Background

Objective

Outline
Results

Discussion
Sacubitril/Valsartan
(Entresto)

(1)
Background

Sacubitril/Valsartan (Entresto) reduced mortality and hospitalizations in patients with

HFrEF in PARADIGM-HF (2).

Retrospective analyses and registry data have shown that patients with HFrEF taking
Entresto have beneficial changes to RV function with increases in TAPSE and decrease
in mean PA pressures (3,4).

Patients with systemic RV dysfunction are usually excluded from drug trials
Prior Investigations of Entresto in Patients
with Systemic RV Dysfunction
Maurer et al., 2019:

• Retrospective evaluation of 23 patients with moderate to severe congenital heart

disease (52% systemic RV) showed no improvement in system RV function or NYHA
functional status (5)

Zandstra et al., 2021:

• Prospective 20 patient cohort of patients with a failing systemic RV (RVEF <35%)

treated with Entresto showed
• Reduction in NT-pro-BNP (950 ng/L -> 358 ng/L, p < .001
• Improvement in RV FAC (19% -> 22%, p < .001)
• Improvement in 6 min walking distance (564 -> 600 m, p = .01) (6).
 Methods
Prospective investigation if patients with either d-TGA with prior Senning/Mustard procedure or
ccTGA benefit from Entresto use.

Primary efficacy outcomes:

NT-proBNP Systolic function improvement

Secondary efficacy outcomes:

NYHA class 6-minute walking distance Quality of life change

 Methods
All patients with ccTGA or d-TGA with Senning/Mustard repair at a tertiary ACHD center were
reviewed for study eligibility

Inclusion criteria:
Age > 18 On an ACEi or ARB for at least 3 months sRV EF < 40% or RV FAC < 35%

Exclusion criteria
Univentricular physiology Systolic BP < 90 mmHg K > 5.5 GFR < 30 ml/min.
 Methods
• Patients were started on 49/51mg Entresto if they
were on 80mg Valsartan or equivalent dosage
ACEi/ARB.
• Those on lower doses of ACEi/ARB were started
on 24/26mg BID
• Patients were evaluated at 4 time points: 1, 3, 6
and 12 months.
• Dose adjustments were performed at each
follow up visit with uptitration as tolerated.
• Echocardiographic evaluations included
• Global Longitudinal Strain, RV FAC, RV 3D EF
Results
Patient Population

•51 Patients
•Average age 38
•65% d-TGA
•35% cc-TGA
Results –
Patient
population

8% NYHA I
74% NYHA II
3% NYHA III
One patient refused
treatment and one was lost
to follow up.

Male patients were more

likely to reach target dose
by 1 year (p = .008)
Male: 18/29
Female: 4/18

Target dose of 97/103mg

BID reached in 22 patients
(46%).
Primary Outcomes

FAC RV GLS: RV 3D EF:

29.2% -> 34.9% -13.9 -> -15.1 35.6 -> 41.5%

 Baseline: 239
NT-pro 6 min walk Baseline: 425
12 months: 500
BNP 12 months: 181 distance p = < .001
p = .07
Secondary
Outcomes

NYHA 47% with at least

Improvement in
class
one grade of
improvement
QOL physical functioning
Discussion
• Strengths:
• Largest prospective evaluation of entresto on patients with failing systemic RV
• Well tolerated – 47/50 patients able to tolerate entresto
• Longer follow up period (compared to 6 months on previous prospective evaluation)
• Weaknesses:
• Mix of means and medians reported – unclear what degree of data manipulation is present
• Not randomized
• Other notes
• Appears to be better tolerated as compared to PARADIGM-HF population
• In paradigm-HF: 16% of people developd K > 5.5, 12% withdrawal rate altogether, as compared to just one
patient withdrawing due to side effects here
• Fairly healthy population (20% NYHA class 3; 80% class 1 or 2)
Citations
• 1.https://www.britishcardiovascularsociety.org/resources/editorials/
articles/sacubitrilvalsartan-where-are-we-now
2.https://www.nejm.org/doi/full/10.1056/nejmoa1409077
• 3.https://pubmed.ncbi.nlm.nih.gov/33003523/
• 4.https://pubmed.ncbi.nlm.nih.gov/32140553/
• 5.https://pubmed.ncbi.nlm.nih.gov/31242968/
• 6.https://pubmed.ncbi.nlm.nih.gov/33452121/