Skip Navigation
Skip to contents

KMJ : Kosin Medical Journal

OPEN ACCESS
SEARCH
Search
Advanced Search
mobile menu button

Articles

Page Path
HOME > Kosin Med J > Volume 40(2); 2025 > Article
Review article
 The role of the interatrial shunt device in the treatment of patients with heart failure with preserved ejection fraction: experience from the REDUCE LAP-HF studies
Bong-Joon Kimorcid
Kosin Medical Journal 2025;40(2):88-95.
DOI: https://doi.org/10.7180/kmj.24.150
Published online: February 17, 2025

Division of Cardiology, Department of Medicine, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Corresponding Author: Bong-Joon Kim, MD, PhD Division of Cardiology, Department of Medicine, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 633 North Saint Clair Street 19th FL, Chicago, IL 60611, USA Tel: +1-312-409-1153 Fax: +1-312-695-0063 E-mail: kbj1315450@gmail.com
• Received: October 12, 2024   • Revised: December 5, 2024   • Accepted: December 11, 2024

© 2025 Kosin University College of Medicine.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • 743 Views
  • 13 Download
prev next
Full Article

Download PDF Download PDF

  • Heart failure with preserved ejection fraction (HFpEF) is characterized by increased left ventricular filling pressure and elevated left atrial pressure. Despite advances in medical treatments, the management of HFpEF patients is often challenging due to multiple comorbidities, leading to polypharmacy and associated side effects. Consequently, there is an increasing demand for procedural or device-based therapies in HFpEF management. Over the past decade, the transcatheter interatrial shunt device (IASD), designed to create a passage between the left atrium and the right atrium, has emerged as a novel therapeutic option. The IASD offers potential benefits by reducing left atrial pressure at rest and during exercise. The efficacy and safety of the IASD were demonstrated in the REDUCE LAP-HF (Reduce Left Atrial Pressure in Patients with Heart Failure) study series. Furthermore, IASD has been shown to support positive cardiac remodeling. With the availability of more data, appropriate indications for the use of IASDs are becoming more evident, and criteria for patient selection in future studies are needed.
  • Keywords: Atrial pressure; Heart failure; Interatrial shunt device
The difference between heart failure (HF) with preserved ejection fraction (HFpEF) and HF with reduced left ventricular systolic function (HFrEF) is a lack of significant impairment of left ventricular (LV) systolic function. The global prevalence of HFpEF has been increasing, possibly due to heightened awareness, increasingly older population, and a higher prevalence of comorbidities [1-3]. Effective treatment for HFpEF remains a challenge due to the heterogeneity of the condition and lack of diagnostic criteria [4]. Symptoms of HFpEF may not manifest at rest, leading to underdiagnosis. Although biomarkers aid in HFpEF diagnosis, limitations exist due to variable sensitivity, specificity, and the influence of other factors [5]. Recent medications have shown promise in improving HFpEF prognosis but do not produce the significant improvements observed in HFrEF patients.
Therefore, the interatrial shunt device (IASD) has been developed to lower left atrial (LA) pressure [6]. This device represents an innovative treatment for HFpEF and currently is in various stages of clinical trials. This review will discuss IASDs as a potential interventional option for HFpEF, highlighting findings from the REDUCE LAP-HF (Reduce Left Atrial Pressure in Patients with Heart Failure) studies and exploring appropriate patient selection criteria.
HFpEF is characterized by the presence of HF signs and symptoms, coupled with structural and/or functional cardiac abnormalities with elevated natriuretic peptides and an LV ejection fraction (LVEF) ≥50% [7]. Various cardiovascular (CV) risk factors contribute to HFpEF, particularly LA dysfunction caused by elevated LV filling pressures, resulting in LA myopathy and remodeling [8]. Standard diagnostic tests include measures of LA size (LA volume index), which indicates LV diastolic dysfunction, and E/e′, which reflects elevated LV filling pressure. Thus, reducing LA pressure by unloading is a primary therapeutic target in HFpEF [9]. When LA myopathy progresses beyond a certain level, pulmonary hypertension (PH) occurs, commonly called HFpEF complicated by PH (PH-HFpEF). This corresponds to group 2 in the World Health Organization (WHO) PH classification and is the most prevalent subtype [10]. The typical pathophysiology of PH-HFpEF involves secondary PH arising from left HF or valvular disease. As the disease progresses, pulmonary vascular resistance (PVR) increases, leading to irreversible changes and possibly culminating in right HF and death [11].
In the 2021 European Society of Cardiology guidelines, no medications were conclusively recommended to improve outcomes in HFpEF patients [7]. However, subsequent studies have highlighted the efficacy of certain drugs. Sodium-glucose cotransporter 2 (SGLT2) inhibitors (empagliflozin and dapagliflozin) have shown improved outcomes in the EMPEROR-preserved HF and DELIVER trials [12,13]. In addition, angiotensin receptor-neprilysin inhibitors (ARNIs) have shown benefits for specific patient subsets, with expectations that recommendation levels for these drugs will be changed in future HFpEF guidelines. Recent HF guidelines in Europe, the United States, and Korea are being updated to reflect these latest research results (Table 1) [7,14-16]. In particular, the Korean Heart Failure Society actively reflects recent key trials and actively recommends the use of SGLT2-inhibitors and ARNI in HFpEF patients. Emerging evidence indicates that glucagon-like peptide-1 agonists may also offer benefits for HFpEF patients [17,18]. Furthermore, ongoing research is examining the role of mineralocorticoid receptor antagonist agents in HFpEF [19]. Uses of these drugs are expected to be reflected in future HF guidelines.
Despite the availability of medical therapies, not all HFpEF patients experience significant improvement with guideline-directed medical therapy. Because the etiology of HFpEF is diverse, there is no certainty that the effects of medical treatment will be consistent for all HFpEF patients. In addition, it is unclear whether SGLT2 inhibitors, a class I recommendation in HFpEF, will be effective in HFpEF patients whose symptoms persist even after fluid overload has resolved. Furthermore, as the global population ages, HFpEF patients often present with multiple comorbidities, leading to polypharmacy and increased risk of adverse effects such as renal dysfunction, electrolyte imbalances, and hypotension [20,21]. In particular, patients with HF need to undergo up-titration, which involves gradually increasing the doses of various drugs; however, many HF patients are unable to undergo active up-titration due to concerns regarding side effects. Therefore, a demand remains for procedural or device-based therapies in HFpEF management.
Over the past decade, transcatheter atrial shunt therapy has been developed as a treatment to dynamically unload the LA by creating a passage from the LA to the right atrium (RA). The atrial septum is anatomically thin and can be traversed through septal puncture. In theory, this shunt allows blood in the LA, which has relatively high pressure, to pass into the RA, which has relatively low pressure, reducing LA pressure at rest and during exercise, benefiting HFpEF patients [22]. Among the various IASDs, the Corvia atrial shunt device has shown promising efficacy and safety in clinical trials [23-25]. The Corvia IASD System II, an 8-mm double-disc nitinol-based device, has the most evidence supporting its use. Fig. 1 depicts the device.
The REDUCE LAP-HF studies have provided valuable data on the efficacy and safety of IASD therapy (Table 2) [23-29]. The first REDUCE LAP-HF study, a multicenter, open-label trial, included 64 HF patients with LVEF >40% and pulmonary capillary wedge pressure (PCWP) ≥25 mmHg during exercise. The results showed that IASD implantation reduced PCWP during exercise by approximately 2–3 mmHg without procedural complications [23].
The REDUCE LAP-HF I trial, a randomized controlled trial published in 2018, involved 44 HFpEF patients. The results showed a significant reduction in PCWP during exercise in the IASD group compared with the placebo group after 1 month [24].
In the REDUCE LAP-HF II trial, published in 2022, 626 patients were enrolled, and subjects who received IASD were compared with sham controls. Although the IASD group did not demonstrate superior efficacy on the primary endpoint, post hoc analysis results indicated that certain subgroups based on PVR might benefit more from the treatment [25,27]. Another study has shown the positive effects of IASD on cardiac structure and function, such as reducing LA minimal volume and improving LV systolic tissue Doppler velocity [29].
Flow from the LA to the RA through the IASD could theoretically increase right-side volume, raising concerns about potential right ventricular (RV) dysfunction. However, current data do not show significant RV dysfunction following IASD implantation. Regarding volume overload, RA and RV adapt through various compensatory mechanisms, and remodeling progresses accordingly [11]. There are two mechanisms that may explain why increasing RA volume did not significantly affect RV dynamics. First, lowering LA pressure and PCWP may reduce reflected pressure waves, decreasing pulmonary artery (PA) pressure and RV strain [30]. Second, oxygenated blood entering the RA through the shunt may induce PA vasodilation, ultimately reducing RV pressure overload. In a recent post hoc analysis of the REDUCE LAP-HF II study, results indicated no significant effect on PA pressure, RA pressure, or RV systolic function compared with sham controls although RV and RA volumes increased after treatment [29]. If future analyses using RV strain are conducted, it is expected to be helpful in understanding the pathophysiology of RV mechanics following shunt.
The safety outcomes from the REDUCE LAP-HF study series showed that adverse events were rare (Table 3) [23-25]. In the REDUCE LAP-HF II, the IASD group exhibited slightly higher rates in some safety indicators; however, significant difference was not observed in the composite safety endpoint. Recently, the long-term safety outcomes of REDUCE LAP-HF I (5 years) and REDUCE LAP-HF II (3 years) were published [31]. At 5 years in REDUCE LAP-HF I, there were no differences between the groups in CV mortality, HF events, embolic stroke, or new-onset A-fib. Similarly, after 3 years in REDUCE LAP-HF II, there was no difference in the primary outcome (a hierarchical composite of CV mortality, stroke, HF events, and Kansas City Cardiomyopathy Questionnaire score) between the shunt and sham groups in the overall trial. However, while the stroke rate showed no difference between groups among non-responders, among responders, shunt-treated patients had a higher rate of any ischemic stroke compared to sham control patients at 3 years (3.2% vs. 0.0%, p=0.032). The higher stroke frequency observed in some shunt-treated patients is a noteworthy finding and may indicate a potential risk associated with atrial shunts. Nonetheless, caution is needed when interpreting these findings. The study population had an average age of 72 years, with numerous underlying diseases and CV risk factors that could contribute to HF. Additionally, some patients who experienced strokes had pre-existing A-fib. Therefore, it is important to avoid over-attributing these strokes solely to the shunt.
Although the overall results of the REDUCE LAP-HF II were not positive, the clinical benefit of IASD is evident in certain patient subgroups. A subgroup analysis based on PVR revealed that patients with a peak PVR <1.74 Wood units (WU) during exercise appeared to benefit from the shunt; however, subjects with a peak PVR ≥1.74 WU during exercise experienced worse outcomes from the device. These findings are clinically significant because the concept of a responder group for IASD was introduced, and specific PVR values were identified to classify patients.
Borlaug et al. [27] expanded on this concept, categorizing the REDUCE LAP-HF II population into subjects with and without latent pulmonary vascular disease (PVD) and evaluated the effects of IASD. In their analysis, latent PVD was defined as peak PVR ≥1.74 WU (upper tertile) during exercise. Patients with latent PVD had poorer outcomes of IASD, and subjects without PVD experienced positive effects. PVD plays a crucial role in the complexity of HFpEF pathophysiology and management [32].
In HFpEF patients, functional class deterioration and adverse outcomes are frequently associated with RV dysfunction, characterized by an inability to cope with increased afterload demands caused by PVD and elevated LA pressure [33]. Therefore, careful patient selection, particularly with exercise catheterization to assess for PVD, is essential when considering IASD.
Results of recent key trials have shown that medical treatments for HFpEF can improve prognosis. However, many challenges remain, including low quality of life, persistent symptom burden, adverse effects, and polypharmacy. IASD represents a novel therapeutic approach that may be appropriate for select HF patients. In particular, the Corvia shunt device was shown to have favorable safety and feasibility, with positive clinical outcomes in the REDUCE LAP-HF series. Although IASD may not benefit all HFpEF patients and potentially can be harmful in subjects with high PVR, with appropriate patient selection, IASD could be a valuable treatment option for HFpEF in the future.

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Acknowledgments

Dr. Sanjiv Shah (Northwestern University Feinberg School of Medicine, Chicago, IL, USA) shared the results with me on the REDUCE LAP-HF series and gave me the opportunity to analyze the data.

Funding

None.

Author contributions

All the work was done by Bong-Joon Kim.

Fig. 1.
Interatrial shunt device (IASD; courtesy of Sanjiv Shah). (A) Corvia IASD System II. (B) En face view of the IASD System II (single size). (C) The device creates an interatrial shunt that unloads the LA by shunting blood from the higher-pressure LA to the lower-pressure RA. LA, left atrium; RA, right atrium.
kmj-24-150f1.jpg
Table 1.
Comparison of recommendation levels of GDMT in HFmrEF/HFpEF guidelines
ESC guideline 2021 [7] ACC/AHA 2022 [14] KHFS 2022 [15] ESC guideline update 2023 [16]
HFmrEF
 ACEI/ARB IIb IIb IIb IIb
 Beta blockera) IIb IIb IIb IIb
 MRA IIb IIb IIa IIb
 ARNI IIb IIb IIa IIb
 SGLT2-ib) NA IIa Ib I
HFpEF
 ACEI/ARB NA IIb IIb NA
 Beta blockera) NA NA IIb NA
 MRA NA IIb IIb NA
 ARNI NA IIb IIa NA
 SGLT2-ib) NA IIa Ib I

GDMT, guideline-directed medical treatment; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; ESC, European Society of Cardiology; ACC, American College of Cardiology; AHA, American Heart Association; KHFS, Korean Heart Failure Society; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers; MRA, mineralocorticoid receptor antagonist; ARNI, angiotensin receptor/neprilysin inhibitor; SGLT2-i, sodium-glucose cotransporter 2 inhibitor; NA, not available.

a)Evidence-based beta-blockers for heart failure with reduced left ventricular systolic function.

b)Empagliflozin, dapagliflozin.

Table 2.
Summary of the REDUCE LAP-HF trials
Author (year) Study cohort and enrolled patient number Inclusion criteria Primary endpoint Major findings Clinical meaning
Hasenfub et al. (2016) [23] REDUCE LAP-HF study population (n=64) HFpEF, LVEF >40% with PCWP >15 mmHg at rest or PCWP >25 mmHg during exercise Clinical efficacy; functional capacity and clinical status at 6 mo A total of 52% of patients had a decrease in PCWP at rest and 58% had a decrease in PCWP during exercise over a 6-mo period IASD implantation appears feasible and reduces LA pressure during exercise
Feldman et al. (2018) [24] REDUCE LAP-HF I study population (n=44) NYHA class III or ambulatory class IV HF, LVEF ≥40%, PCWP ≥25 mmHg during exercise, and PCWP during exercise at 1 mo Peak PCWP decreased by 3.5 mmHg in the IASD group vs. 0.5 mmHg in the control group (p=0.14) IASD reduces PCWP during exercise in HFpEF
PCWP-RA pressure gradient ≥5 mmHg
Obokata et al. (2019) [26] REDUCE LAP-HF and REDUCE LAP-HF I population (n=79) In the REDUCE LAP-HF and REDUCE LAP-HF I study cohorts, patients with PVR >4 WU or RV dysfunction were excluded Effects of IASD on hemodynamics, O2 content and delivery, and pulmonary vascular function during exercise After IASD, Qp and PA oxygen content increased by 27% and 7%, respectively IASD improves pulmonary vascular function at rest and during exercise in HFpEF
Shah et al. (2022) [25] REDUCE LAP-HF II (n=626) Symptomatic HF with LVEF ≥40% with PCWP ≥25 mmHg during exercise with RA pressure ≥5 mmHg A hierarchical composite of CV death or nonfatal ischemic stroke at 12 mo, rate of total HF events up to 24 mo, and change in KCCQ overall summary score at 12 mo Differences between groups were not observed in the primary composite endpoint (win ratio 1.0; p=0.85) IASD did not reduce the total rate of HF events or improve health status in the population of patients with HFpEF
Borlaug et al. (2022) [27] REDUCE LAP-HF II (n=570) In REDUCE LAP-HF II, patients with RV dysfunction, resting RA pressure >14 mmHg, PVR >3.5 WU at rest or at peak exercise were excluded A hierarchical composite of CV death, nonfatal ischemic stroke, recurrent HF events, and change in health status IASD was associated with worse outcomes in patients with PVD (win ratio, 0.60; p=0.005) and clinical benefit in patients without PVD (win ratio, 1.31; p=0.038) In patients with HFpEF (EF ≥40%), presence of latent PVD identifies those who may worsen with IASD
Litwin et al. (2023) [28] REDUCE LAP-HF II (n=626) Symptomatic HF (LVEF ≥40%) and PCWP ≥25 mmHg during exercise with RA pressure ≥5 mmHg A hierarchical composite of death, HF hospitalization, intensification of diuretics, and change in health status EILAH is more likely to be associated with IASD responsiveness (peak PVR <1.74 WU during exercise) and no pacemaker (p<0.001) EILAH is associated with favorable response to IASD
Patel et al. (2024) [29] REDUCE LAP-HF II (n=621) Symptomatic HF (LVEF ≥40%) and PCWP ≥25 mmHg during exercise with RA pressure ≥5 mmHg Changes in echocardiographic measures from baseline to 1, 6, 12, and 24 mo IASD reduced LV end-diastolic volume, LA minimal volume and improved LV systolic tissue Doppler velocity and LA emptying fraction compared with sham IASD led to reverse remodeling of LV and LA chambers, IASD increases in volume of RA and RV, consistent with shunt flow without change in RV systolic function compared with sham over a 2-yr period

REDUCE LAP-HF, Reduce Elevated Left Atrial Pressure in Patients with Heart Failure; HFpEF, heart failure with preserved ejection fraction; LVEF, left ventricular ejection fraction; PCWP, pulmonary capillary wedge pressure; IASD, interatrial shunt device; LA, left atrium; NYHA, New York Heart Association; RA, right atrium; PVR, pulmonary vascular resistance; WU, Wood unit; Qp, pulmonary flow; PA, pulmonary artery; CV, cardiovascular; KCCQ, Kansas City Cardiomyopathy Questionnaire; PVD, pulmonary vascular disease; EILAH, exercise-induced left atrial hypertension; LV, left ventricle.

Table 3.
Safety outcomes of the REDUCE LAP-HF trials
Safety outcome Trial
REDUCE LAP-HF [23] REDUCE LAP-HF I [24] REDUCE LAP-HF II [25]
Population number 64 IASD (n=22) vs. sham control (n=22) IASD (n=309) vs. sham control (n=312)
Follow-up duration 6 mo 1 mo 12 mo
Composite safety endpoint NA NA IASD 116/308 (38%)
Sham control 97/308 (31%)
p=0.11
Major cardiac eventsa) 0/64 IASD 0/21 IASD 11/308 (4%)
Sham control 0/22 Sham control 2/308 (1%)
p=0.025
Cardiovascular death 0/64 IASD 0/21 IASD 3/308 (1%)
Sham control 0/22 Sham control 2/308 (1%)
Stroke 0/64 IASD 0/21 IASD 1/308 (<1%)
Sham control 0/22 Sham control 0/308
Systemic embolization 0/64 IASD 0/21 IASD 0/308
Sham control 0/22 Sham control 0/308
Vascular complication 0/64 IASD 0/21 IASD 13/308
Sham control 0/22 Sham control 0/308
New onset or worsening renal dysfunction NA IASD 0/21 IASD 22/308 (7%)
Sham control 1/22 Sham control 25/308 (8%)
p=0.65

REDUCE LAP-HF, Reduce Elevated Left Atrial Pressure in Patients with Heart Failure; IASD, interatrial shunt device; NA, not available.

a)Cardiac death, myocardial infarction, cardiac tamponade, and emergency cardiac surgery.

  • 1. Vasan RS, Larson MG, Benjamin EJ, Evans JC, Reiss CK, Levy D. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort. J Am Coll Cardiol 1999;33:1948–55.ArticlePubMed
  • 2. Steinberg BA, Zhao X, Heidenreich PA, Peterson ED, Bhatt DL, Cannon CP, et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation 2012;126:65–75.ArticlePubMed
  • 3. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006;355:251–9.ArticlePubMed
  • 4. Shah SJ, Borlaug BA, Kitzman DW, McCulloch AD, Blaxall BC, Agarwal R, et al. Research priorities for heart failure with preserved ejection fraction: national heart, lung, and blood institute working group summary. Circulation 2020;141:1001–26.ArticlePubMedPMC
  • 5. Kim BJ, Park JH. Role of biomarkers in the heart failure clinic. Kosin Med J 2022;37:4–17.ArticlePDF
  • 6. Jagadeesan V, Gray WA, Shah SJ. Atrial shunt therapy for heart failure: an update. J Soc Cardiovasc Angiogr Interv 2023;2(6Part B):101203.ArticlePubMedPMC
  • 7. Task Force Members, McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2022;24:4–131.ArticlePubMed
  • 8. Thomas L, Abhayaratna WP. Left atrial reverse remodeling: mechanisms, evaluation, and clinical significance. JACC Cardiovasc Imaging 2017;10:65–77.ArticlePubMed
  • 9. Park SM, Lee SY, Jung MH, Youn JC, Kim D, Cho JY, et al. Korean Society of Heart Failure guidelines for the management of heart failure: management of the underlying etiologies and comorbidities of heart failure. Korean Circ J 2023;53:425–51.ArticlePubMedPMCPDF
  • 10. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2022;43:3618–731.ArticlePubMed
  • 11. Rako ZA, Kremer N, Yogeswaran A, Richter MJ, Tello K. Adaptive versus maladaptive right ventricular remodelling. ESC Heart Fail 2023;10:762–75.ArticlePubMedPMCPDF
  • 12. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Bohm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021;385:1451–61.ArticlePubMed
  • 13. Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med 2022;387:1089–98.ArticlePubMed
  • 14. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. J Am Coll Cardiol 2022;79:e263–421.ArticlePubMed
  • 15. Youn JC, Kim D, Cho JY, Cho DH, Park SM, Jung MH, et al. Korean Society of Heart Failure guidelines for the management of heart failure: treatment. Int J Heart Fail 2023;5:66–81.ArticlePubMedPMCPDF
  • 16. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, et al. 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2023;44:3627–39.ArticlePubMed
  • 17. Kosiborod MN, Petrie MC, Borlaug BA, Butler J, Davies MJ, Hovingh GK, et al. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. N Engl J Med 2024;390:1394–407.ArticlePubMed
  • 18. Butler J, Shah SJ, Petrie MC, Borlaug BA, Abildstrom SZ, Davies MJ, et al. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet 2024;403:1635–48.ArticlePubMedPMC
  • 19. Solomon SD, Ostrominski JW, Vaduganathan M, Claggett B, Jhund PS, Desai AS, et al. Baseline characteristics of patients with heart failure with mildly reduced or preserved ejection fraction: the FINEARTS-HF trial. Eur J Heart Fail 2024;26:1334–46.ArticlePubMed
  • 20. Minamisawa M, Claggett B, Suzuki K, Hegde SM, Shah AM, Desai AS, et al. Association of hyper-polypharmacy with clinical outcomes in heart failure with preserved ejection fraction. Circ Heart Fail 2021;14:e008293.ArticlePubMedPMC
  • 21. Wu JR, Moser DK. Medication adherence mediates the relationship between heart failure symptoms and cardiac event-free survival in patients with heart failure. J Cardiovasc Nurs 2018;33:40–6.ArticlePubMedPMC
  • 22. Emani S, Burkhoff D, Lilly SM. Interatrial shunt devices for the treatment of heart failure. Trends Cardiovasc Med 2021;31:427–32.ArticlePubMed
  • 23. Hasenfub G, Hayward C, Burkhoff D, Silvestry FE, McKenzie S, Gustafsson F, et al. A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trial. Lancet 2016;387:1298–304.ArticlePubMed
  • 24. Feldman T, Mauri L, Kahwash R, Litwin S, Ricciardi MJ, van der Harst P, et al. Transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction (REDUCE LAP-HF I [REDUCe Elevated Left Atrial Pressure in Patients with Heart Failure]): a phase 2, randomized, sham-controlled trial. Circulation 2018;137:364–75.ArticlePubMed
  • 25. Shah SJ, Borlaug BA, Chung ES, Cutlip DE, Debonnaire P, Fail PS, et al. Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial. Lancet 2022;399:1130–40.ArticlePubMed
  • 26. Obokata M, Reddy YNV, Shah SJ, Kaye DM, Gustafsson F, Hasenfub G, et al. Effects of interatrial shunt on pulmonary vascular function in heart failure with preserved ejection fraction. J Am Coll Cardiol 2019;74:2539–50.ArticlePubMed
  • 27. Borlaug BA, Blair J, Bergmann MW, Bugger H, Burkhoff D, Bruch L, et al. Latent pulmonary vascular disease may alter the response to therapeutic atrial shunt device in heart failure. Circulation 2022;145:1592–604.ArticlePubMedPMC
  • 28. Litwin SE, Komtebedde J, Hu M, Burkhoff D, Hasenfub G, Borlaug BA, et al. Exercise-induced left atrial hypertension in heart failure with preserved ejection fraction. JACC Heart Fail 2023;11:1103–17.ArticlePubMedPMC
  • 29. Patel RB, Silvestry FE, Komtebedde J, Solomon SD, Hasenfub G, Litwin SE, et al. Atrial shunt device effects on cardiac structure and function in heart failure with preserved ejection fraction: The REDUCE LAP-HF II randomized clinical trial. JAMA Cardiol 2024;9:507–22.ArticlePubMedPMC
  • 30. Dixon DD, Trivedi A, Shah SJ. Combined post- and pre-capillary pulmonary hypertension in heart failure with preserved ejection fraction. Heart Fail Rev 2016;21:285–97.ArticlePubMedPDF
  • 31. Litwin SE, Komtebedde J, Borlaug BA, Kaye DM, Hasenfub G, Kawash R, et al. Long term safety and outcomes after atrial shunting for heart failure with preserved or mildly reduced ejection fraction: 5-year and 3-year follow-up in the REDUCE LAP-HF I and II trials. Am Heart J 2024;278:106–16.ArticlePubMed
  • 32. Huston JH, Shah SJ. Understanding the pathobiology of pulmonary hypertension due to left heart disease. Circ Res 2022;130:1382–403.ArticlePubMedPMC
  • 33. Guazzi M, Dixon D, Labate V, Beussink-Nelson L, Bandera F, Cuttica MJ, et al. RV contractile function and its coupling to pulmonary circulation in heart failure with preserved ejection fraction: stratification of clinical phenotypes and outcomes. JACC Cardiovasc Imaging 2017;10(10 Pt B):1211–21.ArticlePubMed

Figure & Data

References

    Citations

    Citations to this article as recorded by  

      • PubReader PubReader
      • ePub LinkePub Link
      • Cite
        CITE
        export Copy
        Close
      • Download Citation
        Download Citation
        Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.
        Format:
        • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
        • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
        Include:
        • Citation for the content below
        The role of the interatrial shunt device in the treatment of patients with heart failure with preserved ejection fraction: experience from the REDUCE LAP-HF studies
        Kosin Med J. 2025;40(2):88-95.   Published online February 17, 2025
        DOI: https://doi.org/10.7180/kmj.24.150
        Close
      • XML DownloadXML Download
      Figure
      • 0
      Related articles
      The role of the interatrial shunt device in the treatment of patients with heart failure with preserved ejection fraction: experience from the REDUCE LAP-HF studies
      Image
      Fig. 1. Interatrial shunt device (IASD; courtesy of Sanjiv Shah). (A) Corvia IASD System II. (B) En face view of the IASD System II (single size). (C) The device creates an interatrial shunt that unloads the LA by shunting blood from the higher-pressure LA to the lower-pressure RA. LA, left atrium; RA, right atrium.

      Fig. 1.

      The role of the interatrial shunt device in the treatment of patients with heart failure with preserved ejection fraction: experience from the REDUCE LAP-HF studies
      ESC guideline 2021 [7] ACC/AHA 2022 [14] KHFS 2022 [15] ESC guideline update 2023 [16]
      HFmrEF
       ACEI/ARB IIb IIb IIb IIb
       Beta blockera) IIb IIb IIb IIb
       MRA IIb IIb IIa IIb
       ARNI IIb IIb IIa IIb
       SGLT2-ib) NA IIa Ib I
      HFpEF
       ACEI/ARB NA IIb IIb NA
       Beta blockera) NA NA IIb NA
       MRA NA IIb IIb NA
       ARNI NA IIb IIa NA
       SGLT2-ib) NA IIa Ib I
      Author (year) Study cohort and enrolled patient number Inclusion criteria Primary endpoint Major findings Clinical meaning
      Hasenfub et al. (2016) [23] REDUCE LAP-HF study population (n=64) HFpEF, LVEF >40% with PCWP >15 mmHg at rest or PCWP >25 mmHg during exercise Clinical efficacy; functional capacity and clinical status at 6 mo A total of 52% of patients had a decrease in PCWP at rest and 58% had a decrease in PCWP during exercise over a 6-mo period IASD implantation appears feasible and reduces LA pressure during exercise
      Feldman et al. (2018) [24] REDUCE LAP-HF I study population (n=44) NYHA class III or ambulatory class IV HF, LVEF ≥40%, PCWP ≥25 mmHg during exercise, and PCWP during exercise at 1 mo Peak PCWP decreased by 3.5 mmHg in the IASD group vs. 0.5 mmHg in the control group (p=0.14) IASD reduces PCWP during exercise in HFpEF
      PCWP-RA pressure gradient ≥5 mmHg
      Obokata et al. (2019) [26] REDUCE LAP-HF and REDUCE LAP-HF I population (n=79) In the REDUCE LAP-HF and REDUCE LAP-HF I study cohorts, patients with PVR >4 WU or RV dysfunction were excluded Effects of IASD on hemodynamics, O2 content and delivery, and pulmonary vascular function during exercise After IASD, Qp and PA oxygen content increased by 27% and 7%, respectively IASD improves pulmonary vascular function at rest and during exercise in HFpEF
      Shah et al. (2022) [25] REDUCE LAP-HF II (n=626) Symptomatic HF with LVEF ≥40% with PCWP ≥25 mmHg during exercise with RA pressure ≥5 mmHg A hierarchical composite of CV death or nonfatal ischemic stroke at 12 mo, rate of total HF events up to 24 mo, and change in KCCQ overall summary score at 12 mo Differences between groups were not observed in the primary composite endpoint (win ratio 1.0; p=0.85) IASD did not reduce the total rate of HF events or improve health status in the population of patients with HFpEF
      Borlaug et al. (2022) [27] REDUCE LAP-HF II (n=570) In REDUCE LAP-HF II, patients with RV dysfunction, resting RA pressure >14 mmHg, PVR >3.5 WU at rest or at peak exercise were excluded A hierarchical composite of CV death, nonfatal ischemic stroke, recurrent HF events, and change in health status IASD was associated with worse outcomes in patients with PVD (win ratio, 0.60; p=0.005) and clinical benefit in patients without PVD (win ratio, 1.31; p=0.038) In patients with HFpEF (EF ≥40%), presence of latent PVD identifies those who may worsen with IASD
      Litwin et al. (2023) [28] REDUCE LAP-HF II (n=626) Symptomatic HF (LVEF ≥40%) and PCWP ≥25 mmHg during exercise with RA pressure ≥5 mmHg A hierarchical composite of death, HF hospitalization, intensification of diuretics, and change in health status EILAH is more likely to be associated with IASD responsiveness (peak PVR <1.74 WU during exercise) and no pacemaker (p<0.001) EILAH is associated with favorable response to IASD
      Patel et al. (2024) [29] REDUCE LAP-HF II (n=621) Symptomatic HF (LVEF ≥40%) and PCWP ≥25 mmHg during exercise with RA pressure ≥5 mmHg Changes in echocardiographic measures from baseline to 1, 6, 12, and 24 mo IASD reduced LV end-diastolic volume, LA minimal volume and improved LV systolic tissue Doppler velocity and LA emptying fraction compared with sham IASD led to reverse remodeling of LV and LA chambers, IASD increases in volume of RA and RV, consistent with shunt flow without change in RV systolic function compared with sham over a 2-yr period
      Safety outcome Trial
      REDUCE LAP-HF [23] REDUCE LAP-HF I [24] REDUCE LAP-HF II [25]
      Population number 64 IASD (n=22) vs. sham control (n=22) IASD (n=309) vs. sham control (n=312)
      Follow-up duration 6 mo 1 mo 12 mo
      Composite safety endpoint NA NA IASD 116/308 (38%)
      Sham control 97/308 (31%)
      p=0.11
      Major cardiac eventsa) 0/64 IASD 0/21 IASD 11/308 (4%)
      Sham control 0/22 Sham control 2/308 (1%)
      p=0.025
      Cardiovascular death 0/64 IASD 0/21 IASD 3/308 (1%)
      Sham control 0/22 Sham control 2/308 (1%)
      Stroke 0/64 IASD 0/21 IASD 1/308 (<1%)
      Sham control 0/22 Sham control 0/308
      Systemic embolization 0/64 IASD 0/21 IASD 0/308
      Sham control 0/22 Sham control 0/308
      Vascular complication 0/64 IASD 0/21 IASD 13/308
      Sham control 0/22 Sham control 0/308
      New onset or worsening renal dysfunction NA IASD 0/21 IASD 22/308 (7%)
      Sham control 1/22 Sham control 25/308 (8%)
      p=0.65
      Table 1. Comparison of recommendation levels of GDMT in HFmrEF/HFpEF guidelines

      GDMT, guideline-directed medical treatment; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; ESC, European Society of Cardiology; ACC, American College of Cardiology; AHA, American Heart Association; KHFS, Korean Heart Failure Society; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers; MRA, mineralocorticoid receptor antagonist; ARNI, angiotensin receptor/neprilysin inhibitor; SGLT2-i, sodium-glucose cotransporter 2 inhibitor; NA, not available.

      Evidence-based beta-blockers for heart failure with reduced left ventricular systolic function.

      Empagliflozin, dapagliflozin.

      Table 2. Summary of the REDUCE LAP-HF trials

      REDUCE LAP-HF, Reduce Elevated Left Atrial Pressure in Patients with Heart Failure; HFpEF, heart failure with preserved ejection fraction; LVEF, left ventricular ejection fraction; PCWP, pulmonary capillary wedge pressure; IASD, interatrial shunt device; LA, left atrium; NYHA, New York Heart Association; RA, right atrium; PVR, pulmonary vascular resistance; WU, Wood unit; Qp, pulmonary flow; PA, pulmonary artery; CV, cardiovascular; KCCQ, Kansas City Cardiomyopathy Questionnaire; PVD, pulmonary vascular disease; EILAH, exercise-induced left atrial hypertension; LV, left ventricle.

      Table 3. Safety outcomes of the REDUCE LAP-HF trials

      REDUCE LAP-HF, Reduce Elevated Left Atrial Pressure in Patients with Heart Failure; IASD, interatrial shunt device; NA, not available.

      Cardiac death, myocardial infarction, cardiac tamponade, and emergency cardiac surgery.

      Table 1.

      Table 2.

      Table 3.

      KMJ : Kosin Medical Journal
      © Kosin University College of Medicine.
      TOP