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

Oct 12, 2023
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC; Kim A. Eagle, MD, MACC
Trial Sponsor:
Corvia Medical
Date Published:
10/02/2023
Date Updated:
10/12/2023
Original Posted Date:
02/22/2022
References

Contribution To Literature:

Highlighted text has been updated as of October 12, 2023.

The use of the Corvia IASD System II was not superior to a sham procedure in improving cardiovascular events or functional status among patients with EF ≥40% and documented invasive exercise PCWP of ≥25 mm Hg.

Description:

The goal of the trial was to assess the safety and efficacy of an interatrial shunt device (IASD) for patients with heart failure (HF) and ejection fraction (EF) ≥40% and with evidence of elevated filling pressures on exercise.

Study Design

Eligible patients were randomized in a 1:1 open-label fashion to either Corvia IASD (n = 314) or a sham procedure (n = 312).

  • Total screened: 1,072
  • Total number of enrollees: 626
  • Duration of follow-up: 12 months
  • Median patient age: 72.5 years
  • Percentage female: 62%

Inclusion criteria:

  • Age ≥40 years
  • Symptomatic HF
  • EF ≥40%
  • Evidence of pulmonary capillary wedge pressure (PCWP) during exercise of ≥25 mm Hg while exceeding right atrial pressure by ≥5 mm Hg

Exclusion criteria:

  • Stage D HF
  • Cardiac index <2.0
  • Previous documented EF <30%
  • History of stroke, transient ischemic attack, deep vein thrombosis, or pulmonary embolism within the past 6 months
  • Hemodynamically significant valve disease (including moderate or greater tricuspid regurgitation)
  • Hypertrophic, restrictive, or infiltrative cardiomyopathy
  • Constrictive pericarditis
  • Mild right ventricular dysfunction
  • Resting right atrial pressure >14 mm Hg
  • Pulmonary vascular resistance (PVR) >3.5 Wood units (WU)
  • Severe obstructive sleep apnea
  • Chronic pulmonary disease requiring oxygen
  • Body mass index of >45 kg/m²
  • Estimated glomerular filtration rate <25 mL/min per 1.73 m²

Other salient features/characteristics:

  • Permanent pacemaker: 20%
  • Atrial fibrillation: 52%
  • New York Heart Association (NYHA) class III: 78%, IV: 2%
  • Median left ventricular EF: 60% (93% with HF with preserved EF [HFpEF])
  • Median H2FPEF score: 6

Principal Findings:

The primary endpoint (cardiovascular death, nonfatal ischemic stroke, total or recurrent HF events, change in Kansas City Cardiomyopathy Questionnaire overall summary [KCCQ-OS] score) at 12 months: Win ratio: 1.0 (95% confidence interval [CI] 0.8-1.2; p = 0.85).

  • Cardiovascular death or nonfatal ischemic stroke: 1% vs. 1% (p = 0.41)
  • HF events: 0.28 vs. 0.25 per patient-year (p = 0.45)
  • Median change in KCCQ-OS from baseline to 12 months: 10.2 vs. 9.4 (p = 0.73)

Secondary outcomes for IASD vs. sham:

  • Change in NYHA class from baseline to 12 months: -0.5 vs. 0% (p = 0.006)
  • Composite safety endpoint at 12 months: 38% vs. 31% (p = 0.11)
  • Major adverse cardiovascular events (MACE) at 12 months: 4% vs. 1% (p = 0.025)

For the primary endpoint, there appeared to be a benefit among patients with peak exercise PVR <1.74 WU (p for interaction = 0.002).

Impact of AF burden: AF burden was assessed among 59% of patients in the REDUCE LAP-HF II trial using ambulatory cardiac patch monitoring. Of the 53% of patients with any patch-detected AF during the baseline period, 26% did not have a clinical history of AF or AF on the baseline ECG; 38% had patch-detected AF during follow-up without history of AF or atrial flutter (AFL). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with HF events (hazard ratio 2.00, 95% CI 1.17-3.44, p = 0.01) both with and without AF/AFL history (p for interaction = 0.68). Atrial shunt therapy did not change AF incidence or burden during follow-up.

Interpretation:

The results of this trial indicate that use of the Corvia IASD System II was not superior to a sham procedure in improving cardiovascular events or functional status among patients with EF ≥40% and documented invasive exercise PCWP of ≥25 mm Hg. MACE were higher with IASD; the composite safety endpoint was similar between the two arms. Benefit in certain subgroups is hypothesis-generating and needs to be viewed in the context of an overall negative trial. Subclinical AF burden is high in this patient population.

Although an interesting concept, the use of IASD for patients with HFpEF and confirmed elevation in filling pressures with exercise does not appear to be helpful.

References:

Patel RB, Reddy VY, Komtebedde J, et al. Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail 2023;11:1351-62.

Editorial Comment: Absence of Atrial Fibrillation Reduction in REDUCE LAP-HF II. JACC Heart Fail 2023;11:1363-4.

Shah SJ, Borlaug BA, Chung ES, et al. Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomized, multicenter, blinded, sham-controlled trial. Lancet 2022;399:1130-40.

Editorial Comment: Kapur NK, Upshaw JN, Wessler BS. REDUCE LAP-HF II interatrial shunt trial: neutral, but necessary. Lancet 2022;399:1094-5.

Clinical Topics: Arrhythmias and Clinical EP, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Vascular Medicine, Acute Heart Failure

Keywords: Atrial Pressure, Brain Ischemia, Cardiomyopathies, Exercise Test, Functional Status, Geriatrics, Heart Failure, Ischemic Stroke, Pulmonary Wedge Pressure, Stroke, Stroke Volume, Vascular Diseases


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