Author + information
- Received December 28, 2009
- Revision received May 3, 2010
- Accepted May 18, 2010
- Published online July 27, 2010.
- Daniel G. Kramer, MD⁎,
- Thomas A. Trikalinos, MD, PhD†,
- David M. Kent, MD, MS†,
- George V. Antonopoulos, MD⁎,
- Marvin A. Konstam, MD⁎ and
- James E. Udelson, MD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. James E. Udelson, Division of Cardiology, Tufts Medical Center, 750 Washington Street, Box 70, Boston, Massachusetts 02111
Objectives The purpose of this study was to quantitatively assess the relationship between therapy-induced changes in left ventricular (LV) remodeling and longer-term outcomes in patients with left ventricular dysfunction (LVD).
Background Whether therapy-induced changes in left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), and end-systolic volume (ESV) are predictors of mortality in patients with LVD is not established.
Methods Searches for randomized controlled trials (RCTs) were conducted to identify drug or device therapies for which an effect on mortality in patients with LVD was studied in at least 1 RCT of ≥500 patients (mortality trials). Then, all RCTs involving those therapies were identified in patients with LVD that described changes in LVEF and/or volumes over time (remodeling trials). We examined whether the magnitude of remodeling effects is associated with the odds ratios for death across all therapies or associated with whether the odds ratio for mortality was favorable, neutral, or adverse (i.e., statistically significantly decreased, nonsignificant, or statistically significantly increased odds for mortality, respectively).
Results Included were 30 mortality trials of 25 drug/device therapies (n = 69,766 patients; median follow-up 17 months) and 88 remodeling trials of the same therapies (n = 19,921 patients; median follow-up 6 months). The odds ratio for death in the mortality trials was correlated with drug/device effects on LVEF (r = −0.51, p < 0.001), EDV (r = 0.44, p = 0.002), and ESV (r = 0.48, p = 0.002). In (ordinal) logistic regressions, the odds for neutral or favorable effects in the mortality RCTs increased with mean increases in LVEF and with mean decreases in EDV and ESV in the remodeling trials.
Conclusions In patients with LVD, short-term trial-level therapeutic effects of a drug or device on LV remodeling are associated with longer-term trial-level effects on mortality.
This article was partially funded by the grant NIH/NCRR UL1RR025752, Tufts Clinical and Translational Science Institute. Dr. Konstam is a consultant for Boehringer-Ingelheim, Trevena, Johnson & Johnson, Cardioxyl, Merck, and Forest. Dr. Udelson is a consultant for Cytori, Angioblast, and Medtronic.
- Received December 28, 2009.
- Revision received May 3, 2010.
- Accepted May 18, 2010.
- American College of Cardiology Foundation