Interatrial septal device therapy in HFpEF

Interatrial septal device therapy in HFpEF

Effective therapeutic modalities for heart failure with preserved ejection fraction (HFpEF) are lesser than those available for heart failure with reduced ejection fraction (HFrEF). All the same, prevalence, morbidity and mortality for HFpEF are not lower than that of HFrEF. Ongoing search for therapeutic options has led to the development of interatrial septal devices to decompress the left atrium, which are still in investigational phase [1].

A unidirectional left-to-right interatrial shunting device was initially tested in patients with HFrEF as a safety and proof-of-principle cohort study. The device could be successfully implanted in all the 10 patients enrolled with no device or procedure related adverse events. Transesophageal echocardiography at one month showed patent shunts with no thrombosis or migration. NYHA functional class improved in all but one. No patient was admitted to hospital for worsening of heart failure. One patient died at 2 months with incessant ventricular tachycardia and heart failure [2].

REDUCE LAP-HF was a multicentre, open-label, single-arm, phase 1 trial of another type of interatrial septal device for HFpEF. Twenty-one centres across two continents participated in the trial. Successful device placement could be achieved in 64 of the 68 patients enrolled. No patient had a peri-procedural or major adverse cardiac or cerebrovascular event or need for cardiac surgical intervention for device related complications during the 6 month follow up [3].

At 6 months, 52% had a reduction of pulmonary capillary wedge pressure at rest while 58% had reduction during exertion. 39% had reduction of pulmonary capillary wedge pressure at rest and during exertion. Sustained device patency was also confirmed at 6 months with a left to right shunt of 1:1.27.

One year outcome of the trial was reported later with sustained improvements in New York Heart Association functional class, Minnesota Living with Heart Failure score, and 6-minute walk distance. Survival at 1 year was 95%. Echocardiography showed a small stable reduction in left ventricular end diastolic volume index with a concomitant small stable increase in right ventricular end diastolic volume index [4].

REDUCE LAP-HF I (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a phase 2, randomized, sham-controlled trial. Sham procedure was femoral venous access with intracardiac echocardiography but no interatrial septal device placement. The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. There were 22 patients in each group [5].

At one month, those with interatrial septal device had significantly greater reduction in pulmonary capillary wedge pressure during exercise. There were no peri-procedural or 1 month major adverse cardiac, cerebrovascular or renal events in the device group. One event of worsening renal function occurred in the control group. Authors suggested further evaluation for sustained improvement in symptoms and outcome.

REDUCE LAP-HF II was a pivotal international multi-centre randomised controlled trial of an interatrial septal device. Patients will continue to be enrolled in an open label REDUCE LAP-HF IV study at existing trial centres [6].

REDUCE LAP-HF II randomly assigned 314 patients to the device group and 312 patients to the sham procedure group. This was a neutral trial in which there were no differences between the groups in the primary composite endpoint. There was also no difference in the composite safety endpoint between the groups. Primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months [7].

An editorial comment on the report was titled “REDUCE LAP-HF II interatrial shunt trial: neutral, but necessary” [8]. Now we will have to look out for the results of open label REDUCE LAP-HF IV study. RELIEVE-HF trial (Reducing Lung Congestion Symptoms in Advanced Heart Failure, NCT03499236) of another interatrial septal device is expected to be completed in October 2023. It is a trial enrolling heart failure patients irrespective of left ventricular ejection fraction [9].

References

  1. Al-Sadawi M, Ortega RR, Ariyaratnam J, Battisha A, Madoukh B, Bukharovich I. State-of-the-Art Review of Current Therapies for HFpEF: An Overview of Interatrial Septal Device Therapy in Heart Failure. Curr Cardiol Rev. 2021;17(5):e230421189012. doi: 10.2174/1573403X16999201210195455. PMID: 33305708; PMCID: PMC8950450.
  2. Del Trigo M, Bergeron S, Bernier M, Amat-Santos IJ, Puri R, Campelo-Parada F, Altisent OA, Regueiro A, Eigler N, Rozenfeld E, Pibarot P, Abraham WT, Rodés-Cabau J. Unidirectional left-to-right interatrial shunting for treatment of patients with heart failure with reduced ejection fraction: a safety and proof-of-principle cohort study. Lancet. 2016 Mar 26;387(10025):1290-7. doi: 10.1016/S0140-6736(16)00585-7. PMID: 27025435.
  3. Hasenfuß G, Hayward C, Burkhoff D, Silvestry FE, McKenzie S, Gustafsson F, Malek F, Van der Heyden J, Lang I, Petrie MC, Cleland JG, Leon M, Kaye DM; REDUCE LAP-HF study investigators. 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 Mar 26;387(10025):1298-304. doi: 10.1016/S0140-6736(16)00704-2. PMID: 27025436.
  4. Kaye DM, Hasenfuß G, Neuzil P, Post MC, Doughty R, Trochu JN, Kolodziej A, Westenfeld R, Penicka M, Rosenberg M, Walton A, Muller D, Walters D, Hausleiter J, Raake P, Petrie MC, Bergmann M, Jondeau G, Feldman T, Veldhuisen DJ, Ponikowski P, Silvestry FE, Burkhoff D, Hayward C. 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 Dec;9(12):e003662. doi: 10.1161/CIRCHEARTFAILURE.116.003662. PMID: 27852653; PMCID: PMC5175994.
  5. Feldman T, Mauri L, Kahwash R, Litwin S, Ricciardi MJ, van der Harst P, Penicka M, Fail PS, Kaye DM, Petrie MC, Basuray A, Hummel SL, Forde-McLean R, Nielsen CD, Lilly S, Massaro JM, Burkhoff D, Shah SJ; REDUCE LAP-HF I Investigators and Study Coordinators. 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 Jan 23;137(4):364-375. doi: 10.1161/CIRCULATIONAHA.117.032094. Epub 2017 Nov 15. PMID: 29142012.
  6. Nanayakkara S, Kaye DM. Device therapy with interatrial shunt devices for heart failure with preserved ejection fraction. Heart Fail Rev. 2022 Apr 19. doi: 10.1007/s10741-022-10236-8. Epub ahead of print. PMID: 35438418.
  7. Shah SJ, Borlaug BA, Chung ES, Cutlip DE, Debonnaire P, Fail PS, Gao Q, Hasenfuß G, Kahwash R, Kaye DM, Litwin SE, Lurz P, Massaro JM, Mohan RC, Ricciardi MJ, Solomon SD, Sverdlov AL, Swarup V, van Veldhuisen DJ, Winkler S, Leon MB; REDUCE LAP-HF II investigators. 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 Mar 19;399(10330):1130-1140. doi: 10.1016/S0140-6736(22)00016-2. Epub 2022 Feb 1. PMID: 35120593.
  8. Kapur NK, Upshaw JN, Wessler BS. REDUCE LAP-HF II interatrial shunt trial: neutral, but necessary. Lancet. 2022 Mar 19;399(10330):1094-1095. doi: 10.1016/S0140-6736(22)00108-8. Epub 2022 Feb 1. PMID: 35120591.
  9. Reducing Lung CongestIon Symptoms in Advanced Heart Failure (RELIEVE-HF). ClinicalTrials.gov Identifier: NCT03499236. Available at: https://clinicaltrials.gov/ct2/show/NCT03499236. Accessed on 4 October 2022.