Sacubitril/Valsartan Improves Hemodynamic Parameters of Pulmonary and Systemic Circulation in Patients Awaiting Heart Transplantation

<b>Background/Objectives</b>: Heart transplantation (HTX) is the definitive treatment for advanced heart failure (AdHF). The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (S/V) has been shown to reduce heart failure (HF) hospitalizations and mortality when compared to conventionally administered HF medications (i.e. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs)). Nevertheless, limited data are available on the hemodynamic (HD) effects of ARNI in patients with AdHF. Therefore, the aim of the present study was to compare echocardiographic, laboratory, and HD parameters relevant to HF before and after switching to ARNI in patients with AdHF awaiting HTX. <b>Methods</b>: A retrospective analysis was conducted utilizing available data on HD parameters, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, data on kidney function, HF therapy, and comorbidities. The study cohort comprised 13 AdHF patients (3 women, 10 men; mean age 56.4 ± 9 years) of whom 53.8% presented with non-ischemic and 46.2% with ischemic etiology. All patients were awaiting heart transplantation (HTX) and were transitioned to ARNI therapy between 2018 and 2021. <b>Results</b>: After switching to ARNI, we observed significant improvements: in left ventricular ejection fraction (LVEF: 27.27 ± 1.04% vs. 23.65 ± 1.02%, <i>p</i> = 0.03; data are given as mean ± SEM after vs. before ARNI therapy, respectively), cardiac output (CO: 4.90 ± 0.35 L/min vs. 3.83 ± 0.24 L/min, <i>p</i> = 0.013), and stroke volume (SV: 70.9 ± 5.9 mL vs. 55.5 ± 4.12 mL, <i>p</i> = 0.013). Significant reductions in systemic vascular resistance (SVR: 1188 ± 79.8 vs. 1600 ± 100 DS/cm⁵, <i>p</i> = 0.004) and pulmonary vascular resistance (PVR: 232.5 ± 34.8 vs. 278.9 ± 31.7 DS/cm⁵, <i>p</i> = 0.04) were also noted. Central venous pressure (CVP), pulmonary arterial systolic and diastolic pressures (PAPs and PAPd), pulmonary capillary wedge pressure (PCWP), and NT-proBNP levels did not exhibit significant changes upon ARNI administration. <b>Conclusions</b>: Early transition to ARNI therapy offers significant benefits for invasively measured hemodynamic parameters in patients with AdHF, potentially aiding in the stabilization and improvement of this vulnerable patient population.