End-stage Chronic Heart Failure Research Articles

ORGANIZATION OF TRANSPLANTATION ASSISTANCE THROUGH TRANSPORTATION OF THE RECIPIENT TO THE REGIONAL EXPLANTATION BASE FOR HEART TRANSPLANTATION

Introduction. To date, heart transplantation remains the only effective method of treatment for patients with end-stage chronic heart failure. Due to the short time of ischemia of the donor heart and the lack of an alternative to deliver the organ on time over long distances, the strategy in organizing transplantation was changed. The aim of this study was to analyze the effectiveness of transporting the recipient to the donor to reduce the ischemia time of the donor organ during martial law. Materials and methods. This retrospective study includes all cases of heart transplantation carried out by specialists of the State Institution "Heart Institute of the Ministry of Health of Ukraine" during 2022–2024. Heart transplantations were performed directly in our center and on-site. Outpatient surgery involved heart transplantation in the medical facility where the donor was located or in the nearest hospital. The results. The study included 55 patients who underwent orthotopic heart transplantation, of which 20.0% were women and 80.0% were men. Depending on the place of heart transplantation, all patients were divided into two groups: the first group (32 patients) – heart transplantation in the State Institution "Heart Institute of the Ministry of Health of Ukraine" and the second group (23 patients) – heart transplantation elsewhere. The duration of donor heart ischemia was not significantly different between the study groups (95.4±15.3 min vs. 90.3±10.8 min, p=0.167), although there was a tendency to decrease in the patients of the second group. Hospital survival was 93.8±4.28% among patients of the first group and 91.3±5.87% among patients of the second group (p=0.408). 12-month survival in the study groups was 87.5±5.84% versus 86.9±7.02% (p=0.375). Conclusions. The use of recipient-to-donor transportation not only made it possible to reduce the duration of ischemia of the donor heart, but also presented with a similar level of hospital and 12-month survival, which makes it possible to effectively apply this method in wartime conditions when there is no possibility of helicopter transportation.

Tolerability of an Individualized Physical Rehabilitation Program in Patients Dependent on Inotropic Support With End-Stage Chronic Heart Failure

Aim To assess the tolerability of an individualized physical rehabilitation program (PRP) in inotrope-dependent patients with end-stage chronic heart failure (CHF).Material and methods This prospective randomized study included 120 men aged 18-65 years with left ventricular ejection fraction ≤30 % and blood pressure ≥90 / 60 mm Hg. Patients who have received dobutamine or dopamine for ≥2 weeks were randomized into two groups: group 1, 40 patients who participated in the PRP and group 2, 40 patients who did not participate in the PRP. Group 3 included 40 patients without inotropic support who participated in the PRP.Results Patients of groups 1 and 3 attended >80 % of the scheduled classes without developing life-threatening adverse events (AEs) associated with exercise (E). After 6 months of the study, the exercising patients achieved a comparable (average) E intensity: 44 [35; 50]% and 45 [40;52]% of heart rate reserve and Borg scale scores 14 [12; 14] and 13 [11; 14] in groups 1 and 3, respectively (p>0.05). Initially, after 3 and 6 months at the peak of physical activity in groups 1 and 3, there was no decrease in arterial blood oxygen saturation according to pulse oximetry (SpO2) <93 %. At baseline, lactate levels in central venous blood at rest were normal in all groups. After 6 months, the lactate concentration was 1.1 mmol / l in group 1, 2.3 mmol / l in group 2, and 1.4 mmol / l in group 3 (р1-2=0.005; p2-3=0.008, respectively). At the E peak at baseline, after 3 and 6 months, comparable increases in lactate not exceeding 3 mmol / l were detected in groups 1 and 3.Conclusion The study allowed assessment of the tolerability of individualized PRP performed at the aerobic level of energy supply, in inotropic-dependent patients with CHF. Individualized 6-month PRP in inotropic-dependent patients with end-stage CHF, provided safety criteria are met, is well tolerated and does not increase the number of AEs associated with CHF and physical rehabilitation (PR). Continued inotropic support with dopamine or dobutamine should not be considered as a contraindication to PR in patients with CHF in the absence of E intolerance or life-threatening AEs.

Abstract 14302: Heart Logic Directed Uptitration of Guideline Directed Medical Therapy Improves EF Across All Device Categories

Introduction: Historically data for CHF management in ICD patients had been for adjustments in diuretics. GDMT changes are often limited due to BP, renal function, or concerns for hypotension. Hypothesis: Using the Heart Logic score on Boston Scientific ICDs we could up-titrate GDMT in a safe reliable fashion which would allow for further improvement in LVEF and avoid complications. Methods: 30 patients with either a new implant or generator change (single, dual, or resynchronization) with a compatible ICD were enrolled. The alert threshold was lowered from the standard of 16 to 10. The goal was to identify patients before congestion occurred. All patients were followed with remote monitoring. When an alert occurred, a single class of GDMT was increased. If alert did not go back to zero on repeat transmission, then a second class of medicine was up-titrated, changed, or added. The patients were followed for one year with yearly echo. Results: 30 patients were enrolled. 2 died during the year follow-up from end stage CHF after being turned down for transplant or MCS. 1 patient did not have a one year follow-up echo. A total of 47 medicine changes or up-titrations were made. The average EF improved from baseline 27.5% to 37.2%. There were no syncopal events, worsening renal function, or hyperkalemia reported. The only subjective complaints were transient dizziness. Conclusions: Heart Logic based medication management allows a safe mechanism for increase or change in GDMT in the CHF population. Up-titration is necessary for better outcomes in CHF care but is also often limited to subjective concerns regarding potential complications.

Pediatric mechanical circulatory support: pathophysiology of pediatric hemostasis and postoperative management algorithms

Chronic heart failure (CHF) against the background of congenital heart disease, mostly in early childhood, or various forms of cardiomyopathies, more common in teenage age, represents an important cause of morbidity and mortality in the pediatric population [1, 2]. Due to the increase in the number of patients suffering from refractory end-stage CHF over the last two decades, and the current shortage of donor organs in pediatric practice, the issue of long-term mechanical circulatory support (MCS) is becoming increasingly a pressing problem. Patient management is a multidisciplinary task, since prolonged use of anticoagulant and antiplatelet therapy to prevent ventricular thrombosis has potentially life-threatening complications - acute hemorrhagic stroke and bleeding of varying severity.

Endovascular Versus Medical Management of Atherosclerotic Renovascular Disease: Update and Emerging Concepts.

Atherosclerotic renovascular disease is the most frequent cause of renovascular hypertension and its prevalence increases with age and in specific subset of patients, such as those with end-stage chronic kidney disease, heart failure, and coronary artery disease. Besides hypertension, atherosclerotic renovascular disease is responsible for several clinical manifestations, including life-threatening conditions, such as recurrent flash pulmonary edema, rapidly progressive chronic kidney disease, or acute kidney injury. Atherosclerotic renovascular disease is usually part of a more diffuse atherosclerotic process and requires a combination therapy including antihypertensive, antiplatelet and lipid-lowering agents, as well as optimization of antidiabetic treatment, if needed. Besides medical therapy, percutaneous renal angioplasty was supposed to be the most effective therapy for atherosclerotic renovascular disease, by leading to blood flow restoration. However, despite an apparently solid rationale, several randomized clinical trials failed to confirm the favorable effects of percutaneous renal angioplasty on blood pressure control, kidney function, cardiovascular and renal outcomes, previously reported in observational, retrospective and single-center cohorts, switching off the enthusiasm for this procedure. Several studies' limitations may partly account for this failure, including heterogeneity of diagnostic techniques, overestimation of the degree of renal artery stenosis, inappropriate timing of revascularization, multiple protocol revisions, frequent crossovers, and most importantly exclusion of patients at higher likelihood to respond to angioplasty. The purpose of this review is to summarize studies' potential weaknesses and provide guidance to the clinician for identification of patients who may benefit most from revascularization.

Outcomes of continuous flow left ventricular assist device after surgical left ventricular restoration

ObjectivesThis study aimed to report the clinical outcomes of continuous flow left ventricular assist device implantation in end-stage chronic heart failure patients with a history of surgical left ventricular restoration.MethodsWe retrospectively identified 190 patients undergoing continuous flow left ventricular assist device implantation at our center from November 2007 to April 2020. In total, six patients underwent continuous flow left ventricular assist device implantation after various types of surgical left ventricular restoration procedures, including endoventricular circular patch plasty (n = 3), posterior restoration procedure (n = 2), and septal anterior ventricular exclusion (n = 1).ResultsContinuous flow left ventricular assist device (Jarvik 2000, n = 2; EVAHEART, n = 1; HeartMate II, n = 1; DuraHeart, n = 1; HVAD, n = 1) was successfully implanted in all patients. During a median follow-up of 48 months (interquartile range, 39–60 months; censoring heart transplantation), no death was documented, which means that overall survival after left ventricular assist device implantation was 100% at any time point. Finally, three patients received heart transplantation (waiting time: 39, 56, and 61 months, respectively) and the other three patients are still awaiting heart transplantation (waiting time: 12, 41, and 76 months, respectively).ConclusionsIn our series, continuous flow left ventricular assist device implantation after surgical left ventricular restoration was safe and feasible, even if an endoventricular patch was used, and effective for bridge to transplant strategy.

RELEVANCE OF DEIODINASE ENZYMES IN HEART TRANSPLANT – PRELIMINARY STUDY

<h3>Objective</h3> The hypothalamic-pituitary-thyroid (HPT) axis plays a critical role in the regulation of metabolism throughout the neuroendocrine system. The low triiodothyronine (T3) syndrome appears in several critical conditions that require intensive care, such as heart transplant (HTx) which is the gold standard therapeutic intervention for patients with end-stage chronic heart failure. Low T3 syndrome is hallmarked by reduced serum thyroid hormone (TH) levels; missing or reduced response of the HPT axis; and tissue-specific changes of the expression of deiodinase enzymes, catalyzing TH hormone metabolism. Current research aimed to study the interaction between cardiac deiodinase expression and adverse outcomes after HTx. <h3>Design and Method</h3> This prospective, single center study was approved by the IRB (65/2017). Patients who underwent heart transplant at the Heart and Vascular Centre of Semmelweis University between 2012 and 2020 were enrolled in current research. Demographic and perioperative laboratory parameters, thyroid disorders and adverse outcomes were recorded in our database. Expression of the TH activating Deiodinase 2 (DIO2) and TH inactivating Deiodinase 3 (DIO3) enzymes was measured with TaqMan qPCR in cardiac tissue samples and were normalized to hypoxanthine phosphoribosyl transferase (HPRT). cDNA content of samples was measured by Qubit, and 30 ng of cDNA was used in each qPCR reaction. Descriptive statistics, Spearman's correlation and Mann-Whitney U test were applied for the statistical analysis. <h3>Results</h3> The final analysis was performed on 294 patients, of whom 77 were female (26.2%) and 217 were male (73.8%). The median age of donors was 54 years (IQR 25-75: 45-59), while the median follow-up was 1223 days (IQR 25-75: 399-1990). Prior to surgery, 53 patients (18.0%) had subclinical serum TH levels, of whom 37 (12.6%) were on TH replacement. Patients required postoperative mechanical circulation support (n: 50; 17.0%), underwent rejection (n: 47; 16.0%), and reoperation (n: 34; 11.6%) had significantly lower DIO2 and DIO3 expression (respectively p: 0.016; 0.001; 0.044). However, cardiac DIO2 expression was significantly higher in patients with postoperative acute kidney injury (n: 75; 25.5%) (p: 0.033). <h3>Conclusions</h3> Our results emphasize the importance of cardiac TH metabolism during the perioperative period of heart transplant as DIO2 and DIO3 enzymes expressions may predict the occurrence of some complications after heart transplant. Unidirectional changes of the TH activating and inactivating deiodinases during the perioperative period of heart transplant do not suggest a coordinated cellular effort to shift TH signaling in the cardiac tissue except in patients with postoperative acute kidney injury.for observation.

Abstract 14519: End Stage Heart Failure Patients With Do-Not-Resuscitate Code Status Have Dramatically Reduced Hospitalization Cost and Length of Stay

Introduction: End-stage CHF (ES-CHF) poses a significant burden on healthcare system, DNR orders are often associated with comfort care measures, decreased pain and suffering, as well as healthcare resource utilization (cost and LOS). Objective: To quantify the discrepancy in cost and LOS between ES-CHF patients with DNR orders versus without DNR code status. Methodology: Nationwide Inpatient Sample (NIS) database years 2017-2018 was invoked for hospitalizations with primary or secondary diagnosis of ES-CHF, DNR status, comorbidities, and hospitalization outcome using ICD-10 codes. Characteristics of ES-CHF hospitalization with DNR versus no DNR code status were compared. Because of the nature of NIS database, timing of diagnoses and DNR code status could not be established, thus regression analysis for predictors of hospital charges, cost, and LOS was not feasible. Regression analyses were performed to explore predictors of mortality. Stata/MP 16.0 software was used. Results: 40,655 adult hospitalization had the diagnosis of ES-CHF in years 2017-2018 in the United States, among them, 12,300 (30%) had DNR code status, 35% were females, 83% of patients had &gt;=3 comorbid conditions (Charlson comorbidity index&gt;=3). Overall inpatient mortality rate was 12% (25% vs 7% in DNR vs no DNR group, respectively, p&lt;0.001), mean LOS was 10+-15 days (8 vs 11 days in DNR vs no DNR group, respectively, p&lt;0.001), mean total hospital charges was $159,122+-358,186 ($79,434 vs $193,873 in DNR vs no DNR group, respectively, p&lt;0.001). Significantly higher rates of CABG history, atrial fibrillation, COPD, peripheral vascular disease, hypothyroidism, CKD, liver disease, electrolyte disturbances, AKI, and sepsis were found among DNR group. In all patients with ES-CHF, independent predictors of inpatient mortality included older age, DNR status, history of CABG, peripheral vascular disease, liver disease, electrolyte disturbances, smoking, AKI, and sepsis. Conclusion: The presence of DNR code status in ES-CHF patients admitted to the hospital for any was associated with had dramatically reduced hospital charges and cost by more than the half, and with significantly shorter LOS.

Mortality risk factors in patients who are in heart transplantation waiting list

Objective: to estimate the survival of patients in the heart transplantation waiting list (HTx WL) at Almazov National Medical Research Centre (V.A. Almazov NMRC), Saint-Petersburg, Russia, from 2010 to 2018 and to define factors for death among these patients.Materials and methods: it was a single-centre retrospective study involving 151 patients with end-stage chronic heart failure (CHF) classes III-IV (NYHA) in the HTx WL.Results: the dynamic of decreasing mortality was revealed. Based on the results of constructing the discriminant function, four factors predicting the survival of patients in the HTx WL, namely, ACE inhibitors/ARBs, beta-blockers, status 1 of UNOS, CHF NYHA class IV, were pointed out. The model has sufficient resolving power but is not capable of predicting the outcome in the presence of acute decompensation of CHF.Conclusion: mortality in the HTx WL for the period 2010-2018 decreased that was associated with an active implementation of cardiac surgical methods as a «bridge» to transplant and optimal medical therapy, including ACE inhibitors/ARBs and beta-blockers in patients supported with inotropes (UNOS 1B). The greatest risk of mortality was found in CHF class IV and status 1 by UNOS.

Clinical outcome in patients with end-stage heart failure who underwent continuous-flow left ventricular assist devices in a single center.

Background/AimsThe continuous flow left ventricular assist device (cf-LVAD) has improved the survival of chronic end-stage heart failure (HF) patients. Here we describe our clinical experience of the initial 50 LVAD patients from a single center.MethodsA total of 50 patients underwent LVAD implantation as bridge to transplantation (BTT; n = 28, 56%), bridge to candidacy (BTC; n = 2, 4%), or as destination therapy (DT; n = 20, 40%) from 2012 to 2019. Pre-implant characteristics and clinical outcomes were compared between BTT/BTC and DT.ResultsThe median age of patients was 67 years (range, 59 to 73). Men were more likely to receive LVAD (76% vs. 24%) than women. DT patients were older, had smaller body surface area, and worse laboratory profiles than BTT/BTC patients. There was no in-hospital mortality. During an average of 14 months (range, 8 to 23), the all-cause mortality was 22%. The first-year survival was 86 and 90% in BTT/BTC and DT groups, respectively. Hemorrhagic stroke was the most common cause (27%) of death. In the BTT/BTC group, 22 patients successfully underwent heart transplantation during median duration of 10 months (range, 7 to 14). The most common post-LVAD complication during the first year of LVAD implantation was major bleeding (44%). A significant proportion (76%) of patients experienced rehospitalization with gastrointestinal bleeding as the most common cause.ConclusionsWe describe short-term clinical outcome of LVAD patients from a single center for the first time in Korea. With the newer generation LVAD and a dedicated team approach, improved clinical outcomes of LVAD for end-stage HF are expected.

Inotropic therapies in heart failure and cardiogenic shock: an educational review.

Reduced systolic function is central to the pathophysiology and clinical sequelae of acute decompensated heart failure (ADHF) with reduced ejection fraction and cardiogenic shock. These clinical entities are the final common pathway for marked deterioration of right or left ventricular function and can occur in multiple clinical presentations including severe ADHF, myocardial infarction, post-cardiac surgery, severe pulmonary hypertension, and advanced or end-stage chronic heart failure. Inotropic therapies improve ventricular systolic function and may be divided into three classes on the basis of their mechanism of action (calcitropes, mitotropes, and myotropes). Most currently available therapies for cardiogenic shock are calcitropes which can provide critical haemodynamic support, but also may increase myocardial oxygen demand, ischaemia, arrhythmia, and mortality. Emerging therapies to improve cardiac function such as mitotropes (e.g. perhexiline, SGLT2i) or myotropes (e.g. omecamtiv mecarbil) may provide useful alternatives in the future.

Postoperative pericardial effusion: peculiarities of the development and course

Heart transplantation continues to be the gold standard treatment for end-stage chronic heart failure. As with any cardiac surgery, heart transplantation is associated with postoperative complications. One of the most common complications is postoperative pericardial effusion. Heart recipients have a greater risk of developing pericardial effusion than patients after cardiac surgery on their own heart, due to surgical and immunological features. Severe pericardial effusions negatively affect the postoperative period and may be the cause of life-threatening conditions. Identification of risk factors, prevention, early diagnosis and treatment of this disease can significantly reduce the risks of adverse events in this group of patients. The purpose of this literature review is to analyze the development and course of pericardial effusion in heart recipients in world practice.

Evaluation of the suitability of a donor heart for transplantation after various asystole periods in experiment

The lack of donor hearts for transplantation in patients with end-stage chronic heart failure makes us look for new ways to increase the pool of donors. One of the possible ways to increase the donor base may be the use of asystolic donors, i. e. patients with in-hospital cardiac arrest or patients with cardiac arrest after brain death. The aim of the study was to examine the morphofunctional state of the heart after various periods of normothermic asystole in an experiment on rats. Materials and methods . Experiments were performed on female Wistar rats. After cervical dislocation and registration of respiratory arrest, the body temperature of the rat was maintained above at 36.5±0.5 °C for 10, 15 and 20 minutes, depending on the group. After asystole period, the heart was connected to the Langendorff apparatus to provide perfusion for 90 minutes. During perfusion of the heart, the pulse pressure inside the left ventricle (LVPP) and the volumetric flow rate of coronary perfusion (CP) were recorded every 15 minutes. After the end of the experiment, the volume of necrosis was calculated. Results . In the group with 20-minute ischemia, there was no recovery of ventricular contractions, the volume of necrosis was 34,9±11,7 %. In the group with 15-minute ischemia, the volume of necrosis was 19,5±7,6 %. In the group with 10-minute normothermic ischemia, the volume of necrosis was 13,1±5,1 %. Conclusions . 15 minutes of normothermic cardiac arrest in situ causes irreversible damage to the heart of the animal, which does not allow us to consider it as a potential donor heart. However, this volume of damage to the myocardium and microvasculature, together with the restoration of the contractile activity of the heart, makes this group the main one for the continuation of such experiments using various methods of heart reconditioning.

Atrial fibrillation is not associated with altered left atrial microRNA expression profile in ischemic end-stage human heart failure

Abstract Introduction In patients with chronic heart failure (CHF) left ventricular dysfunction results in elevated left atrial (LA) pressure, triggering pathological atrial remodelling and atrial fibrillation (AF). Nevertheless, it has been reported that some patients with CHF remain in sinus rhythm (SR) despite of the pathological structural alterations (e.g. dilation and fibrosis) of the LA. Of particular interest, data is scarce regarding the molecular explanation for the observed variability in AF development among CHF patients. Recent studies have indicated that alterations in microRNA (miRNA) expression might contribute to the pathogenesis of AF. However, the majority of previous studies focusing on miRNA expression compared healthy LA with SR to pathologically remodelled, dilated LA with AF. Consequently, whether dysregulation of miRNA expression directly contribute to AF and not only to pathological LA remodelling has not been tested before. Purpose The present study aimed to investigate miRNA expression in comparably remodelled LA from end-stage CHF patients with permanent AF (CHF-AF) or SR (CHF-SR). Methods LA samples were collected from male, non-diabetic, ischemic end-stage CHF patients undergoing heart transplantation (n=24). Patients were carefully selected to avoid any differences in age (55±2 vs. 54±2 years, CHF-AF vs. CHF-SR, n.s.), ejection fraction ([EF]: 22.5±1.8 vs. 23.3±2.5%, CHF-AF vs. CHF-SR, n.s.) LA diameters (longitudinal LA diameter: 56±4 vs. 48±5mm.; CHF-AF vs. CHF-SR, n.s.; horizontal LA diameter: 61±2 vs. 54±3, CHF-AF vs. CHF-SR, n.s.) and NYHA stage. As a molecular marker of atrial load, the mRNA expression of atrial natriuretic peptide (ANP) was measured with qRT-PCR. The extent of left atrial fibrosis was assessed on picrosirius red stained histological sections. Global LA miRNA expression profiling (including the measurement of 800 human miRNA) was carried out using a commercially available kit. Results LA mRNA expression of ANP was comparable between the AF-CHF and the SR-CHF groups, suggesting that atrial load occurred to the same level in the two experimental groups. Furthermore, no differences could be observed in the extent of atrial collagen content between the AF-CHF and the SR-CHF groups (collagen area: 20.3±1.3% vs. 23.9±3.1%, n.s.), providing evidence that fibrotic remodelling had occurred to a similar magnitude. The high-throughput miRNA measurement revealed no differences in atrial miRNA expression between the two study groups. Conclusion The present study provides evidence for the first time that AF is not associated with different LA miRNA expression in end-stage CHF patients with comparable level of LA dilatation, ANP expression (atrial load) and interstitial fibrosis. Based on these findings, the potential of miRNA-based therapeutic interventions might be limited in AF patients with ischemic end-stage CHF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NVKP_16-1-2016-0017

AIM2-driven inflammasome activation in chronic heart failure

Abstract Background Inflammation and cytokine release have been implicated in the pathogenesis of chronic heart failure (CHF). Of particular interest, Canakinumab, a monoclonal antibody against interleukin-1b (IL-1β), had provided benefit against cardiovascular events, suggesting that blockade of IL-1β secretion and signaling might be a promising new therapeutic target. Although, recent studies have provided evidence that inflammasome activation is the main contributor to IL-1β maturation, the role of inflammasome activation in CHF remains unknown. Objective Therefore, we aimed to assess inflammasome activation in myocardial samples from end-stage failing hearts. Methods Inflammasome activation was assessed by immunoblotting in left ventricular myocardial specimens harvested from patients with end-stage CHF. Furthermore, immunoblot measurements were also performed on translational animal models of CHF (e.g. rat models of permanent coronary artery ligation and transverse aortic constriction). Left ventricular monocyte and macrophage infiltration was detected by immunohistochemistry. To investigate the molecular background of inflammasome activation, a series of cell culture experiments were performed on AC16 human cardiomyocytes and THP-1 human monocytic cell lines. Results Out of the 4 major inflammasome sensors tested, expression of the inflammasome protein absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) increased in human CHF while the NLRP1 and NLRP3 (NLR family, pyrin domain containing 1 and 3) inflammasome showed no change. A similar expression pattern in AIM2 and NLRC4 was also noted in CHF animal models. Furthermore, robust infiltration of Iba1+ monocytes/macrophages was observed in human failing hearts as well as in different animal models of CHF. In vitro AIM2 inflammasome activation, as induced by transfection with double-stranded DNA [poly(deoxyadenylic-deoxythymidylic)] was reduced significantly by the pharmacological blockade of pannexin-1 channels. Conclusions AIM2 and NLRC4 inflammasome activation might contribute to chronic inflammation in CHF. Our findings suggest that pannexin-1 channels might be a promising novel target to reduce inflammasome activation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NVKP_16-1-2016-0017

Correlation between microRNA expression levels and plasma concentrations of biomarkers of post-transplant complications in heart transplant recipients

Objective: to analyze the correlation between the expression levels of microRNA-101, microRNA-142, microRNA-27, microRNA-339, and microRNA-424 and the plasma concentrations of biomarkers that are potentially significant for the diagnosis of post-transplant complications in heart recipients. Materials and methods. The study enrolled 72 heart recipients, among whom were 56 men (77.8%). The average age of recipients was 48.6 ± 10.9 (16 to 70) years. There were 38 patients with severe chronic heart failure, among whom were 29 men (76.3%). Patients’ mean age was 48.8 ± 9.9 (26 to 70) years. The control group consisted of 12 healthy individuals who did not differ significantly by sex and age. microRNA expression levels in blood plasma were measured via quantitative polymerase chain reaction. Plasma concentrations of VEGF-A, PLGF, MCP-1, and sCD40L were determined using a multiplex method. ST2 and Galectin-3 concentrations were measured via enzyme-linked immunosorbent assay. Results. Patients with end-stage chronic heart failure were found to have significantly higher expression levels of microRNA-27, microRNA-339 and microRNA-424 in blood plasma compared with the healthy individuals. In potential heart recipients, the expression le vels of microRNA-339 and microRNA-424 correlated with serum galectin-3 concentrations, microRNA-101 expression levels correlated with PLGF-1 concentrations, while microRNA-27 expression levels correlated with plasma MCP-1 concentrations. In the early post-transplant period, the expression levels of microRNA-101, microRNA-339, and microRNA-424 in heart recipients were significantly lower than in patients with severe chronic heart failure. In the early post-transplant period (one year or more after transplantation), microRNA-101 and microRNA-27 expression levels were significantly higher than in heart recipients. A year or more after transplantation, the following correlations were found in heart recipients: microRNA-142 expression level correlated with serum levels of galectin-3 (p = 0.05), microRNA-27 and microRNA-424 expression levels correlated with ST2 concentrations (p = 0.02), microRNA-27 expression level correlated with PLGF-1 concentrations (p = 0.02), while microRNA-101 expression level correlated with serum levels of PAPP-A (p = 0.05). Conclusion. In heart recipients, the expression levels of microRNA-142, microRNA-27, microRNA-424, and microRNA-101 correlate with the concentration levels of biomarkers of fibrosis (Galectin-3), rejection (ST2), neoangiogenesis (PLGF), and tissue destruction (PAPP-A). A comprehensive analysis of pre- and post-translational markers may open up new perspectives in diagnosis, assessment of the risks of post-transplant complications, and in understanding the processes leading to their development.

MicroRNA expression levels in early and long-term period following heart transplantation

Objective : to conduct comparative analysis of the expression levels of microRNA-101, microRNA-142, microRNA- 27, microRNA-339 and microRNA-424 in patients with severe chronic heart failure and in heart recipients in the early and long-term period following heart transplantation and to determine the association with acute transplant rejection. Materials and methods . The study included 46 heart recipients, among whom were 36 men (78.3%); the average age of the recipients was 47.7 ± 10.8 (16 to 67) years, and 12 patients with end-stage chronic heart failure, among whom were 8 men (66.7%); the average age of the patients was 46.1 ± 6.4 (37 to 64) years. The control group consisted of 12 healthy individuals, not significantly different by gender and age. microRNA expression levels in blood plasma were determined through quantitative polymerase chain reaction (Q-PCR). Transplant rejection was verified via morphological analysis of endomyocardial biopsy specimens. Results . Blood plasma of patients with end-stage chronic heart failure had significantly higher expression rates of microRNA-101, microRNA-27, microRNA-339 and microRNA-424 than in healthy individuals (p < 0.02). In the early stages following transplantation, the expression levels of microRNA-101 and microRNA-27 in heart recipients were significantly lower than in patients with severe chronic heart failure (p < 0.003). A year or more after transplantation, there were no significant differences in the expression levels of microRNA-101, microRNA- 142, and microRNA-339 in heart recipients and in healthy individuals. In recipients with acute rejection, the expression levels of microRNA-101 and microRNA-27 significantly differed from that of recipients without signs of rejection (p = 0.04 and p = 0.03, respectively). Conclusion . The obtained data on changes in the expression levels of microRNA-101 and microRNA-27 in heart recipients with acute transplant rejection suggests possible diagnostic value of these biomarkers in determining the risk of rejection.

Clustering of patients with end-stage chronic diseases by symptoms: a new approach to identify health needs.

End-stage chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and chronic renal failure (CRF) are characterized by a high burden of daily symptoms that, irrespective of the primary organ failure, are widely shared. To evaluate whether and to which extent symptom-based clusters of patients with end-stage COPD, CHF and CRF associate with patients' health status, mobility, care dependency and life-sustaining treatment preferences. 255 outpatients with a diagnosis of advanced COPD (n = 95), advanced CHF (n = 80) or CRF requiring dialysis (n = 80) were visited in their home environment and underwent a multidimensional assessment: clinical characteristics, symptom burden using Visual Analog Scale (VAS), health status questionnaires, timed "Up and Go" test, Care Dependency Scale and willingness to undergo mechanical ventilation or cardiopulmonary resuscitation. Three clusters were obtained applying K-means cluster analysis on symptoms' severity assessed via VAS. Cluster characteristics were compared using non-parametric tests. Cluster 1 patients, with the least symptom burden, had a better quality of life, lower care dependency and were more willing to accept life-sustaining treatments than others. Cluster 2, with a high presence and severity of dyspnea, fatigue, cough, muscle weakness and mood problems, and Cluster 3, with the highest occurrence and severity of symptoms, reported similar care dependency and life-sustaining treatment preferences, while Cluster 3 reported the worst physical health status. Symptom-based clusters identify patients with different health needs and might help to develop palliative care programs. Clustering by symptoms identifies patients with different health status, care dependency and life-sustaining treatment preferences.

Current state of the problem and results of &lt;i&gt;ex vivo&lt;/i&gt; perfusion of donor hearts

Patients with drug refractory end-stage heart failure fall into the severe category of cardiological patients. Numerous studies have shown the superior efficacy of heart transplantation over other treatments for end-stage chronic heart failure. However, despite decades of achievements in transplantology, shortage of donor organs remains a pressing and unresolved issue. The only way to reduce shortage of donor organs is to use donors with advanced criteria, which requires the use of latest technologies in organ resuscitation and conditioning.

Effect of cardiac arrest with aortic cross-clamping during left ventricular assist device implantation.

Some patients who undergo continuous-flow left ventricular assist device (CF-LVAD) implantation require concomitant procedures that can be performed with or without cardiac arrest under aortic cross-clamping (AXC). Procedures normally performed with cardiac arrest are sometimes avoided or performed without cardiac arrest because it may be detrimental to right heart function. However, the effects of cardiac arrest on patients with advanced heart failure necessitating CF-LVAD support have not been thoroughly studied. We examined our single-centre experience to determine whether cardiac arrest during CF-LVAD implantation was associated with worse patient outcomes. From November 2003 to March 2016, a total of 526 patients with chronic end-stage heart failure underwent primary CF-LVAD implantation. Preoperative demographics, postoperative complications and mortality rates were compared between patients who required cardiac arrest with AXC (n = 50) and those who did not (n = 476). The most frequently performed procedure requiring AXC was aortic valve closure (n = 23, 26.1%). Although the AXC group had longer cardiopulmonary bypass times (P < 0.01), long-term (5-year) survival was similar in AXC and non-AXC patients (P = 0.13). Also, postoperative right heart failure (P = 0.15) and neurological dysfunction (P = 0.89) rates were not significantly different between the 2 groups. Cox proportional hazards analysis showed that cardiac arrest with AXC was not an independent predictor of mortality (hazard ratio, 0.89; P = 0.73). Cardiac arrest with AXC during CF-LVAD implantation did not negatively affect long-term survival or the incidence of right ventricular failure or stroke. These findings should be considered in deciding surgical strategies. Additional investigation may be warranted to further understand the effects of cardiac arrest during LVAD implantation.