Insights into the Interaction of Heart Failure with Preserved Ejection Fraction and Sleep-Disordered Breathing

Abstract

Heart failure with preserved ejection fraction (HFpEF) is emerging as a widespread disease with global socioeconomic impact. Patients with HFpEF show a dramatically increased morbidity and mortality, and, unfortunately, specific treatment options are limited. This is due to the various etiologies that promote HFpEF development. Indeed, cluster analyses with common HFpEF comorbidities revealed the existence of several HFpEF phenotypes. One especially frequent, yet underappreciated, comorbidity is sleep-disordered breathing (SDB), which is closely intertwined with the development and progression of the “obese HFpEF phenotype”. The following review article aims to provide an overview of the common HFpEF etiologies and phenotypes, especially in the context of SDB. As general HFpEF therapies are often not successful, patient- and phenotype-individualized therapeutic strategies are warranted. Therefore, for the “obese HFpEF phenotype”, a better understanding of the mechanistic parallels between both HFpEF and SDB is required, which may help to identify potential phenotype-individualized therapeutic strategies. Novel technologies like single-cell transcriptomics or CRISPR-Cas9 gene editing further broaden the groundwork for deeper insights into pathomechanisms and precision medicine.

CaMKIIδ-dependent dysregulation of atrial Na+ homeostasis promotes pro-arrhythmic activity in an obstructive sleep apnea mouse model

“…Although SDB is associated with increased incidence of atrial fibrillation and lower sustained success of cardioversion or pulmonary vein isolation ( Gami et al, 2004 ; Gami et al, 2007 ; Linz et al, 2018 ), CPAP therapy has failed to reduce the arrhythmia burden and incidence of adverse cardiovascular events ( Peker et al, 2016 ; Traaen et al, 2021 ). Additionally, SDB patients have been reported to frequently suffer from heart failure, especially HFpEF ( Lebek et al, 2021 ; Levy et al, 2022 ; Wester et al, 2023 ). These aspects highlight the urgent need for more targeted and effective therapies for SDB patients.…”

“…Over the past few decades, sleep-disordered breathing (SDB) has emerged as a highly prevalent disease that currently affects about one billion patients worldwide ( Benjafield et al, 2019 ). SDB is frequently associated with various cardiovascular disorders, such as hypertension ( Pengo et al, 2020 ), heart failure with reduced or preserved ejection fractions (HFrEF/HFpEF) ( Arzt et al, 2016 ; Lebek et al, 2021 ; Wester et al, 2023 ; Hegner et al, 2024 ), and arrhythmias like atrial fibrillation ( Gami et al, 2004 ; Hegner et al, 2021a ; Hegner et al, 2021b ; Mehra et al, 2022 ), which may lead to subsequent strokes ( Arzt et al, 2005 ). The interactions between SDB and these cardiovascular disorders can substantially contribute to patient morbidity and mortality while also posing economic challenges ( Gami et al, 2004 ; Arzt et al, 2005 ; Arzt et al, 2016 ; Benjafield et al, 2019 ; Pengo et al, 2020 ; Lebek et al, 2021 ; Mehra et al, 2022 ; Wester et al, 2023 ).…”

“…SDB is frequently associated with various cardiovascular disorders, such as hypertension ( Pengo et al, 2020 ), heart failure with reduced or preserved ejection fractions (HFrEF/HFpEF) ( Arzt et al, 2016 ; Lebek et al, 2021 ; Wester et al, 2023 ; Hegner et al, 2024 ), and arrhythmias like atrial fibrillation ( Gami et al, 2004 ; Hegner et al, 2021a ; Hegner et al, 2021b ; Mehra et al, 2022 ), which may lead to subsequent strokes ( Arzt et al, 2005 ). The interactions between SDB and these cardiovascular disorders can substantially contribute to patient morbidity and mortality while also posing economic challenges ( Gami et al, 2004 ; Arzt et al, 2005 ; Arzt et al, 2016 ; Benjafield et al, 2019 ; Pengo et al, 2020 ; Lebek et al, 2021 ; Mehra et al, 2022 ; Wester et al, 2023 ). The current therapeutic strategies for SDB are mainly based on lifestyle interventions (e.g., weight loss, reduced alcohol intake, sports, and exercise) and continuous positive airway pressure (CPAP) therapy ( Aurora et al, 2012 ; Randerath et al, 2017 ; Patil et al, 2019 ).…”