Percutaneous Interatrial Shunts May Offer New Hope for Advanced Heart Failure Patients
Percutaneous implantation of an atrial shunt shows promise for improving symptoms and quality of life in patients with advanced heart failure (HF), whether or not they have reduced ejection fraction, two new studies suggest.
“If further substantiated and associated with improved clinical outcomes (eg, a reduction in the risk of hospital admission for heart failure), device-mediated left-to-right atrial shunting would offer an important new approach to treatment of this population of patients with heart failure,” write Maria Del Trigo, MD (Quebec Heart and Lung Institute, Quebec City, Canada), and colleagues, who authored one of the two papers.
Both papers appear in the March 26, 2016, issue of the Lancet.
First-in-Human Study Hints at Safety, Feasibility
Del Trigo and colleagues enrolled 10 advanced HF patients with reduced ejection fraction (mean LVEF 25%), NYHA functional class III, and cardioverter defibrillators. All received a percutaneously implanted V-Wave shunt device (V-Wave, Caesarea, Israel), which decreases left atrial pressure by creating a unidirectional shunt.
Device success was 100%, and each procedure was completed in approximately 59 minutes, with all patients discharged the following day. There were no incidents of thrombosis or device migration at 1 month, and all shunts were patent on imaging. Additionally, there were no device-related adverse events at 3-month follow-up.
Among the functional improvements seen were a shift in NYHA class in 78% of patients from class III to class II. Other assessment measures, including the Duke Activity Status Index and the Kansas City Cardiomyopathy Questionnaire, showed statistically significant score improvement, and 6-minute walk test distances increased by a mean of 74 meters.
Patients also experienced reductions in pulmonary capillary wedge pressure, from a mean of 23 mm Hg at baseline to 17 mm Hg at 3 months (P = 0.035). There were no changes from baseline to follow-up in measures of right atrial pressure, pulmonary arterial pressure, or pulmonary resistance.
Importantly, by 6 months, none of the patients had been admitted to the hospital for worsening heart failure.
Del Trigo and colleagues say the first-in-man experience demonstrates the feasibility and safety of the shunt placement, noting that the procedure is “similar to the placement of atrial septal defect closure devices, and is fairly straightforward compared with other contemporary transcatheter interventions for treating heart failure.” Furthermore, the procedure has a short learning curve, they add, and averages less than one hour.
They report that data on the device are continuing to be collected and more will be forthcoming from a small multicenter trial as well as a randomized trial expected to begin next year.
Senior author Josep Rodés-Cabau, MD (Quebec Heart and Lung Institute), told TCTMD in an interview that patients in the study showed improvements soon after treatment. He also noted that none of the patients experienced a problem with their ICD due to implantation of the shunt device.
“This is a very limited cohort of patients, but the benefits in terms of functional status and quality of life were quite remarkable, especially in that we observed some degree of benefit in nearly all patients,” he said. “The vast majority displayed an improvement that I would say was quite immediate when the patients were seen that night or the next day after the procedure.”
Second Device Equally Promising
In the second study, Gerd Hasenfuss, MD (Georg-August-University Göttingen, Göttingen, Germany), and colleagues report results from the REDUCE LAP-HF study, which looked at a different shunt device—the IASD system II (Corvia Medical, Tewkesbury, MA)—in 68 patients who had HF with preserved ejection fraction (> 40%) and a raised pulmonary capillary wedge pressure at rest (> 15 mm Hg) or during exercise (> 25 mm Hg).
At 6 months, all shunts were patent on imaging. Nearly three-quarters of patients had reductions in pulmonary capillary wedge pressure at rest or during exertion compared with baseline, as well as improvements in quality of life, exercise time, and distance on the 6-minute walk test. No patients experienced periprocedural or 6-month MACCE (death, stroke, MI, pulmonary or systemic embolism, or need for cardiac surgical device removal).
Three patients had the initial device removed due to unsuitable position or suspected small mobile thrombus in the right atrium, but all those affected received a second device without incident.
“Overall, the results of this open-label nonrandomized study show that transcatheter transvenous placement of an interatrial shunt device is feasible and might be associated with improvements in exercise hemodynamics, functional capacity, and quality of life,” Hasenfuss and colleagues write.
Recently, the manufacturer announced that it has received Investigational Device Exemption approval from the US Food and Drug Administration for a randomized, multicenter study of the device.
Preliminary and Provocative
In a commentary accompanying both studies, Patrick Rossignol, MD, PhD, and Faiez Zannad, MD, PhD (Inserm Clinical Plurithematic Investigation Center, Nancy, France), say despite the promising early data, no long-term effects of the devices on the heart and large artery remodeling have yet been demonstrated. Furthermore, most of the endpoints, they note, are “soft, subjective, and certainly not predictive of an outcome benefit.” The possibility of observer bias in the studies also is at issue they say, since neither study was blinded and no controls were used.
As for sustainability, Rossignol and Zannad hypothesize that the IASD device is the more likely of the two to show long-term hemodynamic effects, since it increased pulmonary and systemic output by nearly 20% after 6 months compared with an output of barely 10% with the V-Wave device.
They also caution that the devices must be further tested and carefully regulated to ensure that they are reasonably safe and effective before being offered to a vulnerable population with severe heart failure and few options beyond medical therapy.
“These preliminary provocative data using an apparently simple mechanical approach to heart failure therapy might lead to a change in the treatment of patients with heart failure, with the potential of revolutionizing treatment and prognosis, irrespective of ejection fraction,” Rossignol and Zannad conclude.
To TCTMD, Rodés-Cabau said his group is currently completing 12-month follow-up on V-Wave, which will likely be published later this year. “There is a lot of work to be done in terms of following these patients and increasing the experience with a much larger number of patients in a randomized trial,” he concluded.
- Del Trigo M, Bergeron S, Bernier M, et al. 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; 387:1290-1297.
- 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;387:1298-1304.
- Rossignol P, Zannad F. Left-to-right atrial shunting: new hope for heart failure? Lancet. 2016;387:1253-1255.
- Del Trigo’s study was partly funded by V-Wave.
- Del Trigo and Hasenfuss report no relevant conflicts of interest.
- Rodés-Cabaureports research grants from Edwards Lifesciences, St Jude Medical, Medtronic, and V-Wave.
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