Systems and methods for treating cardiac tissue are disclosed. A method in accordance with one embodiment of the invention is directed to treating cardiac tissue that includes a primum, a secundum adjacent to the primum, and a patent foramen ovale (PFO). The method can include shrinking the primum at a first location spaced apart from the PFO, and at least partially sealing the PFO by applying energy at a second location at least closer to the PFO than the first location. A variety of techniques, including vacuum, mechanical, chemical, RF energy and ultrasound can be used to shrink the primum. In at least some embodiments, shrinking the primum can be performed independently of whether a PFO is also sealed, for example, if the patient receiving the treatment does not have a PFO.