Recovery of Ventricular Function after Myocardial Infarction in the Reperfusion Era: The Healing and Early Afterload Reducing Therapy Study

Recovery of Ventricular Function after Myocardial Infarction in the Reperfusion Era: The Healing and Early Afterload Reducing Therapy Study

From Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Toronto General Hospital, Toronto, and London Science Center, London, Ontario, Canada; Geisinger Medical Clinic, Danville, Pennsylvania; Green Lane Hospital, Remuera, Auckland, New Zealand; and University of Miami, Boca Raton, Florida.

Abstract

Background: Patients with reduced left ventricular function and ventricular enlargement after myocardial infarction are at significantly greater risk for congestive heart failure and death. Nevertheless, recovery of ventricular function occurs in a significant proportion of patients after myocardial infarction, and modern reperfusion strategies have been associated with increased recovery of function.

Objective: To determine the extent and predictors of recovery of ventricular function after anterior Q-wave myocardial infarction in the reperfusion era.

Design: Subgroup analysis of the Healing and Early Afterload Reducing Therapy study.

Setting: 35 medical centers in the United States and Canada.

Patients: 352 patients with Q-wave anterior myocardial infarction.

Intervention: Placebo for 14 days, followed by full-dose (10 mg) ramipril until day 90; low-dose (0.625 mg) ramipril for 90 days; or full-dose ramipril for 90 days. All patients underwent reperfusion therapy.

Measurements: Echocardiography was performed on day 1 (before randomization), day 14, and day 90 after myocardial infarction. Left ventricular volume and ejection fraction were measured and wall-motion analyses were performed at all three time points in 249 patients and at baseline in an additional 12 patients who died during follow-up. Echocardiographic and nonechocardiographic predictors of ventricular recovery were examined.

Results: By day 90, 55 of 252 (22%) patients who had abnormal ejection fraction and wall-motion abnormalities on day 1 demonstrated complete recovery of function (ejection fraction in the normal range and infarct segment length of 0%), and an additional 36% (91 of 252 patients) demonstrated partial recovery of function. At 90 days, 53% (132 of 249) of patients had greater than 5% improvement in ejection fraction, whereas only 16% (39 of 249) had a decrease in ejection fraction of more than 5%. The majority of functional improvement occurred by day 14 after infarction. Of various clinical and echocardiographic measures obtained on day 1, peak creatine kinase level was the strongest independent predictor of subsequent recovery of ventricular function in multivariate analysis. Each 100-unit increase in peak creatine kinase was associated with a 4.3% decreased odds of recovery (P < 0.001) after adjustment for ejection fraction on day 1, extent of akinesis or dyskinesis, treatment regimen, Killip class, age, and sex.

Conclusion: Significant myocardial stunning with subsequent improvement of ventricular function occurred in the majority of patients after Q-wave anterior myocardial infarction. A lower peak level of creatine kinase, an estimate of the extent of necrosis, is independently predictive of recovery of function. Early functional assessment (day 1 after acute myocardial infarction) had limited ability to predict recovery of ventricular function.

Article and Author Information

Grant Support: By Hoechst-Marion Roussel. Dr. Solomon was supported by a Clinician-Scientist Award from the American Heart Association.
Requests for Single Reprints: Scott D. Solomon, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115; e-mail, ssolomon{at}rics.bwh.harvard.edu.
Current Author Addresses: Drs. Solomon and Pfeffer: Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.
Drs. Glynn and Ajani: Division of Preventive Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.
Dr. Greaves: Green Lane Hospital, 27 Buttle Street, Remuera, Auckland, New Zealand.
Dr. Rouleau: Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
Dr. Menapace: Geisinger Medical Clinic, 100 North Academy, Danville, PA 17822.
Dr. Arnold: London Science Center, 375 South Street, London, Ontario N6A 4G5, Canada.
Dr. Hennekens: 1415 Camino Real, Boca Raton, FL 33486.
Author Contributions: Conception and design: S.D. Solomon, S. Greaves, J.-L. Rouleau, C.H. Hennekens, M.A. Pfeffer.
Analysis and interpretation of the data: S.D. Solomon, R.J. Glynn, S. Greaves, U. Ajani, J.-L. Rouleau, C.H. Hennekens, M.A. Pfeffer.
Drafting of the article: S.D. Solomon, J.-L. Rouleau, M.A. Pfeffer.
Critical revision of the article for important intellectual content: S.D. Solomon, R.J. Glynn, S. Greaves, J.-L. Rouleau, F. Menapace, J.M.O. Arnold, C.H. Hennekens, M.A. Pfeffer.
Final approval of the article: S.D. Solomon, R.J. Glynn, S. Greaves, U. Ajani, J.-L. Rouleau, J.M.O. Arnold, C.H. Hennekens, M.A. Pfeffer.
Provision of study materials or patients: S.D. Solomon, J.-L. Rouleau, F. Menapace, J.M.O. Arnold.
Statistical expertise: R.J. Glynn, C.H. Hennekens.
Obtaining of funding: C.H. Hennekens.
Administrative, technical, or logistic support: C.H. Hennekens.
Collection and assembly of data: S.D. Solomon, S. Greaves, U. Ajani, C.H. Hennekens, M.A. Pfeffer.