Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 35
Filter
1.
J Clin Med ; 12(21)2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37959355

ABSTRACT

We present the results of a combined approach for transapical aortic valve replacement and minimally invasive coronary artery bypass grafting (taTAVI-MIDCAB) in patients with combined aortic stenosis and coronary artery disease. BACKGROUND: For patients presenting with aortic stenosis and coronary artery disease, a simultaneous procedure addressing both diseases is recommended to reduce operative risk. In high-risk patients with hostile femoral or coronary axis, taTAVI-MIDCAB can be an alternative minimally invasive approach, offering the benefits of left interior mammary artery to left anterior descending coronary artery (LIMA-LAD) grafting. METHODS: From 2014 to 2022, 10 patients underwent taTAVI-MIDCAB for combined coronary and severe aortic stenosis in the hybrid operation theater at our institution. We assessed perioperative outcomes and follow-up outcomes. RESULTS: The median age was 83 years (81 to 86). The procedure was successfully performed in all patients without conversion to sternotomy. The median length of hospital and intensive care unit stay was 9 days (7 to 16) and 2.5 days (1 to 5), respectively. The median flow over the coronary artery bypass was 31 (22 to 44) mL/min, with a pulsatility index (PI) of 2.4 (2.1 to 3.2). Mild paravalvular leak occurred in 2 patients (10%). There were no neurological events nor acute kidney injury. Pacemaker implantation was required in 1 patient (10%). CONCLUSIONS: Simultaneous surgical coronary revascularization and interventional valve implantation in the setting of a hostile femoral and coronary axis appears to be safe and beneficial.

2.
Front Cardiovasc Med ; 10: 1273785, 2023.
Article in English | MEDLINE | ID: mdl-37886733

ABSTRACT

Introduction: The impact of sex on hospital readmission rate after cardiac surgery is unclear. Therefore, we aimed to analyse sex-specific differences and underlying factors in 30-day readmission rate after cardiac surgery. Methods: We conducted a single center study including all patients after major cardiac surgery (excluding aortic dissection and left ventricular assist device implantation) from January 2012 to September 2020. Reasons for readmission were adjudicated according to all available medical records. We calculated incidence rate ratios (IRR) with 95% confidence intervals (CI) for female sex with re-admission crude and adjusted for plausible confounding factors using negative binomial regression. Results: 4,868 patients were included in the analysis. The median [Interquartile range] age was 68 [60 to 74] years and 24% (n = 1,149) of the patients were female. Female patients were significantly older (median [IQR] age 70 (63 to 76) vs. 67 (59 to 74), p < 0.001) and had lower body mass index and fewer cardiovascular risk factors compared to men. Isolated valve surgery was more frequent in female while coronary artery bypass grafting was more often in men. 30-day readmission was comparable between both sexes (7.0% [n = 81] in female vs. 8.7% [n = 322] in men; p = 0.078). Cardiac related readmissions and infections were the most common reasons for readmission in both groups. The overall incidence rate ratios of female sex with readmission (0.80, 95% CI 0.63 to 1.03, p = 0.078) remained robust after adjustment for EuroSCORE 2 (0.78, CI 0.61 to 1.0, p = 0.051). Conclusion: Readmission rate and reasons for 30-day readmission after major cardiac surgery were similar between men and women.

3.
Biomedicines ; 11(7)2023 Jul 10.
Article in English | MEDLINE | ID: mdl-37509585

ABSTRACT

Due to the advent of interventional therapies for low- and intermediate-risk patients, case complexity has increased in cardiac surgery over the last decades. Despite the surgical progress achieved to keep up with the increase in the number of high-risk patients, the prevention of sternal complications remains a challenge requiring new, individualized sternal closure techniques. The aim of this study was to evaluate the safety and feasibility, as well as the in-hospital and long-term outcomes, of enhanced sternal closure with combined band and plate fixation using the new SternaLock® 360 (SL360) system as an alternative to sternal wiring. From 2020 to 2022, 17 patients underwent enhanced sternal closure using the SL360 at our institution. We analyzed perioperative data, as well as clinical and radiologic follow-up data. The results were as follows: In total, 82% of the patients were treated with the SL360 based on perioperative risk factors, while in 18% of cases, the SL360 was used for secondary closure due to sternal instability. No perioperative complications were observed. We obtained the follow-up data of 82% of the patients (median follow-up time: 141 (47.8 to 511.5) days), showing no surgical revision, no sternal instability, no deep wound infections, and no sternal pain at the follow-up. In one case, a superficial wound infection was treated with antibiotics. In conclusion, enhanced sternal closure with the SL360 is easy to perform, effective, and safe. This system might be considered for both primary and secondary sternal closure in patients at risk of sternal complications.

5.
Article in English | MEDLINE | ID: mdl-37044119

ABSTRACT

BACKGROUND: To evaluate the midterm follow-up and 5-year survival outcome of the minimally invasive direct coronary artery bypass (MIDCAB) procedure compared with the survival of the general Swiss population. METHODS: Retrospective study on preoperative data, intraoperative data, and postoperative outcome of patients who underwent MIDCAB surgery between June 2010 and February 2019. To assess validity of this surgical therapy, outcomes were compared with survival data of a gender- and age-matched cohort of the general Swiss population taken from the database of the Swiss Federal Statistical Office. RESULTS: A total of 88 patients were included. Median (interquartile range [IQR[) age was 66 (56-75) years, and 27% (n = 24) were female. The median (IQR) length of the in-hospital stay was 7 (6-8) days. No postoperative stroke occurred. The 30-day mortality was 1.1% (n = 1). Reintervention for failed left internal mammary artery was needed in 1.1% (n = 1). The median (IQR) ejection fraction was 58% (47-60) preoperatively and remained stable during follow-up. The median (IQR) follow-up period was 3 (1.1-5.2) years. Five years postoperatively, 83% (confidence interval, 69-91) of the patients were alive, showing an overlap with the range of survival of the matched subcohort of the general Swiss population (range, 84-100%). CONCLUSION: Though suffering from coronary heart disease, patients after MIDCAB show almost equal survival rates as an equivalent subcohort corresponding to the general Swiss population matched on age and gender. Thus, our data show this treatment to be safe and beneficial.

7.
J Clin Med ; 11(24)2022 Dec 17.
Article in English | MEDLINE | ID: mdl-36556103

ABSTRACT

Background: We aimed to analyse the performance of minimal invasive extracorporeal circulation (MiECC) concomitantly with Microplegia, in patients with recent myocardial infarction (MI) undergoing urgent coronary artery bypass grafting (CABG) surgery. Methods: We included patients with a recent MI (≤7 days) undergoing isolated CABG surgery using MiECC. The primary endpoint was a major cardiovascular or cerebrovascular event (MACCE). In a secondary analysis, we compared our institutional Microplegia concept with the use of a crystalloid single-shot cardioplegic solution. Results: In total, 139 patients (mean ± standard deviation (SD) age 66 ± 10 years) underwent urgent CABG surgery using Microplegia; 55% (n = 77) of the patients had an acute MI within 1−7 days preoperatively; 20% (n = 28) had an acute MI within 6−24 h; and 24% (n = 34) had an acute MI within <6 h preoperatively. The number of distal anastomoses was a geometric mean of 4 (95% confidence interval 3−4). The MACCE and in-hospital mortality were 7% (n = 10) and 1% (n = 2), respectively. The results were confirmed in a secondary analysis comparing Microplegia with crystalloid cardioplegic solution (n = 271). Conclusion: The use of MiECC with Microplegia in urgent CABG surgery is feasible and safe and provides a straight-forward intraoperative setting. Therefore, it can also be considered to retain the benefits of MiECC in urgent CABG surgery.

8.
Front Cardiovasc Med ; 9: 879378, 2022.
Article in English | MEDLINE | ID: mdl-35845069

ABSTRACT

Background: Repeat hospitalizations, complications, and psychosocial burdens are common in patients with left ventricular assist devices (LVAD). Specialist palliative care (sPC) involvement supports patients during decision-making until end-of-life. In the United States, guidelines recommend early specialist palliative care (esPC) involvement prior to implantation. Yet, data about sPC and esPC involvement in Europe are scarce. Materials and Methods: This is a retrospective descriptive study of deceased LVAD patients who had received sPC during their LVAD-related admissions to two university hospitals in Duesseldorf, Germany and Basel, Switzerland from 2010 to 2021. The main objectives were to assess: To which extent have LVAD patients received sPC, how early is sPC involved? What are the characteristics of those, how did sPC take place and what are key challenges in end-of-life care? Results: In total, 288 patients were implanted with a LVAD, including 31 who received sPC (11%). Twenty-two deceased LVAD patients (19 male) with sPC were included. Mean patient age at the time of implantation was 67 (range 49-79) years. Thirteen patients (59%) received LVAD as destination therapy, eight patients (36%) were implanted as bridge to transplantation (BTT), and one as an emergency LVAD after cardiogenic shock (5%). None of the eight BTT patients received a heart transplantation before dying. Most (n = 13) patients lived with their family and mean Eastern Cooperative Oncology Group (ECOG) performance status was three. Mean time between LVAD implantation and first sPC contact was 1.71 years, with a range of first sPC contact from 49 days prior to implantation to more than 6 years after. Two patients received esPC before implantation. In Duesseldorf, mean time between first sPC contact and in-hospital death was 10.2 (1-42) days. In Basel, patients died 16 (0.7-44) months after first sPC contact, only one died on the external sPC unit. Based on thorough examination of two case reports, we describe key challenges of sPC in LVAD patients including the necessity for sPC expertise, ethical and communicative issues as well as the available resources in this setting. Conclusion: Despite unequivocal recommendations for sPC in LVAD patients, the integration of sPC for these patients is yet not well established.

9.
Eur J Cardiothorac Surg ; 62(2)2022 07 11.
Article in English | MEDLINE | ID: mdl-35758627

ABSTRACT

A 78-year-old patient underwent his third biological aortic valve replacement (25 mm, Inspiris Resilia™, Edwards Lifesciences LLC, Irvine, CA, USA) with COR-KNOT® (LSI Solutions, Victor, NY, USA) due to valve degeneration in 2018 at a foreign hospital. In 2021, the patient was diagnosed with severe aortic regurgitation and admitted to our hospital for his fourth surgery. Intraoperatively, a total of 7 perforations in all 3 valve leaflets have been observed, which were obviously induced by the rigid metallic fasteners. Redo isolated aortic valve replacement (29 mm, Perimount Magna Ease, Edwards Lifesciences LLC) was performed with conventionally knotted, pledget enforced braided threads. Postoperative course was uneventful. This report shows that COR-KNOT-induced defects do not appear immediately after surgery but within the first 4 postoperative months. Since failure of aortic bioprostheses due to aortic insufficiency is often rated as 'early degeneration' and degenerated aortic bioprostheses are mostly replaced by valve-in-valve strategy, the true incidence of this serious complication might be underestimated. COR-KNOT should be used with caution in biological aortic valve replacement and patients should undergo close postoperative follow-ups.


Subject(s)
Aortic Valve Insufficiency , Aortic Valve Stenosis , Bioprosthesis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Insufficiency/diagnostic imaging , Aortic Valve Insufficiency/etiology , Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/surgery , Bioprosthesis/adverse effects , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis Implantation/adverse effects , Humans , Prosthesis Design , Titanium/adverse effects , Treatment Outcome
11.
Article in English | MEDLINE | ID: mdl-35640544

ABSTRACT

OBJECTIVES: We have previously demonstrated beneficial cardiac protection with hypothermic polarizing cardioplegia compared to a hyperkalemic depolarizing cardioplegia. In this study, a porcine model of cardiopulmonary bypass was used to compare the protective effects of normothermic blood-based polarizing and depolarizing cardioplegia during cardiac arrest. METHODS: Thirteen pigs were randomized to receive either normothermic polarizing (n = 8) or depolarizing (n = 5) blood-based cardioplegia. After initiation of cardiopulmonary bypass, normothermic arrest (34°C, 60 min) was followed by 60 min of on-pump and 90 min of off-pump reperfusion. Primary outcome was myocardial injury measured as arterial myocardial creatine kinase concentration. Secondary outcome was haemodynamic function and the energy state of the hearts. RESULTS: During reperfusion, release of myocardial creatine kinase was comparable between groups (P = 0.36). In addition, most haemodynamic parameters showed comparable results between groups, but stroke volume (P = 0.03) was significantly lower in the polarizing group. Adenosine triphosphate levels were significantly (18.41 ± 3.86 vs 22.97 ± 2.73 nmol/mg; P = 0.03) lower in polarizing hearts, and the requirement for noradrenaline administration (P = 0.002) and temporary pacing (6 vs 0; P = 0.02) during reperfusion were significantly higher in polarizing hearts. CONCLUSIONS: Under normothermic conditions, polarizing blood cardioplegia was associated with similar myocardial injury to depolarizing blood cardioplegia. Reduced haemodynamic and metabolic outcome and a higher need for temporary pacing with polarized arrest may be associated with the blood-based dilution of this solution.


Subject(s)
Cardiopulmonary Bypass , Heart Arrest , Animals , Cardioplegic Solutions/pharmacology , Cardiopulmonary Bypass/adverse effects , Cardiopulmonary Bypass/methods , Creatine Kinase, MB Form , Heart , Heart Arrest, Induced/adverse effects , Heart Arrest, Induced/methods , Myocardium/metabolism , Swine
12.
ESC Heart Fail ; 9(4): 2703-2712, 2022 08.
Article in English | MEDLINE | ID: mdl-35438261

ABSTRACT

AIMS: New-onset atrial fibrillation (NOAF) is the most common complication after cardiac surgery, occurring in 25-50% of patients. It is associated with post-operative stroke, increased mortality, prolonged hospital length of stay, and higher treatment costs. Previous small observational studies have identified the left atrium as a source of the electrical rotors and foci maintaining NOAF, but confirmation by a large prospective clinical study is still missing. The aim of the proposed study is to investigate whether the source of NOAF lies in the left atrium. The correct identification of NOAF-maintaining structures in cardiac surgical patients might offer potential therapeutic targets for prophylactic perioperative ablation strategies. METHODS AND RESULTS: This is a prospective single-centre observational study of patients developing NOAF after cardiac surgery. The primary outcome is the description of NOAF-maintaining structures within the atria. Key secondary outcomes include overall mortality, intensive care unit length of stay, hospital-ventilator-free days, and proportion of persistent NOAF. In NOAF patients, the non-invasive electrophysiological mapping will be conducted using a 252-electrode electrocardiogram vest. After mapping, a low-dose computed tomography scan of the chest will be performed to integrate the electrophysiological mapping results into a 3D picture of the heart. The study will include approximately 570 patients, of whom 30% (n = 170) are expected to develop NOAF. Sample size calculation revealed that 157 NOAF patients are necessary to assess the primary outcome. Patients will be tracked for a total of 5 years. CONCLUSIONS: This is the largest prospective study to date describing the electrophysiological mechanisms of NOAF using non-invasive mapping.


Subject(s)
Atrial Fibrillation , Cardiac Surgical Procedures , Atrial Fibrillation/complications , Atrial Fibrillation/etiology , Cardiac Surgical Procedures/adverse effects , Electrocardiography , Humans , Observational Studies as Topic , Prospective Studies , Risk Factors
13.
Interact Cardiovasc Thorac Surg ; 34(5): 841-848, 2022 05 02.
Article in English | MEDLINE | ID: mdl-35137102

ABSTRACT

OBJECTIVES: Up-regulation of tenascin C (TNC), a matricellular protein, produced mainly by vascular smooth muscle cells (VSMC), is associated with the progression and dilation of abdominal aortic aneurysms (AAA). The aims of this study were (i) to evaluate whether serum levels of TNC in patients with AAA patients correlate with aortic diameter and (ii) to clarify the role of TNC in formation and progression of AAA in a murine model. METHODS: In 15 patients with AAA serum levels of TNC were measured and correlated with aortic diameters. Moreover, in a murine calcium chloride AAA model, the impact of TNC deficiency on AAA diameter was evaluated. Finally, human VSMC were incubated with TNC to clarify its regulating potential. RESULTS: In the clinical cohort, there was a trend of correlation between serum TNC levels and AAA diameter (P = 0.055). TNC knock out mice with AAA showed significantly lower diameter ratios compared to the wild-type group (WT) 3 weeks (P < 0.05) and 10 weeks (P < 0.05) after AAA induction. Immunohistochemistry revealed increased TNC expression in aortic tissue from WT with AAA as compared sham-operated mice. Furthermore, WT with AAA showed a more disrupted Elastin structure than TNC knock out mice 10 weeks after AAA induction. In human aortic VSMC, TNC incubation induced expression of remodelling associated proteins. CONCLUSIONS: TNC might play a causative role in the formation, dilation and progression of AAA. Our results indicate that TNC might be a biomarker as well as a potential therapeutic target in the treatment of AAA.


Subject(s)
Aortic Aneurysm, Abdominal , Animals , Aorta, Abdominal , Disease Models, Animal , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Tenascin/metabolism
14.
CJC Open ; 3(10): 1313-1315, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34888513

ABSTRACT

A 70-year-old female heart failure patient could not be weaned from temporary left ventricular mechanical support with Impella CP (Abiomed Inc, Danvers, MA) after myocardial infarction; therefore, she underwent left ventricular assist device implantation (HeartMate 3; Abbott, Chicago, IL). After uneventful surgery, the patient had an early postoperative thrombus in the aortic root, and surgical thrombectomy on extracorporeal circulation was performed on the seventh postoperative day. The patient recovered well and presented in good condition with no neurologic symptoms at the 6-month follow-up visit. Surgical excision of aortic root thrombus is a feasible option even for frail patients with a left ventricular assist device.


Après un infarctus du myocarde, une patiente de 70 ans présentant une insuffisance cardiaque n'a pas pu être sevrée d'une assistance mécanique temporaire pour le ventricule gauche par dispositif Impella CP (Abiomed Inc, Danvers, MA); elle a donc subi l'implantation d'un dispositif d'assistance ventriculaire gauche (HeartMate 3; Abbott, Chicago, IL). Après une intervention sans incident, la patiente a présenté un thrombus postopératoire précoce dans l'anneau aortique, et une thrombectomie chirurgicale sous circulation extracorporelle a été réalisée le septième jour suivant l'intervention. La patiente s'est bien rétablie et semblait en bonne santé, sans symptômes neurologiques, au moment de la visite de suivi six mois plus tard. L'excision chirurgicale du thrombus de l'anneau aortique est une option réaliste même chez les patients fragiles ayant un dispositif d'assistance ventriculaire gauche.

15.
Int J Mol Sci ; 22(15)2021 Jul 24.
Article in English | MEDLINE | ID: mdl-34360685

ABSTRACT

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.


Subject(s)
Adipose Tissue/cytology , Cell Differentiation , Hypoxia , Mesenchymal Stem Cells/physiology , Neovascularization, Physiologic , Cells, Cultured , Humans , Vascular Endothelial Growth Factor A/metabolism
16.
J Clin Med ; 10(16)2021 Aug 20.
Article in English | MEDLINE | ID: mdl-34442010

ABSTRACT

Worldwide, the left ventricular assist device Impella® (Abiomed, Danvers, MA, USA) is increasingly implanted in patients with acute cardiogenic shock or undergoing high-risk cardiac interventions. Despite its long history of use, few studies have assessed its safety and possible complications associated with its use. All patients treated with a left-sided Impella® device at the University Hospital of Basel from 1 January 2011 to 31 December 2019 were enrolled. The primary endpoint was the composite rate of mortality and adverse events (bleeding, acute kidney injury, and limb ischemia). Out of 281 included patients, at least one adverse event was present in 262 patients (93%). Rates of in-hospital, 90-day, and one-year mortality were 48%, 47%, and 50%, respectively. BARC type 3 bleeding (62%) and hemolysis (41.6%) were the most common complications. AKI was observed in 50% of all patients. Renal replacement therapy was required in 97 (35%) of all patients. Limb ischemia occurred in 13% of cases. Bleeding and hemolysis are common Impella®-associated complications. Additionally, we found a high rate of AKI. A careful selection of patients receiving microaxial LV support and defining the indication for its use are essential measures to be taken for the benefits to outweigh potential complications.

17.
Case Rep Cardiol ; 2021: 6651361, 2021.
Article in English | MEDLINE | ID: mdl-33728072

ABSTRACT

In March 2020, a 64-year-old female with mitral valve insufficiency and persistent atrial fibrillation underwent preoperative noninvasive mapping for developing an ablation strategy. In the computed tomography (CT) scan, typical signs of COVID-19 were described. Since the consecutive polymerase chain reaction (PCR) test was negative, the severely symptomatic patient was planned for urgent surgery. Noninvasive mapping showed that atrial fibrillation was maintained by left atrial structures and pulmonary veins only. On admission day, the preoperative routine COVID-19 PCR test was positive, and after recovery, uneventful mitral valve repair with cryoablation of the left atrium and pulmonary veins was performed. Our case describes the potential benefit of preoperative noninvasive mapping for the development of a surgical ablation strategy, as well as the challenges in managing urgent surgical patients during the COVID-19 pandemic and the corresponding diagnostic relevance of CT.

18.
J Clin Med ; 10(4)2021 Feb 03.
Article in English | MEDLINE | ID: mdl-33546164

ABSTRACT

BACKGROUND: Aim of this study was to evaluate the outcomes of endocarditis patients undergoing valve surgery with the Cytosorb® hemoadsorption (HA) device during cardiopulmonary bypass. METHODS: From 2009 until 2019, 241 patients had undergone valve surgery due to endocarditis at the Department of Cardiac Surgery, University Hospital of Basel. We compared patients who received HA during surgery (n = 41) versus patients without HA (n = 200), after applying inverse probability of treatment weighting. RESULTS: In-hospital mortality, major adverse cardiac and cerebrovascular events and postoperative renal failure were similar in both groups. Demand for norepinephrine (88.4 vs. 52.8%; p = 0.001), milrinone (42.2 vs. 17.2%; p = 0.046), red blood cell concentrates (65.2 vs. 30.6%; p = 0.003), and platelets (HA vs. Control: 36.7 vs. 9.8%; p = 0.013) were higher in the HA group. In addition, a higher incidence of reoperation for bleeding (34.0 vs. 7.7 %; p = 0.011), and a prolonged length of in-hospital stay (15.2 (11.8 to 19.6) vs. 9.0 (7.1 to 11.3) days; p = 0.017) were observed in the HA group. CONCLUSIONS: No benefits of HA-therapy were observed in patients with infective endocarditis undergoing valve surgery.

19.
Basic Res Cardiol ; 115(6): 58, 2020 09 03.
Article in English | MEDLINE | ID: mdl-32880713

ABSTRACT

Pulmonary arterial hypertension is a severe and progressive disease characterized by a pulmonary vascular remodeling process with expansion of collateral endothelial cells and total vessel occlusion. Endothelial cells are believed to be at the forefront of the disease process. Vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor, VEGF receptor-2 (VEGFR-2), play a central role in angiogenesis, endothelial cell protection, but also in the destabilization of endothelial barrier function. Therefore, we investigated the consequences of altered VEGF signaling in an experimental model, and looked for translational correlates of this observation in patients. We performed an endothelial cell-specific conditional deletion of the kinase insert domain protein receptor (kdr) gene, coding for VEGFR-2, in C57/BL6 mice (Kdr∆end) and held them in an environmental chamber with 10% FiO2 or under normoxia for 6 weeks. Kdr knockout led to a mild PH phenotype under normoxia that worsened under hypoxia. Kdr∆end mice exhibited a significant increase in pulmonary arterial wall thickness, muscularization, and VEGFR-3+ endothelial cells obliterating the pulmonary artery vessel lumen. We observed the same proliferative vasculopathy in our rodent model as seen in patients receiving anti-angiogenic therapy. Serum VEGF-a levels were elevated both in the experimental model and in humans receiving bevacizumab. Interrupted VEGF signaling leads to a pulmonary proliferative arteriopathy in rodents after direct ablative gene manipulation of Kdr. Histologically, similar vascular lesions can be observed in patients receiving anti-VEGF treatment. Our findings illustrate the importance of VEGF signaling for maintenance of pulmonary vascular patency.


Subject(s)
Arterial Pressure , Cell Proliferation , Endothelial Cells/metabolism , Pulmonary Arterial Hypertension/metabolism , Pulmonary Artery/metabolism , Vascular Endothelial Growth Factor Receptor-2/deficiency , Vascular Remodeling , Angiogenesis Inhibitors/therapeutic use , Animals , Apoptosis , Bevacizumab/therapeutic use , Disease Models, Animal , Endothelial Cells/pathology , Female , Hypertrophy, Right Ventricular/etiology , Hypertrophy, Right Ventricular/metabolism , Hypertrophy, Right Ventricular/pathology , Hypertrophy, Right Ventricular/physiopathology , Hypoxia/complications , Mice, Inbred C57BL , Mice, Knockout , Neoplasms/blood , Neoplasms/diagnosis , Neoplasms/drug therapy , Prospective Studies , Pulmonary Arterial Hypertension/etiology , Pulmonary Arterial Hypertension/pathology , Pulmonary Arterial Hypertension/physiopathology , Pulmonary Artery/pathology , Pulmonary Artery/physiopathology , Signal Transduction , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor Receptor-2/genetics , Ventricular Function, Right , Ventricular Pressure
20.
Clin Cardiol ; 43(10): 1084-1092, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32794309

ABSTRACT

Within the last decade, implantable cardioverter-defibrillator (ICD) systems with non-transvenous leads were developed in order to minimize complications related to the cardiovascular position of transvenous ICD leads. This national expert consensus gives an overview of potential indications for the implantation of non-transvenous ICD systems, and provides specific recommendations for implantation, follow-up, and complication management in patients with subcutaneous ICD. Regarding particular issues like the necessity for shock efficacy testing, or the clinical outcome as compared to transvenous ICD, randomized data are expected in the near future.


Subject(s)
Consensus , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Humans
SELECTION OF CITATIONS
SEARCH DETAIL
...