InterAtrial Shunt Device (IASD®) implantation — a novel treatment method for heart failure with preserved ejection fraction

Michał Kosowski1, 2, Piotr Kübler1, 2, Adam Kołodziej2, Bartosz Krakowiak2, Dorota Kustrzycka-Kratochwil2, Janusz Sławin2, Mateusz Sokolski1, 2, Jan Biegus1, 2, Robert Zymliński2, Waldemar Banasiak2, Piotr Ponikowski1, 2, Krzysztof Reczuch1, 2

1Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
2Department of Cardiology, Centre for Heart Diseases, Clinical Military Hospital, Wroclaw, Poland

Address for correspondence:
Michał Kosowski, MD, Department of Cardiology, Centre for Heart Diseases, Clinical Military Hospital, ul. Weigla 5, 50–981 Wrocław, Poland,
e-mail: mkosowski@gmail.com
Received: 27.12.2016 Accepted: 10.04.2017 Available as AoP: 18.05.2017

INTRODUCTION

A subgroup of patients with symptoms of heart failure (HF) does not present with dilated left ventricular (LV) dimensions or reduced LV ejection fraction (LVEF). The terms ‘heart failure with preserved ejection fraction’ (HFpEF) or ‘diastolic HF’ have been used to describe this population [1, 2]. The incidence of HFpEF is rising, but there is still no treatment that has been proven to reduce mortality or reduce morbidity in a meaningful way in HFpEF [3–8]. Patients suffering from HFpEF are elderly and symptomatic, and their quality of life is often very poor [9, 10].

Exercise intolerance in HFpEF patients is associated with an increase in left atrial pressure and impaired LV diastolic function [11, 12].

Historically, a combination of mitral stenosis and atrial septal defect (Lutembacher’s syndrome) has been described [13]. Patients with this combination had better outcomes than patients with ‘pure’ mitral stenosis. This could be related to reduction of left atrium pressure via the atrial septal defect.

The REDUCe Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF) trial was conducted to assess the InterAtrial Shunt Device (IASD®) (Corvia Medical Inc., Tewksbury, MA, USA) performance and safety in symptomatic patients with HFpEF.

This paper presents our initial experience with IASD® implantation in three consecutive patients.

METHODS

We enrolled three patients with known HFpEF, who met inclusion criteria (adults aged > 40 years, HFpEF with New York Heart Association [NYHA] II–IV functional class, LVEF > 40%, increased pulmonary capillary wedge pressure (PCWP) > 15 mm Hg at rest, or > 25 mm Hg during supine ergometry). Detailed protocol and design of the REDUCE LAP-HF trial were described elsewhere [14, 15]. The study protocol was approved by the local bioethics committee. All patients gave written informed consent.

All enrolled patients underwent right heart catheterisation with assessment of cardiac output and haemodynamic parameters at rest and during supine bicycle exercise, at baseline, six and 12 months after device implantation. Haemodynamic assessment was done according to acknowledged standards [16].

Implantation of the device was performed percutaneously (on a separate hospitalisation from the screening) via the femoral vein. Transseptal puncture of the interatrial septum was done using fluoroscopy and transoesophageal echocardiographic guidance, and the device was positioned using an over-the-wire technique. Two patients not receiving oral anticoagulants for atrial fibrillation were prescribed aspirin (75 mg once daily) indefinitely, and clopidogrel (75 mg once daily) for six months. One patient with atrial fibrillation treated with oral anticoagulants continued on existing oral anticoagulants (warfarin) after the procedure. Endocarditis prophylaxis was advised for a minimum of six months post-implantation.

RESULTS

We successfully implanted the IASD® device in three patients between April 8, 2015 and June 11, 2015 using the techniques described above. We did not observe any major adverse cardiac or cerebrovascular event, including death, stroke, myocardial infarction, pulmonary or systemic embolism, or need for surgical intervention throughout the 12-month follow-up period.

Detailed clinical, locally assessed echocardiography and haemodynamic parameters are shown in Table 1. Figure 1 shows the dynamics of significant haemodynamic parameters, exercise capacity, and quality of life in 12-month observation.

Table 1. Patient characteristics and results

Figure 1. Selected haemodynamic parameters (invasive study), exercise capacity, and quality of life in three patients — 12 months observation; A. Six-minute walk test; B. Minnesota Living with Heart Failure form; C. Pulmonary capillary wedge pressure (PCWP), resting; D. Cardiac output resting; E. Pulmonary capillary wedge pressure (PCWP), exercise; F. Cardiac output exercise; P — patient

Baseline mean PCWP, mean pulmonary pressure, mean right atrial pressure, and cardiac output increased during exercise are shown in Table 1.

At six and 12 months follow-up we observed reduction of PCWP at rest in two of three patients, and during exercise in two of three patients. All three patients had echocardiographic evidence of left-to-right atrial flow. Cardiac output measured with thermodilution was increased in two of three patients. Right atrial pressure at rest was higher in two of three patients, and during supine exercise in one of three patients (in one patient we initially observed increase in right atrial pressure after six months, which subsequently decreased).

Echocardiography showed changes in chamber volumes as described in Table 1. There were no significant changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations. In two of three patients NYHA class improved (II to I), and six-minute walk distance improved in one of three patients. In every patient, the Minnesota Living with Heart Failure total score decreased meaningfully (> 15 points) compared to baseline at 12-month follow-up.

DISCUSSION

The pathophysiology of HFpEF is complex and multifactorial. Many co-morbidities (i.e. arterial hypertension, atrial fibrillation, coronary artery disease, diabetes, obesity, chronic kidney disease, anaemia, chronic obstructive pulmonary disease) contribute to the clinical profile and symptom development in patients with HFpEF [17–20]. According to the current guidelines, HFpEF can be diagnosed if LVEF is equal to or more than 50% (the most recent European Society of Cardiology guidelines on HF defined “mid-range” HF in patients with LVEF 40–49%); however, most of the HFpEF trials included patients with LVEF ≥ 40% [21]. No treatment has been proven to reduce mortality or morbidity in HFpEF so far, so the treatment is focused on relieving symptoms, and improving exercise capability and quality of life [3–8]. Our data, as well as other invasive haemodynamic studies, showed that patients with HFpEF present with increased PCWP during exercise [11, 12]. According to the REDUCE LAP-HF study, novel IASD® device implantation leads to reduction in exercise PCWP, which is consistent with atrial decompression and a reduction in LV end-diastolic volume. Peak exercise PCWP was reduced after device implantation, despite an increase in exercise capacity; this parameter has been associated with mortality in studies on patients with HFpEF [12].

Our observations of three patients are in line with previously reported REDUCE LAP-HF trial results [14, 22]. Partial improvement in terms of haemodynamic parameters was seen, and patients reported better quality of life. The latter may be related to the placebo effect, because there was no clear evidence of better exercise capacity and the levels of NT-proBNP were virtually the same in 12-month observation. REDUCE LAP-HF was a small, open-label, non-randomised study with limited data on mortality. Blinded randomised trials (including a control procedure) with long-term follow-up are ongoing to confirm the IASD® device safety and effectiveness.

Conclusions

The observations to date show that the IASD® device implantation is a promising method in terms of symptom reduction, quality of life, and safety.

Funding: The REDUCE LAP-HF trial was sponsored by Corvia Medical Inc., Tewksbury, MA, USA, and the authors received honoraria as site investigators.

Conflict of interest: Michał Kosowski and Piotr Kubler declare no conflict of interest; the remaining authors received honoraria as investigators.

References

1. 1. Vasan R, Larson MG, Benjamin E, et al. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction. J Am Coll Cardiol. 1999; 33(7): 1948–1955, doi: 10.1016/s0735-1097(99)00118-7.
2. 2. Yancy CW, Lopatin M, Stevenson LW, et al. Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am Coll Cardiol. 2006; 47(1): 76–84, doi: 10.1016/j.jacc.2005.09.022, indexed in Pubmed: 16386668.
3. 3. Steinberg BA, Zhao X, Heidenreich PA, et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012; 126(1): 65–75, doi: 10.1161/CIRCULATIONAHA.111.080770, indexed in Pubmed: 22615345.
4. 4. Cleland JGF, Tendera M, Adamus J, et al. PEP-CHF Investigators. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006; 27(19): 2338–2345, doi: 10.1093/eurheartj/ehl250, indexed in Pubmed: 16963472.
5. 5. Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003; 362(9386): 777–781, doi: 10.1016/S0140-6736(03)14285-7, indexed in Pubmed: 13678871.
6. 6. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014; 370(15): 1383–1392, doi: 10.1056/NEJMoa1313731, indexed in Pubmed: 24716680.
7. 7. Redfield MM, Chen HH, Borlaug BA, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013; 309(12): 1268–1277, doi: 10.1001/jama.2013.2024, indexed in Pubmed: 23478662.
8. 8. Redfield M, Anstrom K, Levine J, et al. Isosorbide mononitrate in heart failure with preserved ejection fraction. N Engl J Med. 2015; 373(24): 2314–2324, doi: 10.1056/nejmoa1510774.
9. 9. Fukuta H, Goto T, Wakami K, et al. Effects of drug and exercise intervention on functional capacity and quality of life in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials. Eur J Prev Cardiol. 2016; 23(1): 78–85, doi: 10.1177/2047487314564729, indexed in Pubmed: 25520380.
10. 10. Lewis EF, Lamas GA, O’Meara E, et al. Characterization of health-related quality of life in heart failure patients with preserved versus low ejection fraction in CHARM. Eur J Heart Fail. 2007; 9(1): 83–91, doi: 10.1016/j.ejheart.2006.10.012, indexed in Pubmed: 17188020.
11. 11. Maeder MT, Thompson BR, Brunner-La Rocca HP, et al. Hemodynamic basis of exercise limitation in patients with heart failure and normal ejection fraction. J Am Coll Cardiol. 2010; 56(11): 855–863, doi: 10.1016/j.jacc.2010.04.040, indexed in Pubmed: 20813283.
12. 12. Dorfs S, Zeh W, Hochholzer W, et al. Pulmonary capillary wedge pressure during exercise and long-term mortality in patients with suspected heart failure with preserved ejection fraction. Eur Heart J. 2014; 35(44): 3103–3112, doi: 10.1093/eurheartj/ehu315, indexed in Pubmed: 25161181.
13. 13. Lutembacher R. De la sténose mitrale avec communication interauriculaire. Arch Mal Coeur 1916; 9: 237–260. (in French).
14. 14. Hasenfuß G, Hayward C, Burkhoff D, 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(10025): 1298–1304, doi: 10.1016/s0140-6736(16)00704-2.
15. 15. Hasenfuß G, Hayward C, Burkhoff D, et al. Rationale and design of the reduce elevated left atrial pressure in patients with heart failure (reduce LAP-HF) trial. J Card Fail. 2015; 21(7): 594–600, doi: 10.1016/j.cardfail.2015.05.008, indexed in Pubmed: 26055211.
16. 16. Kurzyna M, Araszkiewicz A, Błaszczak P, et al. Summary of recommendations for the haemodynamic and angiographic assessment of the pulmonary circulation. Joint statement of the Polish Cardiac Society’s Working Group on Pulmonary Circulation and Association of Cardiovascular Interventions. Kardiol Pol. 2015; 73(1): 63–68, doi: 10.5603/KP.2015.0011, indexed in Pubmed: 25625343.
17. 17. Senni M, Paulus WJ, Gavazzi A, et al. New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes. Eur Heart J. 2014; 35(40): 2797–2815, doi: 10.1093/eurheartj/ehu204, indexed in Pubmed: 25104786.
18. 18. Ferrari R, Böhm M, Cleland JGF, et al. Heart failure with preserved ejection fraction: uncertainties and dilemmas. Eur J Heart Fail. 2015; 17(7): 665–671, doi: 10.1002/ejhf.304, indexed in Pubmed: 26079097.
19. 19. Ather S, Chan W, Bozkurt B, et al. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012; 59(11): 998– 1005, doi: 10.1016/j.jacc.2011.11.040, indexed in Pubmed: 22402071.
20. 20. Henkel DM, Redfield MM, Weston SA, et al. Death in heart failure: a community perspective. Circ Heart Fail. 2008; 1(2): 91–97, doi: 10.1161/CIRCHEARTFAILURE.107.743146, indexed in Pubmed: 19300532.
21. 21. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; 37(27): 2129–2200, doi: 10.1093/eurheartj/ehw128, indexed in Pubmed: 27206819.
22. 22. Kaye DM, Hasenfuß G, Neuzil P, et al. One-Year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction. Circ Heart Fail. 2016; 9(12), doi: 10.1161/CIRCHEARTFAILURE.116.003662, indexed in Pubmed: 27852653.