Atrophy of Myocardium and Its Myocytes by Left Ventricular Assist Device
To the Editor:
Dipla and coworkers1 believe that their data support the notion that a temporary left ventricular assist device (LVAD) obviates the need of cardiac transplantation of the failing heart. Barry2 supports this notion.
The LVAD is a double-edged sword. The beneficial effects of this device are well known. Its action ensures sufficient nutrition to the peripheral tissues so that they can recover from starvation and also eliminates or decreases the harmful effects of the increased catabolic products produced by the starved tissues. Harmful effects of the LVAD are due to the rapid, profound decrease of cardiac work (contraction) that leads to atrophy of the myocardium and its myocytes.
An excellent description of the morphological changes that occur in myocardial atrophy is present in Bargmann and Doerr’s textbook.3 Modern textbooks of medicine and cardiology ignore this subject, with the exception of Braunwald’s,4 which devotes a single sentence published in fine print to it. This is as it should be. To quote Friedberg,5 “myocardial atrophy is a pathological entity and not a clinical disease.”
However, atrophy of the myocardium and its myocytes produced by LVAD tells a different story. It is sudden in onset and affects all the myocytes.
A photograph of the myocytes (not present in the text) taken from hearts that were on LVADs shows that these myocytes are smaller than normal, misshapen, occasionally broken, and separated from each other by wide open spaces. This is the picture of severe atrophy of the myocytes. The legend under Figure 2 states that the resting cell length of the myocytes that had been on the assist and had not been on the assist is similar. This is not true. The resting cell length of the myocytes from the heart failure patients was 175 μm, whereas that on the device was 169 μm.
If one considers the enormous number of myocytes that are in the heart and that they are 3-dimensional, not linear, one can anticipate that the mass of the heart and its size had diminished considerably when on the device. It is very likely that this shrinkage of the heart could have been recognized had a film of the chest and an echocardiogram been taken just before the assist was activated and immediately after it was inactivated.
Furthermore, the authors state that the myocytes on the device were able to maintain a higher percent shortening than the heart failure myocytes that were not on the device. The heart does not recognize percentages. The heart responds to the load imposed on it.
In a series of very elegant and beautiful experiments, Galinanes and coworkers6 used a novel heterotopic rat heart transplant preparation with the objective of investigating the effect of load on cardiac contractile function, mass, and high-energy phosphates over a 7-day period. In 1 group of rabbit hearts, conventional unloaded transplant preparation was used. In another group, novel loaded preparation was used in which the circulation of the blood was changed so as to divert distal venous blood to the left ventricle of the transplanted heart. In the first group, left ventricular developed pressure had fallen to 96 compared with 162 mm Hg in fresh controls. In group 2, left ventricular diastolic pressure and left ventricular volume were significantly higher than in group 1. The unloaded heart exhibited a significant loss of left ventricular weight. However, there was no significant weight loss in the loaded hearts. In conclusion, imposition of a load on the heterotopically transplanted heart prevented the loss of cardiac mass.
Kinoshita and coworkers7 studied the influence of prolonged ventricular assistance on the normal myocardium from the pathological viewpoint. They concluded that long-term ventricular assistance leads to myocardial atrophy. In addition, there is a possibility that compensatory hypertrophic changes in the residual intact myocardium can be limited.
There is, therefore, no likelihood that the assist can obviate the need for cardiac transplantation. Indeed, it is likely that the heart is weaker after the assist is inactivated than it was before the assist was activated, because the compensatory hypertrophy of the failing heart has diminished.
Finally, form and function look at the same object but with different lenses.
- Copyright © 1999 by American Heart Association
Dipla K, Mattiello JA, Jeevanandam V, Houser SR, Margulies KB. Myocyte recovery after mechanical circulatory support in humans with end-stage heart failure. Circulation. 1998;97:2316–2322.
Barry WH. Load-dependent myocyte dysfunction. Circulation. 1999;97:2297–2298.
Bargmann W, Doerr W. Das Herz des Menschen. Stuttgart, Germany: George Thieverlag.
Braunwald E. Heart Disease: A Textbook of Cardiovascular Medicine. Philadelphia, Pa: WB Saunders; 1996.
Friedberg CK. Diseases of the Heart. Philadelphia, Pa: WB Saunders; 1958.
As a respected senior colleague, Dr Soloff offers a valuable perspective concerning the results of our recent studies. Although our findings demonstrate improved in vitro myocyte function after mechanical circulatory support, the ability of mechanical support to induce lasting myocardial recovery from chronic failure remains essentially unproven. Indeed, much of the work that we and others will be performing over the coming years will attempt to address the important issues raised in Dr Soloff’s timely and erudite letter. Better understanding of distinctions between atrophy and recovery, load-dependent versus load-independent responses, cell versus organ function, and transient versus lasting effects will ultimately be the fruits of our ongoing inquiry.