To The Editor,
We read with great interest and commend the contribution of Szabó-Söderberg et al in their recent post-hoc analysis of the TOPCAT-Americas trial “Loop and thiazide diuretics and outcomes in heart failure with preserved ejection fraction.” The study highlights the prognostic indication of diuretics use in HFpEF. Their findings suggested: loop diuretic therapy, especially at higher doses and in combination with thiazides, is associated with increased risk of cardiovascular (CV) death and heart failure hospitalizations (HHFs). In contrast, thiazide monotherapy was not associated with adverse outcomes. That said, I want to bring their attention towards two of my concerns regarding the article.
Firstly, In the study, NT-proBNP levels were not adjusted in primary analysis and only added as a subset in secondary sensitivity analysis. Natriuretic peptides are important in assessing severity of HFpEF and fluid accumulation, elevated NP levels are strongly associated with worse outcomes. Having NP levels would have clarified whether the poorer outcomes in patients receiving diuretics are attributable to the medications themselves or merely a result of more advanced disease in those patients.
Secondly, The research did not provide comprehensive details on patient’s fluid status like peripheral edema, elevated juglar venous pressure, shortness of breath, ascites etc. Since diuretics are primarily used to eliminate excess fluid, understanding fluid levels of each patient would be crucial for analyzing their outcomes. In HFpEF fluid overload is considered a predictor of poor prognosis So without volume status it remains unclear whether the worse clinical outcomes observed in patients receiving higher diuretic doses were due to overdiuresis or whether these patients were already more severely volume-overloaded—thus requiring higher doses—which in turn reflected their worse underlying prognosis.
Clarifying this distinction might be crucial for optimizing treatment strategies in HFpEF. Nonetheless, we sincerely appreciate the efforts of authors on highlighting an important yet complex aspect of HFpEF management. Their evaluation provides significant insights that may guide clinical practice. We value this significant contribution to the field and look forward to ongoing discussions and research on this matter.
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