CardioSource WorldNews Interventions | After years of what sometimes seemed painstakingly slow efforts to bring a less invasive approach to managing mitral valve (MV) disease, things are finally moving forward on several fronts. It’s likely a response to the eye-opening clinical success and rapid adoption of transcatheter aortic valve replacement (TAVR). (The TAVR abbreviation also has been swiftly adopted in the U.S. in place of the original TAVI, with the “I” for intervention still used in many parts of the world.) The success of TAVR has reinvigorated efforts to develop less invasive approaches to the other heart valves. It has not been easy, but the transcatheter revolution marches on. Under no illusion of being comprehensive, keep reading as CardioSource WorldNews: Interventions takes you on a quick transcatheter, semi-invasive tour around the heart, stopping at all four valves to highlight new findings, issues, successes, and challenges.

Valvular heart disease has been called both “the next epidemic” and “the forgotten epidemic.” It is responsible for more than 24,000 deaths and 85,000 hospitalizations each year in the United States, with those numbers increasing as the population ages and life expectancy rises. While approximately 2.5% of the population has moderate or severe valve disease,¹ the prevalence in those 75 years of age and older ranges between 11.7% and 13.3%, depending on the source.^1,2

TAVR Rules the School

TAVR is the valve therapy all the other valve therapies want to be when they grow up. It’s the cool kid in school, the one that gets the most attention, by far, but also the one under the greatest scrutiny—and it’s having a rough time right now.

The TAVR market is expected to generate close to $4 billion in business by 2020, according to a report released in February by Technavio, a global research and advisory company. The report considers revenue generated from the sales of transcatheter aortic valve implants to determine market size. The largest market, according to Technavio, is Europe, the Middle East, and Africa, which contributed a market share of more than 40% in 2015, followed by the Americas, and the Asia-Pacific region.

According to lead cardiovascular device analyst, Brahadeesh Chandrasekaran, “As of 2011, the number of aortic valve replacement procedures stood at 311 per million in Germany, 283 per million each in France and Belgium, and 137 per million in the United Kingdom. A rise in the aging population and increase in the occurrence of cardiovascular diseases are the main contributors to the growth of the market in this region.”

The TAVR market in the Americas was valued at $550 million in 2015, after rapidly emerging as a highly beneficial treatment for patients with severe aortic stenosis (AS) not suitable for surgical aortic valve replacement (SAVR). Despite transforming care in just the last few years, Michael Mack, MD, FACC, of Baylor Scott & White Health in Dallas, TX, emphasizes that the “rational dispersion” of TAVR with about 350 centers now performing the procedure, so far, in more than 30,000 patients since its U.S. approval in Nov. 2011. Add in improved diagnosis of AS and a Medicare decision to reimburse TAVR procedures, albeit with restrictions, and the U.S. market is expected to exceed $1 billion by 2020.

One big question: is TAVR sustainable in the current U.S. health care economy? Matthew R. Reynolds, MD, FACC, of the Harvard Clinical Research Institute, Boston, MA, says so far, so good. He should know. The latest economic analysis data come from the Jan. 5, 2016, issue of JACC and Dr. Reynolds is the first author.³ He and his coauthors report that the higher technology cost of the CoreValve® TAVR system ($32,000 commercially and the system they analyzed) accounted for the largest proportion of TAVR expenses. Shorter intensive care unit and hospital lengths of stay (LOS) offset much of that charge, so overall in-hospital TAVR costs were $11,260 more per patient over SAVR. At 12 months, TAVR cost $9,207 more than SAVR.

And, like Dr. Mack, Dr. Reynolds finds the adoption of TAVR has been measured and thoughtful in terms of commercial roll-out. Randomized clinical trials in high-risk patients have shown meaningful benefits with TAVR versus SAVR. Costs run about the same to slightly increased and, over time, we’re likely to see improved outcomes and efficiency.

TAVR Hits a Rough Patch

In the last year, in particular, cardiology’s journals and meetings have been awash with TAVR studies. Several dozen new datasets and analyses are being revealed monthly, as many details get ironed out: patient selection, procedural planning, adjunctive therapies, new devices, vascular complications, paravalvular leaking, antithrombotic regimens, etc.

The news has been largely positive in terms of outcomes, like the PARTNER 2A findings presented at ACC.16 that showed TAVR with the Sapien XT system to be noninferior to surgical aortic valve replacement in intermediate-risk patients with symptomatic severe AS.⁴ In the trial patients suitable for transfemoral access, TAVR was actually superior to SAVR for the primary endpoint of all-cause death and disabling stroke at 2 years.

There’s always a darker side to any new technology, and it appears that TAVR’s Achilles heel might be durability, with an emphasis on might because the data remain limited.

At May’s EuroPCR meeting, Danny Dvir, MD, St. Paul’s Hospital, Vancouver, Canada, presented long-term durability findings for transcatheter aortic valves. The researchers studied 704 inoperable or very high-risk patients who were among the first to receive TAVR. Of these, 378 patients had repeat echocardiographic examinations for up to 10 years after the procedure. To get the data, researchers actually did home visits on these very elderly patients (mean age at baseline was 82.6 years) carrying along a portable echocardiography unit. The implanted valves included the Edwards Sapien XT in 36% of patients, the Sapien in 50%, and the Cribier-Edwards in 14%.

Median survival time for this cohort was 51 months; 100 patients survived at least 5 years after TAVR and two women, now in their mid-90s, survived 10 years. One of the two had a degenerated transcatheter heart valve (THV) device, according to the study’s definition, which Dr. Dvir pointed out doesn’t necessarily mean the patient is symptomatic or needs reintervention.

The researchers identified 35 cases of valve degeneration, defined as moderate or severe intravalvular regurgitation and/or AS (mean gradient ≥ 20 mm Hg), that appeared more than 30 days after TAVR. Median time to degeneration was 5 years and the majority of failures were associated with intravalvular regurgitation. Based on this “preliminary analysis,” Dr. Dvir’s group reported a Kaplan-Meier estimate for the 8-year rate of structural valve degeneration was approximately 50%. Renal failure was the strongest correlate of THV degeneration.

Obviously, the concern here is that as TAVR expands to lower-risk, younger patients, durability may become a key issue.

Said Dr. Dvir in a EuroPCR press release: “We hope that the next-generation THV devices are more durable than the valves used in this study.” His group has started the VALID Registry (VAlve Long-term durability International Data).

In an interview with CardioSource WorldNews: Interventions, Josep Rodes-Cabau, MD, of the Quebec Heart and Lung Institute, Laval University, Quebec City, Canada, pointed out there were very few patients studied who had more than 5 years of follow-up. Moreover, there were some methodological issues that limit the data’s interpretation.

Dr. Rodes-Cabau asked, “Is the conclusion that these data show we should not move to younger patients? No, because the randomized data [comparing surgical and transcatheter valves up to 5 years] has not shown any difference. I’m not saying that between 5 and 10 years there won’t be some deteriorations in the transcatheter world, but this has not been the case until now.”

He added, “Most of those data presented were not related to structural degeneration leading to reintervention, but were more subclinical changes. Because of all these reasons, I think we should take these data into consideration and that’s it. Not really changing anything because of it, except that those centers who were not following patients after TAVR should follow them.”

Commenting on the study, A. Pieter Kappetein, MD, Erasmus Medical Center, Rotterdam, the Netherlands, said that the Vancouver group’s findings put TAVR in “a little bit of a different light” than the one shone on it only 7 weeks previously when the PARTNER 2A results were presented. The new data and reinforce the need to do more trials on different patient subsets, using newer valve technologies. He noted, however, that not all surgical valve designs have shown great durability either, so the findings are somewhat expected and not terribly surprising. THVs are complex designs with multiple parts, all of which have to maintain integrity under constant use. (And crushing the whole thing into a catheter for delivery probably doesn’t help either.)

“Lifetime durability cannot be reached with any biological heart valve, especially in young age groups,” wrote Hans-Reiner Figulla, MD, and colleagues, in a recent review and clinical update on transcatheter valve technologies.⁵ “Until now there is no evidence that TAVI has less durability when compared with surgical tissue valves,” they added.

This European Heart Journal review was published shortly before the Dvir data were presented at EuroPCR, but the second author on the review was John G. Webb, MD, FACC, who was also the senior author on the Dvir study. The authors concluded: “In the future, TAVI might replace SAVR with biological valves completely.”

Dr. Figulla is from the Friedrich Schiller Universitat Jena, in Jena, Germany, and Dr. Webb from the University of British Columbia in Vancouver, Canada. Dr. Webb and his team were the first to perform a retrograde transfemoral TAVR and the first transapical TAVR, both in 2005.

Mitral Valve Plays Second Fiddle

If TAVR is the prom king, then transcatheter mitral valve intervention is his good-looking best friend. In terms of prevalence and clinical significance mitral regurgitation (MR) is behind aortic stenosis, but only just.

In pooled data from three large, national, population-based epidemiological studies (CARDIA, ARIC, and CHS), mitral valve disease reigned as the most common valvular lesion. At least moderate MR occurred at a frequency of 1.7%, as adjusted to the U.S. adult population of 2000, increasing from 0.5% in participants aged 18 to 44 years to 9.3% in participants aged ≥ 75 years.¹ For comparison, the prevalence of mitral stenosis in the 75 years and older population was just 0.2%.

Surgery remains the gold standard for the treatment of severe MR, but up to 50% of these patients have comorbidities that preclude surgical treatment.⁶ Hence, we have a clear clinical need for a safe and effective transcatheter therapy.

If investment is any indicator of future success, then the transcatheter mitral field looks set to take off. In the last 18 months, there has been a wave of mergers and acquisitions activity in the transcatheter mitral valve arena, with industry heavyweights Edwards Lifesciences, Medtronic, Boston Scientific, HeartWare, and Abbott all making strategic investments.

MitraClip Rules in the Locker Room

Today, transcatheter mitral valve intervention is mainly limited to repair with the MitraClip, which was carefully studied in the EVEREST and EVEREST II trials. Encouragingly, registries including high-risk and inoperable patients report good safety and functional improvement in patients with both primary and secondary MR.

But for all of the success seen with the MitraClip, the field remains wide open. In the US, the device is only approved for severely symptomatic patients with primary MR who are at high or prohibitive surgical risk. It remains unclear how well the MitraClip performs in patients with functional MR, and whether it improves survival. And the procedure clearly does not eradicate the MR, but does improve it.

A number of alternative or complimentary devices are under investigation (Table), including some, such as the Mitralign, that are designed to treat functional MR. The Mitralign system directly tightens the annulus and appears to work in both the mitral and tricuspid valves.

Repair or Replace, Percutaneously Speaking?

One interesting question unanswered in the mitral arena is whether transcatheter repair will be better, worse, or equal to transcatheter replacement. Surgically speaking, repair is recommended when possible to avoid lifelong anticoagulation, prosthesis issues, and operative risk. But will the same hold true for percutaneous mitral valve interventions?

This issue was discussed by Alec Vahanian, MD, Bichat Hospital, Paris, France, at the recent CRT 2016 meeting in Washington, DC. In an interview with CSWN:Interventions, he said that it’s really too early to draw any firm conclusions as to which will be the dominant procedure. When it comes to comparing data, it isn’t even a fair fight: in this corner, mitral repair with the MitraClip device on more than 30,000 patients worldwide, with numerous patients available for at least 5 years of follow-up versus less than 100 patients treated with transcatheter mitral replacement and its limited follow-up.

What we can do, said Dr. Vahanian, is draw some lessons from the surgical field, where mitral valve repair and replacement have been shown to be “somewhat complimentary methods.” However, some lessons learned may go in the other direction with the “new kid” perhaps offering insights that the surgical masters might learn from: that’s because the transcatheter data will be based, as Dr. Vahanian put it, on sound scientific evidence, unlike in the surgical field where there are virtually no prospective randomized data on this issue and where concern persists that too many patients are being sent for replacement instead of repair.

“I think we are probably going to end up with the same kind of combined strategy. On the one hand, we’ll probably have percutaneous mitral valve repair, not in isolation but in combination: we have the MitraClip and we also have direct annuloplasty with the Cardioband. The two of them will work very nicely together and this will be applied in patients probably at a somewhat earlier stage of the disease, in those with less advanced anatomic destruction.” On the other side of the spectrum, patients with very advanced lesions will more likely get a transcatheter valve replacement procedure, he said.

Dr. Vahanian presented promising 1-year data at the CRT meeting on the Cardioband (Valtech) device he mentioned; it’s an adjustable direct annuloplasty device available for patients with MR and heart failure. In Sept. 2015, HeartWare agreed to purchase Israel’s Valtech Cardio for a reported $929 million.

In an interview with CSWN:Interventions executive editor, Rick McGuire, Robert Bonow, MD, MACC, director of the Center for Cardiovascular Innovation at the Northwestern University Feinberg School Medicine in Chicago, was asked to speculate how quickly transcatheter mitral valve intervention might come of age and start to replace surgical options. He put that event more than 5 years in the future, but said that it is likely the treatment of mitral valve disease will one day involve “more and more catheters.”

Said Dr. Bonow: “The mitral field is much more complicated [than the aortic] because it’s a more complicated set of lesions that can cause mitral regurgitation, not one size fits all. The only device we have right now [MitraClip] is evolving. We have lots of highly experienced centers, but it’s the first generation of the device. Now we’re starting to see newer devices for both repair and replacement, but those are very early on.”

Tricuspid Valve: Wanna-be or Budding Big Man on Campus?

The tricuspid valve (TV), sometimes referred to as “the forgotten valve,” could be the sleeper hit of the transcatheter valve world. Moderate or severe tricuspid regurgitation (TR) is estimated to affect 1.6 million people in the U.S. but fewer than 0.5% of them will undergo surgical tricuspid repair or replacement.

Functional TR is more common and more important than most people think. For example, in TAVR patients, about a quarter have moderate-to-severe TR persisting after their aortic intervention, according to Dr. Webb (whom we met earlier).

“I think if there were a [transcatheter] therapy people would look for this disease and be more aggressive about it,” said Dr. Webb in a July 2016 ACCEL interview. “Right now there’s not much to do for a lot of these people so we often ignore TR unless the patient has frank severe edema or ascites or both.”

Which is too bad because moderate-to-severe TR adversely impacts functional status in patients with left heart disease and is an independent risk factor for poor survival.⁵ And tricuspid surgery in high-risk patients can have an operative mortality rate as high as 22%, so surgery is often not even attempted.⁷

Tricuspid annuloplasty remains the go-to technique for functional TR in patients undergoing left-sided valve surgery in an attempt to prevent evolution to severe TR and eventual right ventricular (RV) dysfunction. However, there are currently no specific interventional concepts for tricuspid valve disease other than balloon valvuloplasty for tricuspid stenosis.⁵

Recently, Rodes-Cabau and colleagues reviewed the novel transcatheter treatment options for treating patients with severe TR and right heart failure with prohibitive surgical risk.8 They described the devices for implantation aimed at different levels: the junction between vena cavae and right atrium; the tricuspid annulus; or between TV leaflets, improving coaptation. Outcomes were collated for five different transcatheter TR therapies: Tric valve, Sapien valve, Forma, Trialign (from the same folks who brought us the Mitralign system), and TriCinch (4Tech Cardio Ltd.) None of the patient samples exceeded 10, meaning all we can say is the findings are early but promising.

Another, albeit inelegant, approach has been to use transcatheter valves off-label to treat dysfunctional bioprostheses. To date, the literature on tricuspid valve-in-valve implantation (TVIV) or in a previously repaired valve has been limited to small case series or case reports. TVIV replacement is an appealing option for many patients insofar as it may avoid higher-risk redo sternotomy and TV surgical replacement in patients who are often clinically compromised

Despite this growing practice, this way off-label transcatheter approach is not being studied prospectively. Recently, worldwide data were gathered and reported.⁹ Data were collected on 156 patients with bioprosthetic TV dysfunction who underwent catheterization with planned TVIV. Median age was 40 and 71% of patients were in New York Heart Association (NYHA) class III or IV. TVIV was attempted in 152 patients using either a Melody transcatheter pulmonary valve (n = 94) or a Sapien transcatheter aortic valve (n = 58). (Remember, we’re in the tricuspid valve here!)

After TVIV, both the TV inflow gradient and TR grade improved significantly. The vast majority of procedures were technically successful and resulted in improved TV function, regardless of surgical or transcatheter valve type or size, patient age, or underlying cardiovascular condition. Although there was substantial mortality during median 13.3-month follow-up—22 patients died—there were few early or valve-related deaths, and mortality was concentrated in patients who were in poor condition before TVIV.

At follow-up, 77% of patients were in NYHA class I or II (meaning a complete reversal from baseline, with a p < 0.001 versus before TVIV). Outcomes did not differ according to surgical valve size or TVIV valve type. Given the hemodynamic and clinical improvement and the low incidence of adverse events, the authors concluded that the risk-benefit profile of TVIV is generally favorable, especially considering that most of the hospitalized patients were able to be discharged after TVIV and, in this very sick cohort, most of the survivors reported substantial symptomatic improvement.

As well, there are a few valve devices designed for heterotopic superior vena cava (SVC) and inferior vena cava (IVC) deployment. Heterotopic approaches, of course, do not directly address the TR but do address the regurgitation of blood into the caval veins, which is often seen in patients with severe, long-standing TR and RV enlargement. Caval valve implantation (CAVI) has demonstrated encouraging results in preclinical study and the technique is relatively quick and easy to perform.

The self-expanding Tric Valve (P&F Products & Features) is specifically designed for this purpose, but balloon-expandable valves normally used in the aortic positions have also been tested for CAVI, including the 29 mm Edwards Sapien XT or Sapien 3, which is under evaluation for this indication in a few open-label studies. The Tric Valve uses a 27-F flexible catheter for transvenous implantation and comes sized as large as 43 mm for the IVC and up to 38 mm for the SVC.

“If you implant two of these in the SVC and IVC, you sort of replicate the function of the tricuspid valve except you still have regurgitation into the atrium, but at least not into the SVC or IVC,” explained Dr. Webb. “Most implants have just been in the IVC alone with the hopes that this would reduce abdominal bloating, reduce ascites, pedal edema, hepatic congestion, and that’s where most of the symptoms come from.”

Transcatheter tricuspid valve replacement is so far just a dream. To date, it appears there have not been any attempts at a full transcatheter tricuspid valve replacement in humans.⁸ “The problem is the tricuspid valve is very asymmetric,” said Dr. Webb. “It doesn’t have a fibrotic or calcific structure so it’s difficult to transplant a valve in the tricuspid position percutaneously; secure fixation just isn’t going to happen.”

“Nonetheless,” Figulla et al. wrote, “it is probably correct to predict that the percutaneous approach will be the treatment of choice in patients requiring a reintervention on the tricuspid valve after previous tricuspid surgery.”⁵

Pulmonic Valve: The Wallflower

Pulmonary valve stenosis is related to a congenital or genetic disorder in the vast majority of cases, but 80% occur in isolation.¹⁰ Most with mild-to-moderate stenosis—and even some with severe stenosis—are asymptomatic. Generally, pulmonary balloon valvotomy is indicated if the instantaneous transpulmonary gradient exceeds 50 mm Hg. But in patients with degenerated RV outflow conduits (RVOT) and biological valve restenosis, balloon dilation alone is associated with frequent restenosis.

Transcatheter pulmonic valve replacement can be performed for patients with stenotic biological valves or grafts, RVOT dysfunction, or in those with significant pulmonary regurgitation. Available devices include the Melody transcatheter pulmonary valve (TPV; Medtronic) and the Sapien XT valve, both of which are approved for pulmonic use.

The Melody valve has a size limitation (maximum outer diameter of 24 mm), but a good amount of data showing its efficacy and safety. The Sapien valve has a diameter of 29 mm, which allows for treatment of larger diameter RVOTs, but there are few long-term data on the Sapien valve in the pulmonary position.

Aortic root compression can occur during balloon angioplasty of the RVOT prior to pulmonary valve interventions but it appears it can be avoided using precautions and, in most cases, is transient and benign.^11,12

Valve Futures

It seems pretty likely that more and more valve interventions will be performed percutaneously in the near and, let’s say, less-near future. What’s next? “We are at the beginning of understanding the genetic background of [aortic stenosis] but the understanding of environmental factors contributing to valvular heart disease is beyond the scope of our present understanding,” wrote Figulla and colleagues in their comprehensive review of transcatheter valve therapies.5 Could prevention be the final frontier, grad school so to speak? They concluded their review with a call for more basic science research looking at the causes of valvular heart disease, going far beyond poorly treated strep infections to gaining a better understanding of the “pathophysiology of valvular tissue destruction.”

References:

1. Nkomo VT, Gardin JM, Skelton TN, et al. Lancet. 2006;368:1005-11.
2. Mozaffarian D, Benjamin EJ, Go AS, et al. Circulation. 2016;133:e38-e360.
3. Reynolds MR, et al. J Am Coll Cardiol. 2016;67:29-38.
4. Leon MB, Smith CR, Mack MJ, et al. New Engl J Med. 2016;374:1609-20.
5. Figulla HR. Eur Heart J. 2016 May 8 [Epub ahead of print].
6. Testa L, Latib A, Montone RA, et al. J Thorac Cardiovasc Surg. 2016 Apr 29 [Epub ahead of print].
7. Filsoufi F, Anyanwu AC, Salzberg SP, et al. Ann Thorac Surg. 2005;80:845-50.
8. Rodes-Cabau J, Hahn RT, Latib A, et al. J Am Coll Cardiol. 2016;67:1829-45.
9. McElhinney DB, Cabalka AK, Aboulhosn JA, et al.
10. Circulation. 2016;133:1582-93.
11. Lin G, Bruce CJ, Connolly HM. Diseases of the tricuspid and pulmonic valve. In: Otto CM, Bonow RO, editors. Valvular Heart Disease, A Companion to Braunwald’s Heart Disease. 4th ed. Philadelphia, PA: Elsevier, 2014.
12. Torres EJ, McElhinney DB, Anderson BR, et al. J Interv Cardiol. 2016;29:197-207.
13. Lindsay I, Aboulhosn J, Salem M, Levi D. Catheter Cardiovasc Interv. 2016 Apr 28 [Epub ahead of print].

Might We Offer You a 5th Valve?

The closing of the foramen ovale ranks as one of the miracles of birth; but when it doesn’t happen, then new parents at least can take some comfort in the miracle of repairing the defect. However, in patients with heart failure (HF), there is some evidence to suggest that shunting of blood from the left atrium to the right atrium might actually be hemodynamically advantageous.

Could an intentional left-to-right atrial shunt work as a decompression and decongestion security valve in individuals with increased left atrial pressure, high pulmonary capillary wedge pressure (PCWP; either at rest or with exercise), and heart failure (either with reduced or preserved ejection fraction)? Think of it is as kind of a detour for blood that will otherwise put pressure on the lungs and cause dyspnea, the main reason for hospital admission in HF patients.

This possibility is being tested and the results look exciting, particularly for those with HF with preserved ejection fraction (HFpEF), for whom no treatments have been proven to reduce morbidity or mortality or even significantly improve symptoms or exercise capacity.

Two companies are currently testing left-to-right shunt devices: V-Wave Medical of Caesaria, Israel, is assessing its Unidirectional Shunt System, and Corvia Medical of Tewkesbury, Massachusetts, has the InterAtrial Shunt Device (IASD®). Both devices are implanted percutaneously via femoral venous access and a trans-septal puncture. Furthermore, both are designed to create a controlled atrial septal defect in symptomatic patients with HF.

The V-Wave device is placed across the fossa ovalis and secured in place by its geometry with the wider entry funnel deployed in the left atrium and a wider exit funnel in the right atrium. The exit funnel has three porcine pericardial leaflets sutured to the frame that remain in the open position and will close when the right atrial pressure exceeds the left atrial pressure by 1 or 2 mm Hg.

The Corvia IASD device—which, by the way, is the first transcatheter device designed to treat HFpEF (and only HFpEF)—works less like a valve and more like a stent. The mesh structure is deployed through a hole made in the atrial septum and allows constant communication between the left and right atria.

In the REDUCe Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF) study, Gerd Hasenfuss, MD, of the Heart Centre at the George-August Universitat, Gottingen, Germany, and colleagues from 21 centers in the Europe, Australia, and New Zealand, assessed the performance and safety of the IASD device in patients with symptomatic HFpEF despite treatment and a raised PCWP at rest or during exercise.¹

In this single-arm, phase I study, there were no reports of peri-procedural, major adverse cardiac, or cerebrovascular events in the 64 eligible patients who had successful IASD placement, nor was there any need for surgical intervention for device-related complications within 6 months of the procedure. Sustained device patency at 6 months was confirmed by left-to-right shunting.

At 6 months, 52% of patients had a reduction in PCWP at rest, 58% had a lower PCWP during exertion, and 39% had both. Mean exercise PCWP was significantly lower at 6 months despite mean exercise duration being significantly increased.

The V-Wave Unidirectional Shunt System was tested in a Canadian single-arm, single-center, proof-of-concept study that enrolled 10 patients with HFrEF.2 This study was led by Josep Rodes-Cabau, MD, of the Quebec Heart and Lung Institute, Laval University, Quebec City, Canada. The device was implanted successfully with transesophageal echocardiographic (TEE) guidance in all patients, with no procedural adverse events reported and shunt patency confirmed by TEE at 1 month.

At 3 months, seven of nine patients (78%) had improved their New York Heart Association functional class from class III to class II, and one patient improved from class III to class I. In one patient, no change was noted. Quality of life and 6-minute walk distance were also significantly improved, while mean PCWP was reduced from 23 mm Hg at baseline to 17 mm Hg at 3 months (p = 0.035).

Patients were empirically treated with oral anticoagulants (warfarin or another) and aspirin for 3 months. No thrombotic complications were observed.

Individuals with larger congenital atrial septal defects, usually more than 10 mm in diameter, can have left-to-right shunting that leads to symptoms and signs of right ventricular volume overload and pulmonary hypertension. So an obvious concern with these devices is that they do not overload the right side of the heart. The V-Wave shunt, for example, is designed to create only a small left-to-right atrial shunt. The device has a 5 mm minimum lumen diameter or a 6.5 mm effective orifice diameter. In the Rodes-Cabau study, there was a mild and nonsignificant increase in pulmonary arterial pressures and pulmonary resistance, but the evidence indicated that this was well tolerated by the right ventricle and pulmonary vasculature.

Next Steps

“I think the proof of concept is there and we have shown that some patients may benefit from this, now it’s time to move ahead with larger studies,” said Dr. Rodes-Cabau. He noted with interest that the proof of concept has been accomplished with two somewhat mechanically different devices that work similarly but were tested in two different patient populations. On the V-Wave device, he added, they saw that the valve shunt remained open most of the time, making the most obvious difference between the two devices less meaningful.

Commenting on the trials, Patrick Rossignol, MD, PhD (Inserm, Nancy, France), and Faiez Zannad, MD, PhD (Universite de Lorraine, Nancy, France), noted that, beyond the significant amount of further clinical testing that is needed to prove safety and efficacy, clinicians also need to understand whether the results have mechanistic plausibility.³

“The mechanisms that lead from a modest hemodynamic change to the striking apparent clinical benefit still need to be understood, particularly in heart failure with reduced ejection fraction,” they wrote. As well, the long-term effects on heart and large artery remodeling need to be shown, along with clear impact on long-term hard clinical outcomes.

In March of this year, Corvia Medical received an investigational device exemption approval from the Food and Drug Administration for a multicenter study of the IASD. In May they gained CE Mark approval. It has been reported that they have inked a strategic agreement for a purchase option with a secret partner.

For its part, the V-Wave shunt is currently under investigation in multiple clinical trials in North America, Europe, and Israel. V-Wave Ltd. announced completion of a $28 million Series B financing deal with investors, including Johnson & Johnson Innovation.

References:

1. Hasenfuss G, Hayward C, Burkhoff D, et al. Lancet. 2016;387:1298-304.
2. Del Trigo M, Bergeron S, Bernier M, et al. Lancet. 2016;387:1290-97.
3. Rossignol P, Zannad F. Lancet. 2016;387:1253-55.

Read the full July/August issue of CardioSource WorldNews Interventions at ACC.org/CSWNI

Keywords: Heart Valve Diseases, Hospitalization, Life Expectancy, Mitral Valve, Prevalence, Transcatheter Aortic Valve Replacement, CardioSource WorldNews Interventions

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