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VNS Does Not Reduce Heart Failure Progression in a Canine High Rate Pacing Model of HF
The 19th Annual Scientific Meeting to study the effects of IABP therapy in patients with advanced heart failure. Initial observations suggest that larger capacity IABP activation reduces LV stroke work in patients with advanced heart failure. The study is actively enrolling through 2015.
070 Elevated Right Atrial Pressure Predicts Post Heart Transplant Outcomes Carolyn M. Rosner, Anthony J. Rongione, Gurusher Panjrath, Palak Shah, Shashank S. Desai, Ramesh Singh; Inova Health System, Falls Church, VA Background: Orthotopic heart transplantation (OHT) is the definitive treatment for end stage heart failure. Patient selection is key in improving post OHT outcomes. Pre-operative right ventricular dysfunction is associated with worse outcomes after mechanical circulatory support but its effect on post OHT outcomes has not been well described. Right atrial (RA) pressure is commonly used as a surrogate for RV function. We compared post OHT outcomes in patients with and without preoperative elevated RA pressure. Methods: An analysis of 124 patients who underwent isolated OHT at our institution from January 2008-October 2014 was performed. Patients undergoing re-transplantation were excluded. One hundred seventeen patients were included in this analysis. Groups were divided based on preoperative RA pressure. Baseline characteristics and post OHT outcomes (post OHT length of stay; 30 day, 1 year and 3 year survival and clinically significant rejection in the 1st year) were compared. Results: Pre OHT characteristics were similar between the 2 groups except for a difference in age and PVR, as shown in Table 1. Post heart transplant survival was worse in the group with pre transplant RA pressure O15mmHg, as shown in Table 2. Conclusion: Pre-operative elevated RA pressure was associated with a worse short and intermediate term (1 and 3 year) survival after OHT. There was no difference in post transplant rejection in the first year. Possible factors for poor survival include underestimation of pulmonary hypertension or organ dysfunction. RA pressures are readily available and may allow for a more accurate prediction of post OHT outcomes.
Table 1. Baseline Characteristics at Time of Transplant
Age Gender (% male) Diagnosis (%ICM) BMI Previous sternotomy Mechanical circulatory support LVAD/BiVAD/TAH ECMO IABP None UNOS status 1A at time of transplant Wait time to transplant (days) RA RVSWI (PAM-CVP) PVR TPG CO
Group A (N594) RA ! 15mmHg
Group B (N523) RA $ 15mmHg
55 73% 38% 27.3 82% 72%
48 70% 30% 28.3 78% 61%
62/4/1 1 0 26 77%
11/2/0 1 0 9 91%
255.4 6 235.2 7.1 6 3.9 13.3 6 6.8
209.3 6 219.2 18.0 6 3.3 13.6 6 8.1
0.40
1.9 6 1.2 8.5 6 4.6 4.7 6 1.2
2.5 6 1.5 9.5 6 3.8 5.1 6 3.8
0.03 0.35 0.60
p 0.02 0.71 0.50 0.37 0.69 0.28
Post transplant LOS (days) 30 day survival 1 year survival 3 year survival Incidence of rejection in the 1st year
18.6 98% 92% 86% 36%
Group B (N523) RA $ 15 17.7 83% 67% 50% 32%
HFSA
S39
071 VNS Does Not Reduce Heart Failure Progression in a Canine High Rate Pacing Model of HF Avram Scheiner; Medtronic, Mounds Veiw, MN Background: There is a significant unmet clinical need for effective therapies for heart failure (HF) patients. One potential therapeutic approach is Vagal Nerve Stimulation (VNS) in which a lead is placed on the cervical portion of the vagus nerve and stimulated using high frequency pulses. Multiple preclinical laboratories have published positive studies using this technique for HF treatment. This study attempts to duplicate one of these studies.1 Method: Sixteen dogs were implanted with a bipolar cuff lead (Inspire Medical Systems, Model 4063) placed on the cervical vagus nerve and connected to a nerve stimulator. A pacemaker was implanted with leads in the RA and in the RV for high rate Pacing (HRP). At post-operative week 2, each animal was randomized into either the control or VNS test group. HRP was started at week 2 in all animals to induce HF. VNS therapy was initiated at week 2 in the test group. For the VNS test group, VNS therapy was cycled continuously at 14 seconds on-12 seconds off. VNS therapy settings were at a frequency of 19 hertz and pulse width of 450 mseconds. Therapy was adjusted just below the level of coughing threshold for chronic VNS delivery. For each animal a series of weekly awake monitors were performed to ensure system integrity and therapy delivery. Echo measurements, ECG and blood samples were taken 2 weeks post-op at the initiation of high rate pacing, and again at weeks 6 and 10. The echo technician was blinded to each animal’s randomization assignment. The primary parameters of interest of the study were echo measures of remodeling and cardiac function. Secondary measures included various plasma biomarkers and post mortem heart size and weight and histological measurements. Results: The results of this study indicate that VNS does not produce a therapeutic effect in this high rate pacing HF canine model. The VNS treatment arm showed no significant difference compared to the control group in the primary endpoints in this study from randomization to 6 weeks or 10 weeks (EF, p5 0.60 and 0.83, EDV, p5 0.75 and 0.53 or ESV p5 0.90 and 0.63). A comparison of the primary endpoints of the control groups in this study and the previous published study1 suggests that similar changes were produced by the HRP model in both studies. Secondary measures of plasma biomarkers also showed no statistical differences between control and treatment arms at 6 and 10 weeks. Pathological findings showed no statistical difference in heart dimensions and weight. Conclusions: Although the canine HF model and VNS therapy technique were duplicated as done in the published positive VNS study, different results are seen. The results of this study indicate that VNS does not produce a therapeutic effect in this high rate pacing HF canine model. 1 Youhua Zhang, et al., “Chronic Vagus Nerve Stimulation Improves Autonomic Control and Attenuates Systemic Inflammation and Heart Failure Progression in a Canine High Rate Pacing Model” Circ Heart Fail published online Sep 22, 2009; DOI: 10.1161/CIRCHEARTFAILURE.109.873968
072 Early Elevated Pump Power and Associated Hemolysis Amongst HeartMate II Left Ventricular Assist Devices Anjan Tibrewala, Michael Nassif, David Raymer, Justin Vader, Shane LaRue, Scott Silvestry, Greg Ewald; Washington University, St. Louis, MO
0.12
!0.0001 0.88
Background: Continuous-flow left ventricular assist devices (CF-LVAD) have become the standard of care for end stage heart failure as bridge to transplant or destination therapy. Recently, an increase in pump thrombosis among HeartMate II (HM II) LVADs within the first 3 months of implant has been reported. The reason behind the observed increase in thrombosis is unknown but thought to be multifactorial. Increased frequency of transiently elevated power in the early postoperative period has been observed. We sought to determine if these increases in power are associated with future pump thrombosis.
Table 2. Post Transplant Outcomes
Group A (N594) RA ! 15mmHg
p 0.49 0.01 !0.01 0.02 0.74 Figure 1.
070 Elevated Right Atrial Pressure Predicts Post Heart Transplant Outcomes Carolyn M. Rosner, Anthony J. Rongione, Gurusher Panjrath, Palak Shah, Shashank S. Desai, Ramesh Singh; Inova Health System, Falls Church, VA Background: Orthotopic heart transplantation (OHT) is the definitive treatment for end stage heart failure. Patient selection is key in improving post OHT outcomes. Pre-operative right ventricular dysfunction is associated with worse outcomes after mechanical circulatory support but its effect on post OHT outcomes has not been well described. Right atrial (RA) pressure is commonly used as a surrogate for RV function. We compared post OHT outcomes in patients with and without preoperative elevated RA pressure. Methods: An analysis of 124 patients who underwent isolated OHT at our institution from January 2008-October 2014 was performed. Patients undergoing re-transplantation were excluded. One hundred seventeen patients were included in this analysis. Groups were divided based on preoperative RA pressure. Baseline characteristics and post OHT outcomes (post OHT length of stay; 30 day, 1 year and 3 year survival and clinically significant rejection in the 1st year) were compared. Results: Pre OHT characteristics were similar between the 2 groups except for a difference in age and PVR, as shown in Table 1. Post heart transplant survival was worse in the group with pre transplant RA pressure O15mmHg, as shown in Table 2. Conclusion: Pre-operative elevated RA pressure was associated with a worse short and intermediate term (1 and 3 year) survival after OHT. There was no difference in post transplant rejection in the first year. Possible factors for poor survival include underestimation of pulmonary hypertension or organ dysfunction. RA pressures are readily available and may allow for a more accurate prediction of post OHT outcomes.
Table 1. Baseline Characteristics at Time of Transplant
Age Gender (% male) Diagnosis (%ICM) BMI Previous sternotomy Mechanical circulatory support LVAD/BiVAD/TAH ECMO IABP None UNOS status 1A at time of transplant Wait time to transplant (days) RA RVSWI (PAM-CVP) PVR TPG CO
Group A (N594) RA ! 15mmHg
Group B (N523) RA $ 15mmHg
55 73% 38% 27.3 82% 72%
48 70% 30% 28.3 78% 61%
62/4/1 1 0 26 77%
11/2/0 1 0 9 91%
255.4 6 235.2 7.1 6 3.9 13.3 6 6.8
209.3 6 219.2 18.0 6 3.3 13.6 6 8.1
0.40
1.9 6 1.2 8.5 6 4.6 4.7 6 1.2
2.5 6 1.5 9.5 6 3.8 5.1 6 3.8
0.03 0.35 0.60
p 0.02 0.71 0.50 0.37 0.69 0.28
Post transplant LOS (days) 30 day survival 1 year survival 3 year survival Incidence of rejection in the 1st year
18.6 98% 92% 86% 36%
Group B (N523) RA $ 15 17.7 83% 67% 50% 32%
HFSA
S39
071 VNS Does Not Reduce Heart Failure Progression in a Canine High Rate Pacing Model of HF Avram Scheiner; Medtronic, Mounds Veiw, MN Background: There is a significant unmet clinical need for effective therapies for heart failure (HF) patients. One potential therapeutic approach is Vagal Nerve Stimulation (VNS) in which a lead is placed on the cervical portion of the vagus nerve and stimulated using high frequency pulses. Multiple preclinical laboratories have published positive studies using this technique for HF treatment. This study attempts to duplicate one of these studies.1 Method: Sixteen dogs were implanted with a bipolar cuff lead (Inspire Medical Systems, Model 4063) placed on the cervical vagus nerve and connected to a nerve stimulator. A pacemaker was implanted with leads in the RA and in the RV for high rate Pacing (HRP). At post-operative week 2, each animal was randomized into either the control or VNS test group. HRP was started at week 2 in all animals to induce HF. VNS therapy was initiated at week 2 in the test group. For the VNS test group, VNS therapy was cycled continuously at 14 seconds on-12 seconds off. VNS therapy settings were at a frequency of 19 hertz and pulse width of 450 mseconds. Therapy was adjusted just below the level of coughing threshold for chronic VNS delivery. For each animal a series of weekly awake monitors were performed to ensure system integrity and therapy delivery. Echo measurements, ECG and blood samples were taken 2 weeks post-op at the initiation of high rate pacing, and again at weeks 6 and 10. The echo technician was blinded to each animal’s randomization assignment. The primary parameters of interest of the study were echo measures of remodeling and cardiac function. Secondary measures included various plasma biomarkers and post mortem heart size and weight and histological measurements. Results: The results of this study indicate that VNS does not produce a therapeutic effect in this high rate pacing HF canine model. The VNS treatment arm showed no significant difference compared to the control group in the primary endpoints in this study from randomization to 6 weeks or 10 weeks (EF, p5 0.60 and 0.83, EDV, p5 0.75 and 0.53 or ESV p5 0.90 and 0.63). A comparison of the primary endpoints of the control groups in this study and the previous published study1 suggests that similar changes were produced by the HRP model in both studies. Secondary measures of plasma biomarkers also showed no statistical differences between control and treatment arms at 6 and 10 weeks. Pathological findings showed no statistical difference in heart dimensions and weight. Conclusions: Although the canine HF model and VNS therapy technique were duplicated as done in the published positive VNS study, different results are seen. The results of this study indicate that VNS does not produce a therapeutic effect in this high rate pacing HF canine model. 1 Youhua Zhang, et al., “Chronic Vagus Nerve Stimulation Improves Autonomic Control and Attenuates Systemic Inflammation and Heart Failure Progression in a Canine High Rate Pacing Model” Circ Heart Fail published online Sep 22, 2009; DOI: 10.1161/CIRCHEARTFAILURE.109.873968
072 Early Elevated Pump Power and Associated Hemolysis Amongst HeartMate II Left Ventricular Assist Devices Anjan Tibrewala, Michael Nassif, David Raymer, Justin Vader, Shane LaRue, Scott Silvestry, Greg Ewald; Washington University, St. Louis, MO
0.12
!0.0001 0.88
Background: Continuous-flow left ventricular assist devices (CF-LVAD) have become the standard of care for end stage heart failure as bridge to transplant or destination therapy. Recently, an increase in pump thrombosis among HeartMate II (HM II) LVADs within the first 3 months of implant has been reported. The reason behind the observed increase in thrombosis is unknown but thought to be multifactorial. Increased frequency of transiently elevated power in the early postoperative period has been observed. We sought to determine if these increases in power are associated with future pump thrombosis.
Table 2. Post Transplant Outcomes
Group A (N594) RA ! 15mmHg
p 0.49 0.01 !0.01 0.02 0.74 Figure 1.