Diffuse coronary artery disease is frequently untreatable by coronary artery bypass or angioplasty. Open chest surgical arterialization of the coronary venous system was successfully performed before the widespread use of coronary artery bypass grafting and has been applied in ungraftable patients thereafter. Percutaneous in situ coronary venous arterialization (PICVA) follows this surgical experience, using a series of unique catheter-based devices to arterialize isolated segments of coronary vein, forcing retroperfusion of severely ischemic myocardium. In a series of animals, this procedure had been shown to reduce ischemia and myocardial damage in an infarction model. In the PICVA European Safety trial, the first 11 percutaneous applications of catheter-based coronary bypass in humans revealed feasibility of the technique in highly symptomatic "no-option" patients. Despite two deaths and six failures to create the bypass, we continue to believe that on further development, the catheter-based coronary bypass can become a broad-based interventional application.