7
7.6 ⫾ 2 19.3 ⫾ 2.7*
8.7 ⫾ 1.4
8.2 ⫾ 1.1
933 ⫾ 94 64 ⫾ 15 91.8 ⫾ 10.1
845 ⫾ 153 57 ⫾ 8 88.8 ⫾ 11.9
1385 ⫾ 194* 98 ⫾ 28 100.9 ⫾ 9.6*
12.1 ⫾ 1
24 ⫾ 5 20.8 ⫾ 4.1 95 ⫾ 10 1.8 ⫾ 0.3
26 ⫾ 6 22.3 ⫾ 6 84 ⫾ 9 1.7 ⫾ 0.4
27 ⫾ 5 27.1 ⫾ 6.4 89 ⫾ 11 2.2 ⫾ 0.4
8.2 ⫾ 3.5 19.2 ⫾ 3.3 11.6 ⫾ 1.8 1368 ⫾ 187 100 ⫾ 27 100.5 ⫾ 9.8 25 ⫾ 4† 24.3 ⫾ 6.2† 90 ⫾ 11 2 ⫾ 0.4†
*p ⬍ 0.05 vs. baseline, †p ⬍ 0.05 vs. phenylephrine.
154 Pre-Transplant Amiodarone Exposure Is Associated with Increased Mortality Following Cardiac Transplantation: An Analysis of the United Network for Organ Sharing Thoracic Registry Andrew D. Feingold,1 Wenjun Li,2 Jessica A. Saunders,1 Marvin A. Konstam,1 Mark S. Link,1 David DeNofrio1—1Division of Cardiology, Tufts - New England Medical Center, Boston, MA; 2Clinical Care Research, Tufts - New England Medical Center, Boston, MA Background: Amiodarone therapy has been associated with a variety of toxic side-effects that may lead to increased morbidity and mortality in transplant recipients. The published literature thus far is conflicting with regard to the effect of amiodarone on early cardiac transplant outcomes. We examined data from the United Nework for Organ Sharing (UNOS) Registry to explore the effect of prior amiodarone therapy on mortality in patients transplanted within the United States. Methods: We conducted a retrospective analysis on the mortality of patients following cardiac transplantation using the UNOS Registry. The analysis was restricted to first time single organ cardiac transplant recipients between 4/1/1994 to 3/31/2001 with a known history of amiodarone treatment (n ⫽ 13,158). The first-year mortality of recipients with a history of treatment with amiodarone prior to transplantation was compared to those not treated with amiodarone. Cumulative mortality rates at each month were estimated using the Kaplan-Meier method and risk ratios were estimated using proportional hazard regression models. For risk factors (amiodarone, donor/ recipient gender match, pre-transplant ventilator, and pre-transplant ventricular assist device) exhibiting nonproportional hazard over time, the hazard was modeled either as a function of time or by stratification. Results: Recipients (n ⫽ 2,710) exposed to amiodarone in the pre-transplant period had a higher cumulative mortality at one year than recipients (n ⫽ 10,448) not exposed to amiodarone (16.3% vs 14.4%; Log-rank test, p ⫽ 0.008). The adverse effect of amiodarone use on early post-transplant mortality exhibited a nonproportional trend over time (p ⫽ 0.011) being highest in the first month (HR ⫽ 1.51, p ⬍ 0.001) following transplantation, monotonically decreasing over time (p ⫽ 0.011), and diminished after 3 months following transplantation (see figure). The increased risk of amiodar one use remains an independent prognostic factor after adjusting for other established risk factors in the literature such as recipient gender, donor/ recipient gender match, recipient age, donor age, CMV status, life-support, ischemic time, UNOS status, year of treatment, primary diagnosis, and peak PRA. Conclusions: Amiodarone treatment prior to cardiac transplantation is independently related to increased early mortality following cardiac transplantation. In the absence of prospective clinical trials, therapy with amiodarone for patients awaiting cardiac transplantation should be used cautiously and alternative treatment strategies should be considered.
•
HFSA
S43
Surgery, Transplantation, Devices 151
152
Survival in Heart Failure as Related to Maximal Oxygen Consumption Is “Shifted Upward” in the Beta Blocker Era Christine Lawless,1 Richard Cooper,2 Guichan Cao,2 Mirjana Vekich,2 Jeanne Nacpil2— 1 Cardiology, DuPage Medical Group, Winfield, IL; 2Epidemiology, Loyola University Medical Center, Maywood, IL
Percutaneous Mitral Annuloplasty Device Reduces Mitral Regurgitation in Experimental Heart Failure Calin V. Maniu,1 David G. Reuter,2 Margaret M. Redfield1—1Division of Cardiovascular Disease, Mayo Clinic and Foundation, Rochester, MN; 2Cardiac Dimensions, Inc., Kirkland, WA
Cardiopulmonary exercise testing (CPX) has been shown to be a useful tool in predicting outcomes and survival in heart failure patients in the transplant age group. Several studies have indicated that peak oxygen consumption (MVO2) less than 14ml/ kg/min is useful in determining timing of cardiac transplantation. This data was obtained prior to the beta blocker era. Since beta blockers improve survival, but do not have much effect on maximal oxygen consumption in heart failure, we hypothesized that beta blockers may shift the survival curve related to MVO2 upward, such that 14 ml/kg/min may no longer be predictive of a poor outcome. Thus this value may no longer be an appropriate cut-off for consideration for cardiac transplantation. To test this hypothesis, from a cohort of 2200 heart failure patients seen at our institution between 1993 and 2000, we analyzed the CPX results of 228 candidates for transplantation who were able to undergo testing, and achieve respiratory quotient (RER) greater than 1.00 ( mean age 52.2 ⫾ 12.6 yrs, 75% male, 46% ischemic cardiomyopathy, left ventricular ejection fraction 24 ⫾ 11%). Patients were divided according to whether they underwent CPX testing prior to the beta blocker era, (1993–1996), or after the beta blocker era (1997–2000). Results:
Background: Surgical mitral annuloplasty to decrease the degree of functional mitral regurgitation (MR) in patients with advanced heart failure (HF) may improve symptoms and possibly survival but is associated with perioperative morbidity and mortality. The current study objectives are to determine if percutaneous placement of an annuloplasty device in the coronary sinus will decrease the degree of MR associated with chronic experimental HF and to determine if placement has adverse hemodynamic effects. Methods and Results: Six dogs underwent rapid ventricular pacing for six weeks and developed severe left ventricular (LV) dysfunction and moderate MR. Dogs were studied with echocardiography and pressure volume analysis in the open-chest anesthetized state. LV function, LV volume and degree of MR were assessed at baseline and after reduction of annulus dimension by percutaneous placement of the annuloplasty device. The device was released and measurements repeated before and after device placement in the presence of phenylephrine (PE) infusion to increase the degree of MR. Percutaneous placement of the annuloplasty device resulted in a reduction of the mitral annulus diameter that was associated with a decrease in the degree of MR as assessed by the MR jet area to left atrial (LA) area ratio, in the absence and in the presence of phenylephrine infusion. Deployment of the device did not result in significant hemodynamically unfavorable consequences. Data are presented as mean ⫾ SEM. Conclusion: The present study provides “proof of principle” that deployment of a new percutaneous annuloplasty device results in reduction of functional MR associated with severe LV dysfunction.
Kaplan- Meier Survival (Death or Transplant)
Survival (%) 6 month 12 month 24 month
MVO2 ⱕ 14
MVO2 ⱕ 14
MVO2 ⬎ 14
MVO2 ⬎ 14
1993–1996 86% 69% 48%
1997–2000 90% 80% 65%*
1993–1996 98% 96% 86%
1997–2000 98% 96% 92%
*p less than 0.05 for beta blocker era vs non beta blocker era Conclusions: In the beta blocker era, MVO2 still appears to be a powerful predictor of survival. However, use of beta blockade shifts the survival curve upward, suggesting a new standard for MVO2 cut-off in determining survival in candidates for cardiac transplantation in the beta blocker era.
153 DeBakey VAD쑓 Performance Characteristics Edward R. Teitel,1 Robert J. Benkowski,1 Deborah Morley,1 George P. Noon,2 Michael DeBakey2—1MicroMed Technology, Inc., Houston, TX; 2Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX Since its introduction into clinical use in 1998, the 183 DeBakey VADs implanted in patients in Europe and the United States represent the largest experience for the new generation miniaturized left ventricular assist devices (LVAD). In Europe the device has earned the CE mark and in the U.S. the bridge to transplant feasibility trial is now complete with 65% of patients successfully bridged to transplant. (N ⫽ 30) The DeBakey VAD was run in mock loop simulations for 2 12 years to determine the durability of its bearings, which were analyzed by BAE Systems (formerly British Aerospace), and its flow performance envelope. Clinical report forms from the clinical trial patients were then analyzed to look at the actual physiology observed in patients with the device implanted. The front and rear zirconium/ruby bearings, after 212 years of continuous running, showed no appreciable wear, and analysis by BAE estimated the bearing’s durability to be at least 5 years. Of 150 pumps returned for analysis after explant, no bearings have failed and none have shown appreciable wear. To date, the longest supported patient is 470 days and he continues to do well on support. Although a continuous flow device, all the DeBakey VAD patients have achieved at least some degree of pulsatility within 2 weeks as seen on the pressure/flow waveforms as directly measured by its implanted dual channel ultrasound flow probe which is an integral part of the DeBakey VAD system. See Fig. 1. This pulsatility appears as the left ventricle recovers some function thereby modulating the ∆ P across the pump. The DeBakey VAD will deliver 10 l/min of flow at a ∆ P of 90 mm/Hg. See Fig. 2. CRF analysis shows that in patients with BSA ranging from 1.3 to 2.4 m2 the device delivers a mean CI
of 2.3 and a mean pump flow of 4.3 l/min which is stable across the entire BSA range and supports end organ function as measured by BUN, Cr, and total bilirubin. The mean flow is exclusive of any contribution the patient’s native heart may make through the aortic valve. Conclusion: The DeBakey VAD appears to be a durable new generation pump that delivers ample performance to unload the left ventricle and support end organ function, as evidenced by bench testing and patient data. Its durability and ability to deliver a wide spectrum of flow and levels of ventricular support may make it a versatile LVAD for multiple indications, e.g. bridge to recovery.
Peak LV pressure (mm Hg) LV minimum pressure (mm Hg) LV end-diastolic pressure (mm Hg) Mean LA pressure (mm Hg) ⫹dP/dt (mm Hg/sec) Tau (msec) LV end-diastolic volume (mL) LV ejection fraction (%) LV stroke volume (mL) Heart rate (bpm) Cardiac output (L/min)
Baseline
Device
PE
PE ⫹ Device
87.3 ⫾ 4.9
88.3 ⫾ 6.2
117.7 ⫾ 10.6*
118.6 ⫾ 11.2
4 ⫾ 0.8
3.2 ⫾ 1.2
11.3 ⫾ 2.5
10.1 ⫾ 2.7
7.6 ⫾ 2 19.3 ⫾ 2.7*
8.7 ⫾ 1.4
8.2 ⫾ 1.1
933 ⫾ 94 64 ⫾ 15 91.8 ⫾ 10.1
845 ⫾ 153 57 ⫾ 8 88.8 ⫾ 11.9
1385 ⫾ 194* 98 ⫾ 28 100.9 ⫾ 9.6*
12.1 ⫾ 1
24 ⫾ 5 20.8 ⫾ 4.1 95 ⫾ 10 1.8 ⫾ 0.3
26 ⫾ 6 22.3 ⫾ 6 84 ⫾ 9 1.7 ⫾ 0.4
27 ⫾ 5 27.1 ⫾ 6.4 89 ⫾ 11 2.2 ⫾ 0.4
8.2 ⫾ 3.5 19.2 ⫾ 3.3 11.6 ⫾ 1.8 1368 ⫾ 187 100 ⫾ 27 100.5 ⫾ 9.8 25 ⫾ 4† 24.3 ⫾ 6.2† 90 ⫾ 11 2 ⫾ 0.4†
*p ⬍ 0.05 vs. baseline, †p ⬍ 0.05 vs. phenylephrine.
154 Pre-Transplant Amiodarone Exposure Is Associated with Increased Mortality Following Cardiac Transplantation: An Analysis of the United Network for Organ Sharing Thoracic Registry Andrew D. Feingold,1 Wenjun Li,2 Jessica A. Saunders,1 Marvin A. Konstam,1 Mark S. Link,1 David DeNofrio1—1Division of Cardiology, Tufts - New England Medical Center, Boston, MA; 2Clinical Care Research, Tufts - New England Medical Center, Boston, MA Background: Amiodarone therapy has been associated with a variety of toxic side-effects that may lead to increased morbidity and mortality in transplant recipients. The published literature thus far is conflicting with regard to the effect of amiodarone on early cardiac transplant outcomes. We examined data from the United Nework for Organ Sharing (UNOS) Registry to explore the effect of prior amiodarone therapy on mortality in patients transplanted within the United States. Methods: We conducted a retrospective analysis on the mortality of patients following cardiac transplantation using the UNOS Registry. The analysis was restricted to first time single organ cardiac transplant recipients between 4/1/1994 to 3/31/2001 with a known history of amiodarone treatment (n ⫽ 13,158). The first-year mortality of recipients with a history of treatment with amiodarone prior to transplantation was compared to those not treated with amiodarone. Cumulative mortality rates at each month were estimated using the Kaplan-Meier method and risk ratios were estimated using proportional hazard regression models. For risk factors (amiodarone, donor/ recipient gender match, pre-transplant ventilator, and pre-transplant ventricular assist device) exhibiting nonproportional hazard over time, the hazard was modeled either as a function of time or by stratification. Results: Recipients (n ⫽ 2,710) exposed to amiodarone in the pre-transplant period had a higher cumulative mortality at one year than recipients (n ⫽ 10,448) not exposed to amiodarone (16.3% vs 14.4%; Log-rank test, p ⫽ 0.008). The adverse effect of amiodarone use on early post-transplant mortality exhibited a nonproportional trend over time (p ⫽ 0.011) being highest in the first month (HR ⫽ 1.51, p ⬍ 0.001) following transplantation, monotonically decreasing over time (p ⫽ 0.011), and diminished after 3 months following transplantation (see figure). The increased risk of amiodar one use remains an independent prognostic factor after adjusting for other established risk factors in the literature such as recipient gender, donor/ recipient gender match, recipient age, donor age, CMV status, life-support, ischemic time, UNOS status, year of treatment, primary diagnosis, and peak PRA. Conclusions: Amiodarone treatment prior to cardiac transplantation is independently related to increased early mortality following cardiac transplantation. In the absence of prospective clinical trials, therapy with amiodarone for patients awaiting cardiac transplantation should be used cautiously and alternative treatment strategies should be considered.