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.

Extracorporeal photopheresis in the treatment of cardiac allograft rejection: A single-centre experience.

Despite novel immunosuppressive (IS) protocols, adverse effects of IS drugs continue to have notable negative impact on patient and cardiac allograft survival after heart transplantation (HTx). Therefore, IS regimens with less toxic side effects are sorely needed. We aimed to evaluate the efficacy of extracorporeal photopheresis (ECP) in combination with tacrolimus-based maintenance IS therapy in the treatment of allograft rejection in adult HTx recipients. Indications for ECP included acute moderate-to-severe or persistent mild cellular rejection, or mixed rejection. Twenty-two patients underwent a median of 22(2-44) ECP treatments after HTx. Median duration of ECP course was 173.5(2-466) days. No relevant adverse effects of ECP were noted. Reduction of methylprednisolone doses was safe throughout the ECP course. ECP, used in conjunction with pharmacological anti-rejection therapy, had a successful reversal of cardiac allograft rejection, decreased the rates of subsequential rejection episodes and normalized the allograft function in patients completing the ECP course. Short- and long-term survivals were excellent (91% at 1 and 5 years post-ECP) and comparable to International Society for Heart and Lung Transplantation registry data on HTx recipient overall survival. In conclusion, ECP can be safely used for the treatment and prevention of cardiac allograft rejection in conjunction with traditional IS regimen.

Biosignal processing methods to explore the effects of side-dominance on patterns of bi- and unilateral standing stability in healthy young adults.

We examined the effects of side-dominance on the laterality of standing stability using ground reaction force, motion capture (MoCap), and EMG data in healthy young adults. We recruited participants with strong right (n = 15) and left (n = 9) hand and leg dominance (side-dominance). They stood on one or two legs on a pair of synchronized force platforms for 50 s with 60 s rest between three randomized stance trials. In addition to 23 CoP-related variables, we also computed six MoCap variables representing each lower-limb joint motion time series. Moreover, 39 time- and frequency-domain features of EMG data from five muscles in three muscle groups were analyzed. Data from the multitude of biosignals converged and revealed concordant patterns: no differences occurred between left- and right-side dominant participants in kinetic, kinematic, or EMG outcomes during bipedal stance. Regarding single leg stance, larger knee but lower ankle joint kinematic values appeared in left vs right-sided participants during non-dominant stance. Left-vs right-sided participants also had lower medial gastrocnemius EMG activation during non-dominant stance. While right-side dominant participants always produced larger values for kinematic data of ankle joint and medial gastrocnemius EMG activation during non-dominant vs dominant unilateral stance, this pattern was the opposite for left-sided participants, showing larger values when standing on their dominant vs non-dominant leg, i.e., participants had a more stable balance when standing on their right leg. Our results suggest that side-dominance affects biomechanical and neuromuscular control strategies during unilateral standing.

Development of a detailed canine gait analysis method for evaluating harnesses: A pilot study.

Dog harnesses are becoming more popular, with their large variety stemming from the idea that different dogs and scenarios require different types of harnesses. While their benefits over collars are self-explanatory, there is a lack of research on their effect on gait, and even the existing studies examine only a limited set of parameters. The goal of present study was to establish a method capable of quantifying canine gait in detail. Based on 3D motion capture, the developed method allows for the examination of 18 joint angles and 35 spatio-temporal parameters throughout multiple gait cycles, and can be used to analyze canine movement in detail in any kind of scenario (e.g. comparing healthy and lame dogs, or measuring the effect of training). The method is presented through the measurement of how different harnesses affect walking kinematics compared to free (unleashed) movements. Four dogs with varying body sizes and breeds and multiple types of harnesses were included. Marker data was filtered using a zero-lag 6th order Butterworth-filter with a cutoff frequency of 20 Hz. The normality of the spatio-temporal and joint range of motion parameters was tested using the Anderson-Darling test (p = 0.05), with most parameters passing in 60+% of test cases. Swing time and range of motion of the sagittal aspect of spinal angle at T1 vertebrae failed more regularly, both resulting from the measurement setup rather than the actual parameters being not normally distributed. Two-sample Kolmogorov-Smirnov tests (p = 0.05) were used to compare each parameter's distribution between cases, showing that most parameters are significantly altered by the harnesses in about 2/3rd of the cases. Based on the results, there's no absolute superior harness, however, it is possible to select the best fit for a specific dog and application, justifying their large variety.

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.

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.

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.

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

AIM: 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). METHODS: Eighty-four OHT patients were separated into the cytokine adsorption (CA)-treated group or controls. Vasopressor demand, inflammatory response described by procalcitonin and C-reactive protein, and postoperative outcome were assessed performing propensity score matching. RESULTS: In the 16 matched pairs, the median noradrenaline requirement was significantly less in the CA-treated patients than in the controls on the first and second postoperative days (0.14 vs 0.3 µg*kg-1 *min-1 , P = .039 and 0.06 vs 0.32 µg*kg-1 *min-1 , P = .047). The inflammatory responses were similar in the two groups. There was a trend toward shorter length of mechanical ventilation and intensive care unit (ICU) stay in the CA-treated group compared to the controls. No difference in adverse events was observed between the two groups. The frequency of renal replacement therapy was less in the CA­treated patients than in the controls. CONCLUSIONS: Intraoperative CA treatment was associated with reduced vasopressor demand with a favorable tendency in length of mechanical ventilation, ICU stay and renal replacement therapy. CA treatment was not linked to higher rates of adverse events.

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.

Influence of the postoperative inflammatory response on cognitive decline in elderly patients undergoing on-pump cardiac surgery: a controlled, prospective observational study.

BACKGROUND: The role of non-infective inflammatory response (IR) in the aetiology of postoperative cognitive dysfunction (POCD) is still controversial. The aim of this controlled, prospective observational study was to assess the possible relationship between the grade of IR, defined by procalcitonin (PCT) changes, and development of POCD related to cardiac surgery. METHODS: Forty-two patients, who were ≥ 60 years of age and scheduled for elective cardiac surgery, were separated into the low inflammatory (LIR) and high inflammatory (HIR) response groups based on their PCT levels measured on the first postoperative day. A matched normative control group of 32 subjects was recruited from primary care practice. The PCT and C-reactive protein (CRP) levels were monitored daily during the first five postoperative days. The cognitive function and mood state were preoperatively tested with a set of five neurocognitive tests and two mood inventories and at the seventh postoperative day. The Reliable Change Index modified for practice (RCIp) using data from normative controls was applied to determine the significant decline in test performance. RESULTS: The LIR (n = 20) and HIR (n = 22) groups differed significantly in the PCT (p < 0.001) but not in the CRP time courses. The incidence of POCD at the first postoperative week was 35.7% in the cohort. The LIR and HIR groups did not vary in the RCIp Z scores of neurocognitive tests and frequencies of POCD (7 vs 8 cases, respectively, p > 0.05). Additionally, there was no difference in the mood states, anxiety levels and perioperative parameters known to influence the development of POCD. CONCLUSIONS: In this study, the magnitude of the non-infective inflammatory response generated by on-pump cardiac surgery did not influence the development of POCD in the early postoperative period in elderly patients.

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.

[Mechanical circulatory support saves lives -- three years' experience of the newly established assist device program at Semmelweis University, Budapest, Hungary]. / A mechanikus keringéstámogatás életet ment -- a muszívprogram elso három évének tapasztalata a Semmelweis Egyetemen.

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.

[2012 -- the year of success in the 20 year-old adult heart transplant program of Hungary]. / A 2012-es év a húszéves hazai felnottszív-transzplantáció sikeréve -- és ami mögötte van.

The Hungarian adult heart transplant program, which started in 1992, has changed gradually in the past 20 years. After the early enthusiasm of the first cases it changed significantly and it became an organized programme. However, low donation activity and moderate referral numbers to the national transplant waiting list slowed down the process therefore, heart transplant numbers did not fulfill expectations in the early years. After a moderate increase in 2007 transplant numbers have dropped again until recently when Hungary partially joined Eurotransplant network. Excess fundamental resources allocated to cardiac transplantation by health care professionals and reorganizing transplant coordination as well as logistics forced dramatic changes in clinical management. In 2011 and 2012 major structural changes had been made at Semmelweis University. The newly established transplant intensive care unit and the initiation of mechanical circulatory support and assist device programme increased transplant numbers by 131% compared to previous years, as well as it resulted an 86.63% 30-day survival rate, hence last year was the most successful year of cardiac transplantation ever.

[Preoperative revascularization in high-risk patients undergoing vascular surgery]. / Preoperatív revascularisatio nagy kockázatú, érsebészeti betegeknél.

Patients undergoing vascular surgery are at increased risk for cardiac complications related to the presence of underlying coronary artery disease. Preoperative cardiac evaluation may help to identify high-risk patients in whom coronary angiography may be planned with subsequent coronary revascularization for the purpose of improving perioperative and long-term cardiac outcomes. However, the indications and efficacy for type of revascularization for the reduction of cardiac complications compared to medical therapy have been controversial. The aim of the review was to summarize the role of preoperative revascularization compared to conservative medical therapy before elective vascular surgery using current evidence from published studies.

[The first successful combined heart-kidney transplantation in Hungary]. / Az elso sikeres kombinált szív- és veseátültetés Magyarországon.

Combined heart-kidney transplantation has become a new therapeutic solution for patients with coexisting, irreversible heart and kidney failure. Though this combined approach has several theoretical advantages over sequential transplantation, it remains to be established whether it has a jeopardizing impact on patient and graft outcome. The authors report their experience of the first successful combined heart-kidney transplantation in Hungary from a single donor and review the literature in order to clarify this issue. Young male patient candidate for heart transplantation was suffering from concurrent end stage kidney disease. Donor was selected on the basis of weight and size matching, AB0 compatibility and negative T-cell cross-match. The heart was grafted first, and after the hemodynamic stabilization kidney from the same donor was transplanted. The surgical procedure was uneventful. Heart and kidney function recovered quickly, and the patient is doing very well with good cardiac and renal function even a year following the double organ transplantation. The first Hungarian experience showed that combined heart-kidney transplantation is a therapeutic solution for patients with end stage heart and kidney failure. The lower rate of rejection compared to single heart or kidney transplantation, known from the literature as well, supports their current approach to immunosuppression.