Johannes Patzelt - Academia.edu (original) (raw)

Papers by Johannes Patzelt

Research paper thumbnail of Improved mid-term stability of MR reduction with an increased number of clips after percutaneous mitral valve repair in functional MR

IJC Heart & Vasculature, Apr 1, 2023

Research paper thumbnail of P4714Individual patient data meta-analysis comparing general anesthesia and deep sedation on safety and length of intensive care unit stay in patients undergoing percutaneous mitral valve repair

European Heart Journal, Oct 1, 2019

Background Percutaneous edge-to-edge mitral valve repair (PMVR) has emerged as a treatment option... more Background Percutaneous edge-to-edge mitral valve repair (PMVR) has emerged as a treatment option for patients with severe mitral regurgitation not considered suitable candidates for surgery. The procedure can be performed in general anesthesia (GA) or deep sedation (DS) without mechanical ventilation. However, debate remains about the optimal approach. Purpose To compare the impact of the anesthetic method on efficacy, safety, and length of intensive care stay. Methods We identified studies comparing GA versus DS in patients undergoing PMVR by searching PubMed and CENTRAL. We included studies for which investigators agreed to provide individual patient data. Analyzed outcomes were a composite safety endpoint comprising all-cause death, stroke, pneumonia, and major to life-threating bleeding as well as length of intensive care unit stay. We performed an one-stage and two-stage meta-analysis on each outcome after multiple imputation of missing data. For two-stage meta-analysis, between-study heterogeneity was estimated according to Paule-Mandel and confidence intervals were derived using the method proposed by Hartung and Knapp. Results We included five observational studies (n=647 patients). Procedural success was achieved in 618 of 647 (95.5%) patients. The composite safety endpoint occurred in 92 of 647 (14.2%) patients with no difference between patients treated with GA or DS. In this regard, risk ratio was 0.78 (95% confidence interval, 0.53 to 1.14; P=0.20) following the one-stage approach and 0.73 (95% confidence interval, 0.30 to 1.80; P=0.39) following the two-stage approach. Length of intensive care stay was longer after GA as compared to DS (adjusted mixed linear regression model, 1.94 days, 95% confidence interval, 1.29 to 2.59 days, P<0.001; random effects model pooling study-specific estimates from adjusted linear models 1.40 days, 95% confidence interval, 0.54 to 2.22 days, P=0.0104). Conclusion Both, DS and GA offer good procedural success rates and a similar safety profile. However, length of intensive care stay is shorter after DS.

Research paper thumbnail of P2575Comparison of deep sedation with general anesthesia in patients undergoing percutaneous mitral valve repair (PMVR)

European Heart Journal, Aug 1, 2018

Research paper thumbnail of P4724Elevated mitral valve pressure gradient is predictive for long-term outcome after percutaneous edge-to-edge mitral valve repair (PMVR) in patients with degenerative MR, but not in functional MR

European Heart Journal, Oct 1, 2019

Research paper thumbnail of Improved mid-term stability of MR reduction with an increased number of clips after percutaneous mitral valve repair in functional MR

IJC Heart & Vasculature

Research paper thumbnail of P4724Elevated mitral valve pressure gradient is predictive for long-term outcome after percutaneous edge-to-edge mitral valve repair (PMVR) in patients with degenerative MR, but not in functional MR

European Heart Journal, 2019

Background To analyze the effects of residual mitral regurgitation (MR) and mean mitral valve pre... more Background To analyze the effects of residual mitral regurgitation (MR) and mean mitral valve pressure gradient (MVPG) after percutaneous edge-to-edge mitral valve repair (PMVR) using the MitraClip-system on long term outcome. Methods and results Two hundred fifty-five patients who underwent PMVR were analyzed. Kaplan-Meier and Cox regression analyses were performed to evaluate the impact of residual MR and MVPG on clinical outcome. A combined clinical endpoint (all-cause mortality, MV surgery, redo procedure, implantation of a left ventricular assist device) was used. After PMVR, mean MVPG increased from 1.6±1.0 mmHg to 3.1±1.5 mmHg (p<0.001). Reduction of MR severity to ≤2+ postintervention was achieved in 98.4% of all patients. In the overall patient cohort, residual MR was predictive for the combined endpoint while elevated MVPG >4.4 mmHg was not according to Kaplan-Meier and Cox regression analyses. We then analyzed the cohort with degenerative and that with functional MR...

Research paper thumbnail of Flow alterations caused by cerebral protection devices during carotid angioplasty. A fluid dynamics study in a carotid artery model

Journal of Biomechanics, 2006

Purpose: to study the influence of different cerebral protection devices on flow patterns in caro... more Purpose: to study the influence of different cerebral protection devices on flow patterns in carotid artery models. Material and Methods: three different protection devices (Embo shield from

Research paper thumbnail of Platelets and Innate Immunity in Atherosclerosis

Cardiac and Vascular Biology, 2017

Platelets are classically considered initiators of hemostasis and-in pathology-intravascular thro... more Platelets are classically considered initiators of hemostasis and-in pathology-intravascular thrombosis causing diseases such as myocardial infarction or stroke. However, platelets are also mediators of innate immunity, secrete inflammatory proteins, mediate leukocyte recruitment, and contribute to tissue remodeling. Inflammation and innate immunity have common intersection points with the hemostatic system at various levels. With the complement system being part of the innate immune system, this chapter focuses on the role of platelets and the complement system in the context of atherosclerosis.

Research paper thumbnail of Deep Sedation versus General Anaesthesia for Transcatheter Mitral Valve Repair: An Individual-Patient Data Meta-analysis of Observational Studies

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 2020

AIMS To compare general anaesthesia (GA) and deep sedation (DS) with regard to safety and length ... more AIMS To compare general anaesthesia (GA) and deep sedation (DS) with regard to safety and length of intensive care unit (ICU) stay in patients undergoing percutaneous edge-to-edge mitral valve repair (PMVR). METHODS AND RESULTS Four studies comparing GA and DS in patients undergoing PMVR were included in an individual patient data meta-analysis. Data were pooled after multiple imputation. The composite safety endpoint of all-cause death, stroke, pneumonia, or major to life-threatening bleeding occurred in 87 of 626 (13.9%) patients with no difference between patients treated with DS as compared to GA (56 and 31 events in 420 and 206 patients, respectively). In this regard, the odds ratio was 1.27 (95% confidence interval, 0.78 to 2.09; p = 0.338) and 1.26 (95% confidence interval, 0.49 to 3.22; p = 0.496) following the one-stage and two-stage approach, respectively. Length of ICU stay was longer after GA as compared to DS (ratio of days 3.08, 95% confidence interval, 2.18 to 4.36, p...

Research paper thumbnail of Strömungsuntersuchungen am Modell einer humanen Karotisbifurkation mittels Laser-Doppler-Anemometrie bei Einsatz dreier verschiedener Filterprotektionssysteme

Die endovaskulare Rekonstruktion der Karotisbifurkation wird bei offenem Blutstrom durchgefuhrt. ... more Die endovaskulare Rekonstruktion der Karotisbifurkation wird bei offenem Blutstrom durchgefuhrt. Um das Risiko einer cerebralen Embolie bei der Operation zu minimieren, werden passager sog. neuroprotektive Filter eingesetzt. Im Karotismodell wurden durch Laser-Doppler-Anemometrie-Messung die Auswirkungen dieser Filter (drei unterschiedliche Systeme: FilterWire, Rx AccuNet, EmboShield) auf die Stromungsmechanik untersucht. Das physiologische Flussprofil wurde detailgenau nachgebildet, die Messung der Stromung erfolgte beruhrungslos mittels Laser-Doppler-Anemometrie.

Research paper thumbnail of Percutaneous Mitral Valve Edge-to-Edge Repair With Simultaneous Biatrial Intracardiac Echocardiography: First-in-Human Experience

Circulation, Jan 12, 2016

Research paper thumbnail of Percutaneous mitral valve repair (PMVR) in a patient with recurrence of mitral regurgitation 17years after surgical reconstruction

International journal of cardiology, Jan 5, 2015

Research paper thumbnail of Cardiac arrest saves a patient's procedure

International Journal of Cardiology, 2015

Research paper thumbnail of Platelets and the complement cascade in atherosclerosis

Frontiers in Physiology, 2015

Atherosclerosis and its late sequels are still the number one cause of death in western societies... more Atherosclerosis and its late sequels are still the number one cause of death in western societies. Platelets are a driving force not only during the genesis of atherosclerosis, but especially in its late stages, as evidenced by complications such as arterial thrombosis, myocardial infarction, and ischemic stroke. Atherosclerosis is increasingly recognized as an inflammatory disease, influenced by various immune mechanisms. The complement system is part of our innate immune system, and its diverse roles in atherosclerosis have become evident over the past years. In this review we identify points of intersection between platelets and the complement system and discuss their relevance for atherosclerosis. Specifically, we will focus on roles for platelets in the onset as well as progression of the disease, a possible dual role for complement in the genesis and development of atherosclerosis, and review emerging literature revealing previously unrecognized cross-talk between platelets and the complement system and discuss its possible impact for atherosclerosis. Finally, we identify limitations of current research approaches and discuss perspectives of complement modulation in the control of the disease.

Research paper thumbnail of Platelets in Angiogenesis

Current Vascular Pharmacology, 2012

Platelets hold an important function as first line of response to seal wounds after vascular and ... more Platelets hold an important function as first line of response to seal wounds after vascular and tissue injury. However, they are much more than just a component of the haemostatic system. They are involved in tissue regeneration and play a role in different pathologic conditions such as atherosclerosis or tumour progression. Angiogenesis being involved in these processes, as well, may represent one of the (patho-) physiological mechanisms, which are modulated by platelets thereby affecting disease. In other diseases involving inflammation, the role of platelets for endothelial cells, which are the most important cell type in angiogenesis, is well established. Recent effort has now highlighted a potential role of platelets and platelet derived mediators for angiogenesis. This article reviews our current understanding of the role of platelets for angiogenesis and how this knowledge could affect future directions in research and therapy.

Research paper thumbnail of The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets

Nature Communications, 2021

Platelets contribute to the regulation of tissue neovascularization, although the specific factor... more Platelets contribute to the regulation of tissue neovascularization, although the specific factors underlying this function are unknown. Here, we identified the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation. Growth factor- and hypoxia-driven vascularization was markedly increased in C5ar1−/− mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with increased collateralization, capillarization and improved pericyte coverage. Mechanistically, we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4) from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo.In concl...

Research paper thumbnail of Reduced left ventricular contractility, increased diastolic operant stiffness and high energetic expenditure in patients with severe aortic regurgitation without indication for surgery

Interactive CardioVascular and Thoracic Surgery

OBJECTIVES Recent mortality studies showed worse prognosis in patients (ARNS) with severe aortic ... more OBJECTIVES Recent mortality studies showed worse prognosis in patients (ARNS) with severe aortic regurgitation and preserved ejection fraction (EF) not fulfilling the criteria of current guidelines for surgery. The aim of our study was to analyse left ventricular (LV) systolic and diastolic function and mechanical energetics to find haemodynamic explanations for the reduced prognosis of these patients and to seek a new concept for surgery. METHODS Global longitudinal strain (GLS) and echo-based single-beat pressure–volume analyses were performed in patients with ARNS (LV end-diastolic diameter <70 mm, EF >50%, GLS > −19% n = 41), with indication for surgery (ARS; n = 19) and in mild hypertensive controls (C; n = 20). Additionally, end-systolic elastance (LV contractility), stroke work and total energy (pressure–volume area) were calculated. RESULTS ARNS demonstrated significantly depressed LV contractility versus C: end-systolic elastance (1.58 ± 0.7 vs 2.54 ± 0.8 mmHg/ml; ...

Research paper thumbnail of Acute changes of global and longitudinal right ventricular function: an exploratory analysis in patients undergoing open-chest mitral valve surgery, percutaneous mitral valve repair and off-pump coronary artery bypass grafting

Cardiovascular Ultrasound

Background Right ventricular (RV) function is an important prognostic indicator. The acute effect... more Background Right ventricular (RV) function is an important prognostic indicator. The acute effects of cardiac interventions or cardiac surgery on global and longitudinal RV function are not entirely understood. In this study, acute changes of RV function during mitral valve surgery (MVS), percutaneous mitral valve repair (PMVR) and off-pump coronary artery bypass surgery (OPCAB) were investigated employing 3D echocardiography. Methods Twenty patients scheduled for MVS, 23 patients scheduled for PMVR and 25 patients scheduled for OPCAB were included retrospectively if patients had received 3D transesophageal echocardiography before and immediately after MVS, PMVR or OPCAB, respectively. RV global and longitudinal function was assessed using a 3D multiparameter set consisting of global right ventricular ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE), longitudinal contribution to RVEF (RVEFlong) and free wall longitudinal strain (FWLS). Results Longitudina...

Research paper thumbnail of Previous TAVR in patients undergoing percutaneous edge-to-edge mitral valve repair (PMVR) affects improvement of MR

PLOS ONE

Background Patients after transcatheter aortic valve replacement (TAVR) and persistent severe mit... more Background Patients after transcatheter aortic valve replacement (TAVR) and persistent severe mitral regurgitation (MR) are increasingly treated with percutaneous edge-to-edge mitral valve repair (PMVR). The impact of a former TAVR on PMVR procedures is not clear. Methods and results We retrospectively analyzed 332 patients undergoing PMVR using the MitraClip system with respect to procedural and clinical outcome. 21 of these 332 patients underwent TAVR before PMVR. Intra-procedural transthoracic (TTE) and transesophageal echocardiograms (TEE) immediately before and after clip implantation as well as invasive hemodynamic measurements were evaluated. At baseline, we found a significantly smaller mitral valve anterior-posterior diameter in the TAVR cohort (p < 0.001). A reduction of MR by at least three grades was achieved in a smaller fraction in the TAVR cohort as compared to the cohort with a native aortic valve (p = 0.02). Accordingly, we observed a smaller post-procedural cardiac output in the TAVR cohort (p = 0.02). Conclusion PMVR in patients who had a TAVR before, is associated with altered MR anatomy before and a reduced improvement of MR after the procedure. Future larger and prospective studies will have to determine, whether a previous TAVR influences long-term clinical outcome of patients undergoing PMVR.

Research paper thumbnail of Treatment of Recurrent MR by MitraClip XTR in a Patient With a PASCAL Device

JACC: Cardiovascular Interventions

Research paper thumbnail of Improved mid-term stability of MR reduction with an increased number of clips after percutaneous mitral valve repair in functional MR

IJC Heart & Vasculature, Apr 1, 2023

Research paper thumbnail of P4714Individual patient data meta-analysis comparing general anesthesia and deep sedation on safety and length of intensive care unit stay in patients undergoing percutaneous mitral valve repair

European Heart Journal, Oct 1, 2019

Background Percutaneous edge-to-edge mitral valve repair (PMVR) has emerged as a treatment option... more Background Percutaneous edge-to-edge mitral valve repair (PMVR) has emerged as a treatment option for patients with severe mitral regurgitation not considered suitable candidates for surgery. The procedure can be performed in general anesthesia (GA) or deep sedation (DS) without mechanical ventilation. However, debate remains about the optimal approach. Purpose To compare the impact of the anesthetic method on efficacy, safety, and length of intensive care stay. Methods We identified studies comparing GA versus DS in patients undergoing PMVR by searching PubMed and CENTRAL. We included studies for which investigators agreed to provide individual patient data. Analyzed outcomes were a composite safety endpoint comprising all-cause death, stroke, pneumonia, and major to life-threating bleeding as well as length of intensive care unit stay. We performed an one-stage and two-stage meta-analysis on each outcome after multiple imputation of missing data. For two-stage meta-analysis, between-study heterogeneity was estimated according to Paule-Mandel and confidence intervals were derived using the method proposed by Hartung and Knapp. Results We included five observational studies (n=647 patients). Procedural success was achieved in 618 of 647 (95.5%) patients. The composite safety endpoint occurred in 92 of 647 (14.2%) patients with no difference between patients treated with GA or DS. In this regard, risk ratio was 0.78 (95% confidence interval, 0.53 to 1.14; P=0.20) following the one-stage approach and 0.73 (95% confidence interval, 0.30 to 1.80; P=0.39) following the two-stage approach. Length of intensive care stay was longer after GA as compared to DS (adjusted mixed linear regression model, 1.94 days, 95% confidence interval, 1.29 to 2.59 days, P&amp;amp;lt;0.001; random effects model pooling study-specific estimates from adjusted linear models 1.40 days, 95% confidence interval, 0.54 to 2.22 days, P=0.0104). Conclusion Both, DS and GA offer good procedural success rates and a similar safety profile. However, length of intensive care stay is shorter after DS.

Research paper thumbnail of P2575Comparison of deep sedation with general anesthesia in patients undergoing percutaneous mitral valve repair (PMVR)

European Heart Journal, Aug 1, 2018

Research paper thumbnail of P4724Elevated mitral valve pressure gradient is predictive for long-term outcome after percutaneous edge-to-edge mitral valve repair (PMVR) in patients with degenerative MR, but not in functional MR

European Heart Journal, Oct 1, 2019

Research paper thumbnail of Improved mid-term stability of MR reduction with an increased number of clips after percutaneous mitral valve repair in functional MR

IJC Heart & Vasculature

Research paper thumbnail of P4724Elevated mitral valve pressure gradient is predictive for long-term outcome after percutaneous edge-to-edge mitral valve repair (PMVR) in patients with degenerative MR, but not in functional MR

European Heart Journal, 2019

Background To analyze the effects of residual mitral regurgitation (MR) and mean mitral valve pre... more Background To analyze the effects of residual mitral regurgitation (MR) and mean mitral valve pressure gradient (MVPG) after percutaneous edge-to-edge mitral valve repair (PMVR) using the MitraClip-system on long term outcome. Methods and results Two hundred fifty-five patients who underwent PMVR were analyzed. Kaplan-Meier and Cox regression analyses were performed to evaluate the impact of residual MR and MVPG on clinical outcome. A combined clinical endpoint (all-cause mortality, MV surgery, redo procedure, implantation of a left ventricular assist device) was used. After PMVR, mean MVPG increased from 1.6±1.0 mmHg to 3.1±1.5 mmHg (p<0.001). Reduction of MR severity to ≤2+ postintervention was achieved in 98.4% of all patients. In the overall patient cohort, residual MR was predictive for the combined endpoint while elevated MVPG >4.4 mmHg was not according to Kaplan-Meier and Cox regression analyses. We then analyzed the cohort with degenerative and that with functional MR...

Research paper thumbnail of Flow alterations caused by cerebral protection devices during carotid angioplasty. A fluid dynamics study in a carotid artery model

Journal of Biomechanics, 2006

Purpose: to study the influence of different cerebral protection devices on flow patterns in caro... more Purpose: to study the influence of different cerebral protection devices on flow patterns in carotid artery models. Material and Methods: three different protection devices (Embo shield from

Research paper thumbnail of Platelets and Innate Immunity in Atherosclerosis

Cardiac and Vascular Biology, 2017

Platelets are classically considered initiators of hemostasis and-in pathology-intravascular thro... more Platelets are classically considered initiators of hemostasis and-in pathology-intravascular thrombosis causing diseases such as myocardial infarction or stroke. However, platelets are also mediators of innate immunity, secrete inflammatory proteins, mediate leukocyte recruitment, and contribute to tissue remodeling. Inflammation and innate immunity have common intersection points with the hemostatic system at various levels. With the complement system being part of the innate immune system, this chapter focuses on the role of platelets and the complement system in the context of atherosclerosis.

Research paper thumbnail of Deep Sedation versus General Anaesthesia for Transcatheter Mitral Valve Repair: An Individual-Patient Data Meta-analysis of Observational Studies

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 2020

AIMS To compare general anaesthesia (GA) and deep sedation (DS) with regard to safety and length ... more AIMS To compare general anaesthesia (GA) and deep sedation (DS) with regard to safety and length of intensive care unit (ICU) stay in patients undergoing percutaneous edge-to-edge mitral valve repair (PMVR). METHODS AND RESULTS Four studies comparing GA and DS in patients undergoing PMVR were included in an individual patient data meta-analysis. Data were pooled after multiple imputation. The composite safety endpoint of all-cause death, stroke, pneumonia, or major to life-threatening bleeding occurred in 87 of 626 (13.9%) patients with no difference between patients treated with DS as compared to GA (56 and 31 events in 420 and 206 patients, respectively). In this regard, the odds ratio was 1.27 (95% confidence interval, 0.78 to 2.09; p = 0.338) and 1.26 (95% confidence interval, 0.49 to 3.22; p = 0.496) following the one-stage and two-stage approach, respectively. Length of ICU stay was longer after GA as compared to DS (ratio of days 3.08, 95% confidence interval, 2.18 to 4.36, p...

Research paper thumbnail of Strömungsuntersuchungen am Modell einer humanen Karotisbifurkation mittels Laser-Doppler-Anemometrie bei Einsatz dreier verschiedener Filterprotektionssysteme

Die endovaskulare Rekonstruktion der Karotisbifurkation wird bei offenem Blutstrom durchgefuhrt. ... more Die endovaskulare Rekonstruktion der Karotisbifurkation wird bei offenem Blutstrom durchgefuhrt. Um das Risiko einer cerebralen Embolie bei der Operation zu minimieren, werden passager sog. neuroprotektive Filter eingesetzt. Im Karotismodell wurden durch Laser-Doppler-Anemometrie-Messung die Auswirkungen dieser Filter (drei unterschiedliche Systeme: FilterWire, Rx AccuNet, EmboShield) auf die Stromungsmechanik untersucht. Das physiologische Flussprofil wurde detailgenau nachgebildet, die Messung der Stromung erfolgte beruhrungslos mittels Laser-Doppler-Anemometrie.

Research paper thumbnail of Percutaneous Mitral Valve Edge-to-Edge Repair With Simultaneous Biatrial Intracardiac Echocardiography: First-in-Human Experience

Circulation, Jan 12, 2016

Research paper thumbnail of Percutaneous mitral valve repair (PMVR) in a patient with recurrence of mitral regurgitation 17years after surgical reconstruction

International journal of cardiology, Jan 5, 2015

Research paper thumbnail of Cardiac arrest saves a patient's procedure

International Journal of Cardiology, 2015

Research paper thumbnail of Platelets and the complement cascade in atherosclerosis

Frontiers in Physiology, 2015

Atherosclerosis and its late sequels are still the number one cause of death in western societies... more Atherosclerosis and its late sequels are still the number one cause of death in western societies. Platelets are a driving force not only during the genesis of atherosclerosis, but especially in its late stages, as evidenced by complications such as arterial thrombosis, myocardial infarction, and ischemic stroke. Atherosclerosis is increasingly recognized as an inflammatory disease, influenced by various immune mechanisms. The complement system is part of our innate immune system, and its diverse roles in atherosclerosis have become evident over the past years. In this review we identify points of intersection between platelets and the complement system and discuss their relevance for atherosclerosis. Specifically, we will focus on roles for platelets in the onset as well as progression of the disease, a possible dual role for complement in the genesis and development of atherosclerosis, and review emerging literature revealing previously unrecognized cross-talk between platelets and the complement system and discuss its possible impact for atherosclerosis. Finally, we identify limitations of current research approaches and discuss perspectives of complement modulation in the control of the disease.

Research paper thumbnail of Platelets in Angiogenesis

Current Vascular Pharmacology, 2012

Platelets hold an important function as first line of response to seal wounds after vascular and ... more Platelets hold an important function as first line of response to seal wounds after vascular and tissue injury. However, they are much more than just a component of the haemostatic system. They are involved in tissue regeneration and play a role in different pathologic conditions such as atherosclerosis or tumour progression. Angiogenesis being involved in these processes, as well, may represent one of the (patho-) physiological mechanisms, which are modulated by platelets thereby affecting disease. In other diseases involving inflammation, the role of platelets for endothelial cells, which are the most important cell type in angiogenesis, is well established. Recent effort has now highlighted a potential role of platelets and platelet derived mediators for angiogenesis. This article reviews our current understanding of the role of platelets for angiogenesis and how this knowledge could affect future directions in research and therapy.

Research paper thumbnail of The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets

Nature Communications, 2021

Platelets contribute to the regulation of tissue neovascularization, although the specific factor... more Platelets contribute to the regulation of tissue neovascularization, although the specific factors underlying this function are unknown. Here, we identified the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation. Growth factor- and hypoxia-driven vascularization was markedly increased in C5ar1−/− mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with increased collateralization, capillarization and improved pericyte coverage. Mechanistically, we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4) from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo.In concl...

Research paper thumbnail of Reduced left ventricular contractility, increased diastolic operant stiffness and high energetic expenditure in patients with severe aortic regurgitation without indication for surgery

Interactive CardioVascular and Thoracic Surgery

OBJECTIVES Recent mortality studies showed worse prognosis in patients (ARNS) with severe aortic ... more OBJECTIVES Recent mortality studies showed worse prognosis in patients (ARNS) with severe aortic regurgitation and preserved ejection fraction (EF) not fulfilling the criteria of current guidelines for surgery. The aim of our study was to analyse left ventricular (LV) systolic and diastolic function and mechanical energetics to find haemodynamic explanations for the reduced prognosis of these patients and to seek a new concept for surgery. METHODS Global longitudinal strain (GLS) and echo-based single-beat pressure–volume analyses were performed in patients with ARNS (LV end-diastolic diameter <70 mm, EF >50%, GLS > −19% n = 41), with indication for surgery (ARS; n = 19) and in mild hypertensive controls (C; n = 20). Additionally, end-systolic elastance (LV contractility), stroke work and total energy (pressure–volume area) were calculated. RESULTS ARNS demonstrated significantly depressed LV contractility versus C: end-systolic elastance (1.58 ± 0.7 vs 2.54 ± 0.8 mmHg/ml; ...

Research paper thumbnail of Acute changes of global and longitudinal right ventricular function: an exploratory analysis in patients undergoing open-chest mitral valve surgery, percutaneous mitral valve repair and off-pump coronary artery bypass grafting

Cardiovascular Ultrasound

Background Right ventricular (RV) function is an important prognostic indicator. The acute effect... more Background Right ventricular (RV) function is an important prognostic indicator. The acute effects of cardiac interventions or cardiac surgery on global and longitudinal RV function are not entirely understood. In this study, acute changes of RV function during mitral valve surgery (MVS), percutaneous mitral valve repair (PMVR) and off-pump coronary artery bypass surgery (OPCAB) were investigated employing 3D echocardiography. Methods Twenty patients scheduled for MVS, 23 patients scheduled for PMVR and 25 patients scheduled for OPCAB were included retrospectively if patients had received 3D transesophageal echocardiography before and immediately after MVS, PMVR or OPCAB, respectively. RV global and longitudinal function was assessed using a 3D multiparameter set consisting of global right ventricular ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE), longitudinal contribution to RVEF (RVEFlong) and free wall longitudinal strain (FWLS). Results Longitudina...

Research paper thumbnail of Previous TAVR in patients undergoing percutaneous edge-to-edge mitral valve repair (PMVR) affects improvement of MR

PLOS ONE

Background Patients after transcatheter aortic valve replacement (TAVR) and persistent severe mit... more Background Patients after transcatheter aortic valve replacement (TAVR) and persistent severe mitral regurgitation (MR) are increasingly treated with percutaneous edge-to-edge mitral valve repair (PMVR). The impact of a former TAVR on PMVR procedures is not clear. Methods and results We retrospectively analyzed 332 patients undergoing PMVR using the MitraClip system with respect to procedural and clinical outcome. 21 of these 332 patients underwent TAVR before PMVR. Intra-procedural transthoracic (TTE) and transesophageal echocardiograms (TEE) immediately before and after clip implantation as well as invasive hemodynamic measurements were evaluated. At baseline, we found a significantly smaller mitral valve anterior-posterior diameter in the TAVR cohort (p < 0.001). A reduction of MR by at least three grades was achieved in a smaller fraction in the TAVR cohort as compared to the cohort with a native aortic valve (p = 0.02). Accordingly, we observed a smaller post-procedural cardiac output in the TAVR cohort (p = 0.02). Conclusion PMVR in patients who had a TAVR before, is associated with altered MR anatomy before and a reduced improvement of MR after the procedure. Future larger and prospective studies will have to determine, whether a previous TAVR influences long-term clinical outcome of patients undergoing PMVR.

Research paper thumbnail of Treatment of Recurrent MR by MitraClip XTR in a Patient With a PASCAL Device

JACC: Cardiovascular Interventions