Decisions regarding cardiac transplantation listing are difficult in patients with heart failure who have relatively discordant peak exercise oxygen consumption (V o 2 ) and cardiac index (CI) values. One hundred five patients with heart failure who underwent cardiopulmonary exercise testing and right-sided cardiac catheterization for transplantation evaluation were studied. Patients were divided into 4 groups on the basis of peak V o 2 and CI: group 1, V o 2 ≥12 ml/min/kg, CI ≥1.8 L/min/m 2 (n = 30); group 2, V o 2 ≥12 ml/min/kg, CI <1.8, L/min/m 2 (n = 27); group 3, V o 2 <12 ml/min/kg, CI ≥1.8 L/min/m 2 (n = 25); and group 4, V o 2 <12 ml/min/kg, CI <1.8 L/min/m 2 (n = 23). Groups were compared for event-free (death or ventricular assist device) survival. The overall CI was 1.9 ± 0.4 L/min/m 2 and peak V o 2 was 12.4 ± 2.8 ml/min/kg; values in the 4 groups were as follows: group 1, peak V o 2 14.7 ± 2.1 ml/min/kg, CI 2.2 ± 0.3 L/min/m 2 ; group 2, peak VO 2 14.2 ± 1.3 ml/min/kg, CI 1.5 ± 0.2 L/min/m 2 ; group 3, peak V o 2 10.2 ± 1.3 ml/min/kg, CI 2.1 ± 0.3 L/min/m 2 ; and group 4, peak V o 2 9.7 ± 2.0 ml/min/kg, CI 1.6 ± 0.2 L/min/m 2 . After a median follow-up period of 3.7 years, 28 patients (26.0%) had events. Event-free survival was 96%, 95%, 96%, and 79% for 6 months (p = 0.04); 88%, 81%, 90%, and 73% for 12 months (p = 0.09); 88%, 73%, 85%, and 65% for 18 months (p = 0.11); and 83%, 73%, 79%, and 53% for 24 months (p = 0.06) for groups 1 to 4, respectively. Median survival was 5.1, 3.0, 3.9, and 2.6 years, respectively, in groups 1 to 4 (p = 0.052). In conclusion, almost half the patients had relatively discordant peak V o 2 and CI measurements. Patients with lower peak V o 2 values but relatively preserved CI values had survival comparable to post-transplantation survival, whereas those with low CI but preserved V o 2 had a lower survival rate. These results suggest that the former group may be safely monitored on medical therapy, whereas the latter may benefit from early listing.
In this study, we sought to assess the proportion of patients with heart failure (HF) with relatively discordant peak exercise oxygen consumption (V o 2 ) and cardiac index (CI) measurements, as opposed to patients with the 2 values relatively preserved or reduced, among those evaluated for cardiac transplantation and to compare their outcomes.
Methods
We retrospectively examined data from 105 patients who underwent symptom-limited cardiopulmonary exercise stress testing and right-sided cardiac catheterization within 6 months as part of cardiac transplantation evaluation. Demographic variables, medication use, device information, co-morbidities, peak V o 2 , and hemodynamic data were recorded. The study was approved by the institutional review board.
Patients were classified into 4 groups on the basis of CI and peak V o 2 values. The cut-off value for peak V o 2 chosen was 12 ml/min/kg on the basis of current recommendations in the practice guidelines of the International Society for Heart and Lung Transplantation. Routine inotrope use in HF is not recommended; however, once patients are listed for cardiac transplantation, the use of inotropes is used to decide listing priority in nonemergent cases (i.e., status 2 vs status 1B). In the absence of consensus guidelines, we arbitrarily used a CI <1.8 L/min/m 2 on the basis of our practice pattern. On the basis of these values, patients were classified into 4 groups: group 1, V o 2 ≥12 ml/min/kg, CI ≥1.8 L/min/m 2 ; group 2, V o 2 ≥12 ml/min/kg, CI <1.8 L/min/m 2 ; group 3, V o 2 <12 ml/min/kg, CI ≥1.8 L/min/m 2 ; and group 4, V o 2 < 12 ml/min/kg, CI <1.8 L/min/m 2 .
Outcome was defined as the composite of death or left ventricular assist device placement, with patients who underwent transplantation (n = 25) being censored at the time of transplantation. All deaths were confirmed using the Social Security Death Index.
Continuous variables are presented as mean ± SD and categorical variables as proportions. The chi-square test for categorical variables and Student’s t test for continuous variables were used for comparisons. Survival at 6, 12, 18, and 24 months was compared among the 4 groups using the chi-square test. Kaplan-Meier survival analysis was performed to assess median survival in the 4 groups and was compared with the log-rank test. A p value <0.05 was considered significant. SPSS version 17.0 (SPSS, Inc., Chicago, Illinois) was used for all analyses.
Results
Table 1 summarizes the baseline characteristics of the patients studied. The average age of the patients was 50.6 ± 11.4 years, 72.4% were men, 61.5% were white, and the mean ejection fraction was 14.7 ± 8.7%. Patients were receiving optimal medical therapy, including 91% β blockers and 88% angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and 89.5% had defibrillators or biventricular pacemaker-defibrillators.
| Variable | Group | p Value | |||
|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | ||
| (n = 30) | (n = 27) | (n = 25) | (n = 23) | ||
| Age (years) | 51.3 ± 10.5 | 50.8 ± 10.7 | 52.8 ± 10.9 | 47.9 ± 13.8 | 0.40 |
| Men | 24 (80%) | 22 (82%) | 17 (68%) | 13 (57%) | 0.16 |
| White | 22 (76%) | 14 (52%) | 19 (68%) | 9 (39%) | 0.05 |
| Ejection fraction (%) | 17.1 ± 10.0 | 11.3 ± 7.1 | 17.6 ± 8.3 | 12.8 ± 7.3 | 0.02 |
| Weight (kg) | 85.4 ± 16.6 | 82.6 ± 15.0 | 84.8 ± 15.0 | 83.5 ± 25.2 | 0.94 |
| Height (cm) | 174.8 ± 8.1 | 176.7 ± 9.4 | 169.8 ± 10.1 | 170.5 ± 10.3 | 0.03 |
| Body mass index (kg/m 2 ) | 27.8 ± 4.7 | 26.3 ± 3.4 | 29.3 ± 3.6 | 28.3 ± 6.9 | 0.15 |
| Ischemic cause | 18 (60%) | 2 (7%) | 15 (60%) | 7 (30%) | <0.01 |
| Hypertension | 9 (30%) | 13 (48%) | 14 (56%) | 14 (61%) | 0.11 |
| Diabetes | 9 (30%) | 6 (22%) | 9 (36%) | 7 (30%) | 0.75 |
| Defibrillator ± biventricular pacemaker | 29 (97%) | 24 (89%) | 21 (84%) | 20 (87%) | 0.67 |
| Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers | 25 (83%) | 23 (85%) | 22 (88%) | 22 (96%) | 0.21 |
| β blockers | 27 (90%) | 24 (89%) | 22 (88%) | 22 (96%) | 0.81 |
| Diuretics | 24 (80%) | 25 (93%) | 22 (88%) | 21 (91%) | 0.47 |
| Aldosterone antagonists | 16 (53%) | 19 (71%) | 10 (40%) | 18 (78%) | 0.03 |
| Peak V o 2 (ml/min/kg) | 14.7 ± 2.1 | 14.3 ± 1.3 | 10.2 ± 1.3 | 9.7 ± 2.0 | <0.01 |
| Cardiac index (L/min/m 2 ) | 2.2 ± 0.3 | 1.5 ± 0.2 | 2.1 ± 0.3 | 1.6 ± 0.2 | <0.01 |
| Right atrial pressure (mm Hg) | 6.1 ± 4.5 | 10.1 ± 6.5 | 9.2 ± 4.8 | 11.1 ± 6.4 | 0.01 |
| Pulmonary artery systolic pressure (mm Hg) | 36.0 ± 11.7 | 46.4 ± 12.0 | 46.0 ± 17.1 | 52.5 ± 14.1 | <0.01 |
| Pulmonary capillary wedge pressure (mm Hg) | 14.7 ± 7.2 | 22.3 ± 7.2 | 19.5 ± 9.3 | 23.9 ± 6.9 | <0.01 |
The mean CI was 1.9 ± 0.4 L/min/m 2 and peak V o 2 was 12.4 ± 2.8 ml/min/kg. Patient distribution according to peak V o 2 and CI was as follows: group 1, V o 2 ≥12 ml/min/kg, CI ≥1.8 L/min/m 2 (n = 30); group 2, V o 2 ≥12 ml/min/kg, CI <1.8 L/min/m 2 (n = 27); group 3, V o 2 <12 ml/min/kg, CI ≥1.8 L/min/m 2 (n = 25); and group 4, V o 2 <12 ml/min/kg, CI <1.8 L/min/m 2 (n = 23). Characteristics according to the 4-group categorization are listed in Table 1 . The mean peak V o 2 and CI in the 4 groups were as follows: group 1, V o 2 14.7 ± 2.1 ml/min/kg, CI 2.1 ± 0.3 L/min/m 2 ; group 2, V o 2 14.2 ± 1.3 ml/min/kg, CI 1.5 ± 0.2 L/min/m 2 ; group 3, V o 2 10.2 ± 1.3 ml/min/kg, CI 2.1 ± 0.3 L/min/m 2 ; and group 4, V o 2 9.7 ± 2.0 ml/min/kg, CI 1.6 ± 0.2 L/min/m 2 .
Median survival in groups 1 to 4 was 5.1, 3.0, 3.9, and 2.6 years, respectively (p = 0.052). After a median follow-up period of 3.7 years, 27 patients (26.0%) had events. Event-free survival was 96%, 95%, 96%, and 79% (p = 0.04) at 6 months; 88%, 81%, 90%, and 73% (p = 0.09) at 12 months; 88%, 73%, 85%, and 65% at 18 months (p = 0.11); and 83%, 73%, 79%, and 53% (p = 0.06) at 24 months for groups 1 to 4, respectively ( Figure 1 , Table 2 ).
