Long-term Outcome Of Heart Transplantation Research Articles

Long-term outcomes of heart transplantation in adults with congenital heart disease: The impact of single-ventricle versus biventricular physiology

ObjectiveCongenital heart disease is a risk factor for mortality after orthotopic heart transplantation; however, the impact of preoperative circulation type and primary congenital heart disease diagnosis remains poorly delineated. MethodsWe retrospectively reviewed patients with adult congenital heart disease aged 16 years or more who underwent orthotopic heart transplantation at our institution between 2008 and 2022. Patients were categorized as having single-ventricle or biventricular circulation. The primary end point was 5-year post-transplant survival. ResultsSixty-one patients with adult congenital heart disease (single-ventricle: n = 26 [42.6%], biventricular: n = 35 [57.4%]) underwent orthotopic heart transplantation at 33.7 [interquartile range, 19.1-48.7] years. The most common congenital heart disease diagnosis was hypoplastic left heart syndrome (n = 11, 42.3%) in the single-ventricle group and congenitally corrected transposition of the great arteries (n = 7, 20.0%) in the biventricular group. Twenty-four patients previously underwent Fontan palliation. At transplant, patients in the single-ventricle group were younger (18.5 [interquartile range, 17.6-32.3] years vs 45.0 [interquartile range, 33.0-52.2] years, P < .001) and more likely to have biopsy-proven cirrhosis (46.2% vs 14.3%, P = .01) and protein-losing enteropathy (42.3% vs 2.9%, P < .001). Patients in the single-ventricle group also had longer bypass times (223.4 ± 65.3 minutes vs 187.4 ± 59.5 minutes, P = .03) and longer durations of mechanical ventilatory support (3.5 [interquartile range, 2.0-6.0] days vs 1.0 [interquartile range, 1.0-2.0] days, P < .001). Operative mortality was comparable (11.5% vs 8.6%, P = 1). Median follow-up was 6.0 [interquartile range, 2.4-10.0] years. Five-year survival was worse in the single-ventricle group (66.0% ± 10.0% vs 91.3% ± 4.8%, P = .03), as was freedom from major rejection (58.3% ± 10.2% vs 84.0% ± 6.6%, P = .02). In univariable analysis, hypoplastic left heart syndrome and Fontan circulation were risk factors for post-transplant mortality (hypoplastic left heart syndrome: hazard ratio, 5.0, P < .001; Fontan: hazard ratio, 3.5, P = .03). ConclusionsAdult patients with congenital heart disease undergoing heart transplant with single-ventricle physiology experienced a more complicated post-transplant course, with worse long-term survival and freedom from rejection. Multicenter studies are required to guide orthotopic heart transplantation decision-making in this complex cohort.

Difficulties in diagnosing and predicting possible complications in patients after heart transplantation: single-center experience in the Krasnodar region

Aim. To evaluate the early and long-term outcomes of heart transplantation (HT) at the Research Institute of the S. V. Ochapovsky Regional Clinical Hospital № 1.Material and methods. On the basis of the Research Institute of the S. V. Ochapovsky Regional Clinical Hospital № 1 from March 2010 to March 2023, 230 HTs were carried out. Among the patients, men predominated 86% (n=198), women — 14% (n=32). The mean age was 48,3±11,7 years. The reason for HT in 42,6% (n=98) was ischemic cardiomyopathy (ICM), in 40% (n=92) — dilated cardiomyopathy (DCM), while 17,4% were operated on for another cardiac pathology (n=40). All recipients underwent immunological examination, endomyocardial biopsy (EMB), 2D-speckle-tracking echocardiography (2D-STE), transthoracic echocardiography (TTE), coronary angiography (CAG), as well as a number of studies for early diagnosis of possible cancer complications.Results. Acute rejection during the first three years was detected in 77 recipients (42,5%), of which cellular rejection (grade ≥2, 3) and humoral rejection was verified in 49 and 28 recipients, respectively. During the entire follow-up period, de novo anti-human leukocyte antigen (HLA) antibodies were detected in 34 recipients in the posttransplantation period, of which 50% (n=17) and 35% (n=12) were diagnosed with humoral and cellular rejection, respectively. Of the 34 patients with anti-HLA antibodies, 11 (32%) died. All of them died due to a humoral rejection. The survival rate of patients with antibodies was lower (59%) than in patients without antibodies (66%), p=0,023. The annual survival rate of all patients after transplantation in our center was 83,1% (during the first year after transplantation, 30 and 9 patients died due to an acute rejection and infectious complications, respectively).Conclusion. Since the introduction and modification of immunosuppressive therapy regimens, tremendous progress has occurred, and the incidence of acute cellular rejection has decreased. However, the risk of humoral rejection and long-term complications remains one of the main reasons for graft failure.

Abstract 19190: The Impact of Donor Age on Long-Term Survival After Heart Transplantation: A Modern Analysis of the Unos Database

Introduction: Despite innovations in organ procurement and preservation, heart transplantation (HT) remains challenged with paucity of donor organs. Data is limited regarding the influence of donor age on long term outcomes of HT. Hypothesis: Our aim was to investigate the impact of donor age on long-term survival of transplant recipients between the past two decades. We hypothesized that the probability of survival has increased significantly over the most recent decade with significant increases in survivability for donor hearts aged 55+ years. Methods: The UNOS heart transplant registry was used to analyze survival of heart transplant patients between 2000-2009 (N= 10178) and 2010-2019 (N=20990). These were further separated into three donor age groups: 18-34, 35-54, and over 55 years. Kaplan-Meier survival curves were generated over a 10-year period. Log-ranked statistical testing was used to test the survival curves for significance. Results: Between 2000-2009, 5895 (58%) HT were performed from donors aged 18-34, 3862 (38%) HT from ages 35-54, and 422 (4%) HT from age 55+ group. The chance of 10-year survival was 62%, 52% and 40% respectively.In the 2010-2019 era, there were 12993 (62%) HT performed from donors aged 18-34, 7363 (35%) from ages 35-54, and 634 (3%) from age 55+ group. The 10-year survival was 81%, 77% and 73% respectively.In the donor group age 55+, there was significant difference (p&lt;0.0001) between the head trauma and cerebrovascular cause of death prior to 2010, but no difference in the new era. Conclusions: Our study of the UNOS database finds that the donor age of transplanted hearts significantly impacted long-term survival during 2000-2009. These significant differences carry for transplants from 2010-2019, however, we find that long-term survivability for all donor groups increased to over 70%. The largest increase was observed for donor hearts 55+ years where the chance of 10-year survival improved from 40% before 2010 to 73% after 2010.

Host CD34+ cells are replacing donor endothelium of transplanted heart

Endothelium dysfunction is a central problem for early rejection due to the host alloimmune response and the late status of arteriosclerosis in heart transplantation. However, reliable pieces of evidence are still limited concerning the source of the regenerated endothelium within the transplanted heart. We analyzed single-cell RNA sequencing data and constructed an inducible lineage tracing mouse, combined heart transplantation with bone marrow transplantation and a parabiosis model, cellular components, and endothelial cell populations in cardiac graft lesions. Our single-cell RNA sequencing analysis of a transplanted heart allowed for the establishment of an endothelial cell atlas with a heterogeneous population, including arterial, venous, capillary, and lymphatic endothelial cells. Along with genetic cell lineage tracing, we demonstrated that the donor cells were mostly replaced by recipient cells in the cardiac allograft, up to 83.29% 2weeks after transplantation. Furthermore, recipient nonbone marrow CD34+ endothelial progenitors contributed significantly to extracellular matrix organization and immune regulation, with higher apoptotic ability in the transplanted hearts. Mechanistically, peripheral blood-derived human endothelial progenitor cells differentiate into endocardial cells via Vascular endothelial growth factor receptor-mediated pathways. Host circulating CD34+ endothelial progenitors could repair the damaged donor endothelium presumably through CCL3-CCR5 chemotaxis. Partial depletion of host CD34+ cells resulted in delayed endothelial regeneration. We created an annotated fate map of endothelial cells in cardiac allografts, indicating how recipient CD34+ cells could replace the donor endothelium via chemokine CCL3-CCR5 interactions. The mechanisms we discovered could have a potential therapeutic effect on the long-term outcomes of heart transplantation.

Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment.

Heart transplantation is the gold standard therapeutic option for select patients with end-stage heart failure. Unfortunately, successful long-term outcomes of heart transplantation can be hindered by immune-mediated rejection of the cardiac allograft, specifically acute cellular rejection, antibody-mediated rejection, and cardiac allograft vasculopathy. Extracorporeal photopheresis is a cellular immunotherapy that involves the collection and treatment of white blood cells contained in the buffy coat with a photoactive psoralen compound, 8-methoxy psoralen, and subsequent irradiation with ultraviolet A light. This process is thought to cause DNA and RNA crosslinking, ultimately leading to cell destruction. The true mechanism of therapeutic action remains unknown. In the last three decades, extracorporeal photopheresis has shown promising results and is indicated for a variety of conditions. The American Society for Apheresis currently recommends the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma, scleroderma, psoriasis, pemphigus vulgaris, atopic dermatitis, graft-versus-host disease, Crohn's disease, nephrogenic systemic fibrosis, and solid organ rejection in heart, lung, and liver transplantation. In this review, we aim to explore the proposed effects of extracorporeal photopheresis and to summarize published data on its use as a prophylactic and therapy in heart transplant rejection.

Functional state of the cardiorespiratory system after orthotopic heart transplantation with prolonged cold ischemia time

Objective: to assess the functional state of the cardiorespiratory system in the long term after orthotopic heart transplantation (HT) with prolonged cold ischemia time. Materials and methods. The results of 60 orthotopic HTs performed at Meshalkin National Medical Research Center were analyzed. A comparison was made of the immediate and long-term outcomes of HTs in the group with cold ischemia time lasting for less than 240 minutes and in those with farther distance between donor and recipient sites with cold ischemia time of 240 minutes or more. In the long-term follow-up after HT, all patients underwent cardiopulmonary exercise testing, body plethysmography, assessment of the diffusing capacity of the lungs, and quality of life assessment. Results. Prolonged cold ischemia showed a negative effect on the early postoperative period – decreased myocardial contractility on postoperative day 1 and longer duration of inotropic support. At the same time, the survival rate and incidence of graft rejection reactions in the early and late post-HT periods in the studied groups did not differ significantly. Peak oxygen consumption in the general group in the long term after HT was 17 (14.7–21.0) mL/kg/min, VE/ VCO2 slope was 30 (29–36) at 100 (90–120) W threshold load power. All the parameters of pulmonary function tests did not differ significantly depending on cold ischemia duration. Quality of life also did not show significant differences depending on the duration of graft ischemia in terms of both physical and psycho-emotional health components of the SF-36 questionnaire. Conclusion. Long-term cold ischemia of the graft did not show any negative impact on the functional state of the cardiorespiratory system and quality of life in the long term after HT. The studied group of recipients was characterized by high efficiency of pulmonary ventilation and gas exchange, as well as high tolerance to physical activity in the long-term post-HT period.

Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation

Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. Modification of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway appears to be one of the most promising among the pharmacological interventional options. We aimed at characterizing the cardio-protective effects of the soluble guanylate cyclase stimulator riociguat in a rat model of heterotopic heart transplantation. Donor Lewis rats were treated orally with either riociguat or placebo for two days (n = 9) in each transplanted group and (n = 7) in donor groups. Following explantation, hearts were heterotopically transplanted. After one hour reperfusion, left ventricular pressure-volume relations and coronary blood flow were recorded. Molecular biological measurements and histological examination were also completed. Left ventricular contractility (systolic pressure: 117 ± 13 vs. 48 ± 5 mmHg, p < 0.001; dP/dtmax: 2963 ± 221 vs. 1653 ± 159 mmHg/s, p < 0.001), active relaxation (dP/dtmin: −2014 ± 305 vs. −1063 ± 177 mmHg/s, p = 0.02; all at 120 µl of left ventricular volume), and alteration of coronary blood flow standardized to heart weight (2.55 ± 0.32 vs. 1.67 ± 0.22 ml/min/g, p = 0.03) were markedly increased following preconditioning with riociguat. Myocardial apoptosis markers were also significantly reduced in the riociguat pretreated group as well as the antioxidant markers were elevated. Pharmacological preconditioning with riociguat decreases ischemia-reperfusion injury and improves donor organ function in our animal model of heart transplantation. Therefore, riociguat might be a potential cardioprotective agent.

Primary Transplantation for Congenital Heart Disease in the Neonatal Period: Long-term Outcomes

Primary transplantation was developed in the 1980s as an alternative therapy to palliative reconstruction of uncorrectable congenital heart disease. Although transplantation achieved more favorable results, its utilization has been limited by the availability of donor organs. This review examines the long-term outcomes of heart transplantation in neonates at our institution. The institutional pediatric heart transplant database was queried for all neonatal heart transplants performed between 1985 and 2017. Follow-up was obtained from medical records and an annually administered questionnaire. Overall survival and time to development of complications were estimated using the Kaplan Meier method. Univariate and multivariate analyses were performed to identify independent predictors of survival. Heart transplantation was performed in 104 neonates. Median age was 17 days. Hypoplastic left heart syndrome (classic or variant) was the primary diagnosis in 77.8% of patients. Survival at 10 years and 25 years was 73.9% and 55.8%, respectively. At 20 years, freedom from allograft vasculopathy and lymphoproliferative disease was 72.0% and 81.9%, respectively. Freedom from re-transplantation was 81.4% at 20 years. Eight patients (7.6%) developed end-stage renal disease. By multivariate analysis, lower glomerular filtration rate and allograft vasculopathy were the only significant predictors of death. Neonatal heart transplantation remains a durable therapy with very acceptable long-term survival. Children transplanted in the newborn period have the potential to reach adulthood with minimal need for reintervention.

Long-term outcome of heart transplantation performed after ventricular assist device compared with standard heart transplantation

Data on the long-term outcome of heart transplantation in patients with a ventricular assist device (VAD) are scarce. To evaluate long-term outcome after heart transplantation in patients with a VAD compared with no mechanical circulatory support. Consecutive all-comers who underwent heart transplantation were included at a single high-volume centre from January 2005 until December 2012, with 5 years of follow-up. Clinical and biological characteristics, operative results, outcomes and survival were recorded. Regression analyses were performed to determine predictors of 1-year and 5-year mortality. Fifty-two patients with bridge to transplantation by VAD (VAD group) and 289 patients transplanted without a VAD (standard group) were enrolled. The mean age was 46±11 years in the VAD group compared with 51±13 years in the standard group (P=0.01); 17% of the VAD group and 25% of the standard group were women (P=0.21). Ischaemic time was longer in the VAD group (207±54 vs 169±60minutes; P<0.01). There was no difference in primary graft failure (33% vs 25%; P=0.22) or 1-year mortality (17% vs 28%; P=0.12). In the multivariable analysis, preoperative VAD was an independent protective factor for 1-year mortality (odds ratio 0.40, 95% confidence interval 0.17-0.97; P=0.04). Independent risk factors for 1-year mortality were recipient age>60 years, recipient creatinine, body surface area mismatch and ischaemic time. The VAD and standard groups had similar long-term survival, with 5-year mortality rates of 35% and 40%, respectively (P=0.72). Bridge to transplantation by VAD was associated with a reduction in 1-year mortality, leading critically ill patients to similar long-term survival compared with patients who underwent standard heart transplantation. This alternative strategy may benefit carefully selected patients.

The Evolving Long-Term Outcome of Heart Transplantation in Amyloid Patients

Purpose Both amyloid light chain (AL) amyloidosis and transthyretin-related (TTR) amyloid are expanding indications for heart transplantation (HTx). In the past, AL amyloid, in particular, had been a contraindication to HTx given its systemic nature and the increased risk for mortality. Modern treatments including proteasome inhibitors have allowed amyloid patients to receive heart transplants at an increasing rate. We sought to assess long-term post-transplant outcome in amyloid patients in the current era. Methods Between 2010 and 2015, we assessed 27 patients (5 AL, 10 TTR-wildtype (wt), 12 TTR-mutant (m)) who underwent heart transplant for cardiac amyloidosis at our single center. A non-amyloid restrictive cardiomyopathy control population was included (n=18). Endpoints included 3-year outcomes including survival, freedom from CAV (as defined by stenosis ≥ 30% by angiography), freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), and freedom from any-treated rejection, acute cellular rejection, and antibody-mediated rejection. Results There was no significant difference between the AL amyloid, TTR-wt, TTR-m, and restrictive non-amyloid patients with respect to 3-year survival and 3-year freedom from CAV, NF-MACE, and rejection (see table). Endomyocardial biopsies post-transplant did not show amyloid. (see Table) Conclusion In the current era, both AL and TTR amyloid patients have acceptable mid-term outcome after heart transplantation. Larger numbers and longer followup are needed to confirm these findings.

Effects of Older Donor Age and Cold Ischemic Time on Long-Term Outcomes of Heart Transplantation

Using older donor hearts in cardiac transplantation may lead to inferior outcomes: older donors have more comorbidities that reduce graft quality, including coronary artery disease, hypertension, diabetes mellitus, and dyslipidemia. Shorter cold ischemic times might overcome the detrimental effect of older donor age. We examined the relationship between donor allograft age and cold ischemic time on the long-term outcomes of heart transplant recipients. rom 1994 through 2010, surgeons at our hospital performed 745 heart transplantations. We retrospectively classified these cases by donor ages of <50 years (younger) and ≥50 years (older), then by cold ischemic times of <120 min (short), 120 to 240 min (intermediate), and >240 min (long). Endpoints included recipient and graft survival, and freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, and rejection. For intermediate ischemic times, the 5-year recipient survival rate was lower when donors were older (70% vs 82.6%; P=0.02). This was also true for long ischemic times (69.8% vs 87.6%; P=0.09). For short ischemic times, we found no difference in 5-year recipient or graft survival rates (80% older vs 85.6% younger; P=0.79), in freedom from nonfatal major adverse cardiac events (83.3% vs 91.5%; P=0.46), or in freedom from cardiac allograft vasculopathy (50% vs 70.6%; P=0.66). Rejection rates were mostly similar. Long-term graft survival in heart transplantation patients with older donor allografts may improve when cold ischemic times are shorter.

Heart transplantation in selected patients aged 60 years and older: a two-decade retrospective and multicentre analysis.

This study analysed survival and long-term outcomes of heart transplantation in patients aged 60 years and older. We also analysed the impact of a national graft allocation priority [Super Emergency (SE)] and compared survival with younger patients in our centres and in France. We performed a multicentre (University Hospitals in Nantes, Rennes and Tours), 2-decade retrospective study between 1 January 1994 and 31 December 2013. Elderly recipients were placed on the same list as younger patients; the use of marginal donors remained occasional. A total of 212 patients aged between 60 and 68 years were included. The 1-, 5-, and 10-year survival rates were 83.2%, 77.4% and 63.8%, respectively, which were significantly worse than those of recipients aged <60 years (1-, 5-, and 10-year survival rates of 87.3%, 80.4% and 68.0%, respectively). The postoperative course was acceptable. The main cause of death was malignancy (29.8% in our cohort). Survival was similar between the first and second decades and among the SE group. Our population exhibited better survival than patients <60 years transplanted in France during the same period with 1-, 5-, and 10-year survival rates of 76.8%, 68.0% and 56.3%, respectively. Predictors of survival in the multivariate analysis included ischaemic cardiomyopathy [hazard ratio (HR) 4.1] and postoperative complications, such as dialysis (HR 9.5) and mechanical circulatory support (HR 4.2). We report positive postoperative course and long-term outcomes after heart transplantation in older recipients using conventional donors. Our satisfactory outcomes may be explained by the stringent selection of recipients combined with regular follow-up.

Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation.

One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast-enhanced ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High-resolution MP mapping may allow for noninvasive detection of heart transplant rejection. The data presented have the potential to help in the development of next-generation imaging approaches to diagnose transplant rejection.

Heart transplantation in endstage rheumatic heart disease-experience of an endemic area.

Rheumatic heart disease (RHD) remains a significant cause of cardiovascular disease in developing countries. The nonsuppurative cardiovascular sequel of group A streptococcal infection is sustained inflammatory and immune reactions toward the myocardium and valves. This study attempted to determine the long-term outcome of heart transplantation in endstage RHD patients.Methods and Results:The 23 patients with endstage RHD at National Taiwan University Hospital between June 1987 and March 2012 were enrolled. In the same period, 226 dilated cardiomyopathy (DCM) patients were enrolled as the control group. The RHD group experienced more right ventricular failure and higher central venous pressure than the control group, which resulted in impaired liver and kidney function. The RHD patients had a lower 15-year survival rate than the DCM patients after transplantation (22.7% vs. 45.7%, P=0.038) and higher incidence of tricuspid regurgitation than the control group (32.2% vs. 11.4%). No differences existed between the groups for the mitral regurgitation rate (RHD 37.7% vs. DCM 29.4%, P=0.562). Preoperatively, the RHD patients suffered more tricuspid regurgitation than the control group. The aortic and mitral valves in both groups functioned well over the long term. Heart transplantation for endstage RHD had a long-term survival rate that was inferior to that for DCM patients.

70 The HeartMate II Risk Score: Predicting Survival in Candidates for Left Ventricular Assist Device Support

Purpose: Nearly one-third of children diagnosed with dilated cardiomyopathy (DCM) receive a transplant or die within the first year after diagnosis. Limited long-term outcome of heart transplantation and scarcity of young donors justify every effort to improve medical therapy and to find alternative therapeutic approaches. There is increasing evidence that cardiac stem cell transplantation induce sustained improvement in cardiac function in patients with heart failure. We describe the compassionate use of intracoronary autologous peripheral stem cell therapy in two young infants diagnosed with DCM and severe heart failure. Methods and Materials: Descriptive study that analyzes the evolution of two pediatric patients diagnosed with DCM and severe heart failure, and who were treated with intracoronary infusion of autologous stem cells. Patient 1 is a 3-month male infant weighing 4 Kg. Patient 2 is a 4-month male infant weighing 5 Kg. Results: At the time of admission, both patients were in poor clinical status (NYHA IV), had high levels of NT-ProBNP and severe LV dilation and systolic dysfunction (EF 30%). Both were mechanically ventilated and needed IV inotropes. Endomyocardial biopsy ruled out myocarditis. In each case, after treatment with G-CSF for 4 days, autologous stem cells were recovered from peripheral blood, implanting them via the coronary arteries afterwards. As soon as one week after the procedure, echocardiography showed a remarkable improvement in LV dilation. One month later a significant gain in their EF ( 40%) was also detected and this was maintained over time. The long-term outcome was favorable. Although first patient has shown LV dilation 17 weeks after the procedure, he is still in functional class I and has adequate weight gain. Conclusions: Although currently heart transplantation is the only established treatment for DCM, stem cell therapy could be an option to improve clinical status, and serve as a bridge to decision, to transplantation or, more importantly, to recovery for these very sick children.

69 Intracoronary Autologous Peripheral Stem Cell Therapy: A Promising Treatment for Heart Failure in Pediatric Dilated Cardiomyopathy

<h3>Purpose</h3> Nearly one-third of children diagnosed with dilated cardiomyopathy (DCM) receive a transplant or die within the first year after diagnosis. Limited long-term outcome of heart transplantation and scarcity of young donors justify every effort to improve medical therapy and to find alternative therapeutic approaches. There is increasing evidence that cardiac stem cell transplantation induce sustained improvement in cardiac function in patients with heart failure. We describe the compassionate use of intracoronary autologous peripheral stem cell therapy in two young infants diagnosed with DCM and severe heart failure. <h3>Methods and Materials</h3> Descriptive study that analyzes the evolution of two pediatric patients diagnosed with DCM and severe heart failure, and who were treated with intracoronary infusion of autologous stem cells. Patient 1 is a 3-month male infant weighing 4 Kg. Patient 2 is a 4-month male infant weighing 5 Kg. <h3>Results</h3> At the time of admission, both patients were in poor clinical status (NYHA IV), had high levels of NT-ProBNP and severe LV dilation and systolic dysfunction (EF<30%). Both were mechanically ventilated and needed IV inotropes. Endomyocardial biopsy ruled out myocarditis. In each case, after treatment with G-CSF for 4 days, autologous stem cells were recovered from peripheral blood, implanting them via the coronary arteries afterwards. As soon as one week after the procedure, echocardiography showed a remarkable improvement in LV dilation. One month later a significant gain in their EF (>40%) was also detected and this was maintained over time. The long-term outcome was favorable. Although first patient has shown LV dilation 17 weeks after the procedure, he is still in functional class I and has adequate weight gain. <h3>Conclusions</h3> Although currently heart transplantation is the only established treatment for DCM, stem cell therapy could be an option to improve clinical status, and serve as a bridge to decision, to transplantation or, more importantly, to recovery for these very sick children.

Endothelial Dysfunction in Cardiac Allograft Vasculopathy: Potential Pharmacological Interventions

Nowadays long-term outcome of heart transplantation is limited by a peculiar type of coronary atherosclerosis, known as cardiac allograft vasculopathy (CAV). Although the exact pathogenesis of CAV remains unclear, emerging evidence indicates that the endothelium plays a significant role in the onset and progression of this disease. Nitric oxide (NO) is the principal mediator of all endothelial protective effects, due to its antinflammatory, antiproliferative, immunomodulatory and vasorelaxant properties. CAV involves immunologic mechanisms operating in the context of common cardiovascular risk factors which lead to impaired endothelial function, mainly as a consequence of decreased NO bioavailability and excessive oxidative stress. Once dysfunctional, the endothelium promotes CAV lesion progression towards the diffuse narrowing of the coronary vasculature which characterizes advanced allograft vasculopathy. Recently, many studies showed the possibility to restore endothelial dysfunction with an associated potential improvement in clinical cardiovascular outcome. Therefore, growing interest deserves the possibility to exert an endothelial protective role shown by some currently used cardiovascular and immunosuppressive drugs, as well as the future development of new pharmacological compounds with selective endothelial protective properties as a target for successful prevention and therapy of CAV.

Long-term Outcomes of Heart Transplantation in Older Recipients

Heart transplantation in the elderly is increasingly common. In the mid-1990s, 25% of recipients in our program were >62 years of age. We evaluated outcomes from one institution with the hypothesis that older recipients may be at higher risk of major complications associated with immunosuppression. We analyzed results for 182 patients aged 62 to 75 years (mean +/- SD: 66.3 +/- 11.4 years) who underwent heart transplantation between January 1995 and July 2001 at a single institution. They were compared with a control group of 348 contemporaneous adult recipients aged 18 to 62 years (mean +/- SD: 48.2 +/- 11.4 years). All recipients in this consecutive cohort had a follow-up of at least at least 5 years. End-points studied were Kaplan-Meier survival, freedom from dialysis and freedom from malignancy at 100 months. Follow-up was 100% at 100 months. At 100 months, survival for the elderly was 55% (46 remaining at risk) and 63% (102 remaining at risk) for controls (p = 0.051, log-rank test). Re-transplant and dialysis, but not recipient age or malignancy, were predictive of survival by regression analysis (p = 0.003, p < 0.001, p = 0.53 and p = 0.84, respectively). Freedom from malignancy at 100 months was 68% for the elderly and 95% for controls (p < 0.001). Age predicted malignancy by regression analysis (p < 0.001). At 100 months, freedom from dialysis was 81% for the elderly and 87% for controls (p = 0.005). Pre-operative creatinine, but not age, was predictive of need for dialysis (p = 0.003 and p = 0.47, respectively). Although long-term survival of older heart transplant recipients is acceptable, it is significantly lower than in young recipients. The increased risk of renal failure and malignancy among elderly patients likely influences the difference in survival observed between the two groups. Pre-operative renal function warrants careful consideration. As ventricular assist device technology improves, it may be used to complement heart transplantation to avoid immunosuppression and its side effect of malignancy in older patients with advanced heart failure.

Ischaemic heart disease is a risk factor for renal failure after heart transplantation

Background The improvement of a long-term outcomes of heart transplantation (HTx) has resulted in a new phenomenon; specifically, the development of renal dysfunction secondary to calcineurin inhibitor toxicity. This study was designed to assess the participation of risk factors in the development of renal dysfunction in HTx. Methods Data from 310 patients undergoing HTx in our center between 1988–1998 with a post-operation survival period for minimum 5 years ( n = 155) were analyzed retrospectively. Study cohort was divided into two groups according to renal function estimated by serum creatinine in the fifth year (Group I n = 72; serum creatinine ≥ 150 μmol/l, Group II: n = 83, serum creatinine < 150 μmol/l). Results We noted that patients with serum creatinine ≥ 150 μmol/l at 5 years post-HTx had renal function significantly worse as early as 1 month ( p < 0.01), and 1 year post-HTx ( p < 0.001). The risk for developing renal dysfunction after HTx was doubled in patients with a history of coronary artery disease (CAD), and 2.5 times higher in those with small body weight gain. End stage renal disease developed in 16 patients (10.3%) and renal transplantation was performed in 13 (8.4%) of them. Conclusion Our data documented that a history of CAD and limited weight gain is a major risk factor for development of renal dysfunction after HTx. Aggressive modification of risk factors for CAD may reduce the occurrence of this complication.

Editorial Comment: Heart Transplantation, Cardiac Allograft Vasculopathy and Proliferation Signal Inhibitors

Editorial Comment: Heart Transplantation, Cardiac Allograft Vasculopathy and Proliferation Signal Inhibitors