EXPEDITED PUBLICATION
Improved Survival of Patients With End-Stage Heart Failure Listed for Heart TransplantationAnalysis of Organ Procurement and Transplantation Network/U.S. United Network of Organ Sharing Data, 1990 to 2005
Katherine Lietz, MD, PhD* and
Leslie W. Miller, MD
Cardiovascular Division, Georgetown University, Washington Hospital Center, Washington, DC.
Manuscript received March 12, 2007;
revised manuscript received April 16, 2007,
accepted April 30, 2007.
* Reprint requests and correspondence: Dr. Katherine Lietz, Center for Advanced Cardiac Care, Division of Cardiology, Columbia-Presbyterian Medical Center, PH12 Stem Rm 134, 622 West 168th Street, New York, New York 10032. (Email: KL2384{at}columbia.edu).
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Abstract
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Objectives: We sought to investigate the actual survival of patients with end-stage heart failure listed for heart transplantation (HT) in the U.S.
Background: The United Network of Organ Sharing (UNOS) reported that the mortality rates on the U.S. HT waiting list have been gradually declining. This suggests that the survival of these patients may have improved.
Methods: The survival censored on the day of HT or removal from the waiting list was calculated for 18,004 UNOS status 1 and 30,978 status 2 candidates listed in eras I (1990 to 1994), II (1995 to 1999), and III (2000 to 2005) in the U.S. The Cox proportional model was employed for multivariable analysis.
Results: The 1-year survival on the HT waiting list improved from 49.5% to 69.0% for status 1 and from 81.8% to 89.4% for status 2 candidates between eras I and III. The predictors of death within 2 months from listing of status 1 candidates included UNOS status 1A, mechanical ventilation, inotropic and intra-aortic balloon pump support, pulmonary capillary wedge pressure >20 mm Hg and serum creatinine >1.5 mg/dl, failed HT, valvular cardiomyopathy, age >60 years, Caucasian ethnicity, and weight  70 kg, as well as the lack of intracardiac cardioverter-defibrillator on the day of listing.
Conclusions: Survival of HT candidates on the waiting list has significantly improved. Survival of status 1 candidates continues to depend on urgent HT. Predictors of 2-month mortality may help identify status 1 candidates who warrant the highest priority for HT and/or mechanical circulatory support. The 1-year survival of status 2 candidates approaches outcomes of HT, thus raising the question of whether early listing of some of these patients is justified.
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Abbreviations and Acronyms
| | HT = heart transplantation | | IABP = intra-aortic balloon pump | | ICD = intracardiac cardioverter-defibrillator | | ICU = intensive care unit | | MCS = mechanical circulatory support | | PCWP = pulmonary capillary wedge pressure | | UNOS = United Network of Organ Sharing |
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Heart transplantation (HT) is the only therapy proven to provide the greatest survival benefit in patients with end-stage heart failure (1,2). However, liberal expansion of HT has been limited by a continued shortage of available donor organs. During the last 2 decades, the number of patients awaiting HT reached its historical high when 7,602 patients were listed in 1998 and only 2,211 transplants were performed (3). The continued disparity between the number of HT candidates and the limited supply of donor organs was associated with longer time spent on the national waiting list by an average HT candidate. At the end of 2005, 48% of HT candidates had spent more than 2 years on the waiting list, compared with 17% in 1993 (4).
According to the recent report of the United Network of Organ Sharing (UNOS) (3), the increasing length of time spent by an average candidate on HT waiting list did not result from a larger number of listed candidates or longer waiting times for HT. In contrary, the number of new candidates decreased from 3,877 to 2,833 and the median waiting time for HT shortened from 354 to 130 days between 1996 and 2005. These observations suggest that the survival of patients referred for HT may have substantially improved. Indeed, since the 1990s, the mortality rates on HT waiting list decreased from 227.4 per 1,000 patient-years at risk for candidates listed in 1996, to the historically lowest level of 152.3 noted for those listed in 2005 (3).
In this study, we sought to investigate the survival of 48,982 patients with advanced heart failure who were listed for HT between the years 1990 and 2005 in the U.S. The aim of the study was 2-fold: 1) to describe changes in the actual survival on the HT waiting list of UNOS status 1 and 2 candidates throughout the study period; and 2) to identify predictors of death within 2 months from listing, which would help identify status 1 and 2 HT candidates at the highest priority for allocation and/or consideration for mechanical circulatory support (MCS).
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Patients and Methods
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Study population.
Forty-nine thousand seven hundred thirty-nine adult patients (older than 18 years) were listed for HT between January 1, 1990, and January, 1 2006 in the U.S. This included 18,004 patients initially listed as UNOS status 1 and 30,978 patients initially listed as UNOS status 2. Seven hundred fifty-seven patients who were initially listed as inactive or had other status on the day of enrollment on the transplant waiting list were excluded from this analysis. The final study sample numbered 48,982 transplant candidates. All patients were followed until death or the day of the last observation on June 1, 2006.
Data source.
Patient data were obtained from the U.S. government-sponsored Scientific Registry of Transplant Recipients. The Registry collects information on all organ transplant recipients and is mandatory in the U.S. All patients were followed from time of enrollment on the HT waiting list until transplantation and/or death with the use of data forms collected by the Organ Procurement and Transplantation Network. Post-transplant information was reported at the end of the annual follow-up period and at the time of death. The date of death after HT was provided by the transplant center, and this information was supplemented by data obtained from the Social Security Administration Death Master File and the Medicare Beneficiary Database provided by the Centers for Medicare and Medicaid Services. Causes of death while on the waiting list were not reported to the Registry.
Medical urgency status.
The medical urgency for HT was assigned by the transplant physician as UNOS status 1 or status 2 on the day of registration. For the purpose of this analysis, the 2-tiered status 1 category (1A and 1B) introduced after 1999 (5) was combined into 1 UNOS status 1 category. The high urgency UNOS status 1 defines candidates who require continuous intravenous inotropes, or require MCS with intra-aortic balloon pump (IABP), left ventricular assist devices, total artificial heart, extracorporeal mechanical oxygenation, or mechanical ventilation, have life expectancy <7 days without transplant, or are considered a justified exceptional case. Status 2 candidates should meet general criteria for HT as outlined in the guidelines (2) but do not meet status 1A or 1B criteria.
Clinical information.
Candidate demographics and the most recent assessment of hemodynamics and serum creatinine were provided on the day of listing. Mechanical circulatory support was defined in this study as presence of temporary or permanent circulatory support devices on the day of listing, including right-, left-, or biventricular support devices or total artificial heart, and did not include IABP support or use of extracorporeal mechanical oxygenation. Inotropic support was reported as the presence or absence of intravenous inotropic drugs on the day of listing and does not indicate inotrope dependence. The information whether medical therapy was intensified or device therapy was introduced after the day of listing, such as implantation of intracardiac cardioverter-defibrillator (ICD) or MCS, was not reported to the Registry.
Statistical analysis.
Survival estimates were calculated using the Kaplan-Meier actuarial survival curves (6). Two approaches were used to assess survival of patients awaiting HT. First, we calculated the probability of survival on the waiting list, as illustrated in Figures 1A and 1B. These analyses calculated time from the day when patients were initially listed as either UNOS status 1 or status 2 candidates until death on the waiting list. They were censored at the time of removal from the waiting list as the result of transplantation, worsening or improvement of condition, or the day of the last observation (June 1, 2006). The second approach was to retrospectively describe survival of patients who did or did not undergo transplantation during the follow-up period, as illustrated in Figures 2A and 2B. In this case, the survival was calculated from the day when patients were initially listed as UNOS status 1 or status 2 candidates until death, either on the waiting list for those who did not undergo HT or after HT for those who received a transplant. The survival was censored at the time of removal of patients from the waiting list as the result of worsening or improvement of condition or on the day of the last observation (June 1, 2006). Both approaches to survival analysis did not account for change of the UNOS status during the follow-up period, including temporary inactivation of status.
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Figure 1 The Actuarial Survival on the U.S. Heart Transplant Waiting List: Years 1990–2005
The actuarial survival on the heart transplant waiting list was calculated for 18,004 United Network of Organ Sharing (UNOS) status 1 candidates (A) and 30,978 UNOS status 2 candidates (B) listed between years 1990 and 2005 in the U.S. The results were stratified by 3 eras of listing: I (years 1990–1994), II (years 1995–1999), and III (years 2000–2005), respectively. The analyses were censored at time of transplantation, removal from the waiting list due to worsening or improvement of condition, or the day of last observation on June 1, 2006, and did not account for subsequent changes of UNOS status or temporary inactivation of status.
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Figure 2 The Survival of Candidates Who Did and Did Not Undergo Heart Transplantation: Years 1990–2005
The actuarial survival of patients who did and did not undergo heart transplantation was calculated for 18,004 United Network of Organ Sharing (UNOS) status 1 candidates (A) and 30,978 UNOS status 2 candidates (B) listed between years 1990 and 2005 in the U.S. The results were stratified by 3 eras of listing: I (years 1990–1994), II (years 1995–1999), and III (years 2000–2005), respectively. The survival was calculated from the day of listing until death on the waiting list for patients who did not undergo transplantation or death after heart transplantation. The analyses were censored at time of removal from the waiting list due to worsening or improvement of condition or the day of last observation on June 1, 2006, and did not account for subsequent changes of UNOS status or temporary inactivation of status.
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Multivariable analysis.
To identify predictors of death within 2 months from the day patients were listed as UNOS status 1 or 2 candidates in the years 2000 to 2005, all parameters listed in Tables 1 and 2
that correlated by univariate analysis with the end point at p < 0.15 were entered and allowed to stay in the multivariable Cox proportional hazards survival model at p < 0.05 using stepwise selection (7). Multicollinearity analysis was subsequently performed to confirm that the final model was not unduly influenced by collinearity between predictors in the model.
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Table 1 Demographics of UNOS Status 1 and 2 Candidates for Heart Transplantation Across Eras: I = 1990 to 1994, II = 1995 to 1999, and III = 2000 to 2005: U.S. Scientific Registry for Transplant Recipients (n = 48,982)
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Differences between groups were examined with chi-square or Student t tests. Results were considered significant for p < 0.05. Values are reported as mean ± SD. Data were analyzed using the SAS System software version 7.0 (SAS Institute, Inc., Cary, North Carolina).
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Results
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Listing trends of HT candidates.
As illustrated in Figure 3, the number of UNOS status 1 candidates enrolled on HT waiting lists increased from 836 patients in 1990 to 1,159 patients in 2005. During the same period of time, the number of patients listed as UNOS status 2 decreased from 2,332 patients listed in 1990 to 1,147 patients listed in 2005. These trends were associated with an increased proportion of the listed-to-transplanted HT candidates per calendar year from 41% in 1990 to 77% in 2005.
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Figure 3 The Number of UNOS Status 1 and 2 Heart Transplant Candidates Listed in the U.S.: Years 1990–2005
The number of the United Network of Organ Sharing (UNOS) status 1 candidates listed for heart transplantation in the U.S. increased from 836 patients in year 1990, to 1,159 patients in year 2005. During the same period of time the number of patients listed as UNOS status 2 decreased from 2,332 patients listed in year 1990 to 1,147 patients listed in year 2005. These trends were associated with an increased proportion of the listed-to-transplanted heart transplant candidates per calendar year from 41% in year 1990 to 77% in year 2005 (red line).
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Eras of listing and characteristics of HT candidates.
The demographic characteristics of UNOS status 1 and UNOS status 2 HT candidates were stratified by the era of listing as shown in Table 1. Overall, the majority (63.2%) of studied patients were listed as UNOS Status 2, men (78.2%), younger than 60 years of age (80.6%), of Caucasian ethnicity (79.3%), and ABO O blood type (43.2%). The 2 major etiologies of heart failure included ischemic (50.4%) and idiopathic dilated cardiomyopathy (31.9%). During the study period, there was a significant trend towards increased enrollment of females, patients of non-Caucasian ethnicity, patients older than 60 years, patients with nonischemic cardiomyopathy, and patients with weight >90 kg among both UNOS status 1 and 2 candidates, as shown in Table 1.
Eras of listing and severity of heart failure in HT candidates.
The clinical and hemodynamic indicators of severity of heart failure in UNOS status 1 and 2 HT candidates were stratified by the era of listing, as shown in Table 2.
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Table 2 Severity of Heart Failure in UNOS Status 1 and 2 Candidates for Heart Transplantation Across Eras: I = 1990 to 1994, II = 1995 to 1999, and III = 2000 to 2005: U.S. Scientific Registry for Transplant Recipients (n = 48,982)
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In the most recent era III, the majority of patients listed as UNOS status 1 candidates were hospitalized at the time of listing (82%), including 56% in the intensive care unit (ICU). The majority (71%) required continuous infusion of inotropes or circulatory support with IABP (12%) or MCS (23%). The least-ill group, as judged by the aforementioned criteria, comprised patients listed in era I. Although 87% of them were hospitalized at the time of listing, only 20% were in the ICU, 14.6% required intravenous inotropes, 3.4% were on IABP support, and 8.4% were on MCS.
In contrast, the vast majority of those listed as UNOS status 2 candidates were not hospitalized at the time of listing (85% to 87% throughout the eras I and III) and did not require inotropic or device circulatory support. There were no major differences across eras in terms of the clinical severity of heart failure in this group.
Outcomes of UNOS status 1 candidates.
Overall, the majority (67%) of 18,004 UNOS status 1 candidates listed from 1990 to 2005 underwent HT after the median waiting time of 2.1 months, 21% died on the waiting list, and the remaining 12% of patients were removed from transplant waiting lists because of improvement (2.5%), deterioration of condition (3.2%), or other reasons (4.6%) or were ongoing at the time of study (1.7%). At the end of the follow-up period, 4.6% of candidates were downgraded to UNOS status 2, and 13.3% were made temporarily inactive. One-year outcomes on the waiting list for UNOS status 1 candidates stratified by the eras of listing are shown in Table 3.
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Table 3 One-Year Outcomes of the Waiting List in UNOS Status 1 and Status 2 Candidates for Heart Transplantation Across Eras: I = 1990 to 1994, II = 1995 to 1999, and III = 2000 to 2005: U.S. Scientific Registry for Transplant Recipients (n = 48,982)
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Eras of listing and HT in UNOS status 1 candidates.
The calculated probability of HT within 1 year from listing of UNOS status 1 candidates censored at the time of removal from the waiting list because of death or other reasons remained nearly unchanged throughout the study period: 86.8%, 84.6%, and 83.5% in eras I, II, and III, respectively (p < 0.001). The corresponding median time to HT has also remained stable, despite the initial increase from 1.45 to 2.41 months in eras I and II and then decrease to 2.14 months in era III (p < 0.001).
Eras of listing and survival on the waiting list of UNOS status 1 candidates.
The 1-year survival on the waiting list of UNOS status 1 candidates censored at the time of removal from the waiting list due to transplant or other reasons increased from 49.5% to 63.3% to 69.0% in eras I, II, and III (p < 0.001), as illustrated in Figure 2A. The 1-year survival of UNOS status 1 patients who remained on the waiting list and did not undergo HT improved from 16.7% to 28.5% to 40.2% of those listed in eras I, II, and III (p < 0.001), whereas for those who underwent HT, survival from the day of listing until death after HT increased from 84.5% to 85.2% to 86.7% of those listed in eras I, II, and III (p < 0.001), as illustrated in Figure 3A.
Predictors of death within 2 months of listing in UNOS status 1 candidates.
The results of multivariable analysis of risk factors for death on the waiting list within 2 months in 5,451 UNOS status 1 candidates listed in the years 2000 to 2005 are shown in Table 4. Twenty-six percent of 7,376 UNOS status 1 candidates were excluded from this analysis because of a lack of information on the presence of ICD on the day of listing and assessment of hemodynamics and renal function. The following risk factors were identified as independent predictors of early death: mechanical ventilation, failed HT, valvular cardiomyopathy, UNOS status 1A, serum creatinine >1.5 mg/dl, presence of IABP, age >60 years, use of intravenous inotropic drugs, Caucasian ethnicity, body weight 70 kg, and pulmonary capillary wedge pressure (PCWP) >20 mm Hg. The presence of ICD on the day of listing was associated with more favorable outcomes. Hospitalization on the day of listing demonstrated statistical collinearity with medical urgency status, and therefore it was removed from the final model.
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Table 4 Multivariable Analysis of Risk Factors for Death Within 2 Months After Listing of UNOS Status 1 Candidates for Heart Transplantation: U.S. Scientific Registry for Transplant Recipients: Years 2000 to 2005 (n = 5,451)
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Outcomes of the waiting list: UNOS status 2 candidates.
Overall, the majority (58%) of 30,978 UNOS status 2 candidates listed from 1990 to 2005 underwent HT after the median waiting time of 12.6 months, 17.1% died on the waiting list, and the remaining 18.7% patients were either removed from transplant waiting lists because of improvement (6.3%), deterioration of condition (3.2%), or other reasons (9.2%), or were ongoing at the time of study (5.6%). At the end of the follow-up period, 46.2% of patients remained listed as UNOS status 2, 31.7% were upgraded to UNOS status 1, and 22% were made temporarily inactive. One-year outcomes on the waiting list in UNOS status 2 candidates stratified by the eras of listing are shown in Table 3.
Eras of listing and HT in UNOS status 2 candidates.
The calculated probability of HT within 1 year from listing of UNOS status 2 candidates censored at the time of removal from the waiting list because of death or other reasons was 52.8%, 44.3%, and 49.2% in eras I, II, and III, respectively (p < 0.001). The corresponding median time to HT initially increased from 10.8 to 15.4 months in eras I and II and then decreased to 12.4 months in era III (p < 0.001).
Eras of listing and survival on the waiting list of UNOS status 2 candidates.
The 1-year survival on the waiting list of UNOS status 2 candidates censored at the time of removal from the waiting list because of transplant or other reasons increased from 81.8% to 85% to 89.4% in eras I, II, and III (p < 0.001), as illustrated in Figure 2B. The 1-year survival of UNOS status 2 patients who remained on the waiting list and did not undergo HT improved from 65% to 72.1% to 81.4% of those listed in eras I, II, and III (p < 0.001), whereas for those who underwent HT, survival from the day of listing until death after HT increased from 89.8% to 91.8% to 92.5% of those listed in eras I, II, and III (p < 0.001), as illustrated in Figure 3B.
Predictors of death within 2 months of listing in UNOS status 2 candidates.
The results of multivariable analysis of risk factors for death on the waiting list within 2 months in 6,937 UNOS status 2 candidates listed in the years 2000 to 2005 are shown in Table 5. Sixteen percent of 8,231 UNOS status 2 candidates were excluded from this analysis because of the lack of information on the presence of ICD on the day of listing or assessment of renal function and hemodynamics. The following risk factors were identified as independent predictors of early death: restrictive cardiomyopathies, use of intravenous intoropic drugs, congenital heart disease, failed HT, secondary causes of dilated cardiomypathy, serum creatinine >1.5 mg/dl, and PCWP >20 mm Hg. Blood group B was associated with more favorable outcomes.
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Table 5 Multivariable Analysis of Risk Factors for Death Within 2 Months After Listing of UNOS Status 2 Candidates for Heart Transplantation: U.S. Scientific Registry for Transplant Recipients: Years 2000 to 2005 (n = 6,937)
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Discussion
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In this retrospective analysis of the U.S. population of HT candidates, we show that the survival of patients awaiting transplantation has significantly improved during the last 15 years. The actual survival on the waiting list censored at time of transplantation or removal from the list increased for UNOS status 1 candidates from 49.5% to 63.3% to 69.0%, and for UNOS status 2 candidates from 81.8% to 85% to 89.4% at 1 year from listing in eras I (years 1990 to 1994), II (years 1995 to 1999), and III (years 2000 to 2005), respectively.
UNOS status 1 candidates for HT.
The number of UNOS status 1 candidates has nearly doubled since the early 1990s from 4,541 to 7,376 patients listed between eras I and III. Despite the rising number of status 1 candidates, transplant organizations were able to accommodate donor organs at the rate and within the median time that remained nearly unchanged throughout the last 15 years. The probability of receiving HT by the waiting list survivors remained stable, ranging between 83.5% and 86.8% at 1 year with the median waiting time to HT averaging 1.4 to 2.4 months throughout the study period.
Although the likelihood of receiving HT has not substantially changed, the 1-year survival of status 1 candidates on the waiting list has improved by nearly 20% (from 49.5% to 68.9% between eras I and III). There are 3 possible explanations of these observations. First, it is possible that the allocation of organs was prioritized to higher-risk candidates, thus leaving on the waiting list patients with better prognosis. This may particularly apply to the early 2000s, when the 2-tiered medical urgency status 1A and 1B was introduced (5). Second, it is possible that patients listed in the recent years were less severely ill. It cannot be excluded that in some instances hospitalization in ICU and infusion of intravenous inotropes resulted from the desire to satisfy status 1 criteria. Finally, the described improvements may have resulted from the advances of medical and device therapy for heart failure. An example of this may be the use of ICD, which significantly increased in early 2000s and was associated with significantly improved survival to HT. Unfortunately, because of the lack of information on the severity of heart failure and details of pharmacologic and device therapies, we were not able to elucidate the specific reasons for these trends from the Registry data.
We further show that, despite the aforementioned improvements, the survival of status 1 candidates continued to depend on urgent cardiac replacement therapy. More than one-half (52.4%) of those listed in the years 2000 to 2005 died within 6 months without HT. The use of MCS on the day of listing as a "bridge" to HT has increased nearly 3-fold since the early 1990s (8.4% to 22.8% patients in eras I and III). Unfortunately, the registry does not collect information on how many of these patients received MCS after they were listed. Given continued high 6-month mortality in this group without HT, it is possible that MCS may be underutilized in this population. We strongly believe that left-ventricular assist device implantation should be considered in all high-risk status 1 candidates who require continuous inotropic support and have expected waiting times exceeding 2 months because of their body habitus, ABO group, or allocation region (8).
To identify status 1 HT candidates who warrant the highest priority for allocation and/or consideration for MCS, we sought to identify risk factors for 2-month mortality among patients listed in the recent years 2000 to 2005. The predictors of early death included markers of worsening pump failure (UNOS status 1A, mechanical ventilation, inotropic and IABP support, elevation of PCWP >20 mm Hg, and renal dysfunction), certain etiologies of heart disease (valvular cardiomyopathy or failed transplant), and patient demographics (age >60 years, Caucasian ethnicity, and body weight 70 kg). The presence of ICD on the day of listing, which in some centers is successfully used as a "bridge" to transplantation, appeared to have a significant and favorable impact on the waiting list outcomes. Hospitalization on the day of listing, which was one of the most powerful predictors of death in this analysis, was removed from the final multivariable model because of its statistical correlation with assigned urgency status. Interestingly, MCS was not an independent predictor of early mortality among those listed as UNOS status 1; however, it did confer increased risk of early death when analyzed in the pooled cohort of status 1 and 2 patients (data not shown). Some of the aforementioned predictors, such as hospitalization, particularly in the ICU, use of inotropic drugs, or MCS and renal dysfunction, have been previously identified as prognostics of early death in the German national data of the pooled status 1 and 2 candidates (9).
UNOS status 2 candidates for HT.
The number of listed UNOS status 2 candidates has significantly decreased from 2,332 to 1,147 patients between the years 1990 and 2005, which has led to major shifts on the HT waiting list, including significant improvement of the listed-to-transplanted patient ratio per year (41% to 77% between 1990 and 2005), and allowed distribution of donor hearts to the growing population of the sicker status 1 candidates.
The 1-year survival of status 2 candidates on the waiting list improved throughout the eras by 8% (from 81.8% to 89.4% between eras I and III), which appeared independent from the rates of HT performed in this group (the probability of HT at 1 year ranged 44.5% to 52.9% and the median time to HT ranged 10.8 to 15.4 months). Demographics, etiology, and markers of severity of heart failure did not substantially change throughout the study period, indicating that the improved outcomes most likely represented advances of heart failure therapy. However, as in the case of improved outcomes of status 1 candidates, we were not able to elucidate the specific reasons of the improved survival of status 2 candidates from the Registry data.
It is important to note that, in the current era of medical therapy, the 1-year survival of status 2 candidates without HT (81.4%) is approaching outcomes of HT (10). These observations raise the question whether early listing is justified in all status 2 candidates. Both European (11) and U.S. experiences in adult (12) and pediatric (13) patients with advanced heart failure consistently show that status 2 candidates are the least likely to benefit from early HT unless an upgrade of status occurs (11). Deng et al. (14) believe that many status 2 candidates may be "too well" to transplant and recently proposed clinical trials to justify replacement therapy for these patients.
The proposal to delay listing or divert organs from status 2 candidates to the sickest patients, however, continues to generate much controversy (15,16) because status 2 candidates are not a homogeneous group and their mortality risk may vary significantly. In this study, nearly one-fifth of those listed in the years 2000 to 2005 did not survive 1 year, clearly proving their need for early HT. Previous analyses revealed that the condition of 40% of status 2 candidates listed in the early 2000s worsened and required upgrade to status 1 (15). Although some of these who deteriorate may be salvaged with MCS, the risks of an emergent procedure may not be negligible.
Unfortunately, there are no specific criteria to prospectively identify status 2 candidates at increased risk for deterioration or death. In this study, risk factors associated with death within 2 months from listing as status 2 included markers of worsening pump failure (increased PCWP, renal dysfunction, or use of intravenous inotropes) and certain etiologies of heart disease (congenital heart disease, restrictive heart disease, and secondary dilated cardiomypathy, or failed HT). This analysis, however, did not include the most powerful predictors of survival in advanced heart failure, such as peak oxygen consumption, as well as use of pharmacologic and device therapies. Future analyses should incorporate these factors to allow more accurate risk stratification of status 2 HT candidates in the era of contemporary heart failure therapy.
On the final note, it is important to mention that the quality of life of status 2 candidates was not assessed in this survey, and although these patients are now able to achieve a remarkably long survival while awaiting HT, their quality of life may have remained very poor. Although it is generally agreed that the scarce donor hearts should be distributed only to those HT candidates with a proven net-survival benefit, the quality of life is an important consideration in the decision of listing status 2 candidates, and the potential changes in listing policies should not be restricted to the survival data alone.
Study limitations.
The results of this study carry limitations associated with the retrospective analysis of a registry database, the quality of the source data, and the lack of standardization associated with multicenter studies, as has been previously described (17). The causes of death on the waiting list and specifics of medical and device therapy of patients awaiting HT were not collected by the Registry. The calculated survival in this study does not account for changes of UNOS status while on the waiting list and may underestimate the mortality rates of patients who were censored at the time of removal from the waiting list due to worsening of condition. A small percentage of analyzed status 2 candidates met criteria of UNOS status 1, such as the support with intravenous inotropes, IABP, or MCS. This may represent erroneous status classification or may reflect the center’s intent to not transplant patients immediately. Therefore, results of this study should be interpreted with caution.
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Conclusions
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In this retrospective analysis of the U.S. population of HT candidates we show that survival on the waiting list has significantly improved. Despite these improvements, survival of UNOS status 1 candidates continues to depend on urgent cardiac replacement. We describe risk factors associated with 2-month mortality that may help identify those patients who are at the highest priority for donor heart allocation and/or consideration for MCS. Better methods of risk stratification of UNOS status 2 candidates are necessary, as in the current era of medical therapy, early listing may not be justified in all of these patients.
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Footnotes
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This work was supported in part by Health Resources and Services Administration contract 231-00-0115.
The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
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References
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