Extracellular Matrix in Heart Failure: Role of ADAMTS5 in Proteoglycan Remodeling.

BACKGROUND: Remodeling of the extracellular matrix (ECM) is a hallmark of heart failure (HF). Our previous analysis of the secretome of murine cardiac fibroblasts returned ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) as one of the most abundant proteases. ADAMTS5 cleaves chondroitin sulfate proteoglycans such as versican. The contribution of ADAMTS5 and its substrate versican to HF is unknown. METHODS: Versican remodeling was assessed in mice lacking the catalytic domain of ADAMTS5 (Adamts5ΔCat). Proteomics was applied to study ECM remodeling in left ventricular samples from patients with HF, with a particular focus on the effects of common medications used for the treatment of HF. RESULTS: Versican and versikine, an ADAMTS-specific versican cleavage product, accumulated in patients with ischemic HF. Versikine was also elevated in a porcine model of cardiac ischemia/reperfusion injury and in murine hearts after angiotensin II infusion. In Adamts5ΔCat mice, angiotensin II infusion resulted in an aggravated versican build-up and hyaluronic acid disarrangement, accompanied by reduced levels of integrin ß1, filamin A, and connexin 43. Echocardiographic assessment of Adamts5ΔCat mice revealed a reduced ejection fraction and an impaired global longitudinal strain on angiotensin II infusion. Cardiac hypertrophy and collagen deposition were similar to littermate controls. In a proteomics analysis of a larger cohort of cardiac explants from patients with ischemic HF (n=65), the use of ß-blockers was associated with a reduction in ECM deposition, with versican being among the most pronounced changes. Subsequent experiments in cardiac fibroblasts confirmed that ß1-adrenergic receptor stimulation increased versican expression. Despite similar clinical characteristics, patients with HF treated with ß-blockers had a distinct cardiac ECM profile. CONCLUSIONS: Our results in animal models and patients suggest that ADAMTS proteases are critical for versican degradation in the heart and that versican accumulation is associated with impaired cardiac function. A comprehensive characterization of the cardiac ECM in patients with ischemic HF revealed that ß-blockers may have a previously unrecognized beneficial effect on cardiac chondroitin sulfate proteoglycan content.

Continuous cytokine haemoadsorption incorporated into a venoarterial ECMO circuit for the management of postcardiotomy cardiogenic and septic shock - a case report.

INTRODUCTION: The acute surgical treatment of infective endocarditis (IE) carries a high risk of postoperative mortality. Most complications are linked to uncontrolled sepsis and inflammatory processes. Cytokine haemoadsorption is an extracorporeal technique which has benefits reported in haemodynamic stability and inflammatory response. CASE REPORT: A 46-year-old male patient underwent emergency cardiac surgery due to progressive IE. Postcardiotomy cardiogenic shock associated with cardiac surgery required the implantation of venoarterial (VA)-ECMO. Three days later, the patient developed secondary septic shock. The novel application of continuous CytoSorbTM treatment installed in the VA-ECMO circuit is demonstrated in this case during the management of simultaneous shocks. Advanced intensive care led to an improvement in the patient's condition, which facilitated successful weaning from mechanical ventilation. However, the patient died from a new onset fulminant septic shock two months after his initial cardiac surgery. DISCUSSION: VA-ECMO is suitable for installation of the CytoSorbTM cartridge. This modality could be an option for high-volume, continuous cytokine haemoadsorption when VA-ECMO is employed without renal replacement therapy. CONCLUSION: This specific application of CytoSorbTM was safe, feasible and contributed to the optimal management of simultaneous shocks.

[Evolution of the Hungarian adult heart transplantation program]. / A felnottszív-átültetés fejlodése Magyarországon.

The authors give a short introduction of the Hungarian and the international history of adult heart transplantation, and highlight the similarities in the evolution of the two programs. Their aim was to show how the Hungarian post-transplant survival changed in the last five years. They wanted to investigate how all the changes they had made in the program affected the post-transplant results. They investigated 496 heart transplantation data and compared to international data. Orv Hetil. 2018; 159(46): 1869-1875.

[The Semmelweis University extracorporeal membrane oxygenation program - 5 years' results and perspectives]. / A Semmelweis Egyetem extracorporalis membránoxigenizációs programja ­ az 5 éves Városmajori-eredmények függvényében.

The mechanical circulatory support (MCS) program of the Semmelweis University Heart and Vascular Centre has become established over the last five years. The main requirements of our MCS program to be developed first were the Heart Transplantation and Heart Failure Intensive Care Unit and a well trained medical team. The wide range of mechanical circulatory support devices provides suitable background for the adequate treatment of our patients in all indications. In this review, we present our results related to extracorporeal membrane oxygenation (ECMO) supports performed in the last five years. Between 2012 and 2017, we applied MCS support in 140 cases, among them 111 patients received ECMO support. The leading indications of ECMO support were the following: primary graft failure after heart transplantation (33 cases), postcardiotomy cardiogenic shock (18 patients), acute decompensation of end-stage heart failure (14 patients), acute myocardial infarction complicated with refractory cardiogenic shock (37 patients), cardiogenic shock developed after transcatheter aortic valve implantation (3 patients), malignant arrhythmia due to drug intoxication (1 patient) and acute respiratory distress syndrome (4 cases). The mortality of patients receiving ECMO support was 46%. The analysis of the results of ECMO support needs to change our approach. The mortality results show that we lost the half of our patients. However, the mortality in the conventionally treated patients would have been 100% without ECMO. In fact, we could save the life of half of these patients. Orv Hetil. 2018; 159(46): 1876-1881.

[Computer-assisted decision-making in cardiac surgery: from 3D preoperative planning to computational fluid dynamics in the design of surgical procedures]. / Számítástechnikai döntéstámogató rendszer kiépítése a szívsebészetben: a 3D tervezéstol a posztoperatív eredményekig.

INTRODUCTION: Although surgical specialties utilize static models for preoperative planning, the evolution of dynamic planning methods and computer simulations created the opportunity for the introduction of dynamic parameters in cardiac surgery. Our aim was to apply 3D models in cardiac surgical practice, predicting fluid dynamic results, ventricular shape, volume and function before the operation. METHODS: Using a script developed by us, the raw DICOM files were imported, the dilated left ventricle was modeled and fluid dynamic parameters were simulated, such as flow kinematic and profile analysis, turbulence calculation and myocardial response to shear stress. Then step-by-step simulation of the surgical ventricle restoration procedure was accomplished and the calculated variables were imbedded in silico model. The length of resection lines was modified based on the previous computer simulation and applied during the operation, if feasible. RESULTS: The sphericity and conicity indexes were improved significantly in postoperative period (0.42 vs. 0.67 and 0.36 vs. 0.72, p < 0.05). The occurred shear stress at endocardium decreased 83% due to the normalization of flow kinematic pattern of the ventricle in postoperative period (132.21 ± 29.5 dyne/cm2 vs. 22.92 ± 10.3 p < 0.05 dyne/|cm2). The postoperative turbulent flow pattern significantly decreased, according to our computational method (2712 vs. 1823, p < 0.0001). CONCLUSION: With our method, the standardization of the surgical ventricle reconstruction was achievable and the surgical steps were predictable. Therefore, a new decision making support system was established in cardiac surgery for high risk patients. A personalized surgical technique was offered to our patients, improving their life expectancy and quality of life.

[Heart transplantation and long-term lvad support cost-effectiveness model]. / Szívtranszplantáció és muszívkezelés költséghatékonysági elemzési modellje.

Heart transplantation is a high priority project at Semmelweis University. In accordance with this, the funding of heart transplantation and mechanical circulatory support also constitutes an important issue. In this report, the authors discuss the creation of a framework with the purpose of comparing the cost-effectiveness of heart transplantation and artificial heart implantation. Our created framework includes the calculation of cost, using the direct allocation method, calculating the incremental cost-effectiveness ratio and creating a cost-effectiveness plane. Using our model, it is possible to compare the initial, perioperative and postoperative expenses of both the transplanted and the artificial heart groups. Our framework can possibly be used for the purposes of long term follow-up and with the inclusion of a sufficient number of patients, the creation of cost-effectiveness analyses and supporting strategic decision-making.

Possible extracardiac predictors of aortic dissection in Marfan syndrome.

BACKGROUND: According to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS. METHODS: A Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-ß (TGF-ß) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and -9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed. RESULTS: Among patients with aortic dissection, TGF-ß serum level was elevated (43.78 ± 6.51 vs. 31.64 ± 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2α = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group. CONCLUSIONS: We found three easily measurable parameters (striae atrophicae, TGF-ß serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR.

"Turtle cage" method in the cardiac surgical treatment of constrictive pericarditis ­ our short-term results / "Turtle cage" módszer a pericarditis constrictiva szívsebészeti kezelésében - rövid távú eredményeink.

Összefoglaló. Bevezetés: A pericarditis constrictiva egy krónikus gyulladásos folyamat révén kialakuló betegség, melynek során a pericardium elveszíti rugalmasságát, gátolja a szív muködését, végso soron szívelégtelenséghez vezet. Egyetlen oki terápiája sebészi. A mutéti megoldásként legelterjedtebben alkalmazott teljes pericardiectomia hosszú idotartamú mutét, amely akár 18%-os mutéti kockázattal járhat, és amelyhez az esetek jelentos részében szívmotor alkalmazása szükséges. Célkituzés: Egy, az irodalomból már ismert, de csak ritkán és a legtöbbször csak a hagyományos pericardiectomia kiegészítéseként alkalmazott mutéti eljárás, a "turtle cage" pericardiectomia hatásosságának, eredményeinek, lehetséges elonyeinek vizsgálata. Módszer: 2008 és 2021 között Klinikánkon 33 "turtle cage" mutétet végeztünk pericarditis constrictiva miatt. A posztoperatív 30 napos idoszak eredményeit több, a nemzetközi irodalomban megjelent közlemény adataival hasonlítottuk össze. Eredmények: Az intraoperatív kép alapján minden esetben sikeres volt a beavatkozás, a 33 beteg egyikénél sem volt szükség szívmotor alkalmazására (0%), szemben a vizsgált közleményekkel. A 33 beavatkozás során 1 beteget veszítettünk el (3%), valamint 1 páciensnél volt szükség vérzés miatti reoperációra (3%), 4 betegnél dialízisre (12,1%). Ezen eredményeink összevethetok a nagy esetszámot felvonultató közleményekkel, és szignifikánsan jobbak az egyik megjelenített európai centrum eredményeinél. Következtetés: Az általunk alkalmazott "turtle cage" pericardiectomia önmagában is megfelelo eljárás a pericarditis constrictiva szívsebészeti kezelésére. Alkalmazásával minimalizálható a szívmotor használatának szükségessége, ezáltal a mutéti kockázat. Eredményeink a technikának köszönhetoen még a nagy esetszámú, sok tapasztalattal rendelkezo centrumok eredményeivel is összevethetok, azokkal megegyezok. Orv Hetil. 2022; 163(10): 393-399. INTRODUCTION: Constrictive pericarditis is a disease caused by a chronic inflammatory process, which is characterized by the pericardium's loss of flexibility, inhibiting the function of the heart, ultimately causing heart failure. The only definitive therapy is surgical. Total pericardiectomy, which is the most common surgical approach, is a lengthy procedure with up to 18% operative risk, and it often requires the use of cardiopulmonary bypass. OBJECTIVE: The evaluation of the effectiveness, results and possible advantages of a surgical technique, "turtle cage" pericardiectomy, which is described in the literature, although rarely used, mainly in addition to conventional pericardiectomy. METHOD: Between 2008 and 2021, we performed 33 "turtle cage" procedures on patients with constrictive pericarditis in our Institute. We compared the results of the 30-day postoperative period with internationally published data from multiple sources. RESULTS: Based on intraoperative findings, the procedure was successful in all cases, there were no instances when the use of cardiopulmonary bypass was required (0%). During the 33 procedures, we lost 1 patient (3%), reoperation was necessary for postoperative bleeding in 1 case (3%), and postoperative dialysis was necessary in 4 cases (12.1%). These results are comparable to those published by high-volume centres, and significantly better than those of one of the European centres published. CONCLUSION: The "turtle cage" pericardiectomy, as performed in our Institute, is suitable for the treatment of constrictive pericarditis on its own. With its use, we were able to minimize the use of cardiopulmonary bypass and the operative risk. Our results with this technique are comparable to those of the high-volume, highly experienced centres. Orv Hetil. 2022; 163(10): 393-399.

Behçet's disease: successful aortic root reconstruction in severely dilated aortoventricular junction after aortic valve replacement with novel surgical method - case report.

BACKGROUND: Behçet's disease is an auto-inflammatory disorder categorized as a primer systemic vasculitis of unknown aetiology. Genetic factors, infectious agents and the irregularity of T-cell homeostasis are presumed to be responsible for the emergence of Behçet's disease. Characteristic symptoms are multisystemic. Although cardiovascular involvement is rare, it should be noted due to the difficulty of surgical treatment options. CASE PRESENTATION: Our 44-year-old male patient underwent aortic valve replacement due to aortic regurgitation. At the 15-month follow-up, echocardiography showed detachment of the prosthetic valve and in the aortic root, multiple pseudo-aneurysms were identified. We performed an aortic root reconstruction with a Bentall procedure using a special "skirted" conduit to reduce strain in the suture line between the conduit and the extremely dilated left ventricular outflow tract. CONCLUSIONS: The surgical treatment of cardiovascular manifestations of Behçet's disease remains challenging. This new technique may be beneficial in well-selected cases where the annulus of the aorta is extremely dilated or annular tissue disorder is present.

[Successful two-step treatment of a ruptured giant thoracoabdominal aortic aneurysm]. / Rupturált óriás thoracoabdominalis aortaaneurysma sikeres kezelése két lépésben.

Treatment of thoracoabdominal aortic aneurysms is one of the most difficult challenges of vascular surgery. Endovascular options for complex aneurysms in urgent situation are limited. Thoracoabdominal giant aortic aneurysms are especially rare phenomena, each of them requires patient-specific treatment. Staged-fashion reconstructions may offer lower rate, especially for spinal cord injury. In our case report, we present a male patient, who had a 19.2 cm maximum diameter modified Crawford type V thoracoabdominal aortic aneurysm with contained rupture. The patient underwent an acute open repair and later a staged endovascular repair successfully. A 64-year-old male patient was admitted to our institution with complaints of chest and lower back pain in stable hemodynamic state. After evaluation, computer tomography angiography revealed a 19.2 cm maximum diameter thoracoabdominal aortic aneurysm, compression signs and hemothorax. Based on the anatomy, the serious compression symptoms and hemothorax associated with the gigantic aneurysm, we decided to perform open aortic repair. To reduce risk of spinal cord ischemia, intraoperatively we chose finishing the full reconstruction in a staged fashion. First, we performed an open repair with a Dacron interpositum distally using an oblique patch involving the visceral orifices. Later we implanted a thoracic endograft. At one-year follow-up, the patient was symptom-free, with no sign of endoleak. Giant aortic aneurysms are rare conditions, especially in the thoracoabdominal region. In the presence of compression symptoms, hemothorax and unsuitable aneurysm anatomy, open repair should be done. Staged repair offers a less invasive approach decreasing the risk of spinal cord ischemia. Orv Hetil. 2020; 161(7): 269-274.

[Osteosynthesis with plates for full sternal dehiscence (Titanium Sternal Fixation System Synthes) -- first use in Hungary]. / Teljes sternumdehiscentia miatt alkalmazott lemezes osteosynthesis (Titanium Sternal Fixation System Synthes) elsô magyarországi alkalmazása.

The prevalence of deep sternal infection after cardiac surgery is between 0,5 and 5%, with an average mortality up to 50%. The authors present the case of the rst sternal osteosynthesis carried out in Hungary after postoperative deep sternal infection. Using this orthopedic reconstructive surgical technique in this patient group, an anatomical reconstruction and reposition of the sternum is feasible. With the Titanium Sternal Fixation Synthes system reconstruction of total or partial sternal absence is possible.

[Successful cardiac surgical removal of migrated Kirschner wires used for fixation of the surgical neck of the humerus]. / Collum chirurgicum törését rögzíto, elvándorolt Kirschner-tuzodrótok sikeres szívsebészeti eltávolítása.

Dislocation and migration of two Kirschner wires were found 13 days after fixation of the surgical neck of the humerus. One of the wires was located between the lateral thoracic muscles, while the other one has perforated the apex of the heart, showing a synchronous motion with heart contractions. An anterolateral thoracotomy was performed and the wires were removed successfully.

Routine aortic valve replacement followed by a myriad of complications: role of 3D printing in a difficult cardiac surgical case.

Aortic valve replacement (AVR) is a routine cardiac surgical intervention that is rarely associated with severe complications. In this report, we present a complex and unique case following AVR in a middle-aged woman. We show the growing necessity for a strong cooperation between interventional cardiologists and cardiac surgeons, together with the emerging role of cardiac tomography based three-dimensional printing technique in planning and executing precision surgery within the chest.

[Analysis of vascular complications of IABP therapy in open-heart surgery patients 1999-2004]. / Szívmuitött betegek intraaortikus ballonpumpa kezelése során kialakult vaszkuláris szövodményeinek elemzése (1999-2004).

Intraaortic balloon pump (IABP) is being used in cardiac surgery in an increased ratio. IABP therapy involves considerable risk, mainly vascular complications, postoperative bleeding and infection can represent danger. Between 1999 and 2004 out of 4443 open heart surgery operations we have performed intraaortic balloon pump treatment in case of 75 patients. The mean age was 64 years, 23 patients had diabetes mellitus, 47 patients had hypertension, 20 patients had peripheral vascular disease as well. We performed IABP therapy most frequently during isolated coronary bypass operations (42 cases), but also combined operations (implantation of valve prosthesis + coronary bypass) represent a significant part (implantation of aortic valve prosthesis + CABG: 5 cases, implantation of mitral valve prosthesis + CABG: 8 cases). Vascular complications occurred in 10 cases--13.3%--out of 75 patients, including 7 fatal ones. Three cases are due to the IABP treatment itself: Crush syndrome was developed leading to the loss of the patient. Applying the multiple logistic regression model we have examined the effect of the following factors on the occurrence of vascular complications: gender, age, body surface, accompanying diseases (hypertension, diabetes, peripheral vascular disease), the method and timing of insertion. Peripheral vascular disease (p < 0.005) and hypertension (p = 0.01) represent independent risk factors regarding the occurrence of complications. Having performed chi-square test we have not identified significant correlations between mortality and vascular complications. In case of prevailing peripheral vascular disease, the application of alternative insertion techniques--via the ascending aorta, the axillary artery--are recommended.

The role of transforming growth factor-beta in Marfan syndrome.

The starting point, in Marfan syndrome (MFS) appears to be the mutation of fibrillin-1 gene whose deconstructed protein product cannot bind transforming growth factor beta (TGF-b), leading to an increased TGF-b tissue level. The aim of this review is to review the already known features of the cellular signal transduction downstream to TGF-b and its impact on the tissue homeostasis of microfibrils, and elastic fibers. We also investigate current data on the extracellular regulation of TGF-b level including mechanotransduction and the feedback cycles of integrin-dependent and independent activation of the latent TGF-b complex. Together these factors, by the destruction of the connective tissue fibers, may play an important role in the development of the diverse cardiac and extracardiac manifestations of MFS and many of them could be a target of conservative treatment. We present currently investigated drugs for the treatment of the syndrome, and explore possible avenues of research into pathogenesis of MFS in order to improve understanding of the disease.

Acute type A aortic dissection complicated by aortic stent graft collapse.

A 57-year-old man complaining of chest pain presented with signs of lower limb ischemia 1 year after implantation of a stent graft at the aortoiliac bifurcation. A computed tomography scan revealed the presence of a type A aortic dissection and complete collapse of the stent graft by bulging of the false lumen. The patient underwent emergency surgical reconstruction of the aortic root and arch, which allowed reexpansion of the previously collapsed stent graft. Stenting of residual stenoses distal to the stent graft and of an occluded left renal artery was also successful.