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Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6–9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial. [ABSTRACT FROM AUTHOR]

Hyperlactatemia (HL) is a common phenomenon after cardiac surgery which is related to tissue hypoperfusion and hypoxia and associated with poor outcomes. It is also often seen in the postoperative period after orthotopic heart transplantation (OHTx), but the association between HL and outcomes after OHTx is not well known. We evaluated the incidence and outcome of HL after OHTx. This was a retrospective study of 209 patients who underwent OHTx between January 2011 and December 2020. Patients were classified into 3 groups according to their peak lactate levels within the first 72 h postoperatively: group 1, normal to mild hyperlactatemia (<5 mmol/L, n = 42); group 2, moderate hyperlactatemia (5–10 mmol/L, n = 110); and group 3, severe hyperlactatemia (>10 mmol/L, n = 57). The primary composite endpoint was all-cause mortality or postoperative initiation of veno-arterial extracorporeal membrane oxygenation (VA ECMO) within 30 days. Secondary endpoints included duration of mechanical ventilation, intensive care unit length of stay, and hospital length of stay. Patients with higher postoperative peak lactate levels were more commonly transplanted from left ventricular assist device support (33.3 % vs 50.9 % vs 64.9, p < 0.01) and had longer cardiopulmonary bypass time [127 min (109–148) vs 141 min (116–186) vs 153 min (127–182), p = 0.02]. Composite primary endpoint was met in 18 patients (8.6 %) and was significantly more common in patients with higher postoperative peak lactate levels (0.0 % vs 6.4 % vs 19.3 %, p < 0.01). Severe hyperlactatemia following orthotopic heart transplant was associated with an increased risk of post-transplant VA ECMO initiation and mortality at 30 days. [Display omitted] • Postoperative hyperlactatemia (HL) >5 mmol/L was seen in 79.9% of patients after OHTx. • Postoperative HL was associated with a higher rate of death and or use of VA ECMO. • Threshold value was high around 10 mmol/L (sensitivity 61.1%, specificity 75.9%). • Total ischemic time was not significantly associated with the peak lactate levels. • Cardiopulmonary bypass time and preoperative durable left ventricular assist device were associated with postoperative severe HL. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the clinical trends, risk factors, and impact of waitlist blood transfusion on outcomes following isolated heart transplantation. Methods: The UNOS registry was queried to identify adult recipients from January 1, 2014, to June 30, 2022. The recipients were stratified into two groups depending on whether they received a blood transfusion while on the waitlist. The incidence of waitlist transfusion was compared before and after the 2018 allocation policy change. The primary outcome was survival. Propensity score‐matching was performed. Multivariable logistic regression was performed to identify predictors of waitlist transfusion. A sub‐analysis was performed to evaluate the impact of waitlist time on waitlist transfusion. Results: From the 21 926 recipients analyzed in this study, 4201 (19.2%) received waitlist transfusion. The incidence of waitlist transfusion was lower following the allocation policy change (14.3% vs. 23.7%, p < 0.001). The recipients with waitlist transfusion had significantly reduced 1‐year posttransplant survival (88.8% vs. 91.9%, p < 0.001) compared to the recipients without waitlist transfusion in an unmatched comparison. However, in a propensity score‐matched comparison, the two groups had similar 1‐year survival (90.0% vs. 90.4%, p = 0.656). Multivariable analysis identified ECMO, Impella, and pretransplant dialysis as strong predictors of waitlist transfusion. In a sub‐analysis, the odds of waitlist transfusion increased nonlinearly with longer waitlist time. Conclusion: There is a lower incidence of waitlist transfusion among transplant recipients under the 2018 allocation system. Waitlist transfusion is not an independent predictor of adverse posttransplant outcomes but rather a marker of the patient's clinical condition. ECMO, Impella, and pretransplant dialysis are strong predictors of waitlist transfusion. [ABSTRACT FROM AUTHOR]

The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is better at preventing organ rejection. For example, the high doses of antibody administered in previous experiments might not be feasible for the treatment of humans, while thrombotic side effects were described for first-generation anti-CD40L antibodies. To address these issues, we conducted six orthotopic pig-to-baboon cardiac xenotransplantation experiments, combining a chimeric anti-CD40 antibody with an investigational long-acting PASylated anti-CD40L Fab fragment. The combination therapy effectively resulted in animal survival with a rate comparable to a previous study that utilized anti-CD40 monotherapy. Importantly, no incidence of thromboembolic events associated with the administration of the anti-CD40L PAS-Fab was observed. Two experiments failed early because of technical reasons, two were terminated deliberately after 90 days with the baboons in excellent condition and two were extended to 120 and 170 days, respectively. Unexpectedly, and despite the absence of any clinical signs, histopathology revealed fungal infections in all four recipients. This study provides, for the first time, insights into a combination therapy with anti-CD40/anti-CD40L antibodies to block this immune checkpoint. [ABSTRACT FROM AUTHOR]

Introduction. Heart transplantation is an effective way of treating patients with end-stage heart failure. Echocardiography allows for the assessment of the transplanted heart functions at all stages of follow-up. The clinical implementation of myocardial deformation imaging by the speckle tracking echocardiography has made it possible to detect subtle changes in myocardial contractility.Objective. To study the structural and functional state of myocardium in recipients in the long term after orthotopic heart transplantation.Material and methods. The study included 13 orthotopic heart transplant recipients (11 men and 2 women) at a mean age of 54.1±9.1 years who underwent orthotopic heart transplantation at the N.V. Sklifosovsky Research Institute for Emergency Medicine. The mean follow-up period after orthotopic heart transplantation was 6±0.7 years. All patients underwent transthoracic echocardiography according to the standard protocol, including determination of left ventricular myocardial deformation.Results. The median volume of the left atrium was 60 (53;76) ml, the left ventricular end-diastolic volume was 76 (70;90) ml, and the end-systolic volume was 30 (24;36) ml. The median ejection fraction of the left ventricle in the studied sample was 64 (57;66)%. The median interventricular septum thickness was 12 (11;13) mm, the left ventricular posterior wall thickness was 9 (8;10) mm. At the same time, the left ventricular myocardial mass and the left ventricular myocardial mass index were within the normal range and amounted to 140 (121;155) g and 65 (58;76) g/m2, respectively. The right heart chambers were not dilated, as the volume of the right atrium was 41 (40;56) ml, and the right ventricular enddiastolic dimension was 32 (30;33) mm. The right ventricular systolic function was unimpaired: the tricuspid annular plane systolic excursion was 18 (17;19) mm, and the right ventricular fractional area change was 46 (37.5;47.0)%. The calculated systolic pulmonary artery pressure was within the normal range 24 (21;28) mm Hg. The measurements of left ventricle global longitudinal and circumferential strains were -19.6 (-18.6;-21.2)% and -30.9 (-28.8;-32.0) %, respectively. Patients in the study sample showed a decrease in the left ventricular global function index to 25 (24.2;29.6)%. The diastolic dysfunction of a restrictive type was present in 10 patients (76.9%).Conclusions. In the long-term period after heart transplantation, the recipients were found to have a low left ventricular ejection fraction and a diastolic dysfunction of the restrictive type. Considering the normal values of left ventricular myocardial strains, we can assume that after 6 years post-orthotopic heart transplantation, the recipients have restored the heart adaptive functions, and a favorable outcome has been achieved. However, long-term monitoring is required.

Abstract A 53-year-old woman with the dilated phase of hypertrophic cardiomyopathy underwent orthotopic heart transplantation. The donor heart was evaluated as normal preoperatively without mitral regurgitation or the left atrium dilation, transplanted using the modified bicaval technique. Although the heart beat satisfactorily after aortic declamping, massive mitral regurgitation was observed without any prolapse or annular dilation. Because of the difficulty in weaning from cardiopulmonary bypass, a second aortic cross-clamp was applied, and we detached the inferior vena cava and the right side of the left atrial anastomosis to approach the mitral valve, obtaining a satisfactory exposure. No abnormalities were observed in the mitral valve leaflets, annulus or subvalvular apparatus. Subsequent in vivo mitral annuloplasty using prosthetic full ring successfully controlled the regurgitation, and the patient was easily weaned from cardiopulmonary bypass. She discharged to home with good mitral valve and cardiac functions. And the patient has been doing well without any recurrence of MR or heart failure for over a year after surgery.

Introduction: Inflammatory responses and coagulation disorders are a relevant challenge for successful cardiac xenotransplantation on its way to the clinic. To cope with this, an effective and clinically practicable anti‐inflammatory and anti‐coagulatory regimen is needed. The inflammatory and coagulatory response can be reduced by genetic engineering of the organ‐source pigs. Furthermore, there are several therapeutic strategies to prevent or reduce inflammatory responses and coagulation disorders following xenotransplantation. However, it is still unclear, which combination of drugs should be used in the clinical setting. To elucidate this, we present data from pig‐to‐baboon orthotopic cardiac xenotransplantation experiments using a combination of several anti‐inflammatory drugs. Methods: Genetically modified piglets (GGTA1‐KO, hCD46/hTBM transgenic) were used for orthotopic cardiac xenotransplantation into captive‐bred baboons (n = 14). All animals received an anti‐inflammatory drug therapy including a C1 esterase inhibitor, an IL‐6 receptor antagonist, a TNF‐α inhibitor, and an IL‐1 receptor antagonist. As an additive medication, acetylsalicylic acid and unfractionated heparin were administered. The immunosuppressive regimen was based on CD40/CD40L co‐stimulation blockade. During the experiments, leukocyte counts, levels of C‐reactive protein (CRP) as well as systemic cytokine and chemokine levels and coagulation parameters were assessed at multiple timepoints. Four animals were excluded from further data analyses due to porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) infections (n = 2) or technical failures (n = 2). Results: Leukocyte counts showed a relevant perioperative decrease, CRP levels an increase. In the postoperative period, leukocyte counts remained consistently within normal ranges, CRP levels showed three further peaks after about 35, 50, and 80 postoperative days. Analyses of cytokines and chemokines revealed different patterns. Some cytokines, like IL‐8, increased about 2‐fold in the perioperative period, but then decreased to levels comparable to the preoperative values or even lower. Other cytokines, such as IL‐12/IL‐23, decreased in the perioperative period and stayed at these levels. Besides perioperative decreases, there were no relevant alterations observed in coagulation parameters. In summary, all parameters showed an unremarkable course with regard to inflammatory responses and coagulation disorders following cardiac xenotransplantation and thus showed the effectiveness of our approach. Conclusion: Our preclinical experience with the anti‐inflammatory drug therapy proved that controlling of inflammation and coagulation disorders in xenotransplantation is possible and well‐practicable under the condition that transmission of pathogens, especially of PCMV/PRV to the recipient is prevented because PCMV/PRV also induces inflammation and coagulation disorders. Our anti‐inflammatory regimen should also be applicable and effective in the clinical setting of cardiac xenotransplantation. [ABSTRACT FROM AUTHOR]

This study evaluates the clinical trends, risk factors, and effects of post-transplant stroke and subsequent functional independence on outcomes following orthotopic heart transplantation under the 2018 heart allocation system. The United Network for Organ Sharing registry was queried to identify adult recipients from October 18, 2018 to December 31, 2021. The cohort was stratified into 2 groups with and without post-transplant stroke. The incidence of post-transplant stroke was compared before and after the allocation policy change. Outcomes included post-transplant survival and complications. Multivariable logistic regression was performed to identify risk factors for post-transplant stroke. Sub-analysis was performed to evaluate the impact of functional independence among recipients with post-transplant stroke. A total of 9,039 recipients were analyzed in this study. The incidence of post-transplant stroke was higher following the policy change (3.8% vs 3.1%, p = 0.017). Thirty-day (81.4% vs 97.7%) and 1-year (66.4% vs 92.5%) survival rates were substantially lower in the stroke cohort (p < 0.001). The stroke cohort had a higher rate of post-transplant renal failure, longer hospital length of stay, and worse functional status. Multivariable analysis identified extracorporeal membrane oxygenation, durable left ventricular assist device, blood type O, and redo heart transplantation as strong predictors of post-transplant stroke. Preserved functional independence considerably improved 30-day (99.2% vs 61.2%) and 1-year (97.7% vs 47.4%) survival rates among the recipients with post-transplant stroke (p < 0.001). There is a higher incidence of post-transplant stroke under the 2018 allocation system, and it is associated with significantly worse post-transplant outcomes. However, post-transplant stroke recipients with preserved functional independence have improved survival, similar to those without post-transplant stroke. [ABSTRACT FROM AUTHOR]

Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface—the endothelial glycocalyx—are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation. [ABSTRACT FROM AUTHOR]

A 53-year-old woman with the dilated phase of hypertrophic cardiomyopathy underwent orthotopic heart transplantation. The donor heart was evaluated as normal preoperatively without mitral regurgitation or the left atrium dilation, transplanted using the modified bicaval technique. Although the heart beat satisfactorily after aortic declamping, massive mitral regurgitation was observed without any prolapse or annular dilation. Because of the difficulty in weaning from cardiopulmonary bypass, a second aortic cross-clamp was applied, and we detached the inferior vena cava and the right side of the left atrial anastomosis to approach the mitral valve, obtaining a satisfactory exposure. No abnormalities were observed in the mitral valve leaflets, annulus or subvalvular apparatus. Subsequent in vivo mitral annuloplasty using prosthetic full ring successfully controlled the regurgitation, and the patient was easily weaned from cardiopulmonary bypass. She discharged to home with good mitral valve and cardiac functions. And the patient has been doing well without any recurrence of MR or heart failure for over a year after surgery. [ABSTRACT FROM AUTHOR]

Introduction. Today, heart failure (HF) is the most common natural outcome of diseases that are not diagnosed and treated in time. Despite the advances in cardiovascular pharmacotherapy, orthotopic heart transplantation is a generally recognized gold standard for the treatment of end-stage heart failure.Brief description. The article describes a 55-year-old male patient admitted to the Cardiology Dispensary (Kabardino-Balkarian Republic) with a clinical picture of non-ST segment elevation acute coronary syndrome (ACS). Earlier in 2017, the patient underwent orthotopic heart transplantation (OHT) for end-stage HF due to dilated cardiomyopathy. Hypertension was registered 2,5 years after surgery, and clinical manifestations of HF were registered for 5 years. In 2024, coronary angiography revealed subtotal stenosis of 95% in the middle segment of the anterior descending artery. Intraoperatively, the consensus assessed the risk and made a decision on surgical endovascular treatment of the stenosis. The postoperative period was uneventful.Discussion. The presented case is an example of timely diagnosis of coronary artery disease in a transplanted heart and successful transluminal balloon angioplasty and stenting of the anterior descending artery.

Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6–9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial.

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HLA donor-specific antibodies (DSAs) pre and post transplant increase the risk of antibody-mediated rejection (AMR) and lead to poor graft survival. Increasing data exist to support the involvement of non-HLA antibodies in triggering an immunological response. The development of non-HLA antibodies specific for AT1R is associated with poor clinical outcomes in orthotopic heart transplant recipients. This case presents an investigation of non-HLA antibodies in a 56-year-old female heart transplant recipient diagnosed with AMR in the absence of DSAs. [ABSTRACT FROM AUTHOR]

Background The geometrical relationship between atrial and ventricular short‐axis cross‐sectional area determines the hydraulic forces acting on intracardiac blood. This is important for diastolic filling. In patients undergoing heart transplantation (HTx), the left atrium is often enlarged as a result of the standard surgical technique. We hypothesized that diastolic filling in HTx patients is affected by the surgery altering the geometrical relationship between atrium and ventricle. Methods and Results This retrospective, cross‐sectional study included 25 HTx patients (median age, 52 [range, 25–70] years), 15 patients with heart failure with reduced ejection fraction (median age, 63 [range, 52–75] years), 15 patients with heart failure with preserved ejection fraction (median age, 74 [range, 56–82] years), and 15 healthy controls (median age, 64 [range, 58–67] years) who underwent cardiac magnetic resonance imaging. Left ventricular, atrial, and total heart volumes (THV) were obtained. Atrioventricular area difference at end diastole and end systole was calculated as the largest ventricular short‐axis area minus the largest atrial short‐axis area. Left atrial minimum volume normalized for THV (LAmin/THV) was larger in HTx patients (median, 0.13 [range, 0.07–0.19]) compared with controls (median, 0.05 [range, 0.03–0.08], P

The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is better at preventing organ rejection. For example, the high doses of antibody administered in previous experiments might not be feasible for the treatment of humans, while thrombotic side effects were described for first-generation anti-CD40L antibodies. To address these issues, we conducted six orthotopic pig-to-baboon cardiac xenotransplantation experiments, combining a chimeric anti-CD40 antibody with an investigational long-acting PASylated anti-CD40L Fab fragment. The combination therapy effectively resulted in animal survival with a rate comparable to a previous study that utilized anti-CD40 monotherapy. Importantly, no incidence of thromboembolic events associated with the administration of the anti-CD40L PAS-Fab was observed. Two experiments failed early because of technical reasons, two were terminated deliberately after 90 days with the baboons in excellent condition and two were extended to 120 and 170 days, respectively. Unexpectedly, and despite the absence of any clinical signs, histopathology revealed fungal infections in all four recipients. This study provides, for the first time, insights into a combination therapy with anti-CD40/anti-CD40L antibodies to block this immune checkpoint.

To investigate whether recipient administration of thyroid hormone (liothyronine [T3]) is associated with reduced rates of primary graft dysfunction (PGD) after orthotopic heart transplantation. Retrospective cohort study. Single-center, university hospital. Adult patients undergoing orthotopic heart transplantation. A total of 609 adult heart transplant recipients were divided into 2 cohorts: patients who did not receive T3 (no T3 group, from 2009 to 2014), and patients who received T3 (T3 group, from 2015 to 2019). Propensity-adjusted logistic regression was performed to assess the association between T3 supplementation and PGD. After applying exclusion criteria and propensity-score analysis, the final cohort included 461 patients. The incidence of PGD was not significantly different between the groups (33.9% no T3 group v 40.8% T3 group; p = 0.32). Mortality at 30 days (3% no T3 group v 2% T3 group; p = 0.53) and 1 year (10% no T3 group v 12% T3 group; p = 0.26) were also not significantly different. When assessing the severity of PGD, there were no differences in the groups' rates of moderate PGD (not requiring mechanical circulatory support other than an intra-aortic balloon pump) or severe PGD (requiring mechanical circulatory support other than an intra-aortic balloon pump). However, segmented time regression analysis revealed that patients in the T3 group were less likely to develop severe PGD. These findings indicated that recipient single-dose thyroid hormone administration may not protect against the development of PGD, but may attenuate the severity of PGD. [Display omitted] [ABSTRACT FROM AUTHOR]

Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface—the endothelial glycocalyx—are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.

Background: Although standard bicaval techniques has become popular in orthotopic heart transplantation, distortion, bleeding, thrombosis and arrhythmia were still causes for concern. This study was designed to compare the standard bicaval techniques and modified bicaval techniques in our institution. Materials and methods: A total of 70 recipients underwent orthotopic heart transplantation at our center from June 2015 to April 2019 (standard group = 24 cases, modified group = 46 cases). The average follow-up period was 46.4 ± 17.4 months. Atrioventricular cavity diameter was measured by ultrasonography and left atrial morphology was evaluated by CT-angiography and three-dimensional reconstruction. Results: Recipients in both groups were similar with pre-operative characteristics. Total ischemic, cardiopulmonary bypass and cross-clamp times were similar. The modified bicaval techniques group has a significantly fewer blood transfusion, lower post-transplant tricuspid regurgitation grade and the incidence of post-operative atrial arrhythmia than standard bicaval techniques group. CT-angiography and three-dimensional reconstruction illustrated ideal and physiologic left atrial morphological structure. Short-term survival differed significantly and the cumulative proportion of survival was significantly higher in the modified bicaval techniques group than that in the standard bicaval techniques group. Conclusions: This study showed that modified bicaval techniques offers a better early outcome than standard bicaval techniques. The significant reduction of intraoperative blood transfusion and post-transplant tricuspid regurgitation grade in the modified bicaval techniques group may has a major impact on the short-term survival.

In cardiogenic shock various short-term mechanical assistances may be employed, including an Extra Corporeal Membrane Oxygenator and other non-dischargeable devices. Once hemodynamic stabilization is achieved and the patient evolves towards a persisting biventricular dysfunction or an underlying long-standing end-stage disease is present, aside from Orthotopic Heart Transplantation, a limited number of long-term therapeutic options may be offered. So far, only the Syncardia Total Artificial Heart and the Berlin Heart EXCOR (which is not approved for adult use in the United States unlike in Europe) are available for extensive implantation. In addition to this, the strategy providing two continuous-flow Left Ventricular Assist Devices is still off-label despite its widespread use. Nevertheless, every solution ensures at best a 70% survival rate (reflecting both the severity of the condition and the limits of mechanical support) with patients suffering from heavy complications and a poor quality of life. The aim of the present paper is to summarize the features, implantation techniques, and results of current devices used for adult Biventricular Mechanical Circulatory Support, as well as a glance to future options.

Pulmonary hypertension (PH) is common in advanced heart failure and often improves quickly after left ventricular assist device (VAD) implantation or orthotopic heart transplantation (OHT), but long-term effects and outcomes are not well-described. This study evaluated PH persistence after VAD as destination therapy (VAD-DT), bridge to transplant (VAD-OHT), or OHTalone. The study constituted a retrospective review of patients who underwent VAD-DT (n = 164), VAD-OHT (n = 111), or OHT-alone (n = 138) at a single tertiary-care center. Right heart catheterization (RHC) data was collected pre-, post-intervention (VAD and/or OHT), and 1-year from final intervention (latest-RHC) to evaluate the longitudinal hemodynamic course of right ventricular function and pulmonary vasculature. PH (Group II and Group I) definitions were adapted from expert guidelines. All groups showed significant improvements in mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), cardiac output, and pulmonary vascular resistance (PVR) at each RHC with greatest improvement at post-intervention RHC (post-VAD or post-OHT). PH was reduced from 98% to 26% in VAD-OHT, 92% -49% in VAD-DT, and 76%-28% in OHT-alone from preintervention to latest-RHC. At latest-RHC mPAP remained elevated in all groups despite normalization of PAWP and PVR. VAD-supported patients exhibited suppressed pulmonary artery pulsatility index (PaPi < 3.7) with improvement only posttransplant at latest-RHC. Posttransplant patients with PH at latest- RHC (n = 60) exhibited lower survival (HR: 2.1 [95% CI: 1.3-3.4], p < 0.001). Despite an overall significant improvement in pulmonary pressures and PH proportion, a notable subset of patients exhibited PH post-intervention. Postintervention PH was associated with lower posttransplant survival. [ABSTRACT FROM AUTHOR]

HLA donor-specific antibodies (DSAs) pre and post transplant increase the risk of antibody-mediated rejection (AMR) and lead to poor graft survival. Increasing data exist to support the involvement of non-HLA antibodies in triggering an immunological response. The development of non-HLA antibodies specific for AT1R is associated with poor clinical outcomes in orthotopic heart transplant recipients. This case presents an investigation of non-HLA antibodies in a 56-year-old female heart transplant recipient diagnosed with AMR in the absence of DSAs.

Abstract Pulmonary hypertension (PH) is common in advanced heart failure and often improves quickly after left ventricular assist device (VAD) implantation or orthotopic heart transplantation (OHT), but long‐term effects and outcomes are not well‐described. This study evaluated PH persistence after VAD as destination therapy (VAD‐DT), bridge to transplant (VAD‐OHT), or OHT‐alone. The study constituted a retrospective review of patients who underwent VAD‐DT (n = 164), VAD‐OHT (n = 111), or OHT‐alone (n = 138) at a single tertiary‐care center. Right heart catheterization (RHC) data was collected pre‐, post‐intervention (VAD and/or OHT), and 1‐year from final intervention (latest‐RHC) to evaluate the longitudinal hemodynamic course of right ventricular function and pulmonary vasculature. PH (Group II and Group I) definitions were adapted from expert guidelines. All groups showed significant improvements in mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), cardiac output, and pulmonary vascular resistance (PVR) at each RHC with greatest improvement at post‐intervention RHC (post‐VAD or post‐OHT). PH was reduced from 98% to 26% in VAD‐OHT, 92%−49% in VAD‐DT, and 76%−28% in OHT‐alone from preintervention to latest‐RHC. At latest‐RHC mPAP remained elevated in all groups despite normalization of PAWP and PVR. VAD‐supported patients exhibited suppressed pulmonary artery pulsatility index (PaPi

Although standard bicaval techniques has become popular in orthotopic heart transplantation, distortion, bleeding, thrombosis and arrhythmia were still causes for concern. This study was designed to compare the standard bicaval techniques and modified bicaval techniques in our institution. A total of 70 recipients underwent orthotopic heart transplantation at our center from June 2015 to April 2019 (standard group = 24 cases, modified group = 46 cases). The average follow-up period was 46.4 ± 17.4 months. Atrioventricular cavity diameter was measured by ultrasonography and left atrial morphology was evaluated by CT-angiography and three-dimensional reconstruction. Recipients in both groups were similar with pre-operative characteristics. Total ischemic, cardiopulmonary bypass and cross-clamp times were similar. The modified bicaval techniques group has a significantly fewer blood transfusion, lower post-transplant tricuspid regurgitation grade and the incidence of post-operative atrial arrhythmia than standard bicaval techniques group. CT-angiography and three-dimensional reconstruction illustrated ideal and physiologic left atrial morphological structure. Short-term survival differed significantly and the cumulative proportion of survival was significantly higher in the modified bicaval techniques group than that in the standard bicaval techniques group. This study showed that modified bicaval techniques offers a better early outcome than standard bicaval techniques. The significant reduction of intraoperative blood transfusion and post-transplant tricuspid regurgitation grade in the modified bicaval techniques group may has a major impact on the short-term survival. [ABSTRACT FROM AUTHOR]

This study evaluated the current clinical trends, risk factors, and temporal effects of post-transplant dialysis on outcomes following orthotopic heart transplantation after the 2018 United States adult heart allocation policy change. The United Network for Organ Sharing (UNOS) registry was queried to analyze adult orthotopic heart transplant recipients after the October 18, 2018 heart allocation policy change. The cohort was stratified according to the need for post-transplant de novo dialysis. The primary outcome was survival. Propensity score-matching was performed to compare the outcomes between 2 similar cohorts with and without post-transplant de novo dialysis. The impact of post-transplant dialysis chronicity was evaluated. Multivariable logistic regression was performed to identify risk factors for post-transplant dialysis. A total of 7,223 patients were included in this study. Out of these, 968 patients (13.4%) developed post-transplant renal failure requiring de novo dialysis. Both 1-year (73.2% vs 94.8%) and 2-year (66.3% vs 90.6%) survival rates were lower in the dialysis cohort (p < 0.001), and the lower survival rates persisted in a propensity-matched comparison. Recipients requiring only temporary post-transplant dialysis had significantly improved 1-year (92.5% vs 71.6%) and 2-year (86.6 % vs 52.2%) survival rates compared to the chronic post-transplant dialysis group (p < 0.001). Multivariable analysis demonstrated low pretransplant estimated glomerular filtration (eGFR) and bridge with extracorporeal membrane oxygenation (ECMO) were strong predictors of post-transplant dialysis. This study demonstrates that post-transplant dialysis is associated with significantly increased morbidity and mortality in the new allocation system. Post-transplant survival is affected by the chronicity of post-transplant dialysis. Low pretransplant eGFR and ECMO are strong risk factors for post-transplant dialysis. [ABSTRACT FROM AUTHOR]

Purpose of Review: Following cardiac transplantation, patients have an increased risk of developing cardiac allograft vasculopathy and atherosclerotic cardiovascular disease. Therefore, aggressive lipid management is indicated. Some patients do not achieve optimal lipid profiles with statin monotherapy, however, or discontinue statins due to intolerance. In this review, we investigated the use of PCSK9 inhibitors as an alternative treatment for hyperlipidemia following cardiac transplantation. Recent Findings: Nine published articles were identified that included 110 patients treated with alirocumab or evolocumab after cardiac transplantation. PCSK9 inhibitors were tolerated by all patients, and each study demonstrated an effective reduction of low-density lipoprotein ranging from 40 to 87% decrease from baseline. Summary: In our study, the 110 patients from literature review were added to a cohort of 7 similar patients from our institution for combined analysis. This report supports that PCSK9 inhibitors should be considered following cardiac transplantation when conventional medial therapy is not tolerated or ineffective. [ABSTRACT FROM AUTHOR]

The human gut microbiota include over 10 trillion microorganisms, such as bacteria, fungi, viruses, archaea, and protozoa. Many reports indicate the strong correlation between dysbiosis and the severity of cardiovascular diseases. Microbiota seem to interact with the host's alloimmunity and may have an immunomodulatory role in graft rejection processes. In our study, we present the current state of the knowledge of microbiota in heart transplant recipients. We present up-to-date microbiota diagnostic methods, interactions between microbiota and immunosuppressive drugs, the immunomodulatory effects of dysbiosis, and the available strategies (experimental and clinical strategies) to modulate host microbiota. [ABSTRACT FROM AUTHOR]

Background: Depression and anxiety (DA) are common mental disorders in patients with chronic diseases, but the research regarding their prevalence in heart transplantation (HTx) is still limited. Methods: We performed an analysis of the prevalence and prognostic relevance of DA in patients who underwent HTx between 2010 and 2018 in Germany. Data were obtained from Allgemeine Ortskrankenkasse (AOK), which is the largest public health insurance provider. Results: Overall, 694 patients were identified. More than a third of them were diagnosed with DA before undergoing HTx (n = 260, 37.5%). Patients with DA more often had an ischaemic cardiomyopathy (p < 0.001) and a history of previous myocardial infarction (p = 0.001) or stroke (p = 0.002). The prevalence of hypertension (p < 0.001), diabetes (p = 0.004), dyslipidaemia (p < 0.001) and chronic kidney disease (p = 0.003) was higher amongst transplant recipients with DA. Patients with DA were more likely to suffer an ischaemic stroke (p < 0.001) or haemorrhagic stroke (p = 0.032), or develop septicaemia (p = 0.050) during hospitalisation for HTx. Our analysis found no significant differences between the groups with respect to in-hospital mortality. The female sex and mechanical circulatory support were associated with an inferior prognosis. Pretransplant non-ischaemic cardiomyopathy was related to a favourable outcome. Conclusions: DA affect up to a third of the population undergoing HTx, with a greater prevalence in patients with comorbidities. DA are associated with a higher incidence of stroke and septicaemia after HTx. [ABSTRACT FROM AUTHOR]

Abstract Background Anomalous coronary arteries arise in a small subset of the population, with each configuration conveying a varying degree of long-term risk. The utilization of cardiac grafts with these anomalies have not been well described. Case presentation An anomalous single coronary artery with the left main coronary artery arising from the right coronary ostium was discovered in a 40-year old male evaluated for cardiac donation. After evaluation, this heart was successfully procured and utilized for orthotopic heart transplantation. Conclusion In this report, we demonstrate that in select cases, a cardiac graft with single coronary artery anatomy can be successfully procured and transplanted with excellent outcomes.

The aim is to evaluate the results of long-term follow-up of patients with various clinical forms of NCCM, associated clinical outcomes, as well as 3-year survival.Materials and methods. 211 patients with NCCM (median age 39 [18; 72] years) were examined, of which: 94 (44.5 %) were diagnosed with an isolated phenotype and 117 (55.5 %) with a combination with other cardiomyopathies, including 103 (48.8 %) patients with a combination with DCM; 14 (6.6 %) with HCM, who, in addition to traditional clinical research methods, underwent CMR imaging with late gadolinium enhancement. The endpoints of the study included SCD, SCD with successful resuscitation and implantation of ICD and the implementation of OHT.Results. During the follow–up period (median follow–up 36 [6-211] months), of 211 patients with NCCM, 24 (11.4 %) had adverse outcomes, including 1 (0.5 %) – SCD, 10 (4.7 %) – SCD with successful resuscitation and ICD implantation, 13 (6.2 %) had OHT. SCD occurred in 11 (5.2 %) patients with FC I-II NYHA, including 10 patients with successful ICD resuscitation and implantation after 23 (from 5 to 152) months after diagnosis. OHT was performed in 13 patients with FC III NYHA at 30 (from 8 to 113) months after diagnosis in a group of patients with a combination of NCCM and DCM. The average age at the time of SCD or OHT was 37±12 years.The 3-year survival rate in the group of patients with the isolated form was 98.9 (96.7-100) %, and significantly differed with the group of patients with a combination of NCCM with DCM 86.5 (79.6-94) %, and with the group of patients with a combination of NCCM with HCM 72.9 (50.7-100) %, p=0.0012. Whereas the 3-year survival rate in the group with a combination of NCCM with DCM and NCCM with HCM did not significantly differ from each other. Conclusion. The prognosis of patients with an isolated form of NCCM is generally favorable and their 3-year survival rate was 98.9 (96.7-100) %. The presence of a combination of NCCM with other cardiomyopathies predicts the risk of adverse clinical outcomes and the 3-year survival rate of a combination of NCCM with DCM was 86.5 (79.6-94) %, and when combined with NCCM with HCM 72.9 (50.7-100) %, which may be useful when choosing a management strategy for patients with NCCM.

A 54‐year‐old man status post heart and kidney transplant presented with dyspnea. Imaging was consistent with lymphangitic carcinomatosis (LC), in the setting of biopsy proven adenocarcinoma. He developed pulmonary hypertension (PH) and died of right ventricular failure (RVF) 3 weeks later. Acute PH with radiographic features of LC in a high‐risk patient warrants expedited malignancy investigation. [ABSTRACT FROM AUTHOR]

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Abstract Adequate immune response to vaccination remains a challenge in patients after solid organ transplantation. We report a case of a 61‐year‐old male patient who received a left ventricular assist device as a bridge to transplant therapy. Three months before transplantation, he suffered mild SARS‐CoV‐2 infection and was successfully discharged thereafter. Eight days before his successful heart transplantation, he received mRNA BNT 162b2 vaccination. Immediately after transplantation, we detected sufficient rise of nucleocapsid and spike antibodies despite immune suppression therapy. We suspect potential booster effects of the previous SARS‐CoV‐2 infection giving rise to adequate immune response following single vaccination.

Abstract A 54‐year‐old man status post heart and kidney transplant presented with dyspnea. Imaging was consistent with lymphangitic carcinomatosis (LC), in the setting of biopsy proven adenocarcinoma. He developed pulmonary hypertension (PH) and died of right ventricular failure (RVF) 3 weeks later. Acute PH with radiographic features of LC in a high‐risk patient warrants expedited malignancy investigation.

BackgroundPredicting complications associated with pulmonary hypertension (PH) after cardiac transplantation is an important factor when considering cardiac transplantation. The transpulmonary gradient (TPG) is recommended to quantify PH in transplant candidates. Nonetheless, PH remains a common driver of mortality. The diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) can differentiate post- from combined pre- and post-capillary PH and may improve estimation of PH-associated risks. We used a large European cohort of transplant candidates to assess whether the pulmonary pulsatility index (PAPi), improves prediction of graft failure and mortality compared to DPG and PVR.MethodsOut of all patients undergoing heart transplantation between 2009 and 2019 in Eurotransplant member states (n = 10,465), we analyzed the impact of PH (mPAP > 25 mmHg) and right heart catheter hemodynamic data on graft failure and mortality within 1–5 years.ResultsIn 1,407 heart transplant patients with PH (79% male, median age 54 years, IQR 39–69 years), the median PVR was 2.5 WU (IQR 1.6 WU) with a median mPAP (pulmonary arterial pressure) of 32 mmHg (IQR 9 mmHg). Patients with low (< 3 mmHg) DPG had a better 5 year survival than those with higher DPG (log rank p = 0.023). TPG, mPAP, PAPi, and PVR did not improve prediction of survival. Low PAPi (OR = 2.24, p < 0.001) and high PVR (OR = 2.12, p = 0.005) were associated with graft failure.ConclusionPAPI and PVR are associated with graft failure in patients with PH undergoing cardiac transplantation. DPG is associated with survival in this cohort.

Renal dysfunction, a prevalent comorbidity in advanced heart failure, is associated with significant morbidity and mortality after heart transplantation. In the recent era, the field of combined heart-kidney transplantation has experienced great success in the treatment of both renal and cardiac dysfunction in end-stage disease states, and the number of transplants has increased dramatically. In this review, we discuss appropriate indications and selection criteria, overall and organ-specific outcomes, and future perspectives in the field of combined heart-kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: Prior studies have demonstrated deleterious outcomes for physician–patient racial discordance. We explored recipient–surgeon racial concordance and short‐term postoperative survival in adults undergoing orthotopic heart transplantation (OHT). Methods: The United Network for Organ Sharing (UNOS) database was queried to identify White and Black adult (≥18 years) patients undergoing isolated OHT between 2000 and 2020. Surgeon race was obtained from publicly available images. All non‐White and non‐Black recipients and surgeons were excluded. Linear probability models were utilized to explore the relationship between recipient–surgeon racial concordance and 30‐, 60‐, and 90‐day post‐transplant mortality using a fixed effects approach. Results: A total of 26,133 recipients were identified (mean age 52.79 years, 74.4% male) with 77.65% (n = 20,292) being White and 22.35% (n = 5841) being Black. A total of 662 White surgeons performed 25,946 (97.56%) OHTs during the study period while 17 Black surgeons performed 437 (1.67%) OHTs. Although some evidence of differences across groups was observed in cross‐tabular specifications, these differences became insignificant after the inclusion of controls (i.e., comorbidities and fixed effects). This suggests that recipient race and physician race are not correlated with post‐OHT survival at 30, 60, or 90 days. Conclusions: Recipient–surgeon racial concordance and discordance among adults undergoing OHT do not appear to impact post‐transplant survival. Nor do we observe significant penalties accruing for Black patients overall once controls are accounted for. Given that worse outcomes have historically been demonstrated for Black patients undergoing OHT, further work will be necessary to improve understanding of racial disparities for patients with end‐stage heart failure. [ABSTRACT FROM AUTHOR]

Heart transplant remains the gold standard treatment for patients with end-stage heart failure. However, given the limited availability of donor hearts, alternative approaches and strategies are required. The development of a variety of mechanical circulation support options, including left ventricular assist devices and total artificial heart, have allowed improved quality of life and eventually have facilitated a bridge to heart transplantation strategies for certain patients. However, the presence of an intracorporeal left ventricular assist device poses a technical challenge at the time of heart transplantation. In this video tutorial, we describe the surgical strategy and removal technique for a patient who had received a HeartMate 3 (Abbott, North Chicago, IL, USA) using a classic implantation technique via sternotomy, who underwent concomitant orthotopic heart transplant., (© The Author 2024. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Despite a record setting number of heart transplants performed annually, the national donor shortage continues to plague transplant teams across the United States. Here we describe the barriers to adaptation of numerous "non-traditional" orthotopic heart transplant donor characteristics including donors with hepatitis C virus, those meeting criteria for donation after cardiac death, donors with coronavirus disease 19 infection, donors with the human immunodeficiency virus, and grafts with left ventricular systolic dysfunction. Our center's objective was to increase our transplant volume by expanding our donor pool from "traditional" donors to these "non-traditional" donors. We detail how medical advances such as certain laboratory studies, pharmacologic interventions, and organ care systems have allowed our center to expand the donor pool thereby increasing transplantation volume without adverse effects on outcomes., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

An orthotopic heart transplant and an aortic operation can be done concomitantly at centres that are experienced in both aortic operations and heart transplants with meticulous surgical strategy., (© The Author 2024. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The human gut microbiota include over 10 trillion microorganisms, such as bacteria, fungi, viruses, archaea, and protozoa. Many reports indicate the strong correlation between dysbiosis and the severity of cardiovascular diseases. Microbiota seem to interact with the host’s alloimmunity and may have an immunomodulatory role in graft rejection processes. In our study, we present the current state of the knowledge of microbiota in heart transplant recipients. We present up-to-date microbiota diagnostic methods, interactions between microbiota and immunosuppressive drugs, the immunomodulatory effects of dysbiosis, and the available strategies (experimental and clinical strategies) to modulate host microbiota.

Introduction: Venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and serious postoperative complication after heart transplantation. We sought to characterize in‐hospital VTE after heart transplantation and its association with clinical outcomes. Method: Adult (≧18 years) patients undergoing heart transplantation from 2015 to 2019 at our center were retrospectively reviewed. Post‐transplant VTE was defined as newly diagnosed venous system thrombus by imaging studies. Results: There were 254 patients. The cohort's median age was 55 years. A total of 61 patients were diagnosed with VTE, including one with right atrial thrombus, 54 with upper extremity DVT in which one patient subsequently developed PE, four with lower extremity DVT, and two with upper and lower extremity DVT. The cumulative incidence of VTE was 42% at 60‐days of post heart transplant. Patients with VTE had longer hospital stay (P <.001), higher in‐hospital mortality (P =.010), and worse 5‐year survival (P =.009). On the multivariable Cox analysis, history of DVT/PE and intubation for more than 3 days were associated with an increased risk of in hospital VTE. Conclusion: The incidence of VTE in heart transplant recipients is high. Post‐transplant surveillance, and appropriate preventive measures and treatment strategies after diagnosis are warranted. [ABSTRACT FROM AUTHOR]

Demand for organs is increasing while the number of donors remains constant. Nevertheless, not all organs are utilized due to the limited time window for heart transplantation (HTX). Therefore, we aimed to evaluate whether an iron-chelator-supplemented Bretschneider solution could protect the graft in a clinically relevant canine model of HTX with prolonged ischemic storage. HTX was performed in foxhounds. The ischemic time was standardized to 4 h, 8 h, 12 h or 16 h, depending on the experimental group. Left ventricular (LV) and vascular function were measured. Additionally, the myocardial high energy phosphate and iron content and the in-vitro myocyte force were evaluated. Iron chelator supplementation proved superior at a routine preservation time of 4 h, as well as for prolonged times of 8 h and longer. The supplementation groups recovered quickly compared to their controls. The LV function was preserved and coronary blood flow increased. This was also confirmed by in vitro myocyte force and vasorelaxation experiments. Additionally, the biochemical results showed significantly higher adenosine triphosphate content in the supplementation groups. The iron chelator LK614 played an important role in this mechanism by reducing the chelatable iron content. This study shows that an iron-chelator-supplemented Bretschneider solution effectively prevents myocardial/endothelial damage during short- as well as long-term conservation. [ABSTRACT FROM AUTHOR]

Background: Orthotopic heart transplantation (OHT) is associated with a high incidence of conduction disturbances (CD) leading to permanent pacemaker (PPM) implantation. However, the improved posttransplant survival raises the question about the pacemaker dependence (PD) in a prolonged follow‐up. Hypothesis: The prevalence of PPM in OHT is high but not all patients are PD in a very long‐term follow‐up. Device implantation has no prognostic relevance. Methods: We performed a retrospective analysis of patient medical records focusing on device interrogation data at the most recent follow‐up. Results: The study population consisted of 183 patients with a mean follow‐up of 15.0 ± 6.8 years. One‐fourth of the patients had undergone PPM implantation (n = 49, 26.8%). Among these, two‐thirds were PD at last follow‐up (n = 32, 65.3%). PPM was more often in biatrial OHT and cardiac allograft vasculopathy (OR 3.0, 95% CI 1.26–7.29, p =.013 and OR 2.0, 95% CI 1.03–3.87, p =.041, respectively). Early sinus node dysfunction (SND) was the most persistent CD. PPM was associated with a poorer outcome in OHT (HR 1.9, 95% CI 1.06–3.46, p =.031) and a higher rate of fatal septicemia (HR 5.1, 95% CI 1.41–18.14, p =.013). Conclusions: One‐fourth of the OHT recipients develop CD requiring PPM implantation, although one‐third among these are not PD in follow‐up. Early SND is associated with a higher rate of PD. PPM is associated with an inferior prognosis. [ABSTRACT FROM AUTHOR]

Introduction: After orthotopic cardiac xenotransplantation, the combination of both the inflammatory responses to the exposure of a recipient to the xenogeneic organ and the use of cardiopulmonary bypass has been assumed to cause detrimental side effects. These have been described not only to affect the transplanted organ (heart) itself, but also the recipient's lungs. In this article, we summarize how these possible detrimental processes can be minimized or even avoided. Methods: Data from eight pig‐to‐baboon orthotopic cardiac xenotransplantation experiments were analyzed with a special focus on early (within the first week) postoperative organ dysfunction and systemic inflammatory responses. Non‐ischemic heart preservation and the careful management of the heart‐lung machine were deemed essential to guarantee not only the immediate function of the transplanted xenogeneic organ but also the prompt recovery of the recipient. Results: After weaning from cardiopulmonary bypass, very low catecholamine amounts were needed to ensure an adequate pump function and cardiac output. Central venous oxygen saturation and serum lactate levels remained within normal ranges. All animals were successfully weaned from ventilation within the first postoperative hours. Serum parameters of the transplants and native kidneys and livers were initially slightly elevated or always normal, as were hemoglobin, LDH, and platelet measurements. Markers of systemic inflammation, C‐reactive protein, and IL‐6 were slightly elevated, but the reactions caused no lasting damage. Conclusion: Consistent short‐term and long‐term results were achieved after orthotopic cardiac pig‐to‐baboon transplantation without detrimental inflammatory responses or signs of multiorgan failure. In comparison to allogeneic procedures, non‐ischemic heart preservation was important for successful immediate organ function, as was the management of the heart‐lung machine. Thus, we believe that genetically modified porcine hearts are ready for use in the clinical setting. [ABSTRACT FROM AUTHOR]

BackgroundCardiac sympathetic denervation (CSD) has been shown to reduce the burden of implantable cardioverter-defibrillator (ICD) shocks in small series of patients with structural heart disease (SHD) and recurrent ventricular tachyarrhythmias (VT).ObjectivesThis study assessed the value of CSD and the characteristics associated with outcomes in this population.MethodsPatients with SHD who underwent CSD for refractory VT or VT storm at 5 international centers were analyzed by the International Cardiac Sympathetic Denervation Collaborative Group. Kaplan-Meier analysis was used to estimate freedom from ICD shock, heart transplantation, and death. Cox proportional hazards models were used to analyze variables associated with ICD shock recurrence and mortality after CSD.ResultsBetween 2009 and 2016, 121 patients (age 55 ± 13 years, 26% female, mean ejection fraction of 30 ± 13%) underwent left or bilateral CSD. One-year freedom from sustained VT/ICD shock and ICD shock, transplant, and death were 58% and 50%, respectively. CSD reduced the burden of ICD shocks from a mean of 18 ± 30 (median 10) in the year before study entry to 2.0 ± 4.3 (median 0) at a median follow-up of 1.1 years (p < 0.01). On multivariable analysis, pre-procedure New York Heart Association functional class III and IV heart failure and longer VT cycle lengths were associated with recurrent ICD shocks, whereas advanced New York Heart Association functional class, longer VT cycle lengths, and a left-sided-only procedure predicted the combined endpoint of sustained VT/ICD shock recurrence, death, and transplantation. Of the 120 patients taking antiarrhythmic medications before CSD, 39 (32%) no longer required them at follow-up.ConclusionsCSD decreased sustained VT and ICD shock recurrence in patients with refractory VT. Characteristics independently associated with recurrence and mortality were advanced heart failure, VT cycle length, and a left-sided-only procedure.

Abstract Background Orthotopic heart transplantation (OHT) is associated with a high incidence of conduction disturbances (CD) leading to permanent pacemaker (PPM) implantation. However, the improved posttransplant survival raises the question about the pacemaker dependence (PD) in a prolonged follow‐up. Hypothesis The prevalence of PPM in OHT is high but not all patients are PD in a very long‐term follow‐up. Device implantation has no prognostic relevance. Methods We performed a retrospective analysis of patient medical records focusing on device interrogation data at the most recent follow‐up. Results The study population consisted of 183 patients with a mean follow‐up of 15.0 ± 6.8 years. One‐fourth of the patients had undergone PPM implantation (n = 49, 26.8%). Among these, two‐thirds were PD at last follow‐up (n = 32, 65.3%). PPM was more often in biatrial OHT and cardiac allograft vasculopathy (OR 3.0, 95% CI 1.26–7.29, p = .013 and OR 2.0, 95% CI 1.03–3.87, p = .041, respectively). Early sinus node dysfunction (SND) was the most persistent CD. PPM was associated with a poorer outcome in OHT (HR 1.9, 95% CI 1.06–3.46, p = .031) and a higher rate of fatal septicemia (HR 5.1, 95% CI 1.41–18.14, p = .013). Conclusions One‐fourth of the OHT recipients develop CD requiring PPM implantation, although one‐third among these are not PD in follow‐up. Early SND is associated with a higher rate of PD. PPM is associated with an inferior prognosis.