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.

Pseudoaneurysm of the ascending aorta: case report of a donor-derived Pseudomonas infection in a heart transplant recipient.

BACKGROUND: Mycotic aortic pseudoaneurysm is a rare complication after heart transplantation (HTX) with remarkable mortality. Intrathoracic infection is a well-documented predisposing factor for this disease. Staphylococcus aureus, Pseudomonas aeruginosa or Candida species are commonly isolated from resected specimens of the pseudoaneurysms. We demonstrate a unique case of mycotic pseudoaneurysm caused by presumably donor-derived Pseudomonas infection in a heart transplant recipient. CASE PRESENTATION: Our 67-year-old male patient treated with diabetes mellitus underwent HTX. The donor suffered from epiglottic abscess and pneumonia with known microorganisms including Pseudomonas, therefore both the donor and recipient received targeted antimicrobial therapy and prophylaxis. Five months after the uneventful HTX, lab test of the asymptomatic patient showed moderate, increasing C-reactive protein level without obviuos source of infection. Chest computed tomography showed a large (90 mm) saccular dilatation of the tubular portion of ascending aorta. Urgent surgical intervention identified a pseudoaneurysm, histological examinations and cultures of the resected aorta verified Pseudomonas aeruginosa aortitis, while all blood cultures remained negative. Retrospective interrogation of other transplanted organs of the donor supported donor-derived infection as the transport fluid of the right kidney grew Pseudomonas. The patient received 3 weeks of ceftazidime followed by 7 months of oral ciprofloxacin therapy. One year after the operation the patient was asymptomatic with normal inflammatory markers. CONCLUSIONS: Donor-derived infection is a rare but potential cause of aortitis. Early diagnosis, surgical intervention and adjuvant antibiotic therapy seem to be the keys to successful management of mycotic pseudoaneurysms after HTX.

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.

Seroconversion after SARS-CoV-2 vaccination is protective against severe COVID-19 disease in heart transplant recipients.

BACKGROUND: Heart transplant (HTX) recipients are prone to develop complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Vaccination is often ineffective due to weaker immunogenicity. In this high-volume single-center study, we aimed to determine factors influencing seroconversion after vaccination and predictors of severe SARS-CoV-2 infection. METHODS: Two hundred twenty-nine HTX recipients were enrolled. Type of the first two vaccine doses included messenger RNA (mRNA), vector, and inactivated vaccines. We carried out analyses on seroconversion after the second and third doses of vaccination and on severity of infection. Antispike protein SARS-CoV-2 immunoglobulin G (IgG) was measured after the second and third vaccines and serostatus was defined. Effect of the first two vaccine doses was studied on patients who did not suffer SARS-CoV-2 infection before antibody measurement (n = 175). The effectivity of the third vaccine was evaluated among seronegative recipients after the second vaccine (n = 53). Predictors for severe infection defined as pneumonia, hospitalization or death were assessed in all patients who contracted SARS-CoV-2 infection (n = 92). RESULTS: 62% of the recipients became seropositive after the second vaccination. Longer time between HTX and vaccination (odds ratio [OR]: 2.35) and mRNA vaccine (OR: 4.83) were predictors of seroconversion. 58% of the nonresponsive patients became seropositive after receiving the third vaccine. Male sex increased the chance of IgG production after the third dose (OR: 5.65). Clinical course of SARS-CoV-2 infection was severe in 32%. Of all parameters assessed, only seropositivity before infection was proven to have a protective effect against severe infection (OR: 0.11). CONCLUSIONS: We found that longer time since HTX, mRNA vaccine type, and male sex promoted seroconversion after SARS-CoV-2 vaccination in HTX recipients. Seropositivity-but not the number of vaccine doses-seemed to be protective against severe SARS-CoV-2 infection. Screening of HTX patients for anti-SARS-COV-2 antibodies may help to identify patients at risk for severe infection.

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.

CYP3A-status is associated with blood concentration and dose-requirement of tacrolimus in heart transplant recipients.

High inter-individual variability in tacrolimus clearance is attributed to genetic polymorphisms of CYP3A enzymes. However, due to CYP3A phenoconversion induced by non-genetic factors, continuous changes in tacrolimus-metabolizing capacity entail frequent dose-refinement for optimal immunosuppression. In heart transplant recipients, the contribution of patients' CYP3A-status (CYP3A5 genotype and CYP3A4 expression) to tacrolimus blood concentration and dose-requirement was evaluated in the early and late post-operative period. In low CYP3A4 expressers carrying CYP3A5*3/*3, the dose-corrected tacrolimus level was significantly higher than in normal CYP3A4 expressers or in those with CYP3A5*1. Modification of the initial tacrolimus dose was required for all patients: dose reduction by 20% for low CYP3A4 expressers, a 40% increase for normal expressers and a 2.4-fold increase for CYP3A5*1 carriers. The perioperative high-dose corticosteroid therapy was assumed to ameliorate the low initial tacrolimus-metabolizing capacity during the first month. The fluctuation of CYP3A4 expression and tacrolimus blood concentration (C0/D) was found to be associated with tapering and cessation of corticosteroid in CYP3A5 non-expressers, but not in those carrying CYP3A5*1. Although monitoring of tacrolimus blood concentration cannot be omitted, assaying recipients' CYP3A-status can guide optimization of the initial tacrolimus dose, and can facilitate personalized tacrolimus therapy during steroid withdrawal in the late post-operative period.

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.

An Interaction Effect Analysis of Thermodilution-Guided Hemodynamic Optimization, Patient Condition, and Mortality after Successful Cardiopulmonary Resuscitation.

Proper hemodynamic management is necessary among post-cardiac arrest patients to improve survival. We aimed to investigate the effects of PiCCO™-guided (pulse index contour cardiac output) hemodynamic management on mortality in post-resuscitation therapy. In this longitudinal analysis of 63 comatose patients after successful cardiopulmonary resuscitation cooled to 32-34 °C, 33 patients received PiCCO™, and 30 were not monitored with PiCCO™. Primary and secondary outcomes were 30 day and 1 year mortality. Kaplan-Meier curves and log-rank tests were used to assess differences in mortality among the groups. Interaction effects to disentangle the relationship between patient's condition, PiCCO™ application, and mortality were assessed by means of Chi-square tests and logistic regression models. A 30 day mortality was significantly higher among PiCCO™ patients, while 1 year mortality was marginally higher. More severe patient condition per se was not the cause of higher mortality rate in the PiCCO™ group. Patients in better health conditions (without ST-elevation myocardial infarction, without cardiogenic shock, without intra-aortic balloon pump device, or without stroke in prior history) had worse outcomes with PiCCO™-guided therapy. Catecholamine administration worsened both 30 day and 1 year mortality among all patients. Our analysis showed that there was a complex interaction relationship between PiCCO™-guided therapy, patients' condition, and 30 day mortality for most conditions.

Pilot analysis of the usefulness of mortality risk score systems at resuscitated patients / Halálozásikockázat-becslo pontrendszerek alkalmazhatóságának elozetes vizsgálata újraélesztett betegek körében.

Összefoglaló. Bevezetés: A cardiovascularis halálokok közül világszerte nagy jelentoségu a hirtelen szívhalál. Annak ellenére, hogy a cardiopulmonalis resuscitatio és a postresuscitatiós intenzív osztályos kezelés is komoly metodikai és technikai fejlodésen ment keresztül az elmúlt idoszakban, kevés az olyan validált pontrendszer, amely jól becsülné a beteg intenzív osztályra kerülésekor a mortalitási rizikót. Célkituzés: A sikeres újraélesztést követo intenzív osztályos kezelés kezdetekor felmért, a cardiogen shock rizikóstratifikációjára alkalmazott CardShock Risk Score (CSRS) és az általunk hozzáadott, specifikus súlyozófaktorokkal (iniciális ritmus, inotropigény) módosított CardShock Risk Score (mCSRS) összevetése a mortalitás elorejelzésében post-cardiac arrest szindrómás betegeknél. Módszerek: Retrospektív vizsgálatunk során 172, kórházon kívül sikeresen újraélesztett és klinikánkon ellátott consecutiv betegbol a CSRS- és mCSRS-pontrendszerek segítségével végül 123 beteg adatait elemeztük. A CSRS- és mCSRS-változók és a korai/késoi mortalitás közötti összefüggést Cox-regressziós analízissel vizsgáltuk. A pontszámok alapján 3 csoportba (1-3, 4-6, 7+) soroltuk a betegeket. Az összevont csoportok túlélését log-rank teszttel hasonlítottuk össze. Eredmények: A betegpopuláció átlagéletkora 63,6 év volt (69% férfi), és a hirtelen szívhalál hátterében 80%-ban akut coronaria szindróma állt. A korai/késoi mortalitást leginkább a felvétel utáni neurológiai állapot, a szérumlaktátszint, a vesefunkció, az iniciális ritmus és a beteg katecholaminigénye határozta meg. A mCSRS alkalmazását követoen mind az "1-3" és a "4-6" (p≤0,001), mind a "4-6" és a "7+" (p = 0,006) csoportok között szignifikáns különbséget találtunk a túlélésben. Következtetés: A felvételkori pontok alapján a mCSRS pontosabban definiálja és differenciálja egymástól az általunk beválasztott két extra súlyozófaktorral az enyhe, a közepes és a magas mortalitási rizikóval bíró betegpopulációkat, mint a CSRS. Orv Hetil. 2021; 162(2): 52-60. INTRODUCTION: Sudden cardiac death is one of the most significant cardiovascular causes of death worldwide. Although there have been immense methodological and technical advances in the field of cardiopulmonary resuscitation and following intensive care in the last decade, currently there are only a few validated risk-stratification scoring systems for the quick and reliable estimation of the mortality risk of these patients at the time of admission to the intensive care unit. OBJECTIVE: Our aim was to correlate the mortality prediction risk points calculated by CardShock Risk Score (CSRS) and modified (m) CSRS based on the admission data of the post-cardiac arrest syndrome (PCAS) patients. METHODS: The medical records of 172 out-of-hospital resuscitated cardiac arrest patients, who were admitted at the Heart and Vascular Centre of Semmelweis University, were screened retrospectively. Out of the 172 selected patients, 123 were eligible for inclusion to calculate CSRS and mCSRS. Based on CSRS score, we generated three different groups of patients, with scores 1 to 3, 4 to 6, and 7+, respectively. Mortality data of the groups were compared by log-rank test. RESULTS: Mean age of the patients was 63.6 years (69% male), the cause of sudden cardiac death was acut coronary syndrome in 80% of the cases. The early and late mortality was predicted by neurological status, serum lactate level, renal function, initial rhythm, and the need of catecholamines. Using mCSRS, a significant survival difference was proven in between the groups "1-3" vs "4-6" (p≤0.001), "4-6" vs "7+" (p = 0.006). CONCLUSION: Compared to the CSRS, the mCSRS expanded with the 2 additional weighting points differentiates more specifically the low-moderate and high survival groups in the PCAS patient population treated in our institute. Orv Hetil. 2021; 162(2): 52-60.