Time course of reverse remodeling of the left ventricle during support with a left ventricular assist device.
BACKGROUND
Support with a left ventricular assist device leads to normalization of left ventricular chamber geometry, regression of myocyte hypertrophy, alterations in left ventricular collagen content, and normalized expression of genes involved with excitation-contraction coupling in patients with heart failure. The objective of this study was to investigate the time course of these processes.


METHODS
Passive left ventricular pressure-volume relationships were obtained from explanted hearts of 19 patients with heart failure undergoing transplantation without left ventricular assist device support, 25 patients with heart failure supported before transplantation (duration of support ranging between 8 and 155 days), and 5 normal human hearts not suitable for transplantation. Left ventricular size was indexed by the volume at which left ventricular pressure reached 30 mm Hg. Left ventricular tissue samples were probed for sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression and processed for analysis of myocyte diameter and relative myocardial collagen content.


RESULTS
The volume at which left ventricular pressure reached 30 mm Hg was not significantly different between hearts without and with assist device support for less than 40 days. However, the volume at which left ventricular pressure reached 30 mm Hg in patients with assist devices supported for more than 40 days was significantly smaller than that of the hearts without assist devices but was larger than that of normal hearts. A similar pattern was observed for myocyte diameter. Sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression increased to normal levels by about 20 days of support with an assist device. Relative collagen content was significantly increased in hearts supported for more than 40 days.


CONCLUSIONS
Maximum structural reverse remodeling by left ventricular assist devices is complete by about 40 days. Molecular reverse remodeling of sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression is quicker, being complete by about 20 days.
Madigan
J D
JD
Departments of Medicine and Surgery, Columbia University, Black Building 812, 650 West 168th Street, New York, NY 10032, USA. jdm50@columbia.edu
Barbone
A
A
Choudhri
A F
AF
Morales
D L
DL
Cai
B
B
Oz
M C
MC
Burkhoff
D
D
D015152:Blotting, Northern; D000252:Calcium-Transporting ATPases / Q000032:analysis; D003094:Collagen / Q000032:analysis; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006352:Heart Ventricles / Q000737:chemistry; D006353:Heart-Assist Devices; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013318:Stroke Volume; D013997:Time Factors; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
D003094:Collagen; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases