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Prevalence and Resolution of Pulmonary Hypertension (PHT) in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI)
46 Potential Anti-Arrhythmic and Cardio-Protective Properties of the Novel B-Blocker Nebivolol C. Pullen ∗ , A. Fenning CQ University, Australia Nebivolol has been shown to display a unique pharmacological profile antagonising 1 -adrenodeptors whilst also increasing nitric oxide bioavailability. Much of the research on nebivolol has focused on its ability to decrease blood pressure in a range of subjects including humans, as well as various animal models of hypertension. The aim of this study was to examine the cardio-protective effects of nebivolol, independent of its haemodynamic properties in rodent models of hypertension and diabetes. Male Wistar rats were randomly divided into either control (C), hypertensive (L-NAME-induced (L)) or diabetic (streptozotocin-induced (S)) groups. A subset of these groups were treated with 0.5 mg/mg/day (oral gavage) of nebivolol commenced at eight weeks of age and continuing until the animals reached sixteen weeks of age. Blood pressure and heart rate were monitored at four-weekly intervals throughout the study. Terminal experiments included vascular organ bath studies in thoracic aorta rings and mesenteric vessels and electrophysiological studies on the left ventricular papillary muscles. Nebivolol did not attenuate the elevated blood pressure seen in L-NAME treated animals (C− 123.12 ± 2.80 mmHg; L− 224.15 ± 7.76 mmHg*; L+N− 187.19 ± 7.21 mmHg**), however reductions in action potential duration were observed in nebivolol treated hypertensive rats (APD20: C− 13.63 ± 0.53 ms; L− 19.52 ± 2.16 ms; L+N− 14.75 ± 0.75 ms). Vascular tissues from animals treatment with nebivolol demonstrated an increased sensitivity to noradrenaline. This indicates that nebivolol may be acting through nitric oxide to provide some anti-arrhythmic and vascular protective effects. http://dx.doi.org/10.1016/j.hlc.2012.05.056 47 Prenatal Psychological Stress Modulates Offspring’s Long-Term Cardiovascular Activity and Reactivity to Stress F. Fan 1,∗ , H. Tian 2 , J. Zhang 2 , Y. Liu 2 , Y. Meng 2 , Z. Hu 2 , Y. Zou 2 , X. Du 1,3 , A. Dart 1,2,3 1 BakerIDI
Heart & Diabetes Institute, Melbourne, VIC, Australia 2 1st Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China 3 Heart Center, Alfred Hospital, Melbourne, VIC, Australia Introduction: Increased cardiovascular activity (CVA) and reactivity (CVR) to psychological stress have been identified as possible new markers for future cardiovascular risk. Animal studies showed psychological stress of pregnant mother, defined as prenatal psychological stress (PPS), modulates offspring’ CVA and CVR. How-
CSANZ 2012 Abstracts
S21
ever, the underlying mechanism is unclear and few studies have examined such possible influences in the human. We investigated the long-term effects and mechanism of PPS on CVA and CVR in seven to nine year-old children. Methods and results: we measured BP and HR at rest (rBP, rHR) and during video game stress (sBP, sHR) in 287 children whose mothers previously had thorough psychological assessment for PPS during pregnancy. rBP and rHR were used for CVA evaluation. CVR was defined as the maximum change in BP (BP) and HR (HR) in response to video game stress. Serum cortisol was serially measured before and during video game by radioimmunoassay to calculate absolute increment (cortisol). The results showed rBP and rHR, baseline cortisol (mean ± SD, 353 ± 37 nmol/L vs. 297 ± 36 nmol/L), BP (21 ± 2/12 ± 1 mmHg vs. 15 ± 1/10 ± 1 mmHg) and HR (18 ± 1 bpm vs. 13 ± 1 bpm), cortisol were all higher in children who experienced PPS than those without (all P < 0.01). Maternal effects on children’s CVA and CVR were most marked for combined maternal anxiety and depression, and least for depression alone. Conclusion: Our study confirms animal findings by demonstrating long lasting effects of PPS on offspring’s CVA and CVR in the human with likely effects on the subsequent risk of cardiovascular disease. http://dx.doi.org/10.1016/j.hlc.2012.05.057 48 Prevalence and Resolution of Pulmonary Hypertension (PHT) in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI) S. Jaijee 1,∗ , J. Yiannikis 2 , M. Wilson 1 , M. Vallely 1 , M. Ng 1 , D. Celermajer 1 1 Royal
Prince Alfred Hospital, Australia Repatriation Hospital, Australia
2 Concord
Background and aim: Left heart disease (LHD) is the most common cause of PHT but its pathogenesis is poorly understood. Severe aortic stenosis (AS) is a cause of LHD related PHT. Our aim was to assess the prevalence and time course of resolution of PHT when AS was relieved by transcatheter aortic valve implantation. Methods: We assessed 60 consecutively treated patients who underwent TAVI with serial echocardiography. PHT was defined as RV-RA pressure gradient ≥40 mmHg and a significant fall in pulmonary arterial pressure (PAP) was defined as >20% reduction in the RV-RA gradient. Results: Of 60 patients, 20/60 (33%) had PHT. From those 20 patients, six had an immediate reduction in PASP based on early echocardiography (<10 days). From the 14 patients who have reached >2 month follow up, six patients had a reduction in PAP, three had persistent PHT, one was lost to follow up and four did not have data available. Significance: In patients with PHT prior to TAVI, PAP falls in the majority but with an unpredictable time course. We have identified three patterns of response; early regression which could be related to relief of subendocardial ischaemia, late regression which may be explained
ABSTRACTS
Heart, Lung and Circulation 2012;21:S1–S142
S22
Heart, Lung and Circulation 2012;21:S1–S142
CSANZ 2012 Abstracts
ABSTRACTS
by a reduction in LV hypertrophy, and persistent PHT in a subset which may suggest irreversible PA remodelling. http://dx.doi.org/10.1016/j.hlc.2012.05.058 49 Pulmonary Vascular Capacitance Measured Using Pressurewire: A Novel Index of Pulmonary Haemodynamics Moneghetti ∗ ,
50 Redox Regulation of Na+ –K+ Pump in Vascular Smooth Muscle Cells: Implications for Vascular Tone in Heath and Disease K. Karimi Galougahi 1,2,∗ , C. Liu 1 , A. Nunez 1 , A. Garcia 1 , N. Fry 1 , H. Rasmussen 1,2 , G. Figtree 1,2 1 North Shore Heart Research Group, Kolling Institute, Australia
S. Palmer, S. Murch, A. LaGerche, D. K. Prior, A. MacIsaac, A. Burns
2 Cardiology
St Vincent’s Hospital, Australia
Na+ –K+ pump establishes electrochemical gradient across membrane in vascular smooth muscle cells (VSMCs) and is a determinant of vascular tone through effects on intracellular Ca2+ homeostatsis, but its regulation in vessels is poorly understood. We examined if glutathionylation of Na+ –K+ pump’s 1 subunit, a reversible oxidative modification shown to inhibit the pump in cardiac myocytes, occurs in VSMCs and is of physiological significance. Glutathionylation of 1 subunit was detected in rabbit VSMCs at baseline and was increased by the chemical oxidant S-nitrosoglutathion, causing a reduction in pump activity. Angiotensin II (Ang II), known to activate NADPH oxidase, increased 1 glutathionylation in VSMCs, rabbit aorta and human arteries ex vivo; and reduced pump activity in VSMCs and rabbit aorta as measured by K+ -induced relaxation of vessels pre-incubated in K+ -free solutions. Incubation of cells or vessels with gp91ds-tat, a peptide inhibitor of NADPH oxidase, abolished the Ang II effects on glutathionylation and pump activity. Angiotensin converting enzyme inhibition in vivo reduced 1 glutathionylaytion and enhanced pump activity, measured as K+ -induced relaxation, in rabbit aorta. FXYD proteins associate with the pump and play a role in regulation by facilitating “deglutathionylation” in cardiac myocytes. Recombinant FXYD3 competitively displaced native FXYD1 in VSMCs and rabbit aorta, and abolished the Ang II-induced increase in 1 glutathionylation and the reduction in pump activity. We identify a mechanism for redox regulation of Na+ –K+ pump in VSMCs with pathophysiological significance in conditions like hypertension that are characterised by oxidative stress and abnormal regulation of vascular tone.
Purpose: Pulmonary hypertension (PH) is associated with a poor prognosis regardless of aetiology. Reduced pulmonary vascular capacitance, in addition to increased resistance, may be an important determinant of pulmonary afterload and thus increasing pulmonary pressure. Methods: Subjects referred for diagnostic right heart catheterisation with suspected PH underwent assessment of pulmonary haemodynamics pre- and post-IV adenosine using a pressure and temperature-sensing guidewire (PressureWire) positioned in a second order branch pulmonary artery (PA) providing high fidelity pressure measurement and thermodilution derived mean transit time (Tmn). Capacitance index (CI, mL/mmHg) was defined as 1000/(heart rate × PA pulse pressure × Tmn). Diastolic dysfunction (DD) was defined as LVEDP greater than 18 mmHg and PH as mean PA pressure greater than 25 mmHg. Results: Thirty-one consecutive patients were analysed: 10 with pulmonary arterial hypertension (PAH, either primary or secondary to scleroderma), six had DD with PH, seven had both scleroderma and DD, four had mitral valve disease and four were normal. Adenosine infusion resulted in decreased Tmn (0.47 ± 0.05 vs 0.33 ± 0.03, p < 0.001) and increased CI (1.79 ± 0.28 vs 2.33 ± 0.3, p < 0.005), but no change in heart rate nor mean PA pressure. Higher PA pressure was associated with lower CI, both pre adenosine (r = −0.62, p < 0.003) and post adenosine (r = −0.54, p < 0.003). Conclusion: Capacitance index is reduced with increasing severity of PH and to a greater extent in patients with PAH than those with DD. This novel index may have utility in early diagnosis and tracking subtle changes in haemodynamics in patients with PH. http://dx.doi.org/10.1016/j.hlc.2012.05.059
Department, Royal North Shore Hospital,
Australia
http://dx.doi.org/10.1016/j.hlc.2012.05.060 51 Reduced Blood Pressure and Risk of Future Cardiovascular Disease from a Structured Care Algorithm in Primary Care Patients with Persistent Hypertension: A Multicentre Randomised Controlled Trial M. Carrington 1,∗ , G. Kurstjens 2 , S. Stewart 1 1 Baker
Jennings 1 , C.
Swemmer 2 , N.
IDI Heart and Diabetes Institute, Australia Pharmaceuticals Australia Pty Ltd, Australia
2 Novartis
Background: To determine the impact of reduced blood pressure (BP) on CVD risk in hypertensive primary care
Heart & Diabetes Institute, Melbourne, VIC, Australia 2 1st Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China 3 Heart Center, Alfred Hospital, Melbourne, VIC, Australia Introduction: Increased cardiovascular activity (CVA) and reactivity (CVR) to psychological stress have been identified as possible new markers for future cardiovascular risk. Animal studies showed psychological stress of pregnant mother, defined as prenatal psychological stress (PPS), modulates offspring’ CVA and CVR. How-
CSANZ 2012 Abstracts
S21
ever, the underlying mechanism is unclear and few studies have examined such possible influences in the human. We investigated the long-term effects and mechanism of PPS on CVA and CVR in seven to nine year-old children. Methods and results: we measured BP and HR at rest (rBP, rHR) and during video game stress (sBP, sHR) in 287 children whose mothers previously had thorough psychological assessment for PPS during pregnancy. rBP and rHR were used for CVA evaluation. CVR was defined as the maximum change in BP (BP) and HR (HR) in response to video game stress. Serum cortisol was serially measured before and during video game by radioimmunoassay to calculate absolute increment (cortisol). The results showed rBP and rHR, baseline cortisol (mean ± SD, 353 ± 37 nmol/L vs. 297 ± 36 nmol/L), BP (21 ± 2/12 ± 1 mmHg vs. 15 ± 1/10 ± 1 mmHg) and HR (18 ± 1 bpm vs. 13 ± 1 bpm), cortisol were all higher in children who experienced PPS than those without (all P < 0.01). Maternal effects on children’s CVA and CVR were most marked for combined maternal anxiety and depression, and least for depression alone. Conclusion: Our study confirms animal findings by demonstrating long lasting effects of PPS on offspring’s CVA and CVR in the human with likely effects on the subsequent risk of cardiovascular disease. http://dx.doi.org/10.1016/j.hlc.2012.05.057 48 Prevalence and Resolution of Pulmonary Hypertension (PHT) in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI) S. Jaijee 1,∗ , J. Yiannikis 2 , M. Wilson 1 , M. Vallely 1 , M. Ng 1 , D. Celermajer 1 1 Royal
Prince Alfred Hospital, Australia Repatriation Hospital, Australia
2 Concord
Background and aim: Left heart disease (LHD) is the most common cause of PHT but its pathogenesis is poorly understood. Severe aortic stenosis (AS) is a cause of LHD related PHT. Our aim was to assess the prevalence and time course of resolution of PHT when AS was relieved by transcatheter aortic valve implantation. Methods: We assessed 60 consecutively treated patients who underwent TAVI with serial echocardiography. PHT was defined as RV-RA pressure gradient ≥40 mmHg and a significant fall in pulmonary arterial pressure (PAP) was defined as >20% reduction in the RV-RA gradient. Results: Of 60 patients, 20/60 (33%) had PHT. From those 20 patients, six had an immediate reduction in PASP based on early echocardiography (<10 days). From the 14 patients who have reached >2 month follow up, six patients had a reduction in PAP, three had persistent PHT, one was lost to follow up and four did not have data available. Significance: In patients with PHT prior to TAVI, PAP falls in the majority but with an unpredictable time course. We have identified three patterns of response; early regression which could be related to relief of subendocardial ischaemia, late regression which may be explained
ABSTRACTS
Heart, Lung and Circulation 2012;21:S1–S142
S22
Heart, Lung and Circulation 2012;21:S1–S142
CSANZ 2012 Abstracts
ABSTRACTS
by a reduction in LV hypertrophy, and persistent PHT in a subset which may suggest irreversible PA remodelling. http://dx.doi.org/10.1016/j.hlc.2012.05.058 49 Pulmonary Vascular Capacitance Measured Using Pressurewire: A Novel Index of Pulmonary Haemodynamics Moneghetti ∗ ,
50 Redox Regulation of Na+ –K+ Pump in Vascular Smooth Muscle Cells: Implications for Vascular Tone in Heath and Disease K. Karimi Galougahi 1,2,∗ , C. Liu 1 , A. Nunez 1 , A. Garcia 1 , N. Fry 1 , H. Rasmussen 1,2 , G. Figtree 1,2 1 North Shore Heart Research Group, Kolling Institute, Australia
S. Palmer, S. Murch, A. LaGerche, D. K. Prior, A. MacIsaac, A. Burns
2 Cardiology
St Vincent’s Hospital, Australia
Na+ –K+ pump establishes electrochemical gradient across membrane in vascular smooth muscle cells (VSMCs) and is a determinant of vascular tone through effects on intracellular Ca2+ homeostatsis, but its regulation in vessels is poorly understood. We examined if glutathionylation of Na+ –K+ pump’s 1 subunit, a reversible oxidative modification shown to inhibit the pump in cardiac myocytes, occurs in VSMCs and is of physiological significance. Glutathionylation of 1 subunit was detected in rabbit VSMCs at baseline and was increased by the chemical oxidant S-nitrosoglutathion, causing a reduction in pump activity. Angiotensin II (Ang II), known to activate NADPH oxidase, increased 1 glutathionylation in VSMCs, rabbit aorta and human arteries ex vivo; and reduced pump activity in VSMCs and rabbit aorta as measured by K+ -induced relaxation of vessels pre-incubated in K+ -free solutions. Incubation of cells or vessels with gp91ds-tat, a peptide inhibitor of NADPH oxidase, abolished the Ang II effects on glutathionylation and pump activity. Angiotensin converting enzyme inhibition in vivo reduced 1 glutathionylaytion and enhanced pump activity, measured as K+ -induced relaxation, in rabbit aorta. FXYD proteins associate with the pump and play a role in regulation by facilitating “deglutathionylation” in cardiac myocytes. Recombinant FXYD3 competitively displaced native FXYD1 in VSMCs and rabbit aorta, and abolished the Ang II-induced increase in 1 glutathionylation and the reduction in pump activity. We identify a mechanism for redox regulation of Na+ –K+ pump in VSMCs with pathophysiological significance in conditions like hypertension that are characterised by oxidative stress and abnormal regulation of vascular tone.
Purpose: Pulmonary hypertension (PH) is associated with a poor prognosis regardless of aetiology. Reduced pulmonary vascular capacitance, in addition to increased resistance, may be an important determinant of pulmonary afterload and thus increasing pulmonary pressure. Methods: Subjects referred for diagnostic right heart catheterisation with suspected PH underwent assessment of pulmonary haemodynamics pre- and post-IV adenosine using a pressure and temperature-sensing guidewire (PressureWire) positioned in a second order branch pulmonary artery (PA) providing high fidelity pressure measurement and thermodilution derived mean transit time (Tmn). Capacitance index (CI, mL/mmHg) was defined as 1000/(heart rate × PA pulse pressure × Tmn). Diastolic dysfunction (DD) was defined as LVEDP greater than 18 mmHg and PH as mean PA pressure greater than 25 mmHg. Results: Thirty-one consecutive patients were analysed: 10 with pulmonary arterial hypertension (PAH, either primary or secondary to scleroderma), six had DD with PH, seven had both scleroderma and DD, four had mitral valve disease and four were normal. Adenosine infusion resulted in decreased Tmn (0.47 ± 0.05 vs 0.33 ± 0.03, p < 0.001) and increased CI (1.79 ± 0.28 vs 2.33 ± 0.3, p < 0.005), but no change in heart rate nor mean PA pressure. Higher PA pressure was associated with lower CI, both pre adenosine (r = −0.62, p < 0.003) and post adenosine (r = −0.54, p < 0.003). Conclusion: Capacitance index is reduced with increasing severity of PH and to a greater extent in patients with PAH than those with DD. This novel index may have utility in early diagnosis and tracking subtle changes in haemodynamics in patients with PH. http://dx.doi.org/10.1016/j.hlc.2012.05.059
Department, Royal North Shore Hospital,
Australia
http://dx.doi.org/10.1016/j.hlc.2012.05.060 51 Reduced Blood Pressure and Risk of Future Cardiovascular Disease from a Structured Care Algorithm in Primary Care Patients with Persistent Hypertension: A Multicentre Randomised Controlled Trial M. Carrington 1,∗ , G. Kurstjens 2 , S. Stewart 1 1 Baker
Jennings 1 , C.
Swemmer 2 , N.
IDI Heart and Diabetes Institute, Australia Pharmaceuticals Australia Pty Ltd, Australia
2 Novartis
Background: To determine the impact of reduced blood pressure (BP) on CVD risk in hypertensive primary care