Editors' ChoiceCardiovascular Medicine

Restoring Rhythm in the Broken Heart

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Science Translational Medicine  19 Sep 2012:
Vol. 4, Issue 152, pp. 152ec168
DOI: 10.1126/scitranslmed.3004931

Even if you survive, a heart attack leaves behind a permanent scar in the heart muscle. This scar can serve as a nidus for electrical instability in the heart, causing a communication breakdown between heart cells and producing life-threatening arrhythmias (abnormal heart beats). In spite of our best medical efforts to combat these effects, sudden cardiac death after heart attack occurs in more than 1000 patients a day in the United States. Now, Greener et al. have created a new therapy involving gene transfer of the gap junction protein connexin 43 (Cx43) that could restore normal electrical conduction to parts of the scarred heart.

Gap junctions are specialized structures that permit direct communication between adjacent cells—you might think of them as portals that allow the flow of ions and other small molecules. Heart cells communicate via Cx43 in gap junctions to achieve organized contraction and efficient pumping of blood. Greener and colleagues first gave a group of pigs a controlled heart attack and implanted them with defibrillators. From this group, they picked those that developed an inducible arrhythmia and treated them with a control adenovirus vector, no virus, or a vector that overexpressed Cx44 (AdCx43) through infusion into the coronary arteries. In 6 out of the 10 animals treated with AdCx43, the inducible arrhythmias disappeared. In contrast, all of the control animals were still able to experience arrhythmias. In addition, electrophysiological studies on the heart showed an increase in conduction in the scarred region in AdCx43-treated animals.

Greener et al. demonstrate that gene transfer after heart attack can reduce the risk of arrhythmias after heart attacks in pigs. However, previous studies have shown that increased Cx43 expression can also increase the damaged area of the heart during heart attack. Thus, the timing of therapy may be a critical component in making the transition to treating human patients. Although their studies show promise for treating human disease, further work is needed to carefully assess safety of such treatment before it can be translated to the clinic.

I. D. Greener et al., Connexin43 gene transfer reduces ventricular tachycardia susceptibility after myocardial infarction. J. Am. Coll .Cardiol., published online 2 August 2012 (10.1016/j.jacc.2012.04.042). [Abstract]

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