Death hath a thousand doors to let out life...

Myocardial structural remodeling, a progressive, often self-perpetuating process, is an important marker of progressive heart failure. Myocardial cell loss, through any number of mechanisms mediating cellular death, is an important component in its genesis.1 Traditionally, necrosis has been regarded as the pathological hallmark of myocardial cell death. However, there is accumulating evidence that cells can die through a number of other mechanisms including programmed and nonprogrammed cell death. The elegant study in this issue of Circulation Research by Kostin and colleagues2 makes an important addition to the list of intriguing ways that life or death decisions are made in the failing heart. They found that in addition to apoptosis and necrosis,3,4 cardiac cells can also die through autophagy associated with ubiquitylated protein accumulation. Apart from mechanistic insights, these kinds of new data might have a therapeutic potential. A broad look at cell survival or death and its implications may thus be in order.