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Histidine-rich Ca2+ Binding Protein Inhibits the Propensity for Store Overload-induced Ca2+ Release (SOICR)
S78
Heart, Lung and Circulation 2013;22:S1–S125
CSANZ 2013 Abstracts
ABSTRACTS
Conclusions: CRT generally reduces mortality and improves outcomes, AdaptivCRT® improves the costeffectiveness of this device class.
185 Histidine-rich Ca2+ Binding Protein Inhibits the Propensity for Store Overload-induced Ca2+ Release (SOICR)
http://dx.doi.org/10.1016/j.hlc.2013.05.184
J. Zhang ∗ , J. McLay, P. Jones
184
Department of Physiology, Otago School of Medical Sciences, University of Otago, New Zealand
Heart Transplant Survival Rates in Patients Requiring a Ventricular Assist Device as a Bridge to Transplant A. Lamanna 1,∗ , S. McKenzie 1 , M. Brown 1 , D. Platts 1 , B. Thomson 2 , P. Tesar 2 , J. Maddicks-Law 1 , J. Bancroft 1 , G. Javorsky 1 1 Advanced
Heart Failure and Transplant Unit, The Prince Charles Hospital, Australia 2 Department of Cardiothoracic Surgery, The Prince Charles Hospital, Australia Background: Ventricular assist devices (VAD) are increasingly used as a bridge to transplant (BTT). However there are conflicting data regarding the post heart transplantation outcomes in patients who require this form of mechanical circulatory support (MCS). These patients are typically more unwell pre transplant which may adversely affect their survival post transplantation. We aimed to compare our institutions post-heart transplant survival rates in VAD BTT and non VAD BTT patients. Method: We performed a retrospective analysis of patients receiving heart transplantation during period 2003–2012 and compared outcomes for those requiring pre transplant VAD insertion to those who did not. The survival rates were estimated with the Kaplan–Meier method. Result: Heart transplant was performed in 132 patients. The median follow-up duration was 72 months. 29/132 (22%) patients required VAD as BTT (age: 42.4 ± 14.9 years). Of these, 16/29 (55%) patients required LVAD support (nine Thoratec PVAD, five Ventrassist and two HeartWare) and 13/29 (45%) required BiVAD support (12 Thoratec PVAD and one Abiomed AB5000). 103/132 (78%) did not require VAD BTT support (age: 46.4 ± 13.9 years). There was no significant difference in long-term posttransplant survival rates between those who required VAD BTT support and those who did not. The estimated one, three and five years survival rates were: 93% vs 90%, 88% vs 89% and 88% vs 86% respectively (p-value = 0.96). Conclusion: Patients who required VAD BTT support had good post-heart transplant survival rates that were comparable to those who did not require VAD support. http://dx.doi.org/10.1016/j.hlc.2013.05.185
Distinct alterations in Ca2+ handling have been implicated in cardiac arrhythmias and contractile dysfunction, particularly in progression of heart failure (HF). Compelling data from the last two decades show that abnormal regulation of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor (RyR2), is a crucial point which disrupts intracellular Ca2+ homeostasis. A number of studies have indicated that changes in the proteins which bind to RyR2 are associated with abnormal Ca2+ release. Histidine-rich Ca2+ binding protein (HRC) is a newly identified RyR2-bound protein whose regulatory function is unclear. Recent studies have shown that HRC is down regulated in HF and its loss is associated with an increased susceptibility to arrhythmias. Given store overload-induced Ca2+ release (SOICR) is a common mechanism of arrhythmias, we hypothesised that the loss of HRC may lead to altered RyR2 function and arrhythmias by increasing propensity for SOICR. We determined the propensity for SOICR in human embryonic kidney (HEK) 293 cells expressing RyR2 alone or co-expressing RyR2 and HRC. We found that the addition of HRC reduced the propensity for SOICR. To investigate the mechanism behind this reduction, the Ca2+ level within endoplasmic reticulum (ER) was monitored. Our results show that HRC supresses SOICR by buffering free ER Ca2+ without changing the sensitivity to SOICR. We, therefore, conclude that HRC reduces the free ER Ca2+ available for triggering SOICR events, suggesting maintenance of stable free Ca2+ level in ER is a potential therapeutic target of arrhythmias. http://dx.doi.org/10.1016/j.hlc.2013.05.186 186 Home Inotrope Therapy for Heart Failure, the Alfred Hospital Experience I. Bader ∗ , L. MacFarlane, D. Kaye, A. Taylor, A. Leet, J. Hare, P. Bergin Alfred Hospital, Australia Background: Waiting times to heart transplant (HTx) continue to lengthen. Ventricular assist devices (VAD) are available as a bridge to HTx (BTT) for some patients (pts), however are expensive and may not suit pts with significant right heart failure. Continuous low dose Home Inotrope Therapy (HIT) offers an alternative BTT option for carefully selected pts. Aim: Assess safety and outcome of HIT as a BTT. Methods: Pts had NYHA Class IV heart failure and a demonstrated response to therapy by improved symptoms and haemodynamics. The inotropes used were Dobu-
Heart, Lung and Circulation 2013;22:S1–S125
CSANZ 2013 Abstracts
ABSTRACTS
Conclusions: CRT generally reduces mortality and improves outcomes, AdaptivCRT® improves the costeffectiveness of this device class.
185 Histidine-rich Ca2+ Binding Protein Inhibits the Propensity for Store Overload-induced Ca2+ Release (SOICR)
http://dx.doi.org/10.1016/j.hlc.2013.05.184
J. Zhang ∗ , J. McLay, P. Jones
184
Department of Physiology, Otago School of Medical Sciences, University of Otago, New Zealand
Heart Transplant Survival Rates in Patients Requiring a Ventricular Assist Device as a Bridge to Transplant A. Lamanna 1,∗ , S. McKenzie 1 , M. Brown 1 , D. Platts 1 , B. Thomson 2 , P. Tesar 2 , J. Maddicks-Law 1 , J. Bancroft 1 , G. Javorsky 1 1 Advanced
Heart Failure and Transplant Unit, The Prince Charles Hospital, Australia 2 Department of Cardiothoracic Surgery, The Prince Charles Hospital, Australia Background: Ventricular assist devices (VAD) are increasingly used as a bridge to transplant (BTT). However there are conflicting data regarding the post heart transplantation outcomes in patients who require this form of mechanical circulatory support (MCS). These patients are typically more unwell pre transplant which may adversely affect their survival post transplantation. We aimed to compare our institutions post-heart transplant survival rates in VAD BTT and non VAD BTT patients. Method: We performed a retrospective analysis of patients receiving heart transplantation during period 2003–2012 and compared outcomes for those requiring pre transplant VAD insertion to those who did not. The survival rates were estimated with the Kaplan–Meier method. Result: Heart transplant was performed in 132 patients. The median follow-up duration was 72 months. 29/132 (22%) patients required VAD as BTT (age: 42.4 ± 14.9 years). Of these, 16/29 (55%) patients required LVAD support (nine Thoratec PVAD, five Ventrassist and two HeartWare) and 13/29 (45%) required BiVAD support (12 Thoratec PVAD and one Abiomed AB5000). 103/132 (78%) did not require VAD BTT support (age: 46.4 ± 13.9 years). There was no significant difference in long-term posttransplant survival rates between those who required VAD BTT support and those who did not. The estimated one, three and five years survival rates were: 93% vs 90%, 88% vs 89% and 88% vs 86% respectively (p-value = 0.96). Conclusion: Patients who required VAD BTT support had good post-heart transplant survival rates that were comparable to those who did not require VAD support. http://dx.doi.org/10.1016/j.hlc.2013.05.185
Distinct alterations in Ca2+ handling have been implicated in cardiac arrhythmias and contractile dysfunction, particularly in progression of heart failure (HF). Compelling data from the last two decades show that abnormal regulation of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor (RyR2), is a crucial point which disrupts intracellular Ca2+ homeostasis. A number of studies have indicated that changes in the proteins which bind to RyR2 are associated with abnormal Ca2+ release. Histidine-rich Ca2+ binding protein (HRC) is a newly identified RyR2-bound protein whose regulatory function is unclear. Recent studies have shown that HRC is down regulated in HF and its loss is associated with an increased susceptibility to arrhythmias. Given store overload-induced Ca2+ release (SOICR) is a common mechanism of arrhythmias, we hypothesised that the loss of HRC may lead to altered RyR2 function and arrhythmias by increasing propensity for SOICR. We determined the propensity for SOICR in human embryonic kidney (HEK) 293 cells expressing RyR2 alone or co-expressing RyR2 and HRC. We found that the addition of HRC reduced the propensity for SOICR. To investigate the mechanism behind this reduction, the Ca2+ level within endoplasmic reticulum (ER) was monitored. Our results show that HRC supresses SOICR by buffering free ER Ca2+ without changing the sensitivity to SOICR. We, therefore, conclude that HRC reduces the free ER Ca2+ available for triggering SOICR events, suggesting maintenance of stable free Ca2+ level in ER is a potential therapeutic target of arrhythmias. http://dx.doi.org/10.1016/j.hlc.2013.05.186 186 Home Inotrope Therapy for Heart Failure, the Alfred Hospital Experience I. Bader ∗ , L. MacFarlane, D. Kaye, A. Taylor, A. Leet, J. Hare, P. Bergin Alfred Hospital, Australia Background: Waiting times to heart transplant (HTx) continue to lengthen. Ventricular assist devices (VAD) are available as a bridge to HTx (BTT) for some patients (pts), however are expensive and may not suit pts with significant right heart failure. Continuous low dose Home Inotrope Therapy (HIT) offers an alternative BTT option for carefully selected pts. Aim: Assess safety and outcome of HIT as a BTT. Methods: Pts had NYHA Class IV heart failure and a demonstrated response to therapy by improved symptoms and haemodynamics. The inotropes used were Dobu-