Use of intraoperative haemoadsorption in patients undergoing heart transplantation: a proof-of-concept randomized trial.

AIMS: The aim of this trial was to compare the clinical effects of intraoperative haemoadsorption versus standard care in patients undergoing orthotopic heart transplantation (OHT). METHODS AND RESULTS: In a randomized, controlled trial, OHT recipients were randomized to receive intraoperative haemoadsorption or standard care. Outcomes were vasoactive-inotropic score (VIS), frequency of vasoplegic syndrome (VS) in the first 24 h; post-operative change in procalcitonin (PCT) and C-reactive protein (CRP) levels; intraoperative change in mycophenolic acid (MPA) concentration; frequency of post-operative organ dysfunction, major complications, adverse immunological events and length of in-hospital stay and 1-year survival. Sixty patients were randomized (haemoadsorption group N = 30, control group N = 25 plus 5 exclusions). Patients in the haemoadsorption group had a lower median VIS and rate of VS (VIS: 27.2 [14.6-47.7] vs. 41.9 [22.4-63.2], P = 0.046, and VS: 20.0% vs. 48.0%, P = 0.028, respectively), a 6.4-fold decrease in the odds of early VS (OR: 0.156, CI: 0.029-0.830, P = 0.029), lower PCT levels, shorter median mechanical ventilation (MV: 25 [19-68.8] hours vs. 65 [23-287] hours, P = 0.025, respectively) and intensive care unit stay (ICU stay: 8.5 [8.0-10.3] days vs. 12 [8.5-18.0] days, P = 0.022, respectively) than patients in the control group. Patients in the haemoadsorption versus control group experienced lower rates of acute kidney injury (AKI: 36.7% vs. 76.0%, P = 0.004, respectively), renal replacement therapy (RRT: 0% vs. 16.0%, P = 0.037, respectively) and lower median per cent change in bilirubin level (PCB: 2.5 [-24.6 to 71.1] % vs. 72.1 [11.2-191.4] %, P = 0.009, respectively) during the post-operative period. MPA concentrations measured at pre-defined time points were comparable in the haemoadsorption compared to control groups (MPA pre-cardiopulmonary bypass: 2.4 [1.15-3.60] µg/mL vs. 1.6 [1.20-3.20] µg/mL, P = 0.780, and MPA 120 min after cardiopulmonary bypass start: 1.1 [0.58-2.32] µg/mL vs. 0.9 [0.45-2.10] µg/mL, P = 0.786). The rates of cardiac allograft rejection, 30-day mortality and 1-year survival were similar between the groups. CONCLUSIONS: Intraoperative haemoadsorption was associated with better haemodynamic stability, mitigated PCT response, lower rates of post-operative AKI and RRT, more stable hepatic bilirubin excretion, and shorter durations of MV and ICU stay. Intraoperative haemoadsorption did not show any relevant adsorption effect on MPA. There was no increase in the frequency of early cardiac allograft rejection related to intraoperative haemoadsorption use.

T cell immune response predicts survival in severely ill COVID-19 patients requiring venovenous extracorporeal membrane oxygenation support.

Introduction: There is a critical gap in understanding which SARS-CoV-2 patients would benefit most from venovenous extracorporeal membrane oxygenation (VV-ECMO) support. The potential role of a dysregulated immune response is still unclear in this patient population. Objectives: To assess the potential predictive value of SARS-CoV-2 specific cellular and humoral immune responses for survival in critically ill COVID-19 patients requiring VV-ECMO. Methods: We conducted a prospective single-center observational study of unvaccinated patients requiring VV-ECMO support treated at the intensive care unit of Semmelweis University Heart and Vascular Center between March and December 2021. Peripheral blood samples were collected to measure the humoral and cellular immune statuses of the patients at the VV-ECMO cannulation. Patients were followed until hospital discharge. Results: Overall, 35 COVID-19 patients (63% men, median age 37 years) on VV-ECMO support were included in our study. The time from COVID-19 verification to ECMO support was a median (IQR) of 10 (7-14) days. Of the patients, 9 (26%) were discharged alive and 26 (74%) died during their hospital stay. Immune tests confirmed ongoing SARS-CoV-2 infection in all the patients, showing an increased humoral immune response. SARS-CoV-2-specific cellular immune response was significantly higher among survivors compared to the deceased patients. A higher probability of survival was observed in patients with markers indicating a higher T cell response detected by both QuantiFeron (QF) and flow cytometry (Flow) assays. (Flow S1 CD8+ ≥ 0.15%, Flow S1 CD4+ ≥ 0.02%, QF CD4 ≥ 0.07, QF whole genome ≥ 0.59). In univariate Cox proportional hazard regression analysis BMI, right ventricular (RV) failure, QF whole genome T cell level, and Flow S1 CD8+ T cell level were associated with mortality, and we found that an increased T cell response showed a significant negative association with mortality, independent of BMI and RV failure. Conclusion: Evaluation of SARS-CoV-2 specific T cell response before the cannulation can aid the risk stratification and evaluation of seriously ill COVID-19 patients undergoing VV-ECMO support by predicting survival, potentially changing our clinical practice in the future.

Early Application of ECMO after Sudden Cardiac Arrest to Prevent Further Deterioration: A Review and Case Report.

ECMO has become a therapeutic modality for in- and out-of-hospital scenarios and is also suitable as a bridging therapy until further decisions and interventions can be made. Case report: A 27-year-old male patient with mechanical aortic valve prothesis had a sudden cardiac arrest (SCA). ROSC had been achieved after more than 60 min of CPR and eight DC shocks due to ventricular fibrillation (VF). The National Ambulance Service unit transported the patient to our clinic for further treatment. Due to the trauma and therapeutic INR, a CT scan was performed and ruled out bleeding. Echocardiography described severely decreased left ventricular function. Coronary angiography was negative. Due to the therapeutic refractory circulatory and respiratory failure against intensive care, VA-ECMO implantation was indicated. After four days of ECMO treatment, the patient's circulation was stabilized without neurological deficit, and the functions of the end organs were normalized. Cardiac MRI showed no exact etiology behind SCA. ICD was implanted due to VF and SCA. The patient was discharged after 19 days of hospitalization. Conclusion: This case report points out that the early application of mechanical circulatory support could be an outcome-determinant therapeutic modality. Post-resuscitation care includes cardiorespiratory stabilization, treatment of reversible causes of malignant arrhythmia, and secondary prevention.

[The role of extracorporeal life support in cardiopulmonary resuscitation]. / Az extracorporalis keringéstámogatás helye az újraélesztésben.

The frequency of the administration of extracorporeal cardiopulmonary resuscitation is increasing both in the treatment of in-hospital and out-of-hospital cardiac arrest. The latest resuscitation guidelines support the use of mechanical circulatory support devices in the cases of prolonged cardiopulmonary resuscitation in certain selected patient groups. However, only little evidence is available regarding the effectiveness of extracorporeal cardiopulmonary resuscitation, and many open questions remained unanswered regarding the adequate conditions of this modality. The timing and location of extracorporeal cardiopulmonary resuscitation are important factors, as well as the appropriate training of the personnel using extracorporeal techniques. Our review briefly summarizes, according to the current literature and recommendations, in which cases extracorporeal resuscitation may be beneficial, which type of mechanical circulatory support is the first choice of extracorporeal cardiopulmonary resuscitation, which factors influence the efficacy of this supportive treatment, and which complications may be expected during mechanical circulatory support during resuscitation. Orv Hetil. 2023; 164(13): 510-514.

Perioperative Gelatin Use Is Associated With Increased Complication Rates and Does Not Prevent Postoperative Fluid Overload in Patients Undergoing Elective Cardiac Surgery.

OBJECTIVES: The benefit of using gelatin solution in cardiac surgery is still controversial. Previous data suggested adverse interactions of gelatin infusion with acute kidney injury (AKI) or coagulopathy. The purpose of this study was to evaluate the association between perioperative gelatin use and fluid overload (FO), hemodynamic stability, and outcomes compared to crystalloid-based fluid management. DESIGN: A retrospective study design. SETTING: At a single-center tertiary university setting. PARTICIPANTS: Propensity score-matched cohort study of 191 pairs of patients scheduled for cardiac surgery. INTERVENTIONS: Patients received either gelatin + crystalloid or pure crystalloid-based perioperative fluid management. The primary outcomes were the frequency of FO and hemodynamic stability defined by the vasoactive-inotropic score. Postoperative complications and 3-year survival were analyzed also. MEASUREMENTS AND MAIN RESULTS: Patients who received gelatin experienced more frequent postoperative FO than controls (11.0% v 3.1%, p = 0.006) despite comparable hemodynamic stability in both groups. Gelatin administration was linked with a higher rate of postoperative complications, including blood loss, AKI, and new-onset postoperative atrial fibrillation. Use of gelatin infusion resulted in an adjusted odds ratio of 1.982 (95% CI 1.051-3.736, p = 0.035) for developing early postoperative AKI. This study confirmed a dose-dependent relationship between gelatin infusion and AKI. Thirty-day mortality and 3-year survival were similar in the groups. CONCLUSIONS: Gelatin administration versus crystalloid fluid management showed a significant association with a higher rate of FO and an increased risk for early postoperative AKI in a dose-dependent manner.

Evaluating real-patient learning in medical education - Hungarian validation of the Manchester Clinical Placement Index.

Introduction: The Manchester Clinical Placement Index (MCPI) is an instrument to measure medical undergraduates' real-patient learning in communities of practice both in hospital and in GP placements. Its suitability to evaluate the quality of placement learning environments has been validated in an English-language context; however, there is a lack of evidence for its applicability in other languages. Our aim was to thoroughly explore the factor structure and the key psychometric properties of the Hungarian language version. Methods: MCPI is an 8-item, mixed-method instrument which evaluates the quality of clinical placements as represented by the leadership, reception, supportiveness, facilities and organization of the placement (learning environment) as well as instruction, observation and feedback (training) on 7-point Likert scales with options for free-text comments on the strengths and weaknesses of the given placement on any of the items. We collected data online from medical students in their preclinical (1st, 2nd) as well as clinical years (4th, 5th) in a cross-sectional design in the academic years 2019-2020 and 2021-2022, by the end of their clinical placements. Our sample comprises data from 748 medical students. Exploratory and confirmatory factor analyses were performed, and higher-order factors were tested. Results: Although a bifactor model gave the best model fit (RMSEA = 0.024, CFI = 0.999, and TLI = 0.998), a high explained common variance (ECV = 0.82) and reliability coefficients (ωH = 0.87) for the general factor suggested that the Hungarian version of the MCPI could be considered unidimensional. Individual application of either of the subscales was not supported statistically due to their low reliabilities. Discussion: The Hungarian language version of MCPI proved to be a valid unidimensional instrument to measure the quality of undergraduate medical placements. The previously reported subscales were not robust enough, in the Hungarian context, to distinguish, statistically, the quality of learning environments from the training provided within those environments. This does not, however, preclude formative use of the subscales for quality improvement purposes.

Influence of Venoarterial Extracorporeal Membrane Oxygenation Integrated Hemoadsorption on the Early Reversal of Multiorgan and Microcirculatory Dysfunction and Outcome of Refractory Cardiogenic Shock.

Background: The purpose of this investigation was to evaluate the impact of venoarterial extracorporeal membrane oxygenation (VA−ECMO) integrated hemoadsorption on the reversal of multiorgan and microcirculatory dysfunction, and early mortality of refractory cardiogenic shock patients. Methods: Propensity score−matched cohort study of 29 pairs of patients. Subjects received either VA−ECMO supplemented with hemoadsorption or standard VA−ECMO management. Results: There was a lower mean sequential organ failure assessment score (p = 0.04), lactate concentration (p = 0.015), P(v−a)CO2 gap (p < 0.001), vasoactive inotropic score (p = 0.007), and reduced delta C−reactive protein level (p = 0.005) in the hemoadsorption compared to control groups after 72 h. In−hospital mortality was similar to the predictions in the control group (62.1%) and was much lower than the predicted value in the hemoadsorption group (44.8%). There were less ECMO-associated bleeding complications in the hemoadsorption group compared to controls (p = 0.049). Overall, 90-day survival was better in the hemoadsorption group than in controls without statistical significance. Conclusion: VA−ECMO integrated hemoadsorption treatment was associated with accelerated recovery of multiorgan and microcirculatory dysfunction, mitigated inflammatory response, less bleeding complications, and lower risk for early mortality in comparison with controls.

"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.

Perioperative Factor Concentrate Use is Associated With More Beneficial Outcomes and Reduced Complication Rates Compared With a Pure Blood Product-Based Strategy in Patients Undergoing Elective Cardiac Surgery: A Propensity Score-Matched Cohort Study.

OBJECTIVE: The goal of this study was to compare factor concentrate (FC)-based and blood product-based hemostasis management of coagulopathy in cardiac surgical patients in terms of postoperative bleeding, required blood products, and outcome. DESIGN: Retrospective, propensity score-matched analysis. SETTING: Single, tertiary, academic medical center. PARTICIPANTS: One hundred eighteen matched pairs of 433 consecutive patients scheduled for cardiac surgery in two isolated periods with distinct strategies of hemostasis management. INTERVENTIONS: Patients received either blood product-based (period I) or FC-based (period II) hemostasis management to treat perioperative coagulopathy. MEASUREMENTS AND MAIN RESULTS: Patients treated with FC management experienced less postoperative blood loss (907 v 1,153 mL, p = 0.014) and required less red blood cell and fresh frozen plasma transfusion (2.3 v 3.7 units p < 0.0001, and 2.0 v 3.4 units p < 0.0001, respectively) compared with subjects in the blood product-based management group. The frequency of Stage 3 acute kidney injury and 30-day mortality rate were significantly higher in the blood product-based group than in the FC management group (6.8% v 0.8%, p = 0.016, and 7.2% v 0.8%, p = 0.022, respectively). FC management-related thromboembolic events were not registered. The FC strategy was associated with a 2.19-fold decrease in the odds of massive postoperative bleeding (p < 0.0001), a 2.56-fold decrease in the odds of polytransfusion (p < 0.0001), and a 13.16-fold decrease in the odds of early postoperative death (p = 0.003). CONCLUSIONS: FC-based versus blood product-based management is associated with reduced blood product needs and fewer complications, and was not linked to a higher frequency of thromboembolic events or a decrease in long-term survival in cardiac surgical patients developing perioperative coagulopathy and bleeding.

Predictors of mortality following extracorporeal membrane oxygenation support in an unselected, critically ill patient population.

INTRODUCTION: Mechanical circulatory support (MCS) has been established as a means of augmenting circulation in patients with critically decreased systolic function due to a variety of underlying clinical reasons. Different methods of MCS may be used, with the venous-arterial extracorporeal membrane oxygenation system (VA-ECMO) being one of the most utilized devices in everyday care. AIM: To determine independent predictors influencing mortality outcomes following VA-ECMO therapy in a large, unselected, adult, critically ill patient population in cardiogenic shock (CS). MATERIAL AND METHODS: Data on 235 consecutive, real-world VA-ECMO treatments were assessed. Analysis was conducted for all subjects requiring MCS with the VA-ECMO as the first instalment, regardless of underlying cause or eventual upgrade. All potential clinical factors influencing mortality were examined and evaluated. RESULTS: Overall mortality was ~66% at median 28 days follow-up and significantly depended upon pH < 7.3 (HR = 3.56; p < 0.001), and age ≥ 65 years (HR = 1.96; p = 0.001). Acute coronary syndrome (ACS) as an indication for VA-ECMO displayed a nearly significant value (HR = 1.44; p = 0.07). Heart transplant (hTX) primary graft failure as an indication for the VA-ECMO displayed a clearly favorable outcome (HR = 0.51, p = 0.025); all data based on multivariate Cox regression analysis. CONCLUSIONS: Mortality in patients requiring VA-ECMO remains high. We conclude that only decreased pH values and advanced age clearly influence mortality in this MCS scenario. ACS also bodes unfavorably, whereas hTX as an indication clearly shows better survival.

Changing strategies in aortic root reconstruction in Marfan syndrome / Stratégiai szemléletváltás a Marfan-szindrómás betegeken végzett aortagyök-rekonstrukciókban.

Összefoglaló. Bevezetés: A Marfan-szindróma autoszomális domináns módon öröklodo, szisztémás kötoszöveti betegség. A hosszú távú túlélés szempontjából fontos a nagyérkatasztrófák megelozése. Szívsebészeti szempontból a legfontosabb elváltozás az aortagyök tágulata. Aortagyök-rekonstrukciós beavatkozásaink Bentall-DeBono-, David I. és módosított Yacoub-mutétek, melyek mind preventív jelleggel, mind dissectio esetén jó eredménnyel végezhetok. Célkituzés: A marfanos betegeknél eltéro technikával végzett aortagyök-rekonstrukciós mutéteink összehasonlítása. Módszer: A Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinikáján 1993 és 2020 között Marfan-szindrómásoknál elvégzett Bentall-DeBono-, David I. és módosított Yacoub-féle aortagyök-rekonstrukciókat elemeztük. A mutét szerinti csoportok életkora a beavatkozás idején 29,69 (21,98-41,25) év, 29,15 ± 11,99 év és 35,29 ± 14,14 év volt, a fenti sorrendben. Az adatok forrásául a Magyar Marfan Regiszter és az Aortagyök-rekonstrukciós Regiszter szolgált. Eredmények: Az utánkövetési ido 132 ± 81,04 hónap volt a Bentall-, 76 ± 27,77 hónap a David-, valamint 4,5 (0,75-11,75) hónap a Yacoub-mutét esetén. A David- és a Yacoub-beavatkozások gyakrabban voltak profilaktikusak, mint a Bentall-operációk (p = 0,0153; p = 0,0085). A Bentall-mutéteknél ritkább volt a primer mutét esetleges késobbi elégtelenségébol fakadó reoperáció, mint a David-operációknál (p<0,001). David-beavatkozásnál a Bentall-mutéthez képest hosszabb volt a cardiopulmonaris bypass (p = 0,0013) és az aortalefogás ideje (p = 0,0048), valamint David- és Yacoub-mutét esetén gyakrabban lépett fel korai posztoperatív szövodmény, mint Bentall-operációnál (p = 0,0005; p = 0,0037). A késoi szövodmények és a túlélés tekintetében a csoportok nem különböztek. Következtetés: Marfan-szindrómában a leggyakrabban halált okozó szövodmény az akut aortaruptura, illetve akut aortadissectio. Eredményeink alapján mindhárom profilaktikus aortagyök-rekonstrukciós mutéti típus jól reprodukálható és jó eredménnyel végezheto Marfan-szindrómában. Orv Hetil. 2021; 162(18): 696-704. INTRODUCTION: Marfan syndrome is an autosomal dominant, systemic connective tissue disorder. Preventing vascular complications is essential for long-term survival. Aortic dilation is the main cardiac surgical manifestation. Bentall-DeBono, David I and modified Yacoub aortic root reconstructions treat and prevent aortic dissections with great outcomes. OBJECTIVE: Comparing results of aortic root reconstructions in Marfan syndrome. METHOD: We analysed the data of Bentall-DeBono, David I and modified Yacoub operations performed in Marfan syndrome at the Heart and Vascular Center, Semmelweis University between 1993 and 2020. Ages of surgical groups at the time of operation were 29.69 (21.98-41.25) years, 29.15 ± 11.99 years and 35.29 ± 14.14 years, respectively. Data were obtained from the Hungarian Marfan Register and the Aortic Root Reconstruction Register. RESULTS: Follow-up time was 132 ± 81.04 months for Bentall, 76 ± 27.77 months for David and 4.5 (0.75-11.75) months for Yacoub groups. David and Yacoub operations were prophylactic more frequently than Bentall ones (p = 0.0153; p = 0.0085). Freedom from reoperation after primary surgery insufficiency was more common for Bentall than for David procedure (p<0.001). Compared to Bentall, David surgeries required longer cardiopulmonary bypass (p = 0.0013) and aortic cross clamp time (p = 0.0048), more early postoperative complications occurred after David and Yacoub, than after Bentall operations (p = 0.0005; p = 0.0037). Late complications and survival did not differ among the groups. CONCLUSION: In Marfan syndrome, acute aortic rupture and dissection are the main contributors to mortality. Based on our results, the prophylactic aortic root reconstructions are reproducible and can be performed with great outcomes. Orv Hetil. 2021; 162(18): 696-704.

Acute heart transplantation from mechanical circulatory support in a human immunodeficiency virus-positive patient with fulminant myocarditis.

Since the establishment of highly active antiretroviral therapy, survival rates have improved among patients with human immunodeficiency virus infection giving them the possibility to become transplant candidates. Recent publications revealed that human immunodeficiency virus-positive heart transplant recipients' survival is similar to non-infected patients. We present the case of a 40-year-old human immunodeficiency virus infected patient, who was hospitalized due to severely decreased left ventricular function with a possible aetiology of acute myocarditis, that has later been confirmed by histological investigation of myocardial biopsy. Due to rapid progression to refractory cardiogenic shock, extracorporeal membrane oxygenation implantation had been initiated, which was upgraded to biventricular assist device later. On the 35th day of upgraded support, the patient underwent heart transplantation uneventfully. Our clinical experience confirms that implementation of temporary mechanical circulatory support and subsequent cardiac transplantation might be successful in human immunodeficiency virus-positive patients even in case of new onset, irreversible acute heart failure.

Reaction Kinetics Modeling of eHsp70 Induced by Norepinephrine in Response to Exercise Stress.

Exercise elicits a systemic adaptation reaction, involving both neuroendocrine and cellular/paracrine stress responses, exemplified by the sympathoadrenergic activity and the release of cellular Hsp70 into the circulation. Regular sports training is known to result in increased fitness. In this study, we characterized the plasma norepinephrine and Hsp70 levels and modeled their relationship in response to exercise stress by bicycle ergometer in 12 trained judoka athletes and in 10 healthy controls. Resting norepinephrine was similar in both groups, whereas Hsp70 was significantly higher in controls compared to athletes. Intense exercise load induced both norepinephrine and Hsp70 elevation. However, both norepinephrine and Hsp70 were significantly lower in athletes compared to the control group. A reaction kinetic model was developed that provided a quantitative description of norepinephrine-facilitated extracellular Hsp70 release, congruent with the experimental data. Our study indicates that exercise-induced norepinephrine and extracellular Hsp70 may be coordinated responses to physiological stress, which are robustly affected by regular sports activity.

Right ventricular mechanical pattern in patients undergoing mitral valve surgery: a predictor of post-operative dysfunction?

AIMS: The PREPARE-MVR study (PRediction of Early PostoperAtive Right vEntricular failure in Mitral Valve Replacement/Repair patients) sought to investigate the alterations of right ventricular (RV) contraction pattern in patients undergoing mitral valve replacement/repair (MVR) and to explore the associations between pre-operative RV mechanics and early post-operative RV dysfunction (RVD). METHODS AND RESULTS: We prospectively enrolled 42 patients (63 ± 11 years, 69% men) undergoing open-heart MVR. Transthoracic three-dimensional (3D) echocardiography was performed pre-operatively, at intensive care unit discharge, and 6 months after surgery. The 3D model of the RV was reconstructed, and RV ejection fraction (RVEF) was calculated. We decomposed the motion of the ventricle to compute longitudinal ejection fraction (LEF) and radial ejection fraction (REF). Pulmonary artery catheterization was performed to monitor RV stroke work index (RVSWi). RVEF was slightly decreased after MVR [52 (50-55) vs. 51 (46-54)%; P = 0.001], whereas RV contraction pattern changed notably. Before MVR, the longitudinal shortening was the main contributor to global systolic RV function [LEF/RVEF vs. REF/RVEF; 0.53 (0.47-0.58) vs. 0.33 (0.22-0.42); P < 0.001]. Post-operatively, the radial motion became dominant [0.33 (0.28-0.43) vs. 0.46 (0.37-0.51); P = 0.004]. However, this shift was temporary as 6 months later the two components contributed equally to global RV function [0.44 (0.38-0.50) vs. 0.41 (0.36-0.49); P = 0.775]. Pre-operative LEF was an independent predictor of post-operative RVD defined as RVSWi < 300 mmHg⋅mL/m2 [OR = 1.33 (95% CI: 1.08-1.77), P < 0.05]. CONCLUSIONS: MVR induces a significant shift in the RV mechanical pattern. Advanced indices of RV mechanics are associated with invasively measured parameters of RV contractility and may predict post-operative RVD.

Circulating Relaxin-1 Level Is a Surrogate Marker of Myocardial Fibrosis in HFrEF.

Introduction: Relaxin-1 (RLN1) has emerged as a possible therapeutic target in myocardial fibrosis due to its anti-fibrotic effects. Previous randomized clinical trials investigated therapeutic role of exogenous relaxin in patients with acute-on-chronic heart failure (HF) and failed to meet clinical endpoints. Here, we aimed to assess endogenous, circulating RLN1 levels in patients with heart failure with reduced ejection fraction (HFrEF) of ischemic origin. Furthermore, we analyzed relation of RLN1 and left ventricular diastolic function, left and right ventricular fibrosis, and invasive hemodynamic measurements. Unique feature of our study is the availability of ex vivo human myocardial tissue. Methods: Human myocardial samples were available from the Transplantation Biobank of the Heart and Vascular Center at Semmelweis University after local ethical approval and informed consent of all participants (n = 47). Tissue was collected immediately after heart explantations; peripheral blood was collected before induction of anesthesia. Myocardial sections were stained for Masson's trichrome and Picrosirius red staining to quantify fibrosis. Medical records were analyzed (ECG, anthropometry, blood tests, medication, echocardiography, and invasive hemodynamic measurements). Results: Average RLN1 levels in HFrEF population were significantly higher than measured in age and gender matched healthy control human subjects (702 ± 283 pg/ml in HFrEF vs. 44 ± 27 pg/ml in control n = 47). We found a moderate inverse correlation between RLN1 levels and degree of myocardial fibrosis in both ventricles (r = -0.357, p = 0.014 in the right ventricle vs. r = -0.321, p = 0.028 in the left ventricle with Masson's trichrome staining). Parallel, a moderate positive correlation was found in left ventricular diastolic function (echocardiography, E/A wave values) and RLN1 levels (r = 0.456, p = 0.003); a negative correlation with RLN1 levels and left ventricular end-systolic diameter (r = -0.373, p = 0.023), and diastolic pulmonary artery pressure (r = -0.894, p < 0.001). RLN1 levels showed moderate correlation with RLN2 levels (r = 0.453, p = 0.0003). Conclusion: Increased RLN1 levels were accompanied by lower myocardial fibrosis rate, which is a novel finding in our patient population with coronary artery disease and HFrEF. RLN1 can have a biomarker role in ventricular fibrosis; furthermore, it may influence hemodynamic and vasomotor activity via neurohormonal mechanisms of action. Given these valuable findings, RLN1 may be targeted in anti-fibrotic therapeutics and in perioperative care of heart transplantation.

Y-chromosomal connection between Hungarians and geographically distant populations of the Ural Mountain region and West Siberia.

Hungarians who live in Central Europe today are one of the westernmost Uralic speakers. Despite of the proposed Volga-Ural/West Siberian roots of the Hungarian language, the present-day Hungarian gene pool is highly similar to that of the surrounding Indo-European speaking populations. However, a limited portion of specific Y-chromosomal lineages from haplogroup N, sometimes associated with the spread of Uralic languages, link modern Hungarians with populations living close to the Ural Mountain range on the border of Europe and Asia. Here we investigate the paternal genetic connection between these spatially separated populations. We reconstruct the phylogeny of N3a4-Z1936 clade by using 33 high-coverage Y-chromosomal sequences and estimate the coalescent times of its sub-clades. We genotype close to 5000 samples from 46 Eurasian populations to show the presence of N3a4-B539 lineages among Hungarians and in the populations from Ural Mountain region, including Ob-Ugric-speakers from West Siberia who are geographically distant but linguistically closest to Hungarians. This sub-clade splits from its sister-branch N3a4-B535, frequent today among Northeast European Uralic speakers, 4000-5000 ya, which is in the time-frame of the proposed divergence of Ugric languages.

Acute thrombosis of the ascending aorta causing right ventricular failure: first manifestation of antiphospholipid syndrome.

Antiphospholipid syndrome is an autoimmune disorder with frequent clinical manifestation of arterial, venous or small vessel thromboembolic events and/or foetal morbidity. Hereby, we present a case report of a patient with a large arterial thrombus originating from the ostium of the right coronary artery accompanied by multiple systemic embolization and right ventricular failure. As a bridge-to-recovery strategy, an extracorporeal right ventricular assist device was successfully applied, representing an effective first choice option in selected patients with isolated acute right heart failure.

[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.

[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.