This 30th adult heart transplant report is based on data submitted on 110,486 heart transplants in recipients of all ages (including 99,008 adults) by 407 centers worldwide since 1982 through June 30, 2012, with follow-up until June 30, 2012. Summary data are provided for the entire cohort of patients, whereas a number of additional analyses focus on cohorts who received transplants more recently. Detailed data analyses can be viewed in the International Society for Heart and Lung Transplantation (ISHLT) Registry slide sets available online (www.ishlt.org/registries). The report is divided into several sections:1.Baseline donor, recipient, and transplant center demographics and characteristics;2.Survival after heart transplantation according to donor and recipient characteristics;3.Immunosuppression and allograft rejection;4.Post-transplant morbidity and quality of life;5.Multivariable analyses where the independent relationships between donor and recipient characteristics and post-transplant mortality and morbidity are examined; and—new for this year—6.Focus theme, where donor age and recipient age are examined in detail. In addition to the standard overview of donor and recipient characteristics and outcomes, this year’s report and online slide set provide an in-depth analysis of age as a specific contemporary focus theme. Numerous analyses are presented that address demographic trends and the role of age in recipient and donor organ selection and their relationship to outcomes. The 6 sections are paralleled with additional and extended analyses presented in the online slide sets. Donor and recipient baseline demographics, characteristics, and immunosuppressive treatments, as well as outcomes in terms of mortality and causes of death, morbidity, hospitalization, and functional status and quality of life, are summarized using numbers and percentages or medians with 5th and 95th percentiles. Survival and event-free survival rates were calculated using the Kaplan-Meier method1Kaplan E. Meier P. Nonparametric estimation from incomplete observations.J Am Stat Assoc. 1957; 53: 457-481Crossref Scopus (47906) Google Scholar and compared using pair-wise and overall log-rank tests. Adjustments for multiple comparisons were done using Scheffe’s method. Many outcomes analyses are unadjusted and should thus be interpreted with caution. Multivariable analyses are presented in section 5 (multivariable analysis) and in the latter parts of section 6 (age analysis). Multivariable analyses were performed using Cox proportional hazard regression analysis.2Cox D. Oakes D. Analysis of survival data. Chapman and Hall, London1984Google Scholar Results of the multivariable analyses are reported as hazard ratios (HR) with corresponding 95% confidence intervals (CIs), and/or p-values. A HR significantly > 1 for a factor indicates that the factor is associated with an increased likelihood of the event occurring. Conversely, a HR < 1 indicates that the event is less likely to occur when that factor is present. For missing data in continuous data fields, multiple imputation was used.3Harrell Jr, F. Regression modeling strategies. Springer, Berlin2001Crossref Google Scholar This method produces an estimated value for the missing value based on the other characteristics of the patient, donor, and/or transplant. The algorithm is performed multiple times, producing new estimates for the missing information. Models are fit on each imputed data set and then combined to produce a final set of estimates from which the relative HR, 95% CIs, and p-values are obtained. A total of 4,096 heart transplants (including 3,529 adult) from 249 centers were performed in 2011 and reported to the ISHLT. After a decline between 1993 and 2004, the number of reported heart transplants remained stable for several years and now appears to be slowly increasing, particularly in North America and in other regions (Figure 1). The Registry captures an estimated 66% of worldwide heart transplants, and ascertaining whether these demographic trends are reflective of the overall worldwide heart transplant volume is difficult. The volume of transplants performed at different centers varies considerably (Figure 2). Most centers (78%) perform fewer than 20 heart transplants per year and are responsible for 49% of all transplant volume.Figure 2Average annual center heart transplant volume (all recipient ages) for transplants from 2006 to June 2012. Columns show the number of centers performing the number of transplants on the x-axis (eg, 109 centers perform 10–19 heart transplants per year) and the curves show the percentages of all transplants performed at centers performing the number of transplants listed on the x-axis (eg, 37% of all heart transplants are performed by the 109 centers).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Donor demographics are presented in Table 1. In the most recent cohort, 69% of donors are male, and female donor-to-male recipient transplantation was less frequent than previously (17%). Donor diabetes mellitus (3.0%) and hypertension (14%) are rare but increasing. The leading cause of donor death is head trauma (46%). Donor age is addressed in detail in section 6.Table 1Donor and Recipient Characteristics for Adult Heart TransplantsVariablesaContinuous factors are expressed as median (5th–95th percentiles).1992–20002001–20052006–6/2012(n = 37,146)(n = 17,183)(n = 22,318)p-valueAge, years Recipient54.0 (28.0–65.0)54.0 (26.0–66.0)54.0 (24.0–67.0)<0.0001 Donor31.0 (15.0–54.0)33.0 (16.0–55.0)34.0 (17.0–56.0)<0.0001Donor and recipient age difference, years–19.0 (–44.0 to 7.0)–17.0 (–43.0 to 10.0)–16.0 (–43.0 to 12.0)<0.0001Recipient Weight, kg75.0 (51.0–102.0)77.6 (53.0–106.6)79.4 (53.1–110.0)<0.0001 Height, cm173.0 (157.0–188.0)174.0 (157.5–188.0)175.0 (157.4–188.0)0.0042 Body mass index, kg/m222.7 (19.5–31.7)24.2 (19.6–33.1)24.4 (19.6–34.3)<0.0001Donor Weight, kg75.0 (52.0–103.3)bBased on April 1994–2000 transplants.76.8 (55.0–108.8)79.4 (56.7–113.0)<0.0001 Height, cm175.0 (155.0–188.0)bBased on April 1994–2000 transplants.175.3 (158.0–189.0)175.0 (158.0–190.0)<0.0001 Body mass index, kg/m224.2 (18.8–32.9)bBased on April 1994–2000 transplants.24.8 (19.5–34.4)25.5 (19.9–36.4)<0.0001Gender (male), % Recipient817876<0.0001 Donor6869690.1103Male recipient/female donor, %211917<0.0001Female recipient/male donor, %9.29.79.90.0055Diabetes mellitus, % Recipient13bBased on April 1994–2000 transplants.2025<0.0001 Donor1.6bBased on April 1994–2000 transplants.2.03.0<0.0001Recipient, % Prior history of dialysis3.0bBased on April 1994–2000 transplants.4.34.2<0.0001 Amiodarone use (U.S. only)22bBased on April 1994–2000 transplants.2931<0.0001Cigarette history, % Recipient…47cBased on July 2004–2005 transplants460.8536 Donor38bBased on April 1994–2000 transplants.2919<0.0001Hypertension, % Recipient35bBased on April 1994–2000 transplants.3845<0.0001 Donor11bBased on April 1994–2000 transplants.1114<0.0001Recipient, % Prior cardiac surgery…39cBased on July 2004–2005 transplants46<0.0001 Peripheral vascular disease3.8bBased on April 1994–2000 transplants.3.22.90.0002 Previous malignancy3.3bBased on April 1994–2000 transplants.4.56.6<0.0001 COPD3.2bBased on April 1994–2000 transplants.3.24.3<0.0001Ischemic time, hours2.9 (1.3–4.8)3.1 (1.5–5.0)3.3 (1.6–5.1)<0.0001Most recent PRA > 10%dPRA was collected as a single percentage outside of U.S. Until mid-2004, PRA was collected in U.S. as a single percentage. After this date, PRA was collected separately for class I and class II. Overall7.78.9eBased on U.S. 2001–June 2004 transplants and non-U.S. 2001–2005 transplants.13.8fBased on non-U.S. transplants.<0.0001 Class I......14.4gBased on U.S. transplants.... Class II......9.6gBased on U.S. transplants....Creatinine at transplant, mg/dl1.2 (0.7–2.5)1.2 (0.7–2.4)1.2 (0.7–2.3)<0.0001Peripheral vascular resistance, Wood units2.2 (0.4–6.1)bBased on April 1994–2000 transplants.2.0 (0.3–5.6)2.1 (0.3–5.5)<0.0001HLA mismatches, %4.34.43.8 0–24040380.0003 3–4555558 5–67.78.9cBased on July 2004–2005 transplants14dPRA was collected as a single percentage outside of U.S. Until mid-2004, PRA was collected in U.S. as a single percentage. After this date, PRA was collected separately for class I and class II.Diagnosis, % Cardiomyopathy464854<0.0001 Coronary artery disease464337 Valvular3.93.52.8 Retransplant1.92.22.5 Congenital1.82.72.9 Other causes0.40.60.9Donor cause of death, % Head trauma465546<0.0001 Stroke293324 Other251330Pre-operative support (multiple items may be reported), % Hospitalized at time of transplant614844<0.0001 On intravenous inotropes56bBased on April 1994–2000 transplants.4742<0.0001 Left ventricular assist device12hBased on November 1999–2000 transplants.1728<0.0001 Intra-aortic balloon pump6.46.76.10.1650 Right ventricular assist device...5.0iBased on 2005 transplants.3.70.0055 Ventilator3.33.22.70.0092 Total artificial heart0.1hBased on November 1999–2000 transplants.0.11.0<0.0001 ECMO0.3jBased on May 1995–2000 transplants.0.51.1<0.0001COPD, chronic obstructive pulmonary disease; ECMO, extracorporeal membrane oxygenation; HLA, human leukocyte antigen; PRA, panel reactive antibody.a Continuous factors are expressed as median (5th–95th percentiles).b Based on April 1994–2000 transplants.c Based on July 2004–2005 transplantsd PRA was collected as a single percentage outside of U.S. Until mid-2004, PRA was collected in U.S. as a single percentage. After this date, PRA was collected separately for class I and class II.e Based on U.S. 2001–June 2004 transplants and non-U.S. 2001–2005 transplants.f Based on non-U.S. transplants.g Based on U.S. transplants.h Based on November 1999–2000 transplants.i Based on 2005 transplants.j Based on May 1995–2000 transplants. Open table in a new tab COPD, chronic obstructive pulmonary disease; ECMO, extracorporeal membrane oxygenation; HLA, human leukocyte antigen; PRA, panel reactive antibody. As shown in previous reports,4Stehlik J. Edwards L.B. Kucheryavaya A.Y. et al.The registry of the International Society for Heart and Lung Transplantation: 29th official adult heart transplant report—2012.J Heart Lung Transplant. 2012; 31: 1052-1064Abstract Full Text Full Text PDF PubMed Scopus (445) Google Scholar, 5Stehlik J. Edwards L.B. Kucheryavaya A.Y. et al.The Registry of the International Society for Heart and Lung Transplantation: twenty-eighth adult heart transplant report—2011.J Heart Lung Transplant. 2011; 30: 1078-1094Abstract Full Text Full Text PDF PubMed Scopus (438) Google Scholar cardiomyopathy and coronary artery disease (CAD) are the leading underlying heart disease diagnoses, with the cardiomyopathy proportion increasing over time (Table 1). There are several changes over time that parallel changes in the overall population and/or appear to reflect a willingness to transplant higher risk patients. These include increases in retransplant and congenital heart disease, now approaching 3% of all transplants each, increasing proportions of sensitized recipients, and increasing comorbidity in the form of diabetes mellitus (25%), hypertension (45%), previous malignancy (6.6%), and previous cardiac surgery (46%; Table 1). Use of mechanical circulatory support (MCS) to bridge patients to transplant, predominantly with left ventricular assist devices (LVADs), continues to increase, and was 37% in 2011 (Figure 3). For all 103,299 pediatric and adult heart transplants between 1982 and June 2011, 1-year survival is 81%, and 5-year survival is 69%, with median survival of 11 years for all and 13 years for those surviving the first year. We have previously reported that survival in adult heart transplant recipients has continued to improve over the years.4Stehlik J. Edwards L.B. Kucheryavaya A.Y. et al.The registry of the International Society for Heart and Lung Transplantation: 29th official adult heart transplant report—2012.J Heart Lung Transplant. 2012; 31: 1052-1064Abstract Full Text Full Text PDF PubMed Scopus (445) Google Scholar However, the most recent cohort of patients who received transplants in 2006 through June 2011 demonstrates survival similar to patients who received transplants in 2002 to 2005, with unadjusted 1-year survival of 84% (Figure 4). In patients surviving past 1 year after transplant, no significant improvement in survival was seen in the last cohort (2006 to June 2011) over 1-year survivors who received transplants in 1992 to 2001 and in 2002 to 2005. The estimated 5-year survival conditional on 1-year survival is 85% (online slide set). Section 5 (multivariable analyses) provides additional insights into survival after transplant in the most recent era. Age is an important determinant of survival and is addressed in detail in the online slide set and in section 6 below. A heart disease diagnosis exerts time-dependent effects on post-transplant survival. One-year survival is highest in patients who receive transplants for cardiomyopathy and CAD and lowest in congenital heart disease, retransplant, and valvular cardiomyopathy (Figure 5A). However, long-term survival is highest in those who receive transplants for congenital heart disease and cardiomyopathy (Figure 5B). In patients who survive the first year after transplant, survival is highest in those who receive transplants for congenital heart disease (Figure 5C). Retransplant is associated with a distinctly worse prognosis, with 1-year survival of 70% compared with 83% for cardiomyopathy, for transplants since 1982. LVAD use pre-transplant, potentially conferring worse post-transplant prognosis, appears less concerning in the era of modern continuous flow-devices, although the need for combined right ventricular assist device (RVAD) and LVAD remains associated with considerably worse post-transplant survival (Figure 6). Additional predictors of mortality are addressed in the online slides and section 5 (multivariable analyses). The overall distribution of the leading causes of death has remained without major change since 1994, but the incidence of cause-specific mortality changes with time after transplant: in the first 3 years, graft failure and infection predominate, whereas after 3 to 5 years, malignancy, cardiac allograft vasculopathy (CAV), and renal failure become progressively more important. Acute rejection accounts for no more than 11% of deaths (in Years 1 to 3), but acute and chronic immune injury are likely important contributors to graft failure, which remains a leading cause of death throughout follow-up (Figure 7). The use of immunosuppressive induction is decreasing and was 47% overall in the first 6 months of 2012. Interleukin-2 receptor (IL-2R) antagonists had become the most frequently used induction agents, in 28% of all transplants, whereas polyclonal antilymphocytic antibodies were used in 19% and alemtuzumab in 1%. OKT3 is no longer available for clinical use in most countries. There is a continued trend for use of tacrolimus as the preferred calcineurin inhibitor (81% at 1 year for January–June 2012 follow-up) and mycophenolate mofetil (MMF)/mycophenolic acid (MPA) as the preferred cell cycle inhibitor (85%). Compared with 2005, prednisone use is declining (66% at 1 year), and use of mammalian target of rapamycin (mTOR) inhibitors is steady (13%). Between Years 1 and 5 after transplant, the use of prednisone decreases and the use of mTOR inhibitors doubles. With improved immunosuppression, the incidence of any rejection between discharge and 1 year has decreased from 32% in 2004 to 25% in 2010. Furthermore, with the recognition that mild cellular rejection may not need acute treatment,6Stewart S. Winters G.L. Fishbein M.C. et al.Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection.J Heart Lung Transplant. 2005; 24: 1710-1720Abstract Full Text Full Text PDF PubMed Scopus (1338) Google Scholar the incidence of treated rejection has decreased from 25% in 2004 to 14% in 2010 (Table 2). Survival in recipients with no rejection and in those with untreated rejection is similar. Survival in patients with treated rejection is worse, however, compared with both former groups (Figure 8). The Registry does not collect data on the type or severity of rejection; therefore analysis of the increasingly recognized antibody-mediated rejection cannot be performed, and the worse outcomes with treated rejection may be confounded by greater severity.Table 2Rejection Between Transplant Discharge and 1-Year Follow-up for Adult Heart RecipientsTransplant yearRejectionTreatedUntreatedNo rejectionTotalNo. (%)No. (%)No. (%)No. (%)2004393 (25)106 (7)1,054 (68)1,553 (100)2005380 (23)96 (6)1,181 (71)1,657 (100)2006368 (21)157 (9)1,200 (70)1,725 (100)2007312 (18)199 (11)1,229 (71)1,740 (100)2008258 (16)196 (12)1,208 (73)1,662 (100)2009278 (16)242 (14)1,212 (70)1,732 (100)2010267 (14)205 (11)1,430 (75)1,902 (100) Open table in a new tab Hypertension, hyperlipidemia, renal dysfunction, diabetes, and CAV are the most common post-transplant morbidities (Table 3). Of these, renal dysfunction and CAV, in addition to graft failure, infection, acute rejection, and malignancy, described above, are the important direct contributors to mortality.Table 3Cumulative Morbidity Rates in Survivors of Adult Heart TransplantsWithin 1 YearTotal with known responseWithin 5 YearsTotal with known responseWithin 10 YearsTotal with known responseFollow-upsOutcome(%)(No.)(%)(No.)(%)(No.)January 1995–June 2012HypertensionaData are not available 10 years post-transplant.7226,8529212,534…Renal dysfunction2629,3015214,680684,879 Abnormal creatinine ≤ 2.5 mg/dl183338 Creatinine > 2.5 mg/dl61520 Chronic dialysis1.52.96.0 Renal transplant0.31.23.6Hyperlipidemiaa6028,1028813,876…DiabetesaData are not available 10 years post-transplant.2629,2893814,470…CAV826,4803010,651502,815CAV, Cardiac allograft vasculopathy.a Data are not available 10 years post-transplant. Open table in a new tab CAV, Cardiac allograft vasculopathy. In patients surviving to the respective follow-up, CAV affects 8% by Year 1, 30% by Year 5, and 50% by Year 10 after transplant. Renal dysfunction affects 26%, 52%, and 68% by Years 1, 5, and 10, respectively. Any malignancy affects 28%, skin malignancy affects 20%, and lymphoma affects 2% by 10 years after transplant. Rejection and infection are important contributors to hospitalization, but 56% of survivors are free from hospitalization during the first year after transplant and more than 70% between 2 and 3 years and between 4 and 5 years. The independent roles of post-transplant morbidities are examined in section 5: Multivariable analyses, and their relation to age in section 6: Age analyses. Compared with advanced heart disease before transplant, heart transplantation in appropriately selected candidates is associated with dramatic improvements in survival and quality of life.7Mehra M.R. Kobashigawa J. Starling R. et al.Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006.J Heart Lung Transplant. 2006; 25: 1024-1042Abstract Full Text Full Text PDF PubMed Scopus (751) Google Scholar The Registry data show that at 1 to 3 years after transplant, functional status remains very favorable, with the proportion of survivors capable of normal activity (Karnofsky score 80%–100%) approaching 90%. In this context, the extent of employment in heart transplant recipients appears disproportionately low, with 35% and 46% of recipients aged 25 to 60 years at the time of follow-up working at 1 and 3 years after transplant, respectively. It is possible that decisions regarding return to gainful employment in these patients may be influenced by factors beyond their functional status, such as employer-based health insurance eligibility and affordability. Unadjusted mortality and morbidity rates are described in the sections above. To determine the independent contributors to mortality and morbidity, we performed multivariable proportional hazards regression analyses for transplants that took place in more recent eras, using donor and recipient pre-transplant and recipient post-transplant characteristics as independent variables. Variables associated with risk of 1-, 5-, and 15-year mortality are reported in Table 4. Numerous additional multivariable data are shown in the online slide set, and the risk associated with age is addressed subsequently in section 6.Table 4Risk Factors for Mortality for Adult Heart TransplantsModelVariableNo.HR (95% CI)p-value1 year mortality, N = 10,473 (January 2006–June 2011)Temporary circulatory supportaTemporary circulatory support includes extracorporeal membrane oxygenation and temporary pulsatile flow devices.1632.80 (2.04–3.83)<0.0001Total artificial heart982.26 (1.43–3.55)0.0004Diagnosis: congenital vs cardiomyopathy2662.21 (1.62–3.02)<0.0001Recipient history of dialysis2741.78 (1.39–2.28)<0.0001Recipient on ventilator at time of transplant3021.66 (1.29–2.15)0.0001Chronic pulsatile-flow device9521.56 (1.27–1.92)<0.0001Chronic continuous-flow device1,8461.50 (1.24–1.81)<0.0001Previous transplant3111.46 (1.08–1.96)0.0125Male recipient/female donor vs male recipient/male donor1,5691.32 (1.12–1.55)0.0009Recipient with infection requiring IV drug therapy ≤ 2 weeks before transplant1,0631.28 (1.08–1.52)0.0043Previous transfusion2,2681.25 (1.08–1.45)0.0034Not hospitalized just before transplant5,7420.87 (0.77–0.99)0.0372Ventricular remodeling1,8350.80 (0.67–0.95)0.0107Transplant year: 2006 vs 2010/20111,9131.40 (1.17–1.68)0.0002Transplant year: 2007 vs 2010/20111,8821.32 (1.10–1.58)0.0031Transplant year: 2008 vs 2010/20111,7991.26 (1.05–1.51)0.0146The continuous variables associated with increased or decreased risk of mortality were recipient age, recipient height, BMI ratio, donor age, transplant center volume, ischemia time, recipient pre-transplant bilirubin and creatinine, panel reactive antibody class II, and recipient systolic PAP.5-year mortality, N = 10,332 (January 2002–June 2007)Temporary circulatory supportaTemporary circulatory support includes extracorporeal membrane oxygenation and temporary pulsatile flow devices.1602.23 (1.72–2.90)<0.0001Total artificial heart371.77 (1.01–3.08)0.0442Continuous-flow device or VAD with type unknown3491.71 (1.16–2.52)0.0065Recipient history of dialysis3261.70 (1.43–2.03)<0.0001Diagnosis: congenital vs cardiomyopathy2841.46 (1.16–1.83)0.0012Recipient on ventilator at time of transplant3011.37 (1.11–1.68)0.0034Female recipient with prior pregnancy; male donor vs male recipient/male donor7521.33 (1.11–1.58)0.0017Panel reactive antibody > 10%6851.25 (1.08–1.45)0.0030Recipient hepatitis B core (+)4041.22 (1.01–1.47)0.0388Recipient with infection requiring IV drug therapy ≤ 2 weeks before transplant1,1171.22 (1.08–1.37)0.0018HLA mismatches at A locus (per locus), No.1.18 (1.03–1.35)0.0196 0 A MM677 1 A MM4,910 2 A MM4,745Donor cause of death: anoxia vs head trauma9561.17 (1.02–1.33)0.0243Recipient history of diabetes2,2751.15 (1.04–1.26)0.0049Chronic pulsatile-flow device1,7301.15 (1.02–1.29)0.0213Diagnosis: coronary artery disease vs cardiomyopathy4,5871.12 (1.02–1.23)0.0206Ventricular remodeling9280.85 (0.73–0.99)0.0415The continuous variables associated with increased or decreased risk of mortality were recipient age, recipient height, recipient BMI, donor age, donor BMI, transplant center volume, ischemia time, recipient pre-transplant bilirubin and creatinine, recipient PVR, and recipient diastolic PAP.15 year mortality, N = 11,055 (January 1992–June 1997)Retransplant2681.67 (1.44–1.94)<0.0001Diagnosis: not cardiomyopathy, coronary artery disease, congenital heart disease, valvular heart disease, or retransplant vs cardiomyopathy731.66 (1.25–2.22)0.0006On ventilator3381.33 (1.16–1.52)<0.0001Recipient hepatitis B core (+)2651.27 (1.09–1.47)0.0024Panel reactive antibody > 20%5341.21 (1.08–1.34)0.0006Transplant year: 1992 vs 1996/19971,8811.17 (1.08–1.27)<0.0001Female recipient/male donor vs male recipient/male donor1,2181.16 (1.05–1.28)0.0040On VAD at transplant7771.16 (1.05–1.27)0.0039Diagnosis: coronary artery disease vs cardiomyopathy5,5061.15 (1.09–1.22)<0.0001Transplant year: 1993 vs. 1996/19972,0171.15 (1.06–1.24)0.0005Male recipient/female donor vs. male recipient/male donor2,2601.14 (1.05–1.24)0.00202 mismatches at DR locus6,7741.11 (1.06–1.17)<0.0001Transplant year: 1994 vs 1996/19972,0721.08 (1.00–1.16)0.0417The continuous variables associated with increased or decreased risk of mortality were recipient age, difference in recipient and donor age, recipient BMI, donor height, transplant center volume, ischemia time, and recipient pre-transplant creatinine,BMI, body mass index; CI, confidence interval; HLA, human leukocyte antigen; HR, hazard ratio; IV, intravenous; PAP, pulmonary artery pressure; PVR, peripheral vascular resistance; VAD, ventricular assist device.a Temporary circulatory support includes extracorporeal membrane oxygenation and temporary pulsatile flow devices. Open table in a new tab BMI, body mass index; CI, confidence interval; HLA, human leukocyte antigen; HR, hazard ratio; IV, intravenous; PAP, pulmonary artery pressure; PVR, peripheral vascular resistance; VAD, ventricular assist device. For mortality up to 1 year, only pre-transplant data are considered. Important risk factors include congenital heart disease and retransplant, history of dialysis and transfusions, infection, ventilator support, and hospitalization before transplant (Table 4). In univariable analysis, male donor-to-female recipient transplants fared worse than other combinations, but in multivariable analysis, male recipients fared worse when receiving a female vs a male donor organ, suggesting a consequence of under-sizing. Several continuous variables were associated with essentially linear increases in risk, such as higher serum creatinine and bilirubin, percentage of class II panel reactive antibody, and lower donor/recipient ratio of body mass index. Other continuous variables exhibited U-shaped or non-linear patterns with higher risk at lower and higher recipient ages. Allograft ischemic time conferred increased risk only beyond 200 minutes. Durable continuous-flow devices, total artificial heart, and temporary circulatory support, including extracorporeal membrane oxygenation (ECMO), are increasingly used and are associated with progressively increased risk. However, the multivariable analysis is based on data registered not at device implant but at the time of transplant, when organ failure (affecting the multivariable model) has often been reversed.8Russell S.D. Rogers J.G. Milano C.A. et al.Renal and hepatic function improve in advanced heart failure patients during continuous-flow support with the HeartMate II left ventricular assist device.Circulation. 2009; 120: 2352-2357Crossref PubMed Scopus (156) Google Scholar Patients supported by a device may still have more underlying morbidity and risk at the time of transplant; nevertheless, the model may not account for it. The effect of MCS on transplant candidacy and survival on the waiting list should also be considered, and this report alone should not guide decisions regarding pre-transplant MCS implantation. The presented risk profiles also shed light on recent trends in survival. In univariable analysis (Figure 4), early survival improved up until the early 2000s but has remained unchanged thereafter. In multivariable analysis, more recent transplantation, in 2010 to 2011, is associated with lower risk, even compared with transplants performed as recently as 2008 (Table 4). Recipients with increasingly higher risk are receiving transplants (eg, age and comorbidity, section 1 above), and when this risk is adjusted for, even very recent years are associated with continued improved outcomes. Risk factors for cumulative 5-year mortality are largely similar to those for short-term mortality but also include prior pregnancy and recipient morbidities that predispose to adverse outcomes in the longer-term, such as elevated body mass index and diabetes mellitus (Table 4). To separate causes of intermediate and early mortality, we also analyzed risk factors for 5-year mortality conditional on survival to 1 year, when numerous post-transplant variables are reported to the Registry (online slide set). Several pre-transplant risk factors are no longer significant, whereas several of the post-transplant factors now included in the model are important, including non-use of calcineurin and cell cycle inhibitors (possibly a marker of complications from these drugs), as well as rejection and dialysis before discharge. Detailed long-term mortality analyses are presented in the online slide set. Data collection in earlier eras was more limited, and fewer variables are included in the models. Risk factors from the 1990s may be different from those of recent years and less applicable to contemporary risk analysis. With increasing time post-transplant, several general patterns emerge (Table 4 and online slide set). Some pre-transplant predictors, such as serum creatinine, remain but generally become less important. Consistent with the univariable analysis (Figure 5), retransplant remains an important predictor of long-term mortality, whereas congenital heart disease is no longer a risk factor in 15-year and 20-year mortality models. Gender mismatch, in both directions, and pregnancy are associated with incre
