It's no secret increasing generic competition and regulatory oversight, combined with the financial challenges of developing a primary care drug, make cardiovascular a tough place for venture-backed biotechs. START-UP takes the pulse of four previously profiled cardiovascular companies -- arca Biopharma, Celladon, NovaCardia and Portola Pharmaceuticals, -- to see what lessons they've learned.

In 2007, what did Series A venture investments reveal about the state of the health care industry? It was very healthy, thank you. There were quite a few deals to choose from, and numbers demonstrated continued growth in diagnostics fundraising, a resurgence in vaccines, and evidence of pharma's interest in proof-of-concept projects and large-molecule platforms. Medical device investors, meanwhile, remain enamored with concept companies seeking to blend electronics-such as neurostimulation or miniature sensors-with devices.

Domain partner Eckard Weber has become a master of the one-two punch in venture investing. The process (now in its third iteration following Merck's $350 million acquisition of NovaCardia): find a drug no one cares about; create a low-infrastructure company around it; find a second drug; sell off the lead drug through an acquisition; develop the second drug a bit more with the same management; then sell that one too. The first deal at a minimum pays back the investors; the second deal juices the returns. It's a model many VCs want to follow.