To examine recent trends in the use of expanded criteria donor organs in heart transplantation, this study assessed center-level variation in acceptance of these allografts and analyzed their posttransplantation outcomes.

Adult (aged ≥18 years) heart transplant recipients between 2011 and 2022 were identified in the Organ Procurement and Transplantation Network database. Expanded criteria allografts were defined using a previously validated risk score. After stratifying centers by cumulative transplantation volume, those centers in the top tertile (≥23/year) were considered high volume. Subsequently, the ratio of transplantations using expanded criteria allografts to total transplantations was calculated for each high-volume center. On the basis of tertiles, centers were then categorized as high-, medium-, and low-use centers. The primary outcome was death after transplantation.

Of 23,290 transplantations performed, 5017 (22%) used expanded criteria donor allografts. High-volume heart transplantation centers performed 72% (3628) of these transplantations-1183 (75%) between 2011 and 2014, 1383 (73%) between 2015 and October 2018, and 1062 (68%) between November 2018 and June 2021. Compared with low-volume programs, undergoing expanded criteria heart transplantation at high-volume centers was associated with a significantly reduced hazard of mortality at 1 year (hazard ratio, 0.78; CI, 0.65-0.94; P = .01) and 5 years (hazard ratio, 0.85; CI, 0.75-0.98; P = .02). During the study period, survival rates 1 year after transplantation were similar across high-volume centers, regardless of their use of expanded criteria allografts.

Undergoing heart transplantation with an expanded criteria donor allograft at a high-volume transplantation center provides a significant survival benefit. Further, the use of more expanded criteria criteria organs, in the right clinical settings, does not negatively affect overall patient outcomes at high-volume centers.

Generally, heart transplantation with marginal donor allografts is reserved for a subset of high-risk patients. However, given the improved survival rates for patients on left ventricular assist devices, it is worth analyzing if they could potentially substitute for marginal donor allografts. This study aimed to compare survival outcomes of waitlisted patients with left ventricular assist devices who did not undergo heart transplantation to those who underwent heart transplantation with marginal allografts.

This was a retrospective cohort study of adults (≥18 years) listed for heart transplantation between 2010 and 2022 in the Organ Procurement and Transplantation Network database. A previously validated risk score was used to define marginal donor organs. The primary outcome was death after transplantation or on the waitlist, as appropriate.

Of 5,713 patients with left ventricular assist devices, 4,683 (82%) comprised the left ventricular assist devices group and 1,030 (18%) the marginal group. The marginal cohort was older (57 [49-64] vs 55 [45-62] years, P < .001), similarly female (26 vs 24%, P = .16), and less often White (51 vs 60%, P < .001). Relative to the left ventricular assist devices group, the marginal group demonstrated higher 5-year survival from 2010 to 2014 (81 vs 43%, P < .001) and from 2015 to 2019 (77 vs 66%, P < .001). After adjustment, marginal patients demonstrated a significantly reduced hazard of 5-year mortality for those listed from 2010 to 2014 (hazard ratio 0.25, confidence interval 0.20-0.31; P < .001) and from 2015 to 2019 (hazard ratio 0.46, confidence interval 0.37-0.57; P < .001).

Our study validates the superiority of transplantation relative to left ventricular assist devices but also underscores the survival benefit of heart transplantation with marginal donor allografts, even in high-risk patients.

Significant scarcity of a donor pool exists for heart transplantation (HT) as the prevalence of patients with end-stage refractory heart failure is increasing exceptionally. With the discovery of effective direct-acting antiviral and favorable short-term outcomes following HT, the hearts from hepatitis C virus (HCV) patient are being utilized to increase the donor pool. Short-term outcomes with regards to graft function, coronary artery vasculopathy, and kidney and liver disease is comparable in HCV-negative recipients undergoing HT from HCV-positive donors compared to HCV-negative donors. A significant high incidence of donor-derived HCV transmission was observed with great success of achieving sustained viral response with the use of direct-acting antivirals. By accepting HCV-positive organs, the donor pool has expanded with younger donors, a shorter waitlist time, and a reduction in waitlist mortality. However, the long-term outcomes and impact of specific HCV genotypes remains to be seen. We reviewed the current literature on HT from HCV-positive donors.

Hepatitis C virus (HCV) infection is an important cause of a variety of otherwise unexplained heart diseases and myocardial injury. A high prevalence of HCV infection has been noted in patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia/cardiomyopathy and myocarditis. Various arrhythmias, conduction disturbances and QT prolongation were also associated with HCV infection. A possible role of HCV infection in the pathogenesis of diabetes and atherosclerosis, and the role of immunogenetics of HCV cardiomyopathies is discussed. Recent studies suggest that mononuclear cells may be the major target of HCV, and clinical applications to test this new hypothesis are discussed.

In this review, we will evaluate the evidence that HCV causes various cardiovascular diseases, and discuss on the pathogenesis of these disorders.

HCV is the cause of many different forms of heart disease worldwide, but their existence has not been recognized by most of cardiologists. The recognition and diagnosis are indispensable for the early treatment of these diseases. The diverse clinical manifestation of HCV infection and the presence of multiple extrahepatic disease syndromes could be explained by a new hypothesis that the target of HCV is leukocytes.

With the growing need for donor hearts and longer transplant waiting lists, there is a growing interest in expanding the donor pool by reconsidering previously excluded donor candidates. There has been an increase in solid organ availability due to drug overdose deaths in the setting of the recent opioid epidemic. However, these donors often have transmissible infections such as hepatitis C. In this review, we discuss the challenges associated with heart transplantation from hepatitis C-infected donors as well as the recent advancements that are making the use of these organs possible.

With the introduction and widespread use of nucleic acid testing (NAT), the ability to distinguish viremic donors and those that have cleared the virus has become a reality. In addition, with the emergence of direct antiviral agents, there is an increase in data showing the short-term outcomes and success of hepatitis C treatment for recipients of viremic donor hearts. As techniques to distinguish donor hepatitis C infection status and successful treatments emerge, the percentage of accepted hepatitis C donor hearts is increasing. A number of studies showing success with hepatitis C organ transplants present a promising new avenue for organ procurement essential to meet the increasing demand for donor hearts.

Increased utilization of hepatitis C virus (HCV)-positive donors has increased transplantation rates. However, high levels of viremia have been documented in recipients of viremic donors. There is a knowledge gap in how transient viremia may impact acute cellular rejections (ACRs).

In this study, 50 subjects received hearts from either viremic or non-viremic donors. The recipients of viremic donors were classified as nucleic acid amplification testing (NAT)+ group, and the remaining were classified as NAT-. All patients were monitored for viremia levels. Endomyocardial biopsies were performed through 180 days, evaluating the incidence of ACRs.

A total of 50 HCV-naive recipients received hearts between 2018 and 2019. A total of 22 patients (44%) who received transplants from viremic donors developed viremia at a mean period of 7.2 ± 0.2 days. At that time, glecaprevir/pibrentasvir was initiated. In the viremia period (<56 days), 14 of 22 NAT+ recipients (64%) had ACR vs 5 of 28 NAT- group (18%) (p = 0.001). Through 180 days, 17 of 22 NAT+ recipients (77%) had a repeat rejection biopsy vs 12 of 28 NAT- recipients (43%) (p = 0.02). NAT+ biopsies demonstrated disparity of ACR distribution: negative, low-grade, and high-grade ACR in 84%, 12%, and 4%, respectively, vs 96%, 3%, and 1%, respectively, in the NAT- group (p = 0.03). The median time to first event was 26 (interquartile range [IQR]: 8-45) in the NAT+ group vs 65 (IQR: 44-84) days in the NAT-. Time to first event risk model revealed that NAT+ recipients had a significantly higher rate of ACR occurrences, adjusting for demographics (p = 0.004).

Transient levels of viremia contributed to higher rates and severity of ACRs. Further investigation into the mechanisms of early immune activation in NAT+ recipients is required.

Low donor heart availability underscores the need to identify all potentially transplantable organs. We sought to determine whether pre-emptive administration of pangenotypic direct-acting antiviral therapy can safely prevent the development of chronic hepatitis C virus (HCV) infection in uninfected recipients of HCV-infected donor hearts.

Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018. Following enrolment, the recipient's status on the heart transplantation waiting list was updated to reflect a willingness to accept either an HCV-positive or HCV-negative heart donor. Patients who underwent transplantation with a viraemic donor heart, as determined by nucleic acid testing (NAT), received pre-emptive oral glecaprevir-pibrentasvir before transport to the operating room followed by an 8-week course of glecaprevir-pibrentasvir after transplantation. Patients receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA were followed using a reactive approach and started glecaprevir-pibrentasvir only if they developed viraemia. The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12). Patients were followed from study enrolment to 1 year after transplantation. This is an interim analysis, initiated after all enrolled patients reached the primary outcome. Results reflect data from Nov 1, 2017, to May 30, 2019. This trial is registered with ClinicalTrials.gov, number NCT03208244.

55 patients were assessed for eligibility and 52 consented to enrolment. 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT-positive, five NAT-negative), three of whom underwent simultaneous heart-kidney transplantation. All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression (median time to clearance 3·5 days, IQR 0·0-8·3), with the subsequent achievement of SVR12 by all 20. The five recipients of NAT-negative grafts did not become viraemic. Median pre-transplant waiting time for patients following enrolment in the HCV protocol was 20 days (IQR 8-57). Patient and allograft survival were 100% at a median follow-up of 10·7 months (range 6·5-18·0).

Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infected donor hearts. Long-term outcomes are not yet known.

American Association for the Study of Liver Diseases, National Institutes of Health, and the Massachusetts General Hospital.

Owing to long waitlist times and high waitlist morbidity and mortality, strategies to increase utilization of hepatitis C viremic-deceased donor organs are under investigation in kidney, liver, heart, and lung transplantation.

Direct-acting antiviral medications for hepatitis C virus infection have high cure rates and are well tolerated. Small, single-center trials in kidney and heart transplant recipients have demonstrated that with early posttransplant direct-acting antiviral therapy, 100% of uninfected recipients of hepatitis C viremic organs have been cured of infection after transplantation.

In this manuscript, we review the risks and rewards of utilizing hepatitis C viremic organs for transplantation.

Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection.

We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation.

A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders.

In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).

Although low (but increasing) rates of lung/lung-heart transplantations of scleroderma (systemic sclerosis [SSc]) patients have been reported, exclusive heart transplantation is a rare approach for treatment of heart failure due to SSc.

We report on 2 cases of SSc patients receiving a heart transplantation (HTx) due to severe and progressive right heart failure without pulmonary artery hypertension. One patient received a hepatitis C virus (HCV)-positive donor heart and recovered excellently from viral transmission after administration of a direct-acting antiviral (DAA) regimen. This is the first published case of an SSc patient who underwent HTx using an HCV-positive donor heart. The clinical course of both patients was monitored by different serum SSc biomarkers. Only xylosyltransferase activity proved to be a promising biomarker for disease stage determination and therapeutic monitoring, precisely reflecting fibrotic remodeling and successful organ recovery.

Successful implementation of the 2 cases described here demonstrates that HTx is a safe and effective therapeutic option for defined SSc sub-patient groups despite the progressive character of the underlying disease. In the future, xylosyltransferase activity might be conducive to simplify the identification of patients with low systemic involvement but a strong indication for single heart transplantation. Finally, we demonstrate that treatment of HCV viral transmission from HCV-positive donor to organ recipient using DAA gives us new opportunities to consider HCV-positive donor organs for HTx and might reveal new possibilities to ease the lack of donor organs.

In 2016, the Transplantation Society of Australia and New Zealand, with the support of the Australian Government Organ and Tissue authority, commissioned a literature review on the topic of infectious disease transmission from deceased donors to recipients of solid organ transplants. The purpose of this review was to synthesize evidence on transmission risks, diagnostic test characteristics, and recipient management to inform best-practice clinical guidelines. The final review, presented as a special supplement in Transplantation Direct, collates case reports of transmission events and other peer-reviewed literature, and summarizes current (as of June 2017) international guidelines on donor screening and recipient management. Of particular interest at the time of writing was how to maximize utilization of donors at increased risk for transmission of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus, given the recent developments, including the availability of direct-acting antivirals for hepatitis C virus and improvements in donor screening technologies. The review also covers emerging risks associated with recent epidemics (eg, Zika virus) and the risk of transmission of nonendemic pathogens related to donor travel history or country of origin. Lastly, the implications for recipient consent of expanded utilization of donors at increased risk of blood-borne viral disease transmission are considered.

Recent reports have shown an increase in the number of organ donors from drug intoxication. The impact of donor drug use on survival after cardiac transplant remains unclear. The aim of our study was to illustrate changes in donor death mechanisms and assess the impact on posttransplant survival. We queried United Network of Organ Sharing thoracic transplant and deceased donor databases to identify patients undergoing heart transplantation between 2005 and 2015. We evaluated annual trends in donor death mechanisms. Recipients were propensity matched (drug-intoxicated-non-drug-intoxicated = 1:2) and posttransplant survival was compared using Kaplan-Meier curves. In total, 19 384 donor hearts were used for transplant during the period (donor age 31.6 ± 11.8 years, 72% male). Use of drug-intoxicated donors increased from 2% (2005) to 13% (2015) and decreased from blunt injury (40%-30%) and intracranial hemorrhage (29%-25%). After propensity matching, posttransplant survival of drug-intoxicated donor hearts was 90%, 82%, and 76% at 1, 3, and 5 years, which was similar to non-drug-intoxicated. Heart transplants using drug-intoxicated donors have significantly increased; however, they have not adversely affected posttransplant survival. Hearts from drug-intoxicated donors should be carefully evaluated and considered for transplant.

Heart donor selection criteria have been progressively widened due to increasing donor recipient mismatch. This study evaluates the outcomes of the use marginal donor hearts for orthotopic heart transplantation (OHT) based on a single center experience in China.

We retrospectively analyzed outcomes of patients undergoing OHT in our hospital between September 2008 and December 2015. All the donor hearts were from voluntary donation of brain-dead patients. The primary outcome was overall survival; secondary outcomes included cardiopulmonary bypass (CPB) time, ventilation time, post-operative mechanical support and medium-term complications.

Overall, 278 patients with OHT were analyzed. Whereas 180 patients (64.7%) underwent OHT utilizing marginal donors (MD group), only 98 patients (35.3%) underwent OHT with standard donors (SD group). Compared to the SD group, the MD group had longer CPB time (P=0.001), ventilation time (P=0.010) and increased mechanical support rate (P=0.011). Survival rates were comparable between the two groups at 30 days, 1 year, 3 years and 5 years (92.2%, 83.3%, 70.6%, 70.6% vs. 95.9%, 91.4%, 80.2%, 80.2% respectively). Multivariate Cox regression analysis revealed that female recipient gender [hazard ratio (HR) =2.632 (1.325-5.227), P=0.006], diagnosis (P=0.014) and abnormal donor heart structure [HR =3.638 (1.005-13.167), P=0.049] were three predictors for 1-year all-cause mortality. The occurrence of complications in the recipients with more than 3-year follow-up did not differ between the two cohorts.

Marginal donor can be reasonably applied to expand the benefits of transplantation. Changing previous MD criteria to include donors with an age greater than 50 years, cold ischemic time less than 6 hours, donor/recipient weight ratio less than 0.8, compatible blood type, hepatitis virus seropositivity and MD used for male recipient will likely offer a good prognosis.

The objective of this study is to describe identifiable risk factors, complications, and pitfalls while listing pediatric patients for heart transplantation, which is the standard of care for end-stage heart disease in children. Since the introduction of cyclosporine in the 1980s, the management in pediatric heart transplantation has shown consistent improvement, mainly because of technological advances and the integration of multidisciplinary teams in the field. However, the complexity of this patient population makes medical providers vulnerable to complications as a result of undesirable mistakes. Transplant survival is impacted negatively when mistakes from health-care providers compound the high-risk status of the patient. The identification of multiple risk factors and undesirable miscalculations may help transplant teams make decisions before allocating organs, intervene or minimize morbidity, and provide the best quality of life to recipients.

Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors.

Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval.

At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients.

In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.

The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

Orthotopic heart transplantation (OHT) is the gold-standard therapy for end-stage heart failure. An increasing deficit between suitable allograft availability and clinical demand for OHT exists. The role of donor diabetes mellitus (DM) on post-transplant recipient outcomes in OHT is controversial. The purpose of this study was to examine donor hemoglobin A1c (HbA1c) levels to identify the impact of donor glycemic control on recipient survival.

Adult OHT recipients with donor HbA1c data were identified in the UNOS database from 2010 to 2015. Recipients were stratified on the basis of donor glycemic status: Hyperglycemic-donor and euglycemic-donor cohorts were defined as HbA1c levels ≥6.5% and <6.5%, respectively. Outcomes were compared between unadjusted and propensity-matched hyperglycemic versus euglycemic donors. Primary end point was three-year survival.

Of 5342 OHT recipients, 208 (3.89%) received an allograft from a hyperglycemic donor and 5134 (96.1%) received an allograft from a euglycemic donor. There was no significant difference in survival in the hyperglycemic group before (P=.87) or after (P=.78) propensity matching.

No difference in four-year survival was noted in recipients who received allografts from hyperglycemic donors. These results suggest that recent cumulative donor glycemic status alone may not be an important predictor of recipient outcomes.

Should organs from hepatitis C antibody positive donors (HCVD+) be used for transplantation? Organ shortage forces transplant teams to use donors with extended criteria. The decision to transplant a HCVD+ graft is a balance between the risk of transmission of a virus that could lead to end-stage liver diseases and the benefit of access to transplantation, specifically in patients with life-threatening disease. The other issue is the impact of HCV-related liver fibrosis in the donor graft on the long-term outcome in the recipient. Thus, the use of HCVD+ demonstrated a shorter meantime on the waiting list in kidney transplantation. When a HCVD+ graft is transplanted, the risk of HCV transmission depends on; 1) the quality of screening of the donor; 2) the presence of viral replication in the donor at the time of transplantation and the ability to detect it; and 3) the HCV status of the recipient but also the type of transplanted organ. In liver transplantation, the use of HCVD+ graft is usually restricted to recipients with a chronic HCV infection. Several reports showed some competition between HCV donor and recipient strain without deleterious impact on graft and patient survival. Controversies are still pending regarding the quality of the graft and the progression of fibrosis. The recent approval of direct-acting antiviral agents (DAA) dramatically changes the landscape of HCV infection treatment. After transplantation, combinations of DAA show high efficacy and good safety profile. In the near future, extensive use of DAA should reduce the number of HCVD+ with a positive HCV RNA, limiting the risk of transmission but also the number of patients on waiting lists for a disease related to HCV.

Hepatitis C virus (HCV)-positive donor allografts may be considered for HCV-positive recipients, but are underutilized. With new effective antiviral treatments, we aim to review data on the use of HCV-positive allografts in solid organ transplantation and place them in the context of the changing HCV landscape.

Hepatitis C is the most common indication for liver transplant in the USA and Europe and a significant comorbidity in patients on the waitlist for nonliver solid organ transplantation. Patients with HCV on the waitlist for nonliver solid organ transplantation have worse outcomes compared with those without HCV. However, survival after transplantation is improved compared with those who remain on the waitlist. There has been concern that use of HCV-positive allografts would lead to worse post-transplant outcomes. However, more recent data suggest that transplant outcomes for recipients who accept HCV-positive donor allografts may be comparable with those who receive HCV-negative allografts. Emerging treatments to eradicate HCV have further improved the course of HCV-positive individuals, with improved efficacy and reduced side-effects.

In view of the changing landscape of hepatitis C treatment and reduced wait time on the transplant waiting lists for those accepting HCV-positive donors, future use of select HCV-positive donors in solid organ transplantation should be encouraged.

The hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwide. A significant portion of the morbidity and mortality associated with HCV is a consequence of numerous HCV-associated comorbidities. Type 2 diabetes and atherosclerosis, two known complications of the metabolic syndrome, are noteworthy, because HCV has been suggested to play a role in their pathogenesis. In addition, HCV also causes steatosis, which may increase the risk of cardiovascular events. This review summarizes the evidence supporting the association between HCV and steatosis, insulin resistance/type 2 diabetes and cardiovascular morbidity and mortality. Their diagnostic, prognostic and management aspects are discussed.

In order to assess the quality of the donor liver, procuring surgeons should accurately evaluate not only general donor risk indices, such as donor age, causes of brain death and cold ischemic time, but also consider the specific donor risk indices. In this review, we focus on liver-specific deceased donor risk indices, including liver steatosis, anti-hepatitis B core (HBc) positive or hepatitis C virus (HCV) positive donors, hypernatremia and anatomical variations. Liver steatosis is strongly associated with poor graft function after liver transplantation. Liver with more than 40-50% macrosteatosis should not be used. However, at present the quantity of fatty livers lack accepted standards. The computerized image analysis programs should be used to automate the determination of fat content in liver biopsy specimens. Liver grafts from anti-HBc positive donors can be safely used, preferentially in hepatitis B surface antigen (HBsAg) positive or anti-HBc/anti-HBs positive recipients. HCV positive allografts free from fibrosis or severe inflammation are a safe option for HCV positive recipients. The procurement team should consider liver biopsy to evaluate these HCV positive allografts. Donor serum sodium over 150 mm may predict a higher rate of graft primary non-functions. Recently, however, some investigators reported the sodium level likely has little clinical impact on post-transplant liver function. The incidence of hepatic artery variations has been reported to be approximately 30%. To avoid injuries, it is very important to know and identify these variations with precision at the time of organ procurement.

International Society of Heart and Lung Transplantation guidelines for adult heart transplantation (HT) suggest a donor to recipient body weight ratio (WR) of greater than 0.8. For female to male transplants, a WR of greater than 0.9 is recommended.

The United Network for Organ Sharing database was examined for adult HT from 1999 to 2011. Controls with a WR of 0.9 or greater (normal donor to recipient weight ratio) were compared with patients with a WR of 0.6 to 0.89 (WRL) and a WR of less than 0.59 (WRVL). The primary measured outcome was survival.

Of the 21,928 patients undergoing HT, 14,592 (66.6%) were performed with a normal donor to recipient weight ratio, 7212 (32.9%) were performed with WRL, and 124 (0.6%) were performed with WRVL. In male donor to male recipient, male donor to female recipient, and female donor to female recipient HT, the use of WRL did not influence median survival (P = .3621) and was not associated with increased mortality (P = .7273). In female donor to male recipient HT, WRL was associated with decreased median survival (435 days, P = .0241) and was associated with increased mortality (hazard ratio, 1.201; P = .0383).

HT can be safely performed using WRL donors between sex-matched and male to female transplants. However, in female to male transplants, WRL donors are associated with decreased survival. Although clinical circumstances will guide decision making, consensus criteria may be revisited to liberalize the pool of acceptable donors in an era of unprecedented donor shortage.

: Hepatitis C virus (HCV) infection is common in solid organ allograft recipients and is a significant cause of morbidity and mortality after transplantation, so effective management will improve outcomes. In this review, we discuss the extent of the problem associated with HCV infection in donors and kidney, heart, and lung transplant candidates and recipients and recommend follow-up and treatment.Patients with end-stage kidney disease without cirrhosis and selected patients with early-stage cirrhosis can be considered for kidney transplant alone. In HCV-infected kidney allograft recipients, the progression of fibrosis should be evaluated serially by Fibroscan or serologic measures of fibrosis. Transplantation of kidneys from HCV-positive donors should be restricted to HCV-positive recipients as it is associated with a reduced time waiting for a graft and does not affect posttransplant outcomes. Hepatitis C virus antiviral therapy should be considered for all HCV-RNA-positive kidney transplant candidates, irrespective of the baseline liver histopathology. Protease inhibitors have yet to be fully evaluated in patients with renal dysfunction and in the transplant population. As these agents may cause anemia in patients with normal renal function, tolerability may be a problem in patients with end-stage kidney disease.The impact of HCV infection on survival in heart and lung transplantation is unclear. Because of the shortage of organs, few HCV-infected patients are accepted for transplantation.Universal use of nucleic acid amplification testing (NAT) for the screening of potential organ donors should be reserved to high-risk donors. Assays that quantify HCV core antigen may become more cost-effective than NAT for the screening of potential organ donors.

Cardiac transplantation (OHT) using diabetic donors (DDs) is thought to adversely influence survival. We attempt to determine if adult OHT can be safely performed using selected DDs.

The United Network for Organ Sharing (UNOS) database was examined for adult OHT from 2000 to 2010.

Of the 20,348 patients undergoing OHT, 496 (2.4%) were with DDs. DDs were older (39.6 vs 31.3 years; P < .001), more likely female (41.5% vs 28.3%; P < .001), and had a higher body mass index (BMI) (29.9 vs 26.4; P < .001). Recipients of DD hearts were older (53.4 vs 51.8; P = .004) and more likely to have diabetes (18.9% vs 14.9%; P = .024). The 2 groups were evenly matched with regard to recipient male gender (78.0% vs 76.1%; P = .312), ischemic time (3.3 vs 3.2 hours; P = .191), human leukocyte antigen mismatches (4.7 vs 4.6; P = .483), and requirement of extracorporeal membrane oxygenation (ECMO) as a bridge to transplant (0.8% vs 0.5%; P = .382). Median survival was similar (3799 vs 3798 days; P = .172). On multivariate analysis, DD was not associated with mortality (hazard ratio [HR], 1.155; 95% confidence interval [CI], 0.943-1.415; P = .164). As previously demonstrated, donor age, decreasing donor BMI, ischemic time, recipient creatinine, recipient black race, recipient diabetes, race mismatch, and mechanical ventilation or ECMO as a bridge to transplant were associated with mortality. On multivariate analysis of subgroups, neither insulin-dependent diabetes (1.173; 95% CI, 0.884-1.444; P = .268) nor duration of diabetes for more than 5 years (HR, 1.239; 95% CI, 0.914-1.016; P = .167) was associated with mortality.

OHT can be safely performed using selected DDs. Consensus criteria for acceptable cardiac donors can likely be revised to include selected DDs.

Hepatitis C (HCV) infection is prevalent in recipients of, and candidates for, solid organ transplants. The outcomes of HCV infection in cardiac and lung transplant recipients have yet to be clearly established, and future prospective studies are needed. In the absence of safe and effective antiviral treatment for HCV infection in heart and lung transplant recipients, the management of these patients remains a challenge and must be considered on an individual basis. Interferon therapy for HCV before transplantation appears to improve outcomes; however, post-transplant interferon therapy in the cardiac and pulmonary transplant setting may be associated with an increased risk of graft rejection. Given the paucity of information regarding HCV treatment in these transplant recipients, and with appropriate concerns that graft loss from rejection may not be amenable to a second transplant (given the scarcity of suitable cadaveric organs), multicentre, randomized controlled trials are needed to determine the optimal approach for treatment of HCV infection in this population.

In tissue and organ transplantation, it is of great importance to avoid the transmission of blood-borne viruses to the recipient. While serologic testing for anti-human immunodeficiency virus (HIV)-1 and -2, anti-hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg), anti-hepatitis B core antigen (HBc), and Treponema pallidum infection is mandatory, there is until now in most countries no explicit demand for nucleic acid amplification testing (NAT) to detect HIV, hepatitis B virus (HBV), and HCV infection. After a review of reports in the literature on viral transmission events, tissue-specific issues, and manufacturing and inactivation procedures, we evaluated the significance of HIV, HCV, and HBV detection using NAT  in  donors of various types of tissues and compared our results with the experiences of blood banking organizations. There is a significant risk of HIV, HCV, and HBV transmission by musculoskeletal tissues because of their high blood content and the high donor-recipient ratio. If no effective virus inactivation procedure for musculoskeletal tissue is applied, donors should be screened using NAT  for  HIV, HCV, and HBV. Serologically screened cardiovascular tissue carries a very low risk of HIV, HCV, or HBV transmission. Nevertheless, because effective virus inactivation is impossible (retention of tissue morphology) and the donor-recipient ratio may be as high as 1:10, we concluded that NAT  should be performed for HIV, HCV, and HBV as an additional safety measure. Although cornea allografts carry the lowest risk of transmitting HIV, HCV, and HBV  owing to corneal physiology, morphology, and the epidemiology of corneal diseases, NAT  for  HCV should still be performed. If the NAT  screening of a donor for HIV, HCV, and HBV is negative, quarantine storage of the donor tissue seems dispensable. In view of numerous synergistic effects with transfusion medicine, it would be advantageous for tissue banks to cooperate with blood bank laboratories in performing virological tests.

The association between hepatitis C virus (HCV) infection and cerebrovascular disease remains controversial. This study aimed to assess the risk of lethal cerebrovascular diseases associated with chronic HCV infection.

In this community-based prospective cohort study, 23 665 residents (aged 30 to 65 years) were enrolled in 1991 to 1992. They were personally interviewed using structured questionnaires and provided blood samples for various serological and biochemical tests at study entry. Serum HCV RNA level and HCV genotype were tested for participants seropositive for antibodies against HCV (anti-HCV). Deaths from cerebrovascular disease during follow-up were ascertained by computerized linkage with National Death Certification profiles from 1991 to 2008 (International Classification of Diseases, 9th Revision 430 to 438). Multivariate-adjusted hazard ratio with 95% CI was estimated for each risk predictor.

There were 255 cerebrovascular deaths during 382 011 person-years of follow-up. The cumulative risk of cerebrovascular deaths was 1.0% and 2.7% for seronegatives and seropositives of anti-HCV, respectively (P<0.001). The hazard ratio (95% CI) of cerebrovascular death was 2.18 (1.50 to 3.16) for anti-HCV seropositives after adjustment for several conventional risk factors of cerebrovascular disease. Compared with participants seronegative for anti-HCV as the referent, the multivariate-adjusted hazard ratio (95% CI) was 1.40 (0.62 to 3.16), 2.36 (1.42 to 3.93), and 2.82 (1.25 to 6.37), respectively, for anti-HCV-seropositive participants with undetectable, low, and high serum levels of HCV RNA (P<0.001 for trend). However, no significant association was observed between HCV genotype and cerebrovascular death.

Chronic HCV infection is an independent risk predictor of cerebrovascular deaths showing a biological gradient of cerebrovascular mortality with increasing serum HCV RNA level.

With improved immunosuppressive regimens, transplantation techniques, and postoperative care, heart transplantation (HTx) has been established as a definite therapy for end-stage heart disease. Because of a donor shortage, we have accepted marginal individuals. In this study, we identified donor-related factors influencing survival after HTx by retrospective analysis of recipient data after primary HTx from February 2002 to December 2006. The Cox regression model was used to examine the effects of the following variables on survival of 112 heart transplant recipients: demographic data of gender, age, body weight, donor-recipient body weight ratio; history of smoking, alcohol drinking, diabetes mellitus, hypertension, hepatitis B surface antigen, anti-hepatitis C virus antibody; donor condication before transplantation including catecholamine doses, hypotension, cardiopulmonary resuscitation, creatine MB isoenzyme of creatine kinase (CK-MB), tropinin I, and cold ischemic time of the allograft. Catecholamines and smoking showed significant influences on HTx survival. In our series, the percentage of donors receiving inotropic support before donation was 88% (n = 99), and the percentage of donors with a history of smoking was 25% (n = 28). There was no influence of donor status of diabetes, hypertension, or hepatitis B or C infection on postoperative survival. Our results showed that inotropic support of and a history of smoking by the donor were significant factors influencing posttransplant survival.

Generally accepted donor criteria for heart transplantation limit allografts from donors within approximately 20% to 30% of the recipient's weight. We analyzed the impact of donor-to-recipient weight ratio on survival after heart transplantation.

Adult heart transplant recipients reported to the United Network for Organ Sharing from 1999 to 2007 were divided into 3 groups based on donor-to-recipient weight ratio: <0.8, 0.8 to 1.2, and >1.2. Kaplan-Meier methodology was used to estimate survival. Propensity-adjusted Cox regression modeling was used to analyze predictors of mortality. A total of 15 284 heart transplant recipients were analyzed; 2078 had weight ratio of <0.8, 9684 had 0.8 to 1.2, and 3522 had >1.2. Kaplan-Meier survival was not statistically different between groups at 5 years (P=0.26). Among patients with weight ratio <0.8, 5-year survival was lower for recipients with high pulmonary vascular resistance (>4 Woods units; P=0.02). Among recipients with high pulmonary vascular resistance, 5-year survival was similar for those with weight ratio 0.8 to 1.2 and >1.2 (P=0.44). Furthermore, male recipients with elevated pulmonary vascular resistance who received hearts from female donors had a significantly worse survival than males who received hearts from male donors (P=0.01). Propensity-adjusted multivariable analysis demonstrated that weight ratio <0.8 did not predict mortality (hazard ratio, 1.09; 95% CI, 0.94 to 1.27; P=0.21). Five-year survival after propensity matching was not statistically different between those with weight ratio <0.8 versus >/=0.8 (P=0.37).

Weight ratio did not predict mortality after heart transplantation. However, recipients with elevated pulmonary vascular resistance who received undersized hearts had poor survival. Furthermore, in the setting of high pulmonary vascular resistance, male recipients who received hearts from female donors had worse survival than those who received hearts from male donors. Extending donor criteria to include undersized hearts in select recipients should be considered.

Hospital-based studies suggest that hepatitis C virus (HCV) infection causes frequent cirrhosis, hepatocellular carcinoma, and mortality, but epidemiologic studies have shown less morbidity and mortality. The authors performed a retrospective cohort study of 10,259 recombinant immunoblot assay-confirmed, HCV antibody-positive (HCV+), allogeneic blood donors from 1991 to 2002 and 10,259 HCV antibody-negative (HCV-) donors matched for year of donation, age, gender, and Zone Improvement Plan Code (ZIP Code). Vital status through 2003 was obtained from the US National Death Index, and hazard ratios with 95% confidence intervals were calculated by survival analysis. After a mean follow-up of 7.7 years, there were 601 (2.92%) deaths: 453 HCV+ and 148 HCV- (hazard ratio (HR) = 3.13, 95% confidence interval (CI): 2.60, 3.76). Excess mortality in the HCV+ group was greatest in liver-related (HR = 45.99, 95% CI: 11.32, 186.74), drug- or alcohol-related (HR = 10.81, 95% CI: 4.68, 24.96), and trauma/suicide (HR = 2.99, 95% CI: 2.05, 4.36) causes. There was also an unexpected increase in cardiovascular mortality among the HCV+ donors (HR = 2.21, 95% CI: 1.41, 3.46). HCV infection is associated with a significant, threefold increase in overall mortality among former blood donors, including significantly increased mortality from liver and cardiovascular causes. High rates of mortality from drug/alcohol and trauma/suicide causes are likely due to lifestyle factors and may be at least partially preventable.

Clinical success with modern heart transplantation (HT) has led to the development of an alternate list (AL) HT strategy, matching marginal cardiac allografts with recipients who do not meet standard criteria for HT. Marginal allografts may be at an increased risk for primary graft dysfunction (PGD), the leading cause of early mortality after HT.(1) The incidence of PGD in AL HT relative to standard list (SL) HT has not been evaluated, and may contribute to the greater mortality associated with AL HT.(2) The objective of this study was to determine the incidence of and predictors for PGD.

A retrospective analysis was performed on 260 consecutive adult patients undergoing either SL HT (n=207) or AL HT (n=53) at our institution from 1/2000 to 1/2005. PGD was defined by requirement for mechanical circulatory support immediately post-HT or more broadly as the need for either mechanical support or high-dose inotrope (epinephrine > or = 0.07 microg/kg/min). Donor hearts allocated to AL recipients were turned down for SL HT for reasons that included coronary disease, left ventricular dysfunction or hypertrophy, and high-dose inotropic requirement. AL HT recipients were significantly older, with a higher proportion of diabetes mellitus and ischemic cardiomyopathy. Both groups experienced a similar incidence of significant rejection, but overall mortality was higher in the AL HT group. (2) The incidence of PGD did not differ between AL and SL HT recipients. Pre-transplant VAD and prolonged total ischemic times (> or = 4.5 hours) were independent predictors of PGD.

Select marginal donor hearts used in AL HT do not have an increased incidence of PGD. Pre-transplant VAD and prolonged ischemic times are more important determinants of PGD. These data support continued aggressive utilization of marginal donor hearts in AL HT.

Heart transplantation represents a significant life-saving and increased quality-of-life intervention for patients with refractory cardiac failure. Successful transplantation requires continuous immunosuppression to avoid immune rejection. Unfortunately, persistent viral infections in donors may be transmitted to recipients in the process of heart transplantation. With the severe shortage of available organs and significant waiting list mortality there is a rationale for considering use of organs from donors with evidence of prior hepatitis B and/or hepatitis C infection.

Published literature articles were searched using Medline, PaperChase and further review of references in relevant articles on issues related to hepatitis B and hepatitis C and heart transplantation.

Donor and recipient testing for hepatitis B and hepatitis C is important for relative risk assessment. Nucleic acid testing for hepatitis B DNA and hepatitis C RNA represent emerging technologies, which may add valuable information to traditional serologic testing.

Heart transplant recipient risk may be modified by vaccination against hepatitis B before transplantation. There is currently no available vaccine for hepatitis C. Recently described effective treatments for hepatitis B and hepatitis C provide further rationale for reconsideration of using hearts from donors with evidence of hepatitis B and/or hepatitis C infection.

Case reports and unblinded studies suggest that human immunodeficiency virus (HIV) disease is associated with QT prolongation and torsade de pointes ventricular tachycardia. Hepatitis C coinfection is common in patients with HIV disease, and cirrhosis is also associated with QT prolongation. We therefore undertook a systematic analysis of the role of liver injury, nutritional state, and coinfection with hepatitis C in the etiology of QT prolongation in HIV disease.

We performed a blinded, controlled retrospective cohort study of 1648 patients over a 3-year period at a university-affiliated municipal hospital. All electrocardiograms were included if patients with HIV disease had measurements of CD4 count and viral load within 3 months and serum electrolytes within 30 days (n = 816). Control subjects were chosen randomly from the general medicine service (n = 832). QT interval was measured in lead II and corrected for heart rate by Bazett's formula (QTc).

QTc was slightly but significantly longer in patients with HIV disease than in controls (443 +/- 37 vs 436 +/- 36 milliseconds, P < .001). Patients with hepatitis C had more pronounced QTc prolongation (452 +/- 41 vs 437 +/- 35 milliseconds, P < .001). CD4 count, HIV viral load, and HIV medications had no effect on QTc. When patients with hepatitis C were excluded from the analysis, there was no statistical difference between patients with HIV disease and controls (438 +/- 34 vs 436 +/- 36 milliseconds, P = .336). Multiple linear regression revealed that both HIV and hepatitis C infection predicted QTc prolongation, as did age, female sex, history of hypertension, use of opiates, low serum K+ and albumin, and high AST. Hepatitis C coinfection nearly doubled the risk of QTc of 470 milliseconds or greater in patients with HIV disease (29.6% vs 15.8%, P < .001).

Human immunodeficiency virus and hepatitis C infections both independently prolong QTc. Coinfection with hepatitis C greatly increases the likelihood of clinically significant QTc prolongation in patients with HIV disease.