ANAHEIM, CA — A shunt device implanted via catheter across the interatrial septum can safely allow the left atrium to unload, reducing left atrial (LA) pressure during exercise in selected patients with heart failure with preserved ejection fraction (HFpEF), confirms a small randomized study that used a sham control.
The REDUCE LAP-HF I trial's results strengthen those from a single-arm observational study of the device (IASD System II, Corvia Medical) reported last year. They also set the stage, researchers say, for a larger randomized trial with longer follow-up to see whether the device can improve clinical outcomes in a population that has few proven effective therapies.
The significant reductions in pulmonary capillary wedge pressures (PCWP) at exercise using the device, which creates an 8-mm-diameter opening between the atria, improved hemodynamics consistently in other ways that fell short of significance 1 month after its implantation, Dr Sanjiv J Shah (Northwestern University Feinberg School of Medicine, Chicago, IL) told theheart.org | Medscape Cardiology.
"Like any other therapy, there are going to be responders and nonresponders," he said, but across all patients who've received the IASD, "we tend to see a 3- to 5-mm-Hg decrease in peak wedge pressure."
In other studies, improvements exceeding 3 mm Hg have been associated with better survival in such patients, said Shah in an interview following his presentation of REDUCE LAP-HF I here at the American Heart Association (AHA) 2017 Scientific Sessions. It was published at about the same time in Circulation with Dr Ted Feldman (NorthShore University Health System, Evanston, IL) as lead author.
"Device patency is good; for up to 2 years we're seeing left-to-right shunting. We're not seeing any device occlusion, we're not seeing any thrombus on the device. It really seems to be safe in that respect."
In the current study with 44 patients, half of whom received the device and half whom underwent the same catheterization but without transseptal puncture or device placement, adverse events were rare and, as it happened, only in the control group.
The favorable hemodynamic effects of IASD shunting were most apparent during exercise at 20 W (P=0.019) and with legs positioned up at rest (P=0.024). But they were also significant for the prespecified primary end point based on PCWP at variable degrees of exercise up to 60W (P=0.028). Resting right ventricular output also improved significantly compared with effects in the sham control group (P<0.001).
"This transcatheter atrial shunt device is an ingenious new approach to address both the symptoms and progression of this disease," said Dr Lynne Warner Stevenson (Brigham and Women's Hospital, Boston, MA) as assigned discussant following Shah's presentation of the study. "When we look at the increase in filling pressures, you can already see an impact just by putting the legs up at rest."
But she was cautious about the IASD's effectiveness pending future larger, more definitive studies of the device. For example, "It's not clear the degree to which this device will change filling pressures at rest as well as at exercise, which has significant impact on the right ventricle."
The study's entry criteria made for a select population expected to benefit from reduced LA pressures; that is, with NYHA class 3 or ambulatory class 3 heart failure, LVEF at least 40% with elevated LA pressures higher than right-atrial pressures, and either a recent history of HF hospitalization or elevated natriuretic peptides, but without significant valve disease.
Even so, Shah said, the trial represents "a big segment" of the HFpEF population. The treatment is especially suited for patients "who are already well treated [medically] but still very dyspneic." In fact, patients could enter the trial only if they were symptomatic on guideline-based medical therapy, "which in this population is really just diuretics," he said.
"So this is really a therapy for patients in whom you want to lower left atrial pressure and get it to the right side, where maybe it's more accessible to diuretics and other treatments." But it wouldn't be appropriate for HFpEF patients with, for example, right ventricular failure and pulmonary hypertension, Shah said.
The amount of contrast used during the procedure was similar for the 22 patients getting the device and the 22 sham controls, averaging about 19 mL each. Not surprisingly, there were significant differences in total procedure time (58 and 13 min, respectively) and total fluoroscopy time (23.3 vs 5.3 min) (P<0.001 for both).
Total loop-diuretic dosage didn't differ significantly between the two groups either at baseline or for a month after the procedure.
Hemodynamic Changes From Baseline to 1 Month in REDUCE LAP-HF I
|End points||IASD (n=22)||Control (n=22)||P|
|Exercise PCWP (primary end point)|
|At 20 W (mm Hg)||–3.2||+0.9||0.028|
|At 60 W (mm Hg)||–2.3||–1.3|
|PCWP, workload-corrected (mm Hg/W/kg)||–5.7||+10.3||0.231|
|PCWP, legs up at rest (mm Hg)||–5.0||0.0||0.024|
|PCWP, peak exercise (mm Hg)||–3.5||–0.5||0.144|
|RV cardiac output at rest (L/min)||+1.6||–0.5||<0.001|
There were also no significant differences by 1 month in the prospectively defined end points of HF-related hospitalizations or major adverse cardiac, cerebrovascular embolic, or renal events (MACCRE), which included cardiovascular death, embolic stroke, device- and/or procedure-related adverse cardiac events, or new-onset or worsening kidney dysfunction.
There were no instances of stroke or systemic embolism, cardiac perforation, new-onset atrial fibrillation or flutter, major vascular complication, or device embolization.
Stevenson's critical analysis of the study included hopes for future trials of the IASD device. "We greatly look forward to the ongoing trial to track the sustained benefit over time," she said, referring to REDUCE LAP-HF II. That trial is randomizing an estimated 380 patients with HFpEF similar to those in the current trial (although NYHA 2 heart failure is allowed) to the device or a sham control procedure.
"We're interested in the exercise hemodynamics in clinical activity [and] the impact of unloading the right atrium on right ventricular function, particularly over time," Stevenson said, "and we also want to look very closely at the impact on renal function, which does relate to right-atrial pressures."
Also underway is REDUCE LAP-HF III, a postmarket observational study based in Germany with an estimated cohort of 100 patients.
The study was funded by Corvia Medical. Shah discloses receiving research grants from Actelion, AstraZeneca, Corvia, and Novartis; and consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiora, Eisai, Ironwood, Merck, Novartis, Sanofi, and United Therapeutics. Feldman discloses receiving consulting fees from Abbott, Boston Scientific, Edwards Lifesciences, and Gore. Stevenson discloses receiving research grants from Novartis, consulting or serving on an advisory board for Abbott, and travel expenses or meals from Novartis and St Jude Medical.
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Cite this: Device Therapy for Preserved-EF Heart Failure? Shunt Eases Left Atrial Pressures in REDUCE LAP-HF I - Medscape - Nov 24, 2017.