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Sacubitril/Valsartan Reduces mPAP, Improves Functional Capacity in HFpEF-PH


Sacubitril/valsartan reduced mean pulmonary artery pressure (mPAP) and improved lung congestion, functional capacity, and quality of life in a subset of patients with heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH) using a remote monitoring platform.

A study published in ESC Heart Failure found that sacubitril/valsartan (Sac/Val) improved the mean pulmonary artery pressure (mPAP) of patients with heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH) using a remote monitoring platform, along with quality of life, functional capacity, and lung congestion.

The authors said, to their knowledge, this is the first study to examine the effect of Sac/Val in a subset of patients with HFpEF-PH who are monitored with a hemodynamic monitoring (CardioMEMS; Abbott) device.

The study took place from October 2020 to May 2021. There were 3 periods studied in the group:

  • A 6-week period after the implantation of the CardioMEMS device and before Sac/Val treatment (pre-angiotensin receptor-neprilysin inhibitor [pre-ARNI])
  • A 6-week period following initiation of Sac/Val treatment (ARNI ON)
  • A 6-week period following Sac/Val withdrawal (ARNI OFF)

Prescheduled visits occurred at baseline and at weeks 0, 2, 4, 6, and 12. All visits included a clinical assessment, and the visits at baseline, 0, 6, and 12 weeks included a 6-minute walking test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ-12), and European Quality of Life-Visual Analog Scale (EQ-VAS) evaluations.

Fourteen patients were enrolled and participated in the study and received an implantation of the CardioMEMS device. There were 1717 PAP measurements recorded during this study, with a mean (SD) of 122.6 (7.8) per patient.

mPAP significantly declined by 4.99 mm Hg (95% CI, –5.55 to –4.43) between pre-ARNI and ARNI ON periods, but it significantly increased by 2.84 mm Hg (95% CI, 2.26-3.42) between the ARNI ON and ARNI OFF periods. The mean change in mPAP from the day before initiating Sac/Val treatment to day 7 of treatment was a decline of 4.14 (5.7) mm Hg. A decline in mPAP was found during the weeks of the treatment period during the ARNI ON period.

There was a downward trend during the pre-ARNI period with an estimated daily mPAP change of 0.018 mm Hg (95% CI, –0.052 to 0.015). There also was a sharp mPAP decline during the ARNI ON period, with a change of 0.153 mm Hg (95% CI, –0.181 to –0.125) during the first 4 weeks of treatment.

mPAP increased during the ARNI OFF period, with an estimated change of 0.022 mmHg (95% CI, –0.013 to 0.058) during the first 4 weeks of Sac/Val withdrawal.

There was an increase in walked distance between the first pre-ARNI visit and the visit at the end of the ARNI ON period, with mean distances of 270.6 (101.3) vs 298.3 (88.4) m. There was a reduction to 268.5 (109) m at the final ARNI OFF visit. There was also a significant B-line reduction between the first pre-ARNI visit and the visit at the end of the ARNI ON period (9.3 [6.2] vs 4.9 [4.0]) and an increase in B-lines at the final ARNI OFF visit (6.9 [8.4]).

Quality of life was also significantly improved with Sac/Val treatment during the ARNI ON period in both the KCCQ-12 questionnaire and the EQ-VAS questionnaire. There was a greater than 5-point increase in 7 of the 14 patients in the KCCQ-12, and 3 patients had an improvement lower than 5 points. There was a reduced perception of quality of life during the ARNI OFF period. The left atrial diameter index decreased during ARNI ON and increased during ARNI OFF.

There were some limitations to this study. There was a limited sample size for this study that the researchers attempted to mitigate using the 3 study periods. The study also was not designed to evaluate midterm to long-term functional and clinical effects of ARNI on HFpEF-PH. In addition, there were some patients who had a mean pulmonary artery wedge pressure (mPAWP) of less than 15 mm Hg at implantation time because they were clinically stable, although the correct definition of pulmonary hypertension is an mPAWP greater than 15 mm Hg.

The researchers concluded that Sac/Val treatment was able to produce rapid decreases in PAPs and 6MWT, reduction in B-lines, and improvement in quality of life. The researchers suggested that Sac/Val may be a treatment of choice for HFpEF-PH.


Codina P, Domingo M, Barcelo E, et al. Sacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension. ESC Heart Fail. Published online May 19, 2022. doi:10.1002/ehf2.13952

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