Angiotensin receptor neprilysin inhibitor treatment is safe and potentially efficacious in end‑stage hypertrophic cardiomyopathy

Comparison of 12-month kinetics of serum markers of fibrosis between treatment with angiotensin receptor neprilysin inhibitor (ARNI) and angiotensin converting enzyme inhibitor (ACE-I) in patients with heart failure with reduced ejection fraction

“…So far,just three studies have addressed the issue of ARNI treatment with regards to MF in HF patients: two studies on HFrEF (both being sub-analyses of the landmark PARADIGM-HF trial, albeit with populations of slightly different sizes),and one study in HF with preserved EF (HFpEF) [6][7][8]. In a similar manner to our research, these studiesinvestigated MF by means of a variety of circulating markers of fibrosis.In the first sub-analysis of PARADIGM-HF, Zile et al observed that, after eight months of ARNI therapy,concentrations of circulating fibrosisbound biomarkers, including soluble suppression of tumorigenicity 2 (sST2), matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of matrix metalloproteinase (TIMP-1), Galectin-3 (Gal-3), N-terminal propeptide of collagen I (PINP) and PIIINP,fell to a greater degree in the ARNI treatment group compared to the enalaprilgroup [6]. In a comparable analysis, authors from the same team confirmed more pronounced reductions of sST2 levels in ARNI-treated patients and an association between baseline sST2 with outcomes [7].…”

“…show numerous beneficial effects in HFrEF, as well as MF attenuating effects [3]. Arecentlyintroduced class of agentsangiotensin receptor neprilysin inhibitors (ARNI) -have proven to be superior in patients with HFrEF of various etiologiesin comparison to ACE-I/ARB; however, the role of ARNItreatment in MF is as yet poorly understood [4][5][6].…”

Design of the SILICOFCM study: Effect of sacubitril/valsartan vs lifestyle intervention on functional capacity in patients with hypertrophic cardiomyopathy

“…Participants undergo study treatment for 4 months, which was deemed sufficient to observe potentially beneficial effects of the complementary addition of sacubitril/valsartan to the optimal standard therapy of HCM. Comparable treatment durations with sacubitril/valsartan were previously shown to significantly reduce NT‐proBNP in patients with heart failure with preserved ejection fraction and to improve cardiac function in the above mentioned case report of a patient with HCM …”

“…Therefore, first mechanistic insight must be derived from experimental data and a single case report: Sacubitril/valsartan was shown to attenuate left ventricular remodeling and dysfunction by inhibiting cardiac fibrosis and hypertrophy in both in vivo‐ and in vitro‐analyses . The first positive response to treatment with sacubitril/valsartan in HCM has been described in a case report by Rubis et al: a middle‐aged woman with nonobstructive end‐stage HCM was treated with sacubitril/valsartan for 3 months, which resulted in marked improvements in symptoms and exercise tolerance as well as an enhanced left ventricular function and decreased NT‐proBNP levels …”

The Function of Seven Transmembrane Receptors in the Cardiovascular System and Their Role in the Development of Cardiomyopathy

“…Another study showed that this angiotensin receptor-neprilysin inhibitor reduced inflammation, oxidative stress and apoptosis in vitro and in vivo [45]. It has also been stated that in end-stage hypertrophic cardiomyopathy, the modern Angiotensin receptor neprilysin inhibitor treatments are both safe and effective [46]. Angiotensin-converting enzyme 2 (ACE2) has also showed therapeutic potential when looking at doxorubicin-induced cardiomyopathy rat models [47].…”