This article is more than 5 years old. Information may no longer be current.
Eyeing an Unmet Need: Percutaneous Ventricular Restoration Therapy for HF
Click Here to Manage Email Alerts
Once solely for the coronary realm, percutaneous strategies for the treatment of CVD have virtually exploded in recent years. Along with CAD, percutaneous approaches are now also being either used or developed for the treatment of valvular, structural, peripheral, congenital and pediatric diseases.
One of the newest strategies, called ventricular partitioning or percutaneous ventricular restoration (PVR) therapy, may one day further add to the interventional cardiologist’s armamentarium and change the paradigm for HF management. In PVR therapy, a percutaneous device (Parachute, CardioKinetix) is deployed at the apex of the left ventricle to exclude the dysfunctional region and reduce ventricular volume. Currently CE-mark approved and investigational in the United States, the device features nitinol struts with anchors and a fluoropolymer membrane that stretches out over the nitinol frame.
The Parachute percutaneous ventricular restoration therapy device (CardioKinetix).
Image: CardioKinetix; reprinted with permission.
Clinical Significance
Since the development of neurohormonal therapies in the 1980s and 1990s, the field of HF management has experienced many disappointments with investigational drugs. However, with the advent of PVR therapy, many in the cardiology community are hopeful that a device will be able to offer patients what medical therapy — and even surgery — has been unable to do.
William T. Abraham, MD
“What is truly unique about PVR therapy is that it restores a more conical or elliptical geometry to the ventricle, which distinguishes it from the surgical approach,” William T. Abraham, MD, director of the division of cardiovascular medicine and professor of internal medicine, physiology and cell biology at the Ohio State University Wexner Medical Center (OSUWMC), Columbus, told Cardiology Today Intervention. “In surgical ventricular restoration, surgeons place a patch in the heart and exclude dysfunctional myocardium; the problem with that is the patch is more or less flat and it creates a box-shaped ventricle. In the case of the Parachute, the more conical or elliptical shape of the ventricle is restored. Also, because of the way it’s designed with the nitinol struts, it allows a more normal torsional contraction of the left ventricle.”
An additional advantage of the device, he said, is the ease of implantation.
“Our implanter, who did our first implant here in the United States and all seven implants at OSUWMC, is a very talented interventional cardiologist, but at the time he did his first implant, he was 3 years out of his fellowship,” Abraham said. “So, this is not a device that takes your most senior interventional cardiologist or structural heart disease interventionalist to pick up and do.”
Dissecting First-in-Man Data
At the EuroPCR 2012 meeting held in Paris in May, Marco A. Costa, MD, PhD, director, Interventional Cardiovascular Center, University Hospitals Case Medical Center, Cleveland, presented first-in-man data from two trials that put the Parachute device to the test in 39 combined patients with ischemic HF and left ventricular anterior-apical wall dilatation — 19 from the PARACHUTE cohort A trial and 20 from a US feasibility trial.
Marco A. Costa
Twenty-four-month follow-up data showed a reduction in NYHA Class from 2.6 at baseline to 1.9 at 2 years (P<.01) with the therapy, along with a cardiac death rate of 6.5% and a worsening HF and death rate of 32.2%. In addition, 12-month data also indicated reductions in Minnesota Living with HF score (39 vs. 27; P<.05) and a trend toward improvement in 6-minute walking distance (389 m vs. 351.6 m; P<.2).
These findings led Costa to conclude during his presentation that “PVR therapy using the Parachute device … was shown to be safe [and] associated with sustained reduction in LV volumes by echocardiography and relatively low clinical events for up to 2 years.”
Image: CardioKinetix; reprinted with permission.
Also during the presentation, Costa compared the 12-month results of the Parachute device with those obtained from several earlier trials, including CHAMPION, MIRACLE and COMPANION, which tested optimal medical therapy (OMT) alone or combined with implantable cardioverter defibrillator, cardiac resynchronization therapy or both in patients with HF.
“With OMT or OMT plus CRT-D devices, one would expect a 12-month combined risk of HF events, worsening HF, hospitalization for HF and all-cause mortality ranging from 35% to 40%, and what was seen in the Parachute pilot study was a 1-year risk of HF hospitalization and all cause-mortality of 16%,” said Abraham, who was the national primary investigator for the pilot study. “When you extend those observations out to 2 years, the rate was about 32%, which, based on historical data, we would expect to be roughly 60%.
“So what we were able to conclude from those observations was that at 1 and 2 years follow-up there was about a 50% reduction in the combined risk of HF hospitalization and all-cause mortality associated with the Parachute device,” Abraham continued. “Of course that needs to be confirmed in a prospective, randomized controlled trial, but as a clinician and an investigator these are really exciting data.”
Pivotal Trial and Beyond
According to Costa, the promising results of the first-in-man trials “led to the design and conduct of a large multicenter, multinational randomized pivotal trial to evaluate the efficacy of PVR utilizing the Parachute LV partitioning device compared with OMT in patients with ischemic HF and dilated anterior-apical wall.”
Costa along with Abraham will act as co-primary investigators in the pivotal PARACHUTE IV trial, which will randomly assign 478 patients to the Parachute device or warfarin (Coumadin, Bristol-Myers Squibb) plus aspirin for 1 year. Patients will be eligible for the trial if they have NYHA Class III or IV, low ejection fraction (>15% and <35%) and post-left anterior descending MI.
The Parachute percutaneous ventricular restoration therapy device is delivered to the left ventricle.
Image: CardioKinetix; reprinted with permission.
The device is deployed at the apex of the left ventricle to exclude the dysfunctional region and reduce ventricular volume.
Image: CardioKinetix; reprinted with permission.
“What we are doing with this pivotal trial is really addressing one of two potential major indications for this system,” Abraham said. “First, there’s the treatment group, which is going to be tested in the pivotal trial. These patients have had a remote anterior-apical MI and have symptomatic HF, anterior-apical dyskinesia or akinesia and have already undergone the process of pathological ventricular remodeling. In this population, the goals are to improve their HF, help patients feel better, improve their functional capacity and reduce morbidity and mortality.”
The second potential major indication is the prevention group, which will include patients who have had a recent anterior-apical MI but have not yet undergone the process of pathological remodeling.
“One could hypothesize that early intervention with this device would prevent or attenuate the pathological remodeling process and either prevent or delay the onset of HF,” Abraham said. “The reason we are initially focused on the treatment group is very simple: The event rates are higher and, as a result, a clinical outcomes trial can be accomplished with a smaller sample size. Although one might be looking at a 500-patient pivotal trial in the treatment group, it may take 1,000 to 1,500 patients in the prevention group because the event rates are lower.”
Despite being very early on in research, Abraham sees great potential for PVR therapy due to the large size of the treatment and prevention groups, since 60% of the roughly 1 million MIs that occur in the United States every year are anterior events.
“Right now, we’ve got proof of concept and really exciting data leading into a pivotal trial,” he said. “Everything is lined up and ready to go and would predict a high likelihood of success with the pivotal trial.” – by Brian Ellis
References:
Costa M. Percutaneous Ventricular Restoration Therapy in patients with ischemic, dilated heart failure. Presented at: EuroPCR 2012; May 15-18, 2012; Paris.
Mazzaferri EL. Am Heart J. 2012;16:812-820.
Disclosure: Dr. Abraham has received consulting fees from CardioKinetix; Dr. Costa is on the advisory/speakers’ bureau for CardioKinetix.
Perspective
Back to Top
Mandeep R. Mehra, MD, FACC, FACP
Ventricular remodeling has served us as a viable prognostic indicator and therapeutic target in the setting of LV dysfunction. Initially, neurohormonal therapy targeting the renin angiotensin aldosterone system and, subsequently, beta-adrenergic blockers helped change the natural history of an inexorable decline in prognosis with adverse LV remodeling characterized by ventricular dilatation and a decline in resting and reserve contractility of the left heart. Thus, the era of disease-modifying therapy in chronic systolic HF was ushered in. As a consequence of these successes, clinician investigators sought to deploy even more targeted molecular blocking or enhancing therapies, and the role of aldosterone antagonists and balanced vasodilators such as hydralazine and nitrates (thought to enhance nitric oxide pathways) were established in selected populations. However, such efforts at even more focused molecular pathway blockade were met with a string of failures characterized by negative trials with endothelin antagonists, centrally active sympatholytics, neutral endopeptidase inhibitors and cytokine antagonists.
Attention was then shifted to mechanical techniques of enhancing ventricular shape and function. Central among these efforts were a variety of ventricular remodeling surgical therapies that were initially met with enthusiasm and then faded into obscurity once clinical experience or trial data tempered excitement. Among these laudable attempts, the “Batista” procedure, a radical technique of reshaping the left ventricle by excising a portion of normal myocardium along the lateral wall, showed dramatic initial improvement in contractile efficiency, but failed to change the natural history of the treated population. “Jacketing” the heart by externally encircling the ventricle (the “Acorn CorCap”) was touted as a salutary way to improve the cardiac shape and enhance function, but lack of a convincing improvement in clinical outcome led to its demise. Surgical exclusion of necrotic non-viable tissue by performing a LV reconstructive “scar exclusion” procedure was thought promising enough to garner support for a pivotal trial funded by the NHLBI. This trial, dubbed as STICH, failed to demonstrate a clear benefit on outcomes with this technique. Thus, alteration of the fundamental biology of LV failure by pharmacological therapy that leads to reshaping of the ventricle seems to be a dictum that we all embrace. However, once we move into the realm of mechanical approaches to reshaping the diseased ventricle, we cannot always be certain that form will be followed by function and thereby improved outcomes.
Yet, we fundamentally believe that if we can develop an innovative technique to reshape the adversely remodeled ventricle — one that can be achieved with minimal morbidity and complications and universally applied to a vast host of eligible candidates — there is clear merit in investigating such an approach. In this vein, the highly innovative transcatheter approach to ventricular partitioning and exclusion of the infarct-related scar wall by an internal approach anchored at the apex seems to exhibit early merit. The trial presented demonstrates the feasibility of this approach and given the caveats of such uncontrolled observational efforts, even points to early benefit. Concerns that such a technique could display excess risk of thromboembolism or mechanical deployment failure appear to be assuaged by the current experience. However, the sum total of the experience is too small to confirm safety or benefit. The early results definitely point to the need for an ongoing investigation in larger, more diverse cohorts across many different centers and we await the outcome of that randomized control trial initiative.
In summary, although mechanical surgical remodeling has not borne fruit until now, we must support the ongoing effort to investigate this very innovative transcatheter approach, a technique with the potential to alter the natural history of LV remodeling in concert with OMT in the setting of regional myocardial dysfunction due to untreatable scar.
Click Here to Manage Email Alerts