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New triple combination therapy approach for children with advanced heart failure despite having received standard

Isa Ozyilmaz¹, Halise Zeynep Genc¹, Senay Coban¹

¹Basaksehir Cam and Sakura City Hospital, Department of Pediatric Cardiology, Istanbul, Turkey.

Cardiology in the Young

|September 1, 2025

Insights

Triple therapy significantly improved left ventricular function in children with advanced heart failure. This treatment approach resolved inotrope dependency, offering a promising option for pediatric heart failure management.

Area of Science:

Pediatric Cardiology
Cardiovascular Research
Pharmacology

Background:

Limited efficacy of monotherapy in pediatric advanced heart failure.
Insufficient clinical data on triple therapy (levosimendan, dapagliflozin, sacubitril/valsartan).
Need to evaluate novel treatment strategies for inotrope-dependent pediatric heart failure patients.

Purpose of the Study:

To assess the impact of triple therapy on left ventricular function in children with advanced heart failure.
To determine if triple therapy can improve cardiac function in patients unresponsive to standard treatments.
To evaluate the resolution of inotrope dependency with triple therapy.

Main Methods:

Retrospective analysis of 18 pediatric patients with advanced heart failure.
Inclusion criteria: inotrope dependency despite 42 days of classical heart failure treatment.
Initiation of triple therapy (levosimendan, dapagliflozin, sacubitril/valsartan) and assessment of cardiac parameters.

Main Results:

Significant improvements observed in left ventricular ejection fraction (2D and Simpson's), end-diastolic and end-systolic diameters, and volumes.
Marked enhancement in left ventricular global longitudinal strain (four-chamber, three-chamber, and mean values).
All observed improvements were statistically significant (p < 0.05).

Conclusions:

Triple therapy demonstrates potential for improving both systolic and diastolic left ventricular function in pediatric advanced heart failure.
This regimen may lead to the resolution of inotrope dependency.
Triple drug therapy offers a viable treatment option for discharge in pediatric heart failure patients.

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Abstract

Aim:

The limited efficacy of monotherapy and the insufficient clinical experience with triple therapy (levosimendan, dapagliflozin, and sacubitril/valsartan) warrant further investigation. The aim of this study was to evaluate the effects of triple therapy on left ventricular function in children with advanced heart failure whose left ventricular function had not improved despite classical heart failure treatment and who remained dependent on inotropes.

Methods:

The study included children who were admitted to the hospital with advanced heart failure and who were still inotrope-dependent at a mean of 42 days after the start of classical heart failure treatment and then started triple therapy at our hospital.

Results:

The study included 18 patients, 8 (44%) males, with a median age of 4 years (2-7 years). Before and after classical treatment and after triple treatment, statistically significant improvement in two-dimensional left ventricular ejection fraction (%) (median values 30; 38; 55, respectively), left ventricular end-diastolic diameter (median values 44; 45; 40 mm), left ventricular end-systolic diameter (median values 38; 36; 29 mm), left ventricular end-diastolic diameter (z score) (median values 4.2; 3.2; 2.7), left ventricular end-systolic diameter (z score) (median values 5.8; 4.8; 3.2), Simpson left ventricular ejection fraction (%) (median values 29; 36.5; 55), Simpson left ventricular end-diastolic volume (median values 60; 55; 43 ml), left ventricular end-systolic volume (median values 43; 40; 18. 5 ml), left ventricular global longitudinal strain four-chamber (median values -8.1;-10;-19), left ventricular global longitudinal strain three-chamber (median values -5.9;-8.9;-14), and left ventricular global longitudinal strain mean (median values -6.9;-9.7;-19) values was observed ( all values p < 0.05 ).

Conclusions:

In children admitted to the hospital with advanced heart failure whose left ventricular function has not improved with classical therapy, it seems likely that both left ventricular systolic and diastolic function will improve, inotrope dependency will resolve, and patients can be discharged with the new triple drug therapy.

Keywords:

Advanced heart failure dapagliflozin levosimendan sacubitril/valsartan

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