Combined Post- and Precapillary Pulmonary Hypertension in Patients With Advanced Heart Failure

Pulmonary hypertension associated with left heart disease, or group 2 pulmonary hypertension, is common in patients with advanced heart failure. In at least a third of these patients, the pulmonary pressures are disproportionately elevated relative to left heart filling pressures and are classified as combined post- and precapillary pulmonary hypertension (CpcPH). CpcPH is thought to result not only from chronically elevated left heart filling pressures but also from neurohormonal activation, a genetic predisposition, and other risk factors. Traditional pulmonary vasodilator therapies are not efficacious and may be harmful in CpcPH. For patients with advanced heart failure, higher-risk CpcPH hemodynamics, particularly significantly elevated or nonreversible pulmonary vascular resistance and transpulmonary gradient, may preclude isolated heart transplantation, while acute vasodilator testing may identify patients who can proceed with acceptable risk. Strategies to minimize posttransplant risk in recipients with CpcPH based on donor selection, for example, oversizing of the donor by relative predicted heart mass or selecting donors with preexisting PH, remain unproven. This review serves to (1) highlight new insights into the pathophysiology and epidemiology of CpcPH; (2) summarize the existing literature surrounding indications for, and interpretation of response to, acute pulmonary vasodilator testing; (3) provide recommendations for management of patients with heart failure and CpcPH, with a particular focus on advanced therapies; and (4) identify knowledge gaps and future research priorities.