Other limitations arose from the design of the RCTs: heterogeneity in how BNP-guided therapy and symptom-guided therapy was administered; restricted eligibility (mainly younger patients with HFrEF and without co-morbidities), limiting the applicability of the results to the broader HF population; and the potential for bias because most RCTs did not blind clinicians or patients to treatment allocation. Here, NPPB is linked to hydrops fetalis.