Zandstra TE, Nederend M, Jongbloed MRM, Kiès P, Vliegen HW, Bouma BJ, Tops LF, Schalij MJ, Egorova AD.
Heart. 2021 Jan 15:heartjnl-2020-318074. doi: 10.1136/heartjnl-2020-318074. Online ahead of print.
PMID: 33452121 Free Article.
Take Home Points:
- There is a huge lack of evidential medical based treatments for patients with ACHD and heart failure.
- In patients with left ventricular systolic dysfunction, Sacubitril-Valsartan (Entresto). has been proven to significantly reduces mortality and morbidity and clearly superior to ACE-I treatment in such patients.
- This study reports on 20 patients with a systemic RV who were switched from their ACE-I/ARB treatment to sacubitril-valsartan (and also taking a beta blocker).
- All patients had systemic RV dysfunction (EF <35%) and were ‘symptomatic’ despite taking a beta blocker and ACE/ARB pre change.
- Two thirds of patients had an atrial switch and the remainder ccTGA.
- 6 month follow up data was obtained in 18/20 patients.
A change from an ACE-I/ARB to sacubitril-valsartan resulted in:
- A fall in NTproBNP level from 950 ng/L to 358 ng/L (p<0.001).
- Improvement in Echo measured FAC and GLS
- Increase in 6MWT from 564m to 600m (p=0.01).
- Improvement in Quality of life measures.
Commentary by Dr. Damien Cullington (Liverpool, UK), section editor of ACHD Journal Watch:
After many years of a lack of new medical therapies in heart failure and more than enough failures, it is refreshing to see the ‘Next Gen’ of agents coming over the horizon. The future is very bright in heart failure and it’s invigorating for all heart failure enthusiasts out there. PARADIGM-HF reported its findings in 2014 – on reflection, it has taken a very long time from publication to a mass roll out even in spite of the striking ‘in your face’ therapeutic positive effects of sacubitril-valsartan (SV).
Zanstra et al. selected ACHD patients for treatment with SV if the systemic RV function was significantly impaired (RVEF <35%) and patients were ‘symptomatic’ despite treatment with maximal tolerated beta blocker and ACE-I/ARB for at least 3 months. RVEF was measured either by echo and/or MRI. Symptoms were subjectively evaluated in out-patient clinic. Before initiation of SV, as part of standard care, all patients had an echo, cardio-pulmonary exercise test using bike ergometry, 6MWT, blood tests and quality of life assessments. The treatment protocol is shown in Figure 1.
Twenty patients were initially enrolled with systemic RV heart failure – evenly split between men/women. Mean age was 46 ± 11 yrs. Two patients were withdrawn. Two thirds of the final analysis group had an atrial switch (n=12) and the remainder had ccTGA anatomy (n=6).
Change in clinical/echo data captured at baseline then at 6 months is shown in Tables 1 & 2. The percentage change in NTproBNP level from baseline to 6 months is shown in Figure 2. Temporal change in indices in quality of life is shown in Table 3.
Whilst one cannot say this data completely seals the deal on SV use in patients with a systemic RV impairment, there is much optimism here and it is well worth sitting up to take note. The majority of the group had grade I/II systemic AV valve regurgitation so perhaps this cohort comprises a more favourably responsive group to SV compared to such patient with more severe degrees of regurgitation who perhaps destined to fail faster and be more refractive to medical treatment – however this study is not designed to investigate this.
A switch from an ACE-I or ARB (of which there is little evidence to support use) to SV resulted in a drop in NTproBNP (one of the strongest independent prognostic markers); marginally improved RV performance within a relatively short space of time; improved 6MWT distance AND improved QOL. This is very promising.
I am not sure there is much further to add aside from the usual mantra of it being desirable to validate these findings in a larger, randomised dataset –realistically, is this going to happen?
If heart failure with LV dysfunction is the fast line at the moment, ACHD heart failure is still very much confined to the slow lane (or even perhaps the hard shoulder). This was a very welcome article to read – yes, it isn’t a randomised controlled clinical trial but it’s very positive signposting.
One further question to ask is, when should one start treatment with SV? It seems somewhat counter-intuitive to patiently wait until the systemic RV has adversely remodelled, then failing with evolving symptoms before starting a restorative treatment. Surely we should be really thinking of starting treatment sooner rather than later before too much ground is lost. Prevention being better than cure. This requires further study.
Given that there is little evidence for the use of any other neuro-hormonal blocking agents in this niche group of patients, I’m fully behind the groups’ thinking and it certainly reflects /supports my current clinical practice – what about yours?