Endre Németh

Complement activation, inflammation and relative ADAMTS13 deficiency in secondary thrombotic microangiopathies ☆

BACKGROUND The secondary forms of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (secondary TMA) emerge as complications of coexisting diseases. OBJECTIVES We hypothesized that secondary TMA could be characterized by the presence of relative ADAMTS13 deficiency and complement activation, and this relationship may have a prognostic value for outcome. PATIENTS AND METHODS Fifty-three patients with thrombotic microangiopathy (TMA) and coexisting disease (such as malignancies, sepsis, heart surgery with extracorporeal circulation, solid organ transplantation, systemic autoimmune disorders), 41 patient controls, and 34 healthy controls were enrolled in our case-control study with 30days follow-up. Complement profile (from serum) and activation products, von Willebrand factor (VWF, from EDTA plasma), and ADAMTS13 activity were determined. RESULTS ADAMTS13 activity was reduced, while VWF level was elevated in secondary TMA patients. The activity of the classical, lectin and alternative pathways, as well as the levels of C3, C4, and Factor H were significantly lower in secondary TMA patients, and were accompanied by high activation product levels (C3a and sC5b-9). Factor H concentration correlated to relative ADAMTS13 deficiency (i.e. VWF/ADAMTS13 ratio (r=-0.368, p=0.019)). 28/53 patients (53%) died during the follow-up period. Increased sC5b-9, C3a, and C reactive protein levels were all associated with a poor patient outcome. CONCLUSIONS Our results indicate that the secondary TMA syndrome and its poor outcome is characterized by relative ADAMTS13 deficiency, inflammation, and complement activation with consumption via the classical and alternative pathways. It is yet to be determined whether complement inhibition could be a possible therapeutic option for patients with secondary TMA.

Dominance of free wall radial motion in global right ventricular function of heart transplant recipients

Assessment of right ventricular (RV) function using conventional echocardiography might be inadequate as the radial motion of the RV free wall is often neglected. Our aim was to quantify the longitudinal and the radial components of RV function using three‐dimensional (3D) echocardiography in heart transplant (HTX) recipients. Fifty‐one HTX patients in stable cardiovascular condition without history of relevant rejection episode or chronic allograft vasculopathy and 30 healthy volunteers were enrolled. RV end‐diastolic (EDV) volume and total ejection fraction (TEF) were measured by 3D echocardiography. Furthermore, we quantified longitudinal (LEF) and radial ejection fraction (REF) by decomposing the motion of the RV using the ReVISION method. RV EDV did not differ between groups (HTX vs control; 96 ± 27 vs 97 ± 2 mL). In HTX patients, TEF was lower, however, tricuspid annular plane systolic excursion (TAPSE) decreased to a greater extent (TEF: 47 ± 7 vs 54 ± 4% [−13%], TAPSE: 11 ± 5 vs 21 ± 4 mm [−48%], P < .0001). In HTX patients, REF/TEF ratio was significantly higher compared to LEF/TEF (REF/TEF vs LEF/TEF: 0.58 ± 0.10 vs 0.27 ± 0.08, P < .0001), while in controls the REF/TEF and LEF/TEF ratio was similar (0.45 ± 0.07 vs 0.47 ± 0.07). Current results confirm the superiority of radial motion in determining RV function in HTX patients. Parameters incorporating the radial motion are recommended to assess RV function in HTX recipients.

Evaluation of liver function before living donor liver transplantation and liver resection

UNLABELLED Liver resection is the curative therapeutic option for hepatocellular carcinoma, biliary tumors, metastases of colorectal and other extrahepatic tumors, living donor liver transplantation and other benign liver diseases. AIM OF STUDY To summarize the evaluation methods of liver function before living donor liver transplantation and liver resection. METHOD We summarize the literature about the evaluation of liver function. RESULTS Perioperative mortality is determined mostly by the extent of preoperative evaluation focused on the liver. After resection the remnant liver parenchyma must cope with the challenge caused by increased metabolism, portal overflow, decreased vascular bed and biliary tract and oxidative stress following the operation. If the remnant liver is unable to grow up to this challenge, acute liver failure occurs. This maintains the necessity of determining the hepatic functional reserve and the hepatic remnant volume. Child-Pugh classification is widely spread to predict outcome. Dynamic functional tests such as indocyanine green retention test, galactosyl human serum albumin scintigraphy and aminopyrine breath tests can be used to evaluate hepatic reserve. To determine remnant liver volume modern imaging processes such as CT volumetry and hepatobiliary scintigraphy are available. CONCLUSION After the detailed evaluation resection can be limited to an extent which is oncologically radical enough (1% remnant liver tissue/kg) and spares parenchyma which can ensure survival yet. With careful preoperative examination mortality can be reduced even to reach zero.

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.

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.

Impact of intraoperative cytokine adsorption on outcome of patients undergoing orthotopic heart transplantation—an observational study

The aim of this study was to assess the influence of intraoperative cytokine adsorption on the perioperative vasoplegia, inflammatory response and outcome during orthotopic heart transplantation (OHT).

Response to Ivey-Miranda and Farrero-Torres “Is there dominance of free wall radial motion in global right ventricular function in heart transplant recipients or in all heart surgery patients?”

Dear Editor, In our original article—recently published in Clinical Transplantation— we concluded that after orthotopic heart transplantation, the radial motion of right ventricular free wall compensates for the decreased longitudinal shortening to maintain ejection fraction.1 The editorial from IveyMiranda and FarreroTorres questioned whether this finding was true for all heart surgery patients. Certainly, the answer is positive. As we have discussed in our paper, there is extensive corresponding literature, and the phenomenon is very similar in cardiac surgery patients. However, the magnitude and timing of this functional shift may be different in heart transplant recipients. The aim of our study was to confirm the dominance of radial wall motion in right ventricular function in the case of heart transplant patients using a superior, 3D echocardiographic method compared to previous investigations.2 We do agree with the authors of the editorial that another, heart surgery group would have been useful. However, retrospective studies are not necessarily useful to answer every question regarding this functional remodelling. An interesting paper from Raina et al3 reported a direct comparison between heart transplant recipients (n = 54) and patients who underwent coronary artery bypass surgery (n = 23), all with preserved left and also right ventricular global function. In their twodimensional but thorough echocardiographic analysis, they found no difference between the 2 groups regarding the importance of the different right ventricular motion components. Still, if we look at the time elapsed between the operation and the echocardiogram, the difference between the heart transplant (mean 381 days) versus the coronary cohort (mean 70 days) is problematic. We have already commenced a prospective study with regular and frequent followup visits of heart transplant patients using 3D echocardiography. Moreover, the dedicated time points are the same as in the PREPAREMVR (PRediction of Early PostoperAtive Right vEntricular failure in Mitral Valve Replacement/Repair patients) study, where we are aiming to evaluate those preoperative factors that can predict early postoperative right ventricular failure or determine the functional shift seen in right ventricular function after mitral valve replacement/repair (NCT03438825). Beyond 3D echocardiography, the PREPAREMVR study includes right heart catheterization both intraoperatively and in the early postoperative period to correlate directly the results of invasive hemodynamic measurements with the advanced parameters of right ventricular function. We hope that the upcoming results of the aforementioned studies along with the comparison of these 2 cohorts will deepen our understanding of this interesting and clinically relevant topic. It is important to note that the adaptation of the right ventricle to increased afterload would imply a decrease in radial function, which bears prognostic value as well.4 However, radial function is still supernormal after heart transplantation. The selection and even more the results of the “control” population also deserve a comment. Longitudinal shortening was traditionally considered as the main determinant of global right ventricular function in healthy people; however, using the ReVISION method to compare the importance of longitudinal and radial wall motions headtohead, their relative contribution appears to be equal. A study with a larger sample size is required to confirm this, investigating different age groups and potential gender differences. In conclusion, we would like to thank the authors of the editorial for their supportive comments and more importantly, for highlighting the knowledge gap and the need for further research in the field of right ventricular function.

Szívtranszplantáció és műszívkezelés költséghatékonysági elemzési modellje

Absztrakt A szivtranszplantacio kiemelt projekt lett a Semmelweis Egyetemen belul. Ennek megfelelően a szivatultetes es a mechanikus keringestamogatas finanszirozasa is rendkivuli jelentőseget kapott. A szerzők a transzplantacios es műszives betegek koltsegeinek osszehasonlitasarol vegzett koltseghatekonysagi szamitasi modell felepiteseről szamolnak be. A modell megalkotasanal direkt allokacios koltsegszamitast, dontesifa-modellt, inkrementalis koltseghatekonysagi ratat es koltseghatekonysagi terkepmodszert hasznaltak. Modszerukkel ossze tudjak hasonlitani a műszivbeultetesen atesett es a szivtranszplantacios betegcsoportok kezdeti, perioperativ es utokezelesi koltsegeit. Modelljuk alkalmas lehet hosszu tavu utankovetes es kellő elemszamu beteg bevonasaval koltseghatekonysagi elemzesek elkeszitesere, gazdasagi dontestamogato kovetkeztetesek meghozatalara.

[Mechanical circulatory support saves lives -- three years' experience of the newly established assist device program at Semmelweis University, Budapest, Hungary].

INTRODUCTION Since the celebration of the 20th anniversary of the first heart transplantation in Hungary in 2012 the emerging need for modern heart failure management via mechanical circulatory support has evolved. In May 2012 the opening of a new heart failure and transplant unit with 9 beds together with the procurement of necessary devices at Semmelweis University accomplished this need. AIM The aim of the authors was to report their initial experience obtained in this new cardiac assist device program. METHOD Since May, 2012, mechanical circulatory support system was applied in 89 cases in 72 patients. Indication for support were end stage heart failure refractory to medical treatment and acute left or right heart failure. RESULTS Treatment was initiated for acute graft failure after heart transplantation in 27 cases, for end stage heart failure in 24 cases, for acute myocardial infarction in 21 cases, for acute postcardiotomy heart failure in 14 cases, for severe respiratory insufficiency in 2 cases and for drug intoxication in one case. Among the 30 survivor of the whole program 13 patients were successfully transplanted. CONCLUSIONS The available devices can cover all modalities of current bridge therapy from short term support through medium support to heart transplantation or long term support and destination therapy. These conditions made possible the successful start of a new cardiac assist device program.

A mechanikus keringéstámogatás életet ment – a műszívprogram első három évének tapasztalata a Semmelweis Egyetemen@@@Mechanical circulatory support saves lives – three years’ experience of the newly established assist device program at Semmelweis University

INTRODUCTION Since the celebration of the 20th anniversary of the first heart transplantation in Hungary in 2012 the emerging need for modern heart failure management via mechanical circulatory support has evolved. In May 2012 the opening of a new heart failure and transplant unit with 9 beds together with the procurement of necessary devices at Semmelweis University accomplished this need. AIM The aim of the authors was to report their initial experience obtained in this new cardiac assist device program. METHOD Since May, 2012, mechanical circulatory support system was applied in 89 cases in 72 patients. Indication for support were end stage heart failure refractory to medical treatment and acute left or right heart failure. RESULTS Treatment was initiated for acute graft failure after heart transplantation in 27 cases, for end stage heart failure in 24 cases, for acute myocardial infarction in 21 cases, for acute postcardiotomy heart failure in 14 cases, for severe respiratory insufficiency in 2 cases and for drug intoxication in one case. Among the 30 survivor of the whole program 13 patients were successfully transplanted. CONCLUSIONS The available devices can cover all modalities of current bridge therapy from short term support through medium support to heart transplantation or long term support and destination therapy. These conditions made possible the successful start of a new cardiac assist device program.