All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- The reported survival for heart failure patients varies a lot. Some recent trials reported mortality rates of 10% per year. In patients with severe heart failure in the CONSENSUS trial, a one year mortality rate of 36% was seen. Evaluating CHFers means assessing patient risk AFTER adopting best drug therapy. Will all patients with advanced heart failure get worse as time goes by? Will some remain the same? How do we tell one group from the other? Variables such as VO2max, EF, and heart size predict survival to some degree in CHFers. However, we don't really know how to tell from changes in these measures over time how to predict survival. VO2max measured at regular intervals is used to estimate risk in patients being considered for heart transplant. Stevenson reported that patients with VO2max values under 14 ml/min/kg when listed for transplant could be safely taken off the transplant list if their VO2max improved by at least 2 ml/min/kg. However, right now it is unclear whether regular measurements of other factors like exercise, or taken by echo, MUGA, or cath help predict survival. PATIENTS 286 patients with advanced heart failure evaluated for heart transplant at Stanford University between 1986 and 1995 were studied. Each patient had been in heart failure at least one month, and most had at least one hospital admissions for decompensated heart failure. A patient history and exam were done. All patients then went through intensive drug therapy and education. All patients had at least two Vo2max tests done at least 4 weeks apart. Other tests, including echo and cath, were also done. Regular testing over time (serial testing) was part of their ongoing transplant evaluation. TESTING The two exercise tests were done an average of 8 months apart. Exercise tests were done on a cycle at a constant speed of 60 RPM with continuously increasing difficulty, going up 10 Watts per minute. VO2 was measured breath by breath and recorded every 30 seconds. Oxygen uptake, carbon dioxide production (VCO2), and other measurements were also recorded. Peak oxygen uptake was defined as the highest VO2 achieved during exercise. Predicted values for peak VO2 were calculated from a set of standard formulas by Wasserman. Heart rate was recorded continuously and blood pressure was recorded at regular intervals. Other tests done for transplant evaluation included right heart cath, and cardiac output ; EF was measured by cath or MUGA ; heart size was measured by echo. FOLLOW-UP Patients were followed-up at the Stanford Heart Failure Clinic or by a referring doctor. Patient status was determined from medical records, or by telephone interview of patient or family. All surviving patients had at least one year of follow-up. Eight patients were lost to follow-up (3%). Study endpoints included death before transplant, and transplant. CHARACTERISTICS Patient characteristics at study start : 1) 81% were men 2) Dilated cardiomyopathy of unknown cause was the most common cause of heart failure (66%) 3) Despite aggressive drug therapy all patients had CHF symptoms, an average EF of 19%, and VO2max of 17 ml/min kg 4) Right-sided heart pressures were mildly elevated 5) Cardiac output was mildly decreased 6) 86% were taking an ACE inhibitor 7) 79% were taking digoxin 8) 81% were taking diuretics 9) 12% were taking a beta-blocker After transplant evaluation, 112 patients (39%) were put on the transplant waiting list while 174 (61%) were rejected because they were too well, too sick, too old, had pulmonary hypertension, or other disqualifications. During an average follow-up of almost 5 years, 70 patients (25%) died. One year survival rate was 96% and 5-year survival was 68%. Of the patients accepted for transplant, 45 (16% of all patients) actually had a heart transplant. Of these, 16 died later. Twenty-three patients (8% of all patients) died while waiting on the list. Of the patients not qualifying for transplant (174), 33 (12% of that group) died later. RESULTS Patients with coronary artery disease had a risk of death more than twice as high compared to patients with dilated cardiomyopathy of unknown cause. Age, sex, body mass, right heart pressures, cardiac output, and ejection fraction did NOT predict outcome. Exercise capacity, peak heart rate, and peak systolic blood pressure were all higher in survivors than in nonsurvivors. Nonsurvivors had considerably larger hearts. During follow-up, there were small increases in exercise capacity among survivors. Ejection fraction also increased in survivors. No such changes were seen in nonsurvivors. NUMBERS 1) 166 patients (58%) had improved VO2max 2) 116 patients (41%) had worsened VO2max from test one to test 2 3) One-year survival in patients who improved was 93% 4) 5-year survival in patients who improved was 77% 5) In patients whose test scores worsened, one-year survival was 98% 6) In patients whose test scores worsened, 5-year survival was 79% Was there a cutoff point for VO2max change that predicted survival? We compared patients with increased versus patients with decreased VO2max by increments of 1, 2, 3, or 5 ml/min/kg, but no real differences were seen. In survivors, there was a greater proportion of patients with increased VO2max than decreased at each cutoff point, but nonsurvivors did not differ at any of the cutoff points. In the patients as a whole, heart size stayed unchanged, while ejection fraction increased slightly from 19% to 22% between test one and test 2. No survival differences were seen between those with increased EF versus those whose EF got worse. CONCLUSIONS Predictors of survival included maximum systolic blood pressure, percent of maximum predicted VO2 achieved, and change in VO2max from test one to test 2. However, these were weak as predictors go. Our study shows that measuring exercise ability, echo data, and ejection fraction, in stable heart failure patients does not predict survival. Several ways to predict prognosis in CHFers have been proposed : heart class, blood sodium level, heart size, pulmonary pressure, pulmonary vascular resistance, neurohormone activity, and VO2max. HOWEVER, A RECENT ACC TASK FORCE CONCLUDED THAT NO CONSISTENT, OBJECTIVE STANDARDS EXIST THAT ESTABLISH PROGNOSIS IN CONGESTIVE HEART FAILURE. DISCUSSION Although a general marker of survival, ejection fraction loses its prognostic value when it dips under 25%. Levine found that outcome of patients on a transplant waiting list could not be predicted from the first exam. Patients who did best long-term improved over a 2-year period after diagnosis. In that study, VO2max went up from 12 to 19 ml/min/kg in the group with good outcomes. Stevenson reported that of 107 patients awaiting heart transplant with a VO2max under 14 ml/min/kg, 31 increased their VO2max by at least 2 ml/min/kg and went off the transplant list. Those patients had short-term survival as good as patients getting a transplant. However, we did not see any difference in outcome between those who increased versus those who had decreased VO2max. This may result from patient selection, timing of the first exam being before or after stepping up drug therapy, and specific treatment plan for each patient. Both studies described above included patients already listed for transplant. We included all patients under consideration for transplant. Stevenson also used a combination of vasodilators (ACE inhibitors, nitrates, and hydralazine alone or in combination) and diuretics tailored to each patient. It has been proven, however, that ACE inhibitor use gives more benefit than hydralazine. In contrast to these previous studies, our center has been using a pretty consistent program including digoxin, diuretics, and ACE inhibitors since 1986. That a change in VO2max does not necessarily reflect outcome is also supported by some other recent studies. In the V-HeFT II study, the combination of hydralazine and nitrates gave more improvement in exercise capacity than Vasotec (enalapril), even though survival was better in the enalapril group. Coreg, given to CHFers, improves ejection fraction and survival, even though it does not help VO2max. SO A CHANGE IN VO2MAX IS NOT AN ABSOLUTE PREDICTOR OF ANYTHING BY ITSELF. DO OTHER THINGS PREDICT SURVIVAL IN CHF? During our study, we were able to watch changes over time in non-exercise measures like EF and echo measures. Ejection fraction is considered a strong predictor of prognosis in CHFers and is still widely used to help decide treatment options. In our study, changes in EF did not predict outcome, contrary to the V-HeFT studies. In V-HeFT, a decrease in EF over time strongly predicted death, and an increase in EF was linked to improved survival. However, these findings obviously cannot be applied across the board to all patients. In a subset of the SOLVD study, it was shown that heart failure progressively increases left ventricle size, and that this could be prevented or reversed with ACE inhibitor use. Whether this improved survival was not studied. In our study, there were no significant changes in heart size in either survivors or nonsurvivors. Most of the patients in our study were taking ACE inhibitors and left ventricle size stayed stable. LIMITATIONS This was a retrospective study of CHFers referred for heart transplant evaluation. The recommended medical treatment for such patients is constantly changing, and those changes could improve outcomes. Although our follow-up began in 1986, most patients were taking ACE inhibitors, digoxin, and diuretics. Although the follow-up in the present study was fairly long, we included only 2 tests separated by 8 months. Since we studied patients referred for heart transplant evaluation, our conclusions may not apply to patients with milder heart failure. FINALLY Our study suggests that the condition of patients with severe heart failure who are now stable and getting proper drug therapy does not necessarily get worse. Exercise capacity, heart size, and ejection fraction remained stable in most patients during the 8 months after evaluation. Further, our study suggests that changes in VO2max, heart size, or ejection fraction over this period do not mean higher risk of death. Changes in these measurements must be viewed in each individual patient's situation. Title: Serial exercise testing and prognosis in selected patients considered for cardiac transplantation. Authors: Gullestad L, Myers J, Ross H, Rickenbacher P, Slauson S, Bellin D, Do D, Vagelos R, Fowler M Source: Am Heart J 1998 Feb;135(2 Pt 1):221-229 PMID: 9489968, UI: 98149612