2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction

Kittleson, M.; Panjrath, Gurusher; Amancherla, Kaushik; Davis, Leslie L.; Deswal, Anita; Januzzi, James L.; Yancy, Clyde W.

doi:10.1016/j.jacc.2023.03.393

Cited by 132 publications

(88 citation statements)

References 235 publications

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“…In the case of HFpEF, these proposed mechanisms are hypothesized in the context of the pathophysiology of HFpEF consisting of hypertensive ventricular stiffening, obesity-cardiometabolic stress, and microvascular inflammation. 16,17…”

Section: Under S Tanding Mechanis Tic Propertie Smentioning

confidence: 99%

“…Although the full mechanism of SGLT2i in CV disease remains unknown, these potential targets may exert possible direct and indirect beneficial benefits. In the case of HFpEF, these proposed mechanisms are hypothesized in the context of the pathophysiology of HFpEF consisting of hypertensive ventricular stiffening, obesity‐cardiometabolic stress, and microvascular inflammation 16,17 …”

Section: Understanding Mechanistic Propertiesmentioning

confidence: 99%

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Expanded use of sodium‐glucose cotransporter 2 inhibitors: Evidence beyond heart failure with reduced ejection fraction

et al. 2023

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Following the results observed in the DAPA‐HF trial and subsequent FDA approval of dapagliflozin in patients living with heart failure with reduced ejection fraction (HFrEF), numerous trials quickly began to assess the effects of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) in a wide range of cardiovascular (CV) conditions. Since the publication of those findings, multiple SGLT2i have demonstrated benefit in patients regardless of left ventricular ejection fraction (LVEF)—allowing the drug class to establish itself within the first line of guideline‐directed medication therapy. Although the full mechanistic properties of SGLT2i in heart failure (HF) have yet to be fully understood, benefits in other disease states have continued to emerge over the past decade. This review summarizes the findings of 14 clinical trials investigating the use of SGLT2i in various CV disease states, with a special focus on HF with preserved ejection fraction (HFpEF) and acute decompensated HF (ADHF). Additionally, studies assessing the CV‐related mechanisms, cost‐effectiveness, and exploratory effects of dual SGLT1/2 blockade are described. A review of select ongoing trials has also been incorporated to further characterize the research landscape with this medication class. The aim of this review is to serve as a comprehensive tool for healthcare providers to better understand how this class of diabetes medications established its place in the treatment of HF.

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Section: Under S Tanding Mechanis Tic Propertie Smentioning

confidence: 99%

Section: Understanding Mechanistic Propertiesmentioning

confidence: 99%

Expanded use of sodium‐glucose cotransporter 2 inhibitors: Evidence beyond heart failure with reduced ejection fraction

et al. 2023

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“…which regulates the inflammatory and atherogenic balance at a local and systemic level, 12 is associated with an adverse prognosis both in HFpEF 13 and AS. 14 Also, both conditions are characterized by elevated natriuretic peptide serum levels 15,16 and increased extravascular lung water, [16][17][18] all associated with more pronounced haemodynamic derangements and a higher risk of adverse events. [15][16][17] Despite such pathophysiologic similarities, patients with AS and preserved LVEF (≥50%; ASpEF) are not usually considered as actually having HFpEF.…”

Section: Introductionmentioning

confidence: 99%

“…In this regard, epicardial adipose tissue (EAT), which regulates the inflammatory and atherogenic balance at a local and systemic level, 12 is associated with an adverse prognosis both in HFpEF 13 and AS 14 . Also, both conditions are characterized by elevated natriuretic peptide serum levels 15,16 and increased extravascular lung water, 16–18 all associated with more pronounced haemodynamic derangements and a higher risk of adverse events 15–17 …”

Section: Introductionmentioning

confidence: 99%

“…Focusing only on the AV might limit a complete understanding of the pathophysiology behind AS. Indeed, in a recent position paper of the American College of Cardiology, valvular heart disease is defined as an ‘HFpEF mimic’ rather than a potential alternative HFpEF phenotype 18 . We designed the present study to provide a non‐invasive haemodynamic and metabolic characterization of ASpEF at rest and during exercise, highlighting the main similarities and differences with HFpEF.…”

Section: Introductionmentioning

confidence: 99%

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Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction?

De Biase,

Mazzola,

Del Punta

et al. 2023

European J of Heart Fail

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BackgroundDegenerative aortic valve stenosis with preserved left ventricular ejection fraction (ASpEF) and heart failure with preserved left ventricular ejection fraction (HFpEF) display intriguing similarities. We designed this study to provide a non‐invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise.Methods and resultsWe prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate‐to‐severe ASpEF, together with 66 age‐ and sex‐matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary‐exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n=125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high‐gradient aortic stenosis; 6/150 (4%) had normal‐flow, low‐gradient ASpEF, while 10/150 (7%) had low‐flow, low‐gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO2), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p<0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p<0.01 vs controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO2 in all groups. In ASpEF, EAT was directly related to echocardiography‐derived disease severity and CT‐derived aortic valve calcium burden.ConclusionsFunctional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific subphenotype of HFpEF.This article is protected by copyright. All rights reserved.

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Atrial Shunt Device Effects on Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction

Patel,

Silvestry,

Komtebedde

et al. 2024

JAMA Cardiol

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ImportanceAlthough the results of A Study to Evaluate the Corvia Medical Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF II) trial were neutral overall, atrial shunt therapy demonstrated potential efficacy in responders (no latent pulmonary vascular disease and no cardiac rhythm management device). Post hoc analyses were conducted to evaluate the effect of shunt vs sham stratified by responder status.ObjectiveTo evaluate the effect of atrial shunt vs sham control on cardiac structure/function in the overall study and stratified by responder status.Design, Setting, and ParticipantsThis was a sham-controlled randomized clinical trial of an atrial shunt device in heart failure with preserved ejection fraction (HFpEF)/HF with mildly reduced EF (HFmrEF). Trial participants with evaluable echocardiography scans were recruited from 89 international medical centers. Data were analyzed from April 2023 to January 2024.InterventionsAtrial shunt device or sham control.Main Outcome MeasuresChanges in echocardiographic measures from baseline to 1, 6, 12, and 24 months after index procedure.ResultsThe modified intention-to-treat analysis of the REDUCE LAP-HF II trial included 621 randomized patients (median [IQR] age, 72.0 [66.0-77.0] years; 382 female [61.5%]; shunt arm, 309 [49.8%]; sham control arm, 312 [50.2%]). Through 24 months, 212 of 217 patients (98%) in the shunt arm with evaluable echocardiograms had patent shunts. In the overall trial population, the shunt reduced left ventricular (LV) end-diastolic volume (mean difference, −5.65 mL; P &lt;.001), left atrial (LA) minimal volume (mean difference, −2.8 mL; P =.01), and improved LV systolic tissue Doppler velocity (mean difference, 0.69 cm/s; P &lt;.001) and LA emptying fraction (mean difference, 1.88 percentage units; P =.02) compared with sham. Shunt treatment also increased right ventricular (RV; mean difference, 9.58 mL; P &lt;.001) and right atrial (RA; mean difference, 9.71 mL; P &lt;.001) volumes but had no effect on RV systolic function, pulmonary artery pressure, or RA pressure compared with sham. In the shunt arm, responders had smaller increases in RV end-diastolic volume (mean difference, 5.71 mL vs 15.18 mL; interaction P =.01), RV end-systolic volume (mean difference, 1.58 mL vs 7.89 mL; interaction P =.002), and RV/LV ratio (mean difference, 0.07 vs 0.20; interaction P &lt;.001) and larger increases in transmitral A wave velocity (mean difference, 5.08 cm/s vs −1.97 cm/s; interaction P =.02) compared with nonresponders randomized to the shunt, suggesting greater ability to accommodate shunted blood through the pulmonary circulation enabling LA unloading.Conclusions and RelevanceIn this post hoc analysis of the REDUCE LAP-HF II trial, over 2 years of follow-up, atrial shunting led to reverse remodeling of left-sided chambers and increases in volume of right-sided chambers consistent with the shunt flow but no change in RV systolic function compared with sham. Changes in cardiac structure/function were more favorable in responders compared with nonresponders treated with the shunt, supporting the previously identified responder group hypothesis and mechanism, although further evaluation with longer follow-up is needed.Trial RegistrationClinicalTrials.gov Identifier: NCT03088033

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2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction

Cited by 132 publications

References 235 publications

Expanded use of sodium‐glucose cotransporter 2 inhibitors: Evidence beyond heart failure with reduced ejection fraction

Expanded use of sodium‐glucose cotransporter 2 inhibitors: Evidence beyond heart failure with reduced ejection fraction

Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction?

Atrial Shunt Device Effects on Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction

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