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Håvard E. Danielsen - One of the best experts on this subject based on the ideXlab platform.
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increased passive stiffness promotes diastolic dysfunction despite improved ca2 handling during left ventricular Concentric Hypertrophy
Cardiovascular Research, 2017Co-Authors: Åsmund T. Røe, Jan Magnus Aronsen, Kristine Skårdal, Nazha Hamdani, Wolfgang A. Linke, Håvard E. Danielsen, Ole M. SejerstedAbstract:Aims Concentric Hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the Concentrically hypertrophied heart following pressure-overload. Methods and results Rats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular Concentric Hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e' values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+]. Conclusion In the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis.
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Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular Concentric Hypertrophy
Cardiovascular research, 2017Co-Authors: Åsmund T. Røe, Jan Magnus Aronsen, Kristine Skårdal, Nazha Hamdani, Wolfgang A. Linke, Håvard E. Danielsen, Ole M. Sejersted, Ivar Sjaastad, William E. LouchAbstract:Concentric Hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the Concentrically hypertrophied heart following pressure-overload. Rats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular Concentric Hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e' values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+]. In the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.
Carmine Zoccali - One of the best experts on this subject based on the ideXlab platform.
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fibrinogen inflammation and Concentric left ventricular Hypertrophy in chronic renal failure
European Journal of Clinical Investigation, 2003Co-Authors: Carmine Zoccali, F. A. Benedetto, F. Mallamaci, G. Tripepi, Sebastiano Cutrupi, Saverio Parlongo, Lorenzo Malatino, G. Bonanno, Francesco Rapisarda, Pasquale FatuzzoAbstract:Background We investigated the relationship between fibrinogen and echocardiographic measurements of left ventricular (LV) geometry and LV function in a group of 192 patients with end stage renal disease (ESRD). Results Patients in the third fibrinogen tertile had higher mean wall thickness (MWT), relative wall thickness (RWT) and left ventricular mass index (LVMI) and lower LV end diastolic diameter and LV ejection fraction than those in the other tertiles. On multivariate analysis fibrinogen resulted to be an independent correlate of MWT (P = 0·001) and RWT (P = 0·0001) and the first factor in rank explaining the variance in LV ejection fraction (P = 0·0001). Left ventricular Concentric Hypertrophy was more prevalent (P = 0·001) in patients in the third fibrinogen tertile (n = 35, 54%) than in those in the second (n = 24, 37%) and first (n = 13, 21%) tertiles. In a multiple logistic regression model patients in the third tertile of fibrinogen had a risk for left ventricular Concentric Hypertrophy that was 3·56 (95%CI: 1·56–8·14) fold higher than in those in the first tertile (P = 0·003). Conclusions Elevated fibrinogen is independently associated with LV Concentric Hypertrophy and systolic dysfunction in ESRD patients. These relationships may contribute to the negative prognostic impact of elevated fibrinogen levels in ESRD.
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Fibrinogen, inflammation and Concentric left ventricular Hypertrophy in chronic renal failure.
European journal of clinical investigation, 2003Co-Authors: Carmine Zoccali, F. A. Benedetto, F. Mallamaci, G. Tripepi, Sebastiano Cutrupi, Saverio Parlongo, Lorenzo Malatino, G. Bonanno, Francesco Rapisarda, Pasquale FatuzzoAbstract:We investigated the relationship between fibrinogen and echocardiographic measurements of left ventricular (LV) geometry and LV function in a group of 192 patients with end stage renal disease (ESRD). Patients in the third fibrinogen tertile had higher mean wall thickness (MWT), relative wall thickness (RWT) and left ventricular mass index (LVMI) and lower LV end diastolic diameter and LV ejection fraction than those in the other tertiles. On multivariate analysis fibrinogen resulted to be an independent correlate of MWT (P = 0.001) and RWT (P = 0.0001) and the first factor in rank explaining the variance in LV ejection fraction (P = 0.0001). Left ventricular Concentric Hypertrophy was more prevalent (P = 0.001) in patients in the third fibrinogen tertile (n = 35, 54%) than in those in the second (n = 24, 37%) and first (n = 13, 21%) tertiles. In a multiple logistic regression model patients in the third tertile of fibrinogen had a risk for left ventricular Concentric Hypertrophy that was 3.56 (95% CI: 1.56-8.14) fold higher than in those in the first tertile (P = 0.003). Elevated fibrinogen is independently associated with LV Concentric Hypertrophy and systolic dysfunction in ESRD patients. These relationships may contribute to the negative prognostic impact of elevated fibrinogen levels in ESRD.
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Norepinephrine and Concentric Hypertrophy in Patients With End-Stage Renal Disease
Hypertension (Dallas Tex. : 1979), 2002Co-Authors: Carmine Zoccali, Francesca Mallamaci, Giovanni Tripepi, Francesco A. Benedetto, Sebastiano Cutrupi, Saverio Parlongo, Alessandro Cataliotti, Lorenzo MalatinoAbstract:We have recently observed that in patients with end-stage renal disease (ESRD) raised plasma norepinephrine (NE) is an independent predictor of incident cardiovascular events but that its prognostic power is reduced when this sympathetic marker is tested in statistical models including also left ventricular mass. Because left ventricular Hypertrophy (LVH) may be a mechanism whereby NE contributes to the high rate of cardiovascular events in ESRD, we examined the relationship between plasma NE and echocardiographic parameters of left ventricle mass in a large group of ESRD patients. Mean wall thickness (MWT) was higher in patients in the third NE tertile than in the other 2 tertiles (P=0.001), and such an increase was paralleled by a rise in relative wall thickness (RWT) (P=0.006). Concentric LVH was more prevalent in patients in the third NE tertile (46%) than in the second (38%) and first (25%) NE tertiles. Multivariate regression analysis confirmed that the association of plasma NE with the muscular component of left ventricle (MWT) and with RWT was independent (P< or =0.001) of other cardiovascular risk factors, and in these models, plasma NE ranked as the second correlate of MWT and RWT. Similarly, multiple logistic regression analysis showed that the association of plasma NE with Concentric LVH was strong and again independent of other risk factors (P=0.003). Plasma NE is associated to Concentric LVH in ESRD patients. These observations constitute a sound basis for testing the effect of anti-adrenergic drugs on left ventricle mass and on cardiovascular outcomes in patients with ESRD.
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Autonomic neuropathy is linked to nocturnal hypoxaemia and to Concentric Hypertrophy and remodelling in dialysis patients
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2001Co-Authors: Carmine Zoccali, Francesca Mallamaci, Giovanni Tripepi, Francesco A. BenedettoAbstract:Autonomic dysfunction and sleep apnoea are frequent complications of chronic renal failure. Since nocturnal hypoxaemia in sleep apnoea dampens autonomic reflexes, we postulated that altered autonomic control is in part linked to nocturnal hypoxaemia in uraemic patients. To test the hypothesis we performed continuous monitoring of O(2) saturation during night by pulse oximetry (Ohmeda-Biox) as well as echocardiography, 24-h ambulatory blood pressure monitoring, and standard tests of autonomic function in 50 patients on chronic dialysis (40 on haemodialysis and 10 on CAPD). For haemodialysis patients all studies were performed during a mid-week non-dialysis day. Twenty-five patients had at least one episode of nocturnal hypoxaemia (median 13, interquartile range 4-31) while the other 25 patients had no episodes at all. Minimal and average SaO(2) were strongly interrelated (r = 0.64, P = 0.0001). In a multiple regression model, besides age, average nocturnal SaO(2) was the only independent predictor of the parasympathetic function. Similarly, average nocturnal SaO(2) was the only independent predictor of the autonomic response to standing. Sex, 24-h mean arterial pressure, body mass index, haematocrit, serum albumin, serum parathyroid hormone and duration of dialysis treatment had no independent effect on the autonomic tests. Interestingly, the average nocturnal SaO(2) and the interaction between the responses to the autonomic tests were independently related to posterior-wall thickness. This interaction term represented also the stronger independent predictor of the relative wall thickness of the left ventricle. In a multiple logistic regression model the interaction parasympathetic-sympathetic function was the only independent predictor of Concentric remodelling or Hypertrophy, while average nocturnal SaO(2) entered into this model (P = 0.03) only after exclusion of the autonomic function interaction term. Thus, altered cardiovascular autonomic control appears to be linked to nocturnal hypoxaemia and to Concentric Hypertrophy or remodelling in dialysis patients. Since nocturnal hypoxaemia is an established cardiovascular risk factor, altered autonomic control is a potential mechanism whereby hypoxaemia may trigger cardiovascular events in dialysis patients. It remains to be seen whether the link between nocturnal hypoxaemia and autonomic dysfunction is a causal one.
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autonomic neuropathy is linked to nocturnal hypoxaemia and to Concentric Hypertrophy and remodelling in dialysis patients
Nephrology Dialysis Transplantation, 2001Co-Authors: Carmine Zoccali, Francesca Mallamaci, Giovanni Tripepi, Francesco A. BenedettoAbstract:Background Autonomic dysfunction and sleep apnoea are frequent complications of chronic renal failure. Since nocturnal hypoxaemia in sleep apnoea dampens autonomic reflexes, we postulated that altered autonomic control is in part linked to nocturnal hypoxaemia in uraemic patients. Methods To test the hypothesis we performed continuous monitoring of O(2) saturation during night by pulse oximetry (Ohmeda-Biox) as well as echocardiography, 24-h ambulatory blood pressure monitoring, and standard tests of autonomic function in 50 patients on chronic dialysis (40 on haemodialysis and 10 on CAPD). For haemodialysis patients all studies were performed during a mid-week non-dialysis day. Results Twenty-five patients had at least one episode of nocturnal hypoxaemia (median 13, interquartile range 4-31) while the other 25 patients had no episodes at all. Minimal and average SaO(2) were strongly interrelated (r = 0.64, P = 0.0001). In a multiple regression model, besides age, average nocturnal SaO(2) was the only independent predictor of the parasympathetic function. Similarly, average nocturnal SaO(2) was the only independent predictor of the autonomic response to standing. Sex, 24-h mean arterial pressure, body mass index, haematocrit, serum albumin, serum parathyroid hormone and duration of dialysis treatment had no independent effect on the autonomic tests. Interestingly, the average nocturnal SaO(2) and the interaction between the responses to the autonomic tests were independently related to posterior-wall thickness. This interaction term represented also the stronger independent predictor of the relative wall thickness of the left ventricle. In a multiple logistic regression model the interaction parasympathetic-sympathetic function was the only independent predictor of Concentric remodelling or Hypertrophy, while average nocturnal SaO(2) entered into this model (P = 0.03) only after exclusion of the autonomic function interaction term. Conclusions Thus, altered cardiovascular autonomic control appears to be linked to nocturnal hypoxaemia and to Concentric Hypertrophy or remodelling in dialysis patients. Since nocturnal hypoxaemia is an established cardiovascular risk factor, altered autonomic control is a potential mechanism whereby hypoxaemia may trigger cardiovascular events in dialysis patients. It remains to be seen whether the link between nocturnal hypoxaemia and autonomic dysfunction is a causal one.
Ayodele O. Falase - One of the best experts on this subject based on the ideXlab platform.
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Left Ventricular Geometric Patterns in Normotensive Type 2 Diabetic Patients in Nigeria: An Echocardiographic Study
Preventive cardiology, 2009Co-Authors: Dike B. Ojji, Adewole A Adebiyi, Olulola O Oladapo, Jokotade Adeleye, Akinyemi Aje, Okechukwu S Ogah, Adedeji K Adebayo, Ayodele O. FalaseAbstract:Left ventricular Hypertrophy has been linked with diabetes mellitus and abnormal glucose tolerance in several studies. Most previous studies have been carried out in the western world with dearth of data in native Africans. A total of 122 type 2 diabetic patients with a mean age of 55.0+/-8.5 years and another 90 normal patients with a mean age of 55.4+/-8.7 years were recruited for the study. Two-dimensional guided M-mode echocardiography was performed on each patient. In the diabetic patients, 49.2% had normal geometry, 23.0% had Concentric Hypertrophy, 13.0% had Concentric remodeling, and 14.8% had eccentric Hypertrophy. In the control group, 72.2% had normal geometry, 4.4% had Concentric Hypertrophy, 11.2% had Concentric remodeling, and 12.2% had eccentric Hypertrophy. In a multiple regression analysis, there was significant difference in the geometric pattern of the diabetics and controls (chi(2)=11.09, P
Ole M. Sejersted - One of the best experts on this subject based on the ideXlab platform.
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increased passive stiffness promotes diastolic dysfunction despite improved ca2 handling during left ventricular Concentric Hypertrophy
Cardiovascular Research, 2017Co-Authors: Åsmund T. Røe, Jan Magnus Aronsen, Kristine Skårdal, Nazha Hamdani, Wolfgang A. Linke, Håvard E. Danielsen, Ole M. SejerstedAbstract:Aims Concentric Hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the Concentrically hypertrophied heart following pressure-overload. Methods and results Rats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular Concentric Hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e' values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+]. Conclusion In the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis.
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Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular Concentric Hypertrophy
Cardiovascular research, 2017Co-Authors: Åsmund T. Røe, Jan Magnus Aronsen, Kristine Skårdal, Nazha Hamdani, Wolfgang A. Linke, Håvard E. Danielsen, Ole M. Sejersted, Ivar Sjaastad, William E. LouchAbstract:Concentric Hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the Concentrically hypertrophied heart following pressure-overload. Rats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular Concentric Hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e' values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+]. In the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.
Jan Magnus Aronsen - One of the best experts on this subject based on the ideXlab platform.
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increased passive stiffness promotes diastolic dysfunction despite improved ca2 handling during left ventricular Concentric Hypertrophy
Cardiovascular Research, 2017Co-Authors: Åsmund T. Røe, Jan Magnus Aronsen, Kristine Skårdal, Nazha Hamdani, Wolfgang A. Linke, Håvard E. Danielsen, Ole M. SejerstedAbstract:Aims Concentric Hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the Concentrically hypertrophied heart following pressure-overload. Methods and results Rats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular Concentric Hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e' values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+]. Conclusion In the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis.
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Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular Concentric Hypertrophy
Cardiovascular research, 2017Co-Authors: Åsmund T. Røe, Jan Magnus Aronsen, Kristine Skårdal, Nazha Hamdani, Wolfgang A. Linke, Håvard E. Danielsen, Ole M. Sejersted, Ivar Sjaastad, William E. LouchAbstract:Concentric Hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the Concentrically hypertrophied heart following pressure-overload. Rats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular Concentric Hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e' values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+]. In the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.