A neuromodulation system includes a first therapy element adapted for positioning within a superior vena cava, and a second therapy element adapted for positioning within a pulmonary artery. The first therapy element is carried on a first elongate flexible shaft, and the second therapy element is carried on a second elongate flexible shaft. One of the first and second shafts is slidably received within a lumen of the other of the first and second shafts—so that the second therapy element may be advanced within the body relative to the first therapy element. A stimulator is configured to energize the first therapy element within the first blood vessel to deliver therapy to a first nerve fiber disposed external to the superior vena cava and to energize the second therapy element within the pulmonary artery to deliver sympathetic therapy to a second nerve fiber disposed external to the pulmonary artery. For treatment of heart failure, the first nerve fiber may be a vagus nerve and the second nerve fiber may be a sympathetic nerve fiber.