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Cardiac Outreach Program in Heart Failure-Impacts and Outcomes
Abstracts
S100
Background: Cancer cachexia, is observed in more than 50% of advanced cancer patients, and significantly impairs quality of life and prognosis. As a multifactorial disorder it is likely that a variety of pathways are dysregulated, and a broad-spectrum understanding of the disease process is best achieved by a discovery based approach such as proteomics. Aims: Examine the effect of cancer cachexia-induced alterations in proteomic profiles in the heart using the colon 26 (C26) carcinoma murine model of cancer cachexia. Methods and Results: Normal versus C26 heart protein extracts were analysed using two 8-plex iTRAQ experiments and tandem mass spectrometry (LCMSMS). Bioinformatics tools were used to analyse the differentially expressed proteomic lists for protein clustering and enrichment of biological processes, molecular pathways, and disease related pathways. In C26 cardiac muscle, 24 proteins were significantly differentially expressed at a p-value of 0.05, with sarcomeric proteins (mostly upregulated) and energy/metabolism proteins (mostly downregulated) featured. Cardiac muscle of C26 mice was investigated by electron microscopy and findings of disintegration of the sarcomere and morphological aberrations of mitochondria were consistent with the alterations in the proteomic profiles. Conclusions: Proteomic analyses provide a global picture of the molecular events that underlie cancer cachexia in cardiac muscle. Furthermore, the morphological changes in cardiac tissue of disintegration of the sarcomeric structure with increased dissolution of Z-disc and M-line proteins appear to be potentially further exacerbated by disrupted energy homeostasis. These combined findings provide insight into the main biochemical processes driving cancerinduced cachexia in the heart. http://dx.doi.org/10.1016/j.hlc.2016.06.236 236 Cardiac Galectin-3 Contributes to Fibrotic Cardiomyopathy Due to Transgenic Beta-adrenergic Activation M. Nguyen 1,2,∗ , Y. Su 1 , H. Kiriazis 1 , M. Zhang 1 , X. Gao 1 , J. McMullen 1,3 , X. Du 1,2 1 Baker
IDI Heart and Diabetes Institute, Melbourne, Australia 2 Central Clinical School, Monash University, Melbourne, Australia 3 Department of Physiology, Monash University, Melbourne, Australia Background: Recent clinical studies have implicated galectin-3 as a biomarker for heart failure, fibrosis and arrhythmias. Changes in cardiac galectin-3 in relation to cardiomyopathy severity and the mechanism regulating galectin-3 expression are poorly understood. Using a transgenic (TG) mouse model of fibrotic cardiomyopathy, we studied cardiac galectin-3 expression in relation to fibrotic and inflammatory markers and its regulation by -adrenergic receptor (-AR) activation. Methods: Male non-TG and TG mice with cardiac overexpression of human 2 -AR (2 -TG) were studied at 3, 6 and
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .
9 months of age. Galectin-3 and selected fibrotic and inflammatory gene expression was determined by RT-PCR. Protein expression was measured by western blot or ELISA. Effect of galectin-3 inhibitor (N-acetyllactosamine) on fibrotic and inflammatory markers was examined. Regulation of galectin3 by -AR activation was studied by isoproterenol treatment to non-TG mice. Results: Cardiac galectin-3 expression increased by 4∼6fold at the pre-disease age (3 months), and was progressively upregulated with ageing (7∼14-fold, p<0.01). Numerous fibrotic and inflammatory genes were highly correlated to cardiac galectin-3 expression levels (r=0.81∼0.95, p<0.05). Isoproterenol treatment to non-TG mice increased galectin-3 gene and protein expression by 4∼5-fold (p<0.05). Inhibition of galectin-3 with N-acetyllactosamine attenuated expression of selected genes related to fibrotic, inflammatory and oxidative stress signalling (p<0.05). Conclusion: Galectin-3 expression was increased in the 2 -TG cardiomyopathy model and correlated with severity of disease measured by inflammatory or fibrotic markers. Galectin-3 inhibitor suppressed inflammatory and fibrotic signalling supporting a role of galectin-3 in the initiation and progression of cardiomyopathy. http://dx.doi.org/10.1016/j.hlc.2016.06.237 237 Cardiac Outreach Program in Heart Failure-Impacts and Outcomes A. Michael 1,∗ , K. Kadappu 2 , V. Shah 3 , N. Hewett 2 , J. Chow 2 , R. Rajaratnam 2 1 Royal
Brisbane and Women’s Hospital, Brisbane, Australia 2 Liverpool Hospital, Sydney, Australia 3 Campbelltown Hospital, Sydney, Australia Background: Heart failure (HF) is one of the commonest reasons for hospital admissions. To reduce the clinical and economic burden of HF, newer strategies to improve patient outcomes need to be employed. HF outreach program which entails HF Clinical Nurse Consultant (CNC) and cardiac rehabilitation services, has been shown to improve the clinical outcomes by providing medical management and intensive education. We hypothesised that early intervention in HF patients through the outreach program will improve clinical outcomes and minimise cardiac events. Aim: We sought to determine the impact of HF outreach program on the overall mortality, rehospitalisations and average length of hospital stay in patients with HF. Methods: We studied a total of 818 patients admitted with HF in the South Western Sydney Local Health District in the year 2012 and followed them over a period of 3 years until December 2015. Patients were divided into two groups as enrolled and not enrolled in the outreach program. Both these groups were compared for mortality, HF related rehospitalisations and average length of hospital stay during the rehospitalisations.
Abstracts
S101
Results: See Table Not Enrolled in program (n=348) Median Min-Max Inter quartile Range
Enrolled in program (n=470) Median Min-Max Inter quartile Range
P value
6
1-26
4.667 8.200
5.67
1-37
4 - 8.083
0.057
3 132 (37.93%)
0-9 124 (26.38%)
2-5 <0.001
2
0-9
2-4
<0.001
............................................. Average length of stay Total Admissions Mortality
Conclusions: Patients enrolled in the outreach program showed a significant reduction in mortality and rehospitalisations. The average length of hospital stay in the two groups were not significantly different. This indicates that HF outreach program can contribute to improved patient outcomes. http://dx.doi.org/10.1016/j.hlc.2016.06.238 238 Catastrophic Ventricular Failure Secondary to Phaeochromocytoma Requiring Extra-corporeal Membrane Oxygenation J. Teng 1,∗ , I. Shiekh 2 , K. Lam 2 , L. Dembo 2 , R. Alcock 1 1 Royal 2 Fiona
Perth Hospital, Perth, Australia Stanley Hospital, Perth, Australia
A normally healthy 58 year old male presented with increasing headache, abdominal and chest pain, with rapidly worsening dyspnoea. His background included longstanding systemic hypertension which had been well controlled. On arrival; he was hypertensive, tachycardic and markedly dyspnoeic. ECG showed sinus tachycardia with 2 mm upsloping ST-segment depression, chest X-ray demonstrating bilateral diffuse airspace changes. An urgent CT aortogram showed no aortic dissection. Transthoracic echocardiography revealed severe global left ventricular impairment with no valvular or pericardial pathology, and subsequent urgent coronary angiography showed no obstructive disease. Within an hour of presentation his respiratory condition rapidly deteriorated requiring ventilatory support. Progressive haemodynamic collapse followed despite increasing inotropic support and intra-aortic balloon pump insertion. Veno-arterial extra-corporeal membranous oxygenation (VA-ECMO) was commenced, maintaining adequate perfusion and oxygenation. Over the next 24-hours the patient remained haemodynamically stable, left ventricular function normalised on repeat echocardiography and VA-ECMO and inotropes were weaned. Within 48-hours the patient was extubated with no neurological deficit. Cardiac MRI performed 10 days after initial presentation showed no myocardial abnormality, normal perfusion and calculated left ventricular ejection fraction of 66%. The initial CT aortogram was reviewed in further detail, demonstrating a 23x20 mm left-sided adrenal lesion, intensely active on Iodine-123 meta-iodobenzylguanidine scan. Urine and plasma metanephrine levels were consistent with a phaeochromocytoma. The patient was
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started on phenoxybenzamine, underwent uncomplicated adrenalectomy and remains well at 6 month follow-up. This case demonstrates the importance of prompt escalation of resuscitation measures in patients with undifferentiated cardiogenic shock, and the importance of considering rarer causes. http://dx.doi.org/10.1016/j.hlc.2016.06.239 239 Changes in Prevalence of Heart Failure Admissions in the Hunter New England Region Over 10 Years M. Al-Omary ∗ , A. Davies, A. Boyle John Hunter Hospital/Cardiology Department, Newcastle, Australia Introduction: Heart failure carries a major burden on our health system, mainly related to high rate of hospital admission. Heart failure accounted for 1.6% of all hospitalisations in Australia in 2013-14. Method: We prospectively enrolled all patients who were admitted to Hunter New England Health service (HNE) between 2005-2014 and had a discharge diagnosis of heart failure (n=39449). The primary objective of the study was to assess the trend in heart failure admissions over 10 years & compare admission rates based on gender & rurality (rural area is defined as population less than 100,000 & urban area is defined as more than 100,000). Results: The female heart failure hospitalisation rate was higher than male’s rate by about 10%. There was an approximately 10% decrease in the prevalence of heart failure admission over 10 years for both sexes. Rural admission rates were higher than urban admission rates during the study period. Overall, there was a slight decline of heart failure admission prevalence in both rural & urban areas. Conclusion: The prevalence of heart failure admissions has declined slightly over the last 10 years in Hunter New England Health area. Female admission rates were slightly higher than male’s admission rate.
http://dx.doi.org/10.1016/j.hlc.2016.06.240
S100
Background: Cancer cachexia, is observed in more than 50% of advanced cancer patients, and significantly impairs quality of life and prognosis. As a multifactorial disorder it is likely that a variety of pathways are dysregulated, and a broad-spectrum understanding of the disease process is best achieved by a discovery based approach such as proteomics. Aims: Examine the effect of cancer cachexia-induced alterations in proteomic profiles in the heart using the colon 26 (C26) carcinoma murine model of cancer cachexia. Methods and Results: Normal versus C26 heart protein extracts were analysed using two 8-plex iTRAQ experiments and tandem mass spectrometry (LCMSMS). Bioinformatics tools were used to analyse the differentially expressed proteomic lists for protein clustering and enrichment of biological processes, molecular pathways, and disease related pathways. In C26 cardiac muscle, 24 proteins were significantly differentially expressed at a p-value of 0.05, with sarcomeric proteins (mostly upregulated) and energy/metabolism proteins (mostly downregulated) featured. Cardiac muscle of C26 mice was investigated by electron microscopy and findings of disintegration of the sarcomere and morphological aberrations of mitochondria were consistent with the alterations in the proteomic profiles. Conclusions: Proteomic analyses provide a global picture of the molecular events that underlie cancer cachexia in cardiac muscle. Furthermore, the morphological changes in cardiac tissue of disintegration of the sarcomeric structure with increased dissolution of Z-disc and M-line proteins appear to be potentially further exacerbated by disrupted energy homeostasis. These combined findings provide insight into the main biochemical processes driving cancerinduced cachexia in the heart. http://dx.doi.org/10.1016/j.hlc.2016.06.236 236 Cardiac Galectin-3 Contributes to Fibrotic Cardiomyopathy Due to Transgenic Beta-adrenergic Activation M. Nguyen 1,2,∗ , Y. Su 1 , H. Kiriazis 1 , M. Zhang 1 , X. Gao 1 , J. McMullen 1,3 , X. Du 1,2 1 Baker
IDI Heart and Diabetes Institute, Melbourne, Australia 2 Central Clinical School, Monash University, Melbourne, Australia 3 Department of Physiology, Monash University, Melbourne, Australia Background: Recent clinical studies have implicated galectin-3 as a biomarker for heart failure, fibrosis and arrhythmias. Changes in cardiac galectin-3 in relation to cardiomyopathy severity and the mechanism regulating galectin-3 expression are poorly understood. Using a transgenic (TG) mouse model of fibrotic cardiomyopathy, we studied cardiac galectin-3 expression in relation to fibrotic and inflammatory markers and its regulation by -adrenergic receptor (-AR) activation. Methods: Male non-TG and TG mice with cardiac overexpression of human 2 -AR (2 -TG) were studied at 3, 6 and
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .
9 months of age. Galectin-3 and selected fibrotic and inflammatory gene expression was determined by RT-PCR. Protein expression was measured by western blot or ELISA. Effect of galectin-3 inhibitor (N-acetyllactosamine) on fibrotic and inflammatory markers was examined. Regulation of galectin3 by -AR activation was studied by isoproterenol treatment to non-TG mice. Results: Cardiac galectin-3 expression increased by 4∼6fold at the pre-disease age (3 months), and was progressively upregulated with ageing (7∼14-fold, p<0.01). Numerous fibrotic and inflammatory genes were highly correlated to cardiac galectin-3 expression levels (r=0.81∼0.95, p<0.05). Isoproterenol treatment to non-TG mice increased galectin-3 gene and protein expression by 4∼5-fold (p<0.05). Inhibition of galectin-3 with N-acetyllactosamine attenuated expression of selected genes related to fibrotic, inflammatory and oxidative stress signalling (p<0.05). Conclusion: Galectin-3 expression was increased in the 2 -TG cardiomyopathy model and correlated with severity of disease measured by inflammatory or fibrotic markers. Galectin-3 inhibitor suppressed inflammatory and fibrotic signalling supporting a role of galectin-3 in the initiation and progression of cardiomyopathy. http://dx.doi.org/10.1016/j.hlc.2016.06.237 237 Cardiac Outreach Program in Heart Failure-Impacts and Outcomes A. Michael 1,∗ , K. Kadappu 2 , V. Shah 3 , N. Hewett 2 , J. Chow 2 , R. Rajaratnam 2 1 Royal
Brisbane and Women’s Hospital, Brisbane, Australia 2 Liverpool Hospital, Sydney, Australia 3 Campbelltown Hospital, Sydney, Australia Background: Heart failure (HF) is one of the commonest reasons for hospital admissions. To reduce the clinical and economic burden of HF, newer strategies to improve patient outcomes need to be employed. HF outreach program which entails HF Clinical Nurse Consultant (CNC) and cardiac rehabilitation services, has been shown to improve the clinical outcomes by providing medical management and intensive education. We hypothesised that early intervention in HF patients through the outreach program will improve clinical outcomes and minimise cardiac events. Aim: We sought to determine the impact of HF outreach program on the overall mortality, rehospitalisations and average length of hospital stay in patients with HF. Methods: We studied a total of 818 patients admitted with HF in the South Western Sydney Local Health District in the year 2012 and followed them over a period of 3 years until December 2015. Patients were divided into two groups as enrolled and not enrolled in the outreach program. Both these groups were compared for mortality, HF related rehospitalisations and average length of hospital stay during the rehospitalisations.
Abstracts
S101
Results: See Table Not Enrolled in program (n=348) Median Min-Max Inter quartile Range
Enrolled in program (n=470) Median Min-Max Inter quartile Range
P value
6
1-26
4.667 8.200
5.67
1-37
4 - 8.083
0.057
3 132 (37.93%)
0-9 124 (26.38%)
2-5 <0.001
2
0-9
2-4
<0.001
............................................. Average length of stay Total Admissions Mortality
Conclusions: Patients enrolled in the outreach program showed a significant reduction in mortality and rehospitalisations. The average length of hospital stay in the two groups were not significantly different. This indicates that HF outreach program can contribute to improved patient outcomes. http://dx.doi.org/10.1016/j.hlc.2016.06.238 238 Catastrophic Ventricular Failure Secondary to Phaeochromocytoma Requiring Extra-corporeal Membrane Oxygenation J. Teng 1,∗ , I. Shiekh 2 , K. Lam 2 , L. Dembo 2 , R. Alcock 1 1 Royal 2 Fiona
Perth Hospital, Perth, Australia Stanley Hospital, Perth, Australia
A normally healthy 58 year old male presented with increasing headache, abdominal and chest pain, with rapidly worsening dyspnoea. His background included longstanding systemic hypertension which had been well controlled. On arrival; he was hypertensive, tachycardic and markedly dyspnoeic. ECG showed sinus tachycardia with 2 mm upsloping ST-segment depression, chest X-ray demonstrating bilateral diffuse airspace changes. An urgent CT aortogram showed no aortic dissection. Transthoracic echocardiography revealed severe global left ventricular impairment with no valvular or pericardial pathology, and subsequent urgent coronary angiography showed no obstructive disease. Within an hour of presentation his respiratory condition rapidly deteriorated requiring ventilatory support. Progressive haemodynamic collapse followed despite increasing inotropic support and intra-aortic balloon pump insertion. Veno-arterial extra-corporeal membranous oxygenation (VA-ECMO) was commenced, maintaining adequate perfusion and oxygenation. Over the next 24-hours the patient remained haemodynamically stable, left ventricular function normalised on repeat echocardiography and VA-ECMO and inotropes were weaned. Within 48-hours the patient was extubated with no neurological deficit. Cardiac MRI performed 10 days after initial presentation showed no myocardial abnormality, normal perfusion and calculated left ventricular ejection fraction of 66%. The initial CT aortogram was reviewed in further detail, demonstrating a 23x20 mm left-sided adrenal lesion, intensely active on Iodine-123 meta-iodobenzylguanidine scan. Urine and plasma metanephrine levels were consistent with a phaeochromocytoma. The patient was
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .
started on phenoxybenzamine, underwent uncomplicated adrenalectomy and remains well at 6 month follow-up. This case demonstrates the importance of prompt escalation of resuscitation measures in patients with undifferentiated cardiogenic shock, and the importance of considering rarer causes. http://dx.doi.org/10.1016/j.hlc.2016.06.239 239 Changes in Prevalence of Heart Failure Admissions in the Hunter New England Region Over 10 Years M. Al-Omary ∗ , A. Davies, A. Boyle John Hunter Hospital/Cardiology Department, Newcastle, Australia Introduction: Heart failure carries a major burden on our health system, mainly related to high rate of hospital admission. Heart failure accounted for 1.6% of all hospitalisations in Australia in 2013-14. Method: We prospectively enrolled all patients who were admitted to Hunter New England Health service (HNE) between 2005-2014 and had a discharge diagnosis of heart failure (n=39449). The primary objective of the study was to assess the trend in heart failure admissions over 10 years & compare admission rates based on gender & rurality (rural area is defined as population less than 100,000 & urban area is defined as more than 100,000). Results: The female heart failure hospitalisation rate was higher than male’s rate by about 10%. There was an approximately 10% decrease in the prevalence of heart failure admission over 10 years for both sexes. Rural admission rates were higher than urban admission rates during the study period. Overall, there was a slight decline of heart failure admission prevalence in both rural & urban areas. Conclusion: The prevalence of heart failure admissions has declined slightly over the last 10 years in Hunter New England Health area. Female admission rates were slightly higher than male’s admission rate.
http://dx.doi.org/10.1016/j.hlc.2016.06.240