Authors’ reply

We sincerely thank Pagnoni et al¹ for their thoughtful and constructive comments on our paper concerning the use of sacubitril / valsartan in patients with pulmonary hypertension due to heart failure with preserved ejection fraction (HFpEF‑PH).

We agree that our observations are preliminary and descriptive by nature, and that the limitations related to the small sample size and absence of a control group require confirmation in larger, prospective studies. We would like to emphasize that our aim was not to present final results of a clinical trial, but rather preliminary findings that represent part of a larger ongoing project.

The aim of the ongoing project is a comprehensive assessment of patients with HFpEF‑PH at baseline and after 3 months of standard therapy supplemented with angiotensin receptor–neprilysin inhibitor (ARNI) treatment. The project does not involve a control group, although it certainly is an important element of randomized controlled trials. Despite some differences in clinical characteristics, the patients presented with stable HFpEF and received pharmacotherapy according to the European Society of Cardiology recommendations,² including optimal doses of diuretics and sodium‑glucose cotransporter 2 inhibitors.

The key strength of the project is that the clinical assessment was verified through invasive testing. This approach is of particular importance in HFpEF, and is obligatory for the diagnosis of PH. There are very few similiar data available in the literature.

We believe that our preliminary observations were significant enough to be published.³ In each of the 5 consecutive cases included in the study, we observed a clinically meaningful reduction in pulmonary pressure and an improvement in functional status, which pointed to potential beneficial effects of ARNI therapy in the studied population.

The echocardiographic parameters mentioned in the letter¹ are only indirect markers of objective left ventricular (LV) filling conditions and pulmonary pressure. These data were also analyzed in our study, and no significant changes were observed in pulmonary artery wedge pressure or echocardiographic indices of LV filling (E/e′ ratio, left atrial volume index) after ARNI therapy.

We would like to express our sincere gratitude to the authors of the letter for presenting pathophysiological hypotheses that might explain our observations. This is a valuable, literature‑based contribution that we will take into account when analyzing biomarkers in our study population.

We acknowledge that, due to a small number of patients and a lack of a control group, our results should be regarded as descriptive and hypothesis‑generating. However, our intention was to highlight a novel, interesting, invasively confirmed phenomenon, which serves as a starting point for further, more structured research into the mechanisms and scope of potential benefits of ARNI therapy in HFpEF‑PH.⁴

We appreciate your constructive feedback and inspiring references, which will undoubtedly help us in planning the next stages of our work.