Dyspnea was a lousy endpoint. Just reread the releases. They said systolic ejection time (SET) was increased in a concentration dependent manner, and was significant. That almost always results in an increase in the amount of blood the heart propels forward to the body with each beat (which is the fundamental deficiency in congestive heart failure). If they can accomplish this to a significant degree without increasing the heart's oxygen requirements, which has basically been their mantra, the drug should be successful. That's why it was so important that the drug did not increase the heart rate, which is one of the determinants of the heart's oxygen requirements.
I would not say Dyspnea was a lousy endpoint but it has its place as a secondary endpoint among many secondary endpoints.Though Dyspnea might not necessarily be related to mortality,shortness of breath causes panic to a patient and creates frequent hospital visits,which is a financial burden to the health care system.This is also another endpoint in the study,to decrease hospital visits of these patients..
Cohort 3 did show a stat significant trend towards decrease in Dyspnea vs Placebo though trial wasnt powered for this.That result at least opens the door for drug's potential with Dyspnea among other endpoints necessary for future approval.