The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure.
BACKGROUND
Despite its high prevalence, optimal therapy for diastolic heart failure (DHF) has not been determined. Alagebrium chloride (ALT-711) is a novel compound that breaks glucose crosslinks and may improve ventricular and arterial compliance.


RESULTS
A total of 23 patients, mean age 71 years, with stable DHF, ejection fraction (EF) >50%, were enrolled in a 16-week, open-label trial of alagebrium 420 mg per day. Assessments included: peak exercise oxygen consumption, aortic distensibility, and left ventricular EF and mass by magnetic resonance imaging, Doppler diastolic filling, and quality of life by the Minnesota Living with Heart Failure questionnaire. One patient discontinued treatment because of a myocardial infarction after 12 days of treatment, and a second died suddenly after 10 weeks of treatment. Thus 21 patients completed the study. Left ventricular mass was 124 +/- 35 g at baseline and decreased to 119 +/- 34 g at follow up ( P = .036). This was accompanied by a decrease in the ratio of Doppler early diastolic flow velocity to Doppler early diastolic mitral annulus velocity (E') from 10.6 +/- 2.7 to 9.4 +/- 1.9 ( P = .076) and an increase in E' from 7.3 +/- 1.2 to 8.4 +/- 1.7 cm/s ( P = .045). The Minnesota Living with Heart Failure total score improved from 41 +/- 21 to 32 +/- 21 ( P = .01). There were no changes in EF (64 +/- 4% at baseline), blood pressure, peak exercise oxygen consumption, and aortic distensibility.


CONCLUSIONS
Sixteen weeks of treatment with the glucose crosslink breaker, alagebrium, resulted in a decrease in left ventricular mass and improvements in left ventricular diastolic filling and quality of life in patient with DHF.
Little
William C
WC
Department of Internal Medicine, Cardiology Section, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Zile
Michael R
MR
Kitzman
Dalane W
DW
Hundley
W Gregory
WG
O'Brien
Terrence X
TX
Degroof
Robert C
RC
D000368:Aged; D001011:Aorta / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013844:Thiazoles / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D017127:Glycation End Products, Advanced; D013844:Thiazoles; C406794:alagebrium