# SGLT2-remmers, GLP-1-agonisten en MRAs herschrijven de HFpEF-behandeling — pathofysiologische synthese

*geplaatst 2026-09-29 · Hartfalen · Heart failure reviews · doi 10.1007/s10741-026-10671-x · https://hartvaat.nl/2026/09/21/sglt2-remmers-glp-1-agonisten-en-mras-herschrijven-de-hfpef-behandeling-pathofys/*

Deze narratieve review beschrijft hartfalen met een behouden ejectiefractie (HFpEF) als een systemische aandoening waarbij obesitas, type 2-diabetes en chronisch nierfalen samenkomen en leiden tot microvasculaire dysfunctie, endotheelschade en myocardiale fibrose. De auteurs tonen aan dat SGLT2-remmers, GLP-1-agonisten, dual incretintherapieën en (niet-steroïdale) mineralocorticoidreceptorantagonisten complementaire effecten hebben op hemodynamische belasting, metabole dysregulatie, ontsteking en fibrose, wat leidt tot verbeterde cardiovasculaire en renale uitkomsten. Voor de klinische praktijk onderstreept dit de noodzaak van een organ-overkoepelende aanpak waarbij cardiorenale en cardiometabole comorbiditeiten centraal staan in de behandeling van HFpEF.

## English: Heart failure with a preserved ejection fraction: synergy between cardiac and extracardiac mechanisms and effects of novel therapies.

This narrative review frames heart failure with preserved ejection fraction (HFpEF) as a systemic disease driven by the convergence of obesity, type 2 diabetes, and chronic kidney disease, which promote microvascular dysfunction, endothelial impairment, and myocardial fibrosis. It details how SGLT2 inhibitors, GLP-1 receptor agonists, dual incretin therapies, and (non-steroidal) mineralocorticoid receptor antagonists exert complementary effects on hemodynamic stress, metabolic dysregulation, inflammation, and fibrosis, ultimately improving cardiovascular and renal outcomes. For clinical practice, the review underscores the importance of a cardiorenal and cardiometabolic approach, highlighting that effective HFpEF management requires targeting both cardiac and extracardiac pathways.

## Abstract (original, from the publication)

Heart failure with preserved ejection fraction (HFpEF) is a systemic disease in which metabolic comorbidities obesity, type 2 diabetes (T2D), and chronic kidney disease (CKD) converge to drive systemic inflammation, endothelial dysfunction, and myocardial fibrosis. Microvascular dysfunction represents an important link between these comorbidities and abnormalities within and beyond the heart, although its causal contribution to HFpEF remains incompletely established. In addition to promoting myocardial stiffness and diastolic dysfunction, impaired microvascular function across the pulmonary and peripheral circulations may contribute to reduced tissue perfusion, exercise intolerance, and dyspnoea. CKD may further aggravate this process through volume and neurohormonal pathways as well as circulating uraemic and inflammatory factors that impair endothelial function, through a kidney-microvascular axis. Despite its high prevalence and poor prognosis, therapeutic options for HFpEF have historically been limited. Recent advances, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 (GLP-1) receptor agonists and dual incretin therapies (GLP-1/GIP RAs), and (non-steroidal) mineralocorticoid receptor antagonists, have reshaped the therapeutic landscape by improving cardiovascular and renal outcomes in patients with HFpEF. These agents exert complementary effects on hemodynamic stress, metabolic dysregulation, inflammation, and fibrosis, and may also improve microvascular function across multiple vascular beds. In this narrative review, we provide an organ-by-organ synthesis of the pathophysiological interactions among the heart, kidney, systemic microvasculature, pulmonary circulation, and skeletal muscle in CKMS-related HFpEF. We further map the clinical and mechanistic effects of aforementioned therapies across these interconnected organ systems and highlight areas in which mechanistic and clinical evidence gaps remain.

Auteurs: Soufiane Nassiri, M Louis Handoko, Arno A van de Bovenkamp, Vanessa P M van Empel, Daniël H van Raalte, Etto C Eringa

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Bron: Heart failure reviews, https://doi.org/10.1007/s10741-026-10671-x. Bijgewerkt 2026-09-22T01:11:15Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.