The authors sought to assess the benefits of pulmonary artery denervation (PADN) among combined pre- and post-capillary pulmonary hypertension (CpcPH) patients in a prospective, randomized, sham-controlled trial. PADN has been shown to improve hemodynamics of pulmonary arterial hypertension in a series of patients. Additionally, benefits of targeted medical therapy for patients with CpcPH secondary to left-sided heart failure are unknown. PADN is associated with significant improvements in hemodynamic and clinical outcomes in patients with CpcPH. Further studies are warranted to define its precise role in the treatment of this patient population. (Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure [PADN-5]; (J Am Coll Cardiol Intv 2019;12:274–84) ? 2019 by the American College of Cardiology Foundation.