July 01, 2013
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Succeeding at Failure

The development of percutaneous HF approaches will likely usher in a new cardiac subspecialty.

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Cover illustration © Lisa Clark

Cover illustration © Lisa Clark

Currently the leading cause of hospitalization in adults aged at least 65 years, HF represents a mounting public health concern and a growing financial burden on the health care industry. As people continue to live longer lives, HF often becomes an unfortunate eventuality. Particularly as the baby boomer population continues to age, the need for effective treatments for this common condition is unprecedented.

“We know that HF is an increasing diagnosis; it’s on the radar screen of CMS and it’s an increasing health care expenditure,” said William W. O’Neill, MD, medical director of the Center for Structural Heart Disease at Henry Ford Hospital in Detroit. “But recently, there has been a confluence of devices that are starting to work specifically for HF. This field is evolving a great deal.”

According to William T. Abraham, MD, director of the division of cardiovascular medicine at the Ohio State University Wexner Medical Center, Columbus, innovations in devices for HF are showing a tremendous amount of promise.

William T. Abraham

William T. Abraham

“There’s been a lot of excitement in developing new devices, many of them interventional devices, for HF,” Abraham said. “There’s just a lot of excitement in this area. It’s exploding right now.”

Perhaps just as exciting is the potential advent of a new subspecialty — the interventional HF specialist, trained not only in the management of HF, but also in the implantation and management of these newer devices.

“This whole arena of interventional HF is really bringing the subspecialties together,” Abraham said. “We’ll be seeing HF specialists, interventionalists and electophysiologists working together to offer these newer therapies to patients.”

The Parachute Device: Reshaping the Heart

One promising investigational device for HF is the Parachute (CardioKinetix), a catheter-based ventricular partitioning device.

“The Parachute device is intended for patients who have HF related to a prior MI that created an anteroapical wall motion abnormality,” said Abraham, who is a principal investigator in the Parachute IV multicenter, large-scale, randomized outcomes trial, which began to enroll patients in late 2012. “The device essentially walls off or excludes the dysfunctional region of the heart that causes HF.”

The Parachute, which is implanted within the left ventricle, isolates the dysfunctional muscle segment from the functional segment. This decreases the overall ventricular volume and re-establishes a more normal geometry and function in the left ventricle, Abraham said.

“It allows the heart to operate at a mechanical advantage,” he said. “And in our preliminary pilot study, it seems to improve the way patients feel and might even have an impact on their outcomes.”

According to Marco Costa, MD, director of the Interventional Cardiovascular Center at the Harrington Heart and Vascular Institute at Case Western Reserve University, Cleveland, the Parachute device offers a promising alternative to open heart surgery.

Marco Costa

Marco Costa

“One of the challenges with surgical techniques is that when you’re trying to reduce the volume of the heart surgically, you’re obviously going to succeed because you just remove a piece and suture it back up again. But once you’ve done that, what is the new shape of the heart going to be? How can you predict that?” said Costa, who is also a principal investigator of the Parachute IV trial. “Open heart surgery deals with a heart that is empty. So when you fill that heart again with blood, you have to be very creative to imagine how that heart is going to be shaped. That’s why there is a lot of variability.”

Another risk of surgically decreasing heart volume is the possibility of inducing scarring and arrhythmia, Costa said.

“By removing tissue, and sometimes removing some normal tissue, you may induce a scar because of the suture lines,” he said. “And scarring leads to electrical instability, and may cause arrhythmia.”

Costa has also been involved in the initial first-in-man studies of the device. He said data from these studies were presented at the 2012 European Society of Cardiology Congress in Munich. He discussed 2-year clinical data from a study of 31 patients in the United States and Europe treated with the Parachute device.

“It shows results that are unprecedented for that population; the mortality rate was 6% at 3 years,” he said. “Obviously, we need to keep in perspective that there were only 31 patients. But the results so far are very impressive.”

Costa said the Parachute device has also delivered excellent results in terms of rehospitalization rates.

“We have completed [enrolling] more than 150 patients in Europe and the United States, and many of them — at least 100 — have completed 6-month follow-up,” he said. “These patients typically have rehospitalization rates of 20% to 30%, so it’s a huge burden to society and the health care system. And what we’ve seen is, we’ve drastically reduced the incidence of hospitalization already at 6 months. We don’t expect that to change much all the way to 3 years.”

Although Costa said he and colleagues have only treated approximately 200 patients with the Parachute device globally, it is clear that the researchers believe this is “just the beginning.”

“We have seen significant clinical improvements in patients measured by many metrics — from echocardiography to quality-of-life questionnaires to treadmill walking distance to failure class,” he said. “All of the metrics are pointing in the same direction.”

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Hemodynamic Support with pVADs

Another emerging approach to HF is the use of percutaneous ventricular assist devices (pVADs) for hemodynamic support. Through this innovation, proven left ventricular assist device technology is adapted for interventional use. According to Mandeep R. Mehra, MD, executive director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital, these devices are designed for both right and left ventricular support.

“For example, the Impella Pump (Abiomed) has a left-sided Impella pump, and soon, a right-sided Impella pump will be introduced,” Mehra said.

Described as the world’s smallest heart pump, the Impella 2.5 and 5.0 are minimally invasive percutaneous devices. According to the company’s website, the pump is inserted through a standard catheterization procedure via the femoral artery, into the ascending aorta, across the valve and into the left ventricle. The 2.5 delivers partial (2.5 L/minute) hemodynamic support, while the 5.0 provides full (5.0 L/minute) support.

O’Neill cited an article he and colleagues published in Circulation about the use of the Impella device for hemodynamic support in patients with high-risk angioplasty.

William W. O’Neill

William W. O’Neill

“These patients all had severely depressed ejection fraction — about 24% for both the Impella and the balloon pump groups — and what we found in aggregate was that when PCI was performed in those patients, there was about a seven-point increase in ejection fraction,” he said. “And a large majority of the patients became NYHA Class I or II. So using hemodynamic support improves the safety of the procedure, and patients improve LV function and decrease symptoms.”

Mehra also discussed the TandemHeart system (Cardiac Assist), which consists of a transseptal cannula, arterial cannulae, and a centrifugal blood flow pump. It provides 5 L/minute of hemodynamic support.

“The Tandem Heart is another commercially available device that can be used for biventricular support,” he said. “It is used on a short-term basis to provide hemodynamic support and protection from ischemia.”

Abraham discussed a miniature version of the Heart Mate II (Thoratec Corporation), a continuous-flow heart assist device that is FDA approved as a destination therapy for advanced HF patients.

“We’re moving into an arena of ‘micropumps’: taking proven LVAD technology such as the Heart Mate II, an axial flow pump, and in some cases miniaturizing it to the size of a double-A battery,” he said. “And while these devices might still be implanted surgically, techniques are being developed to implant them percutaneously in a cath lab rather than in an operating room. So I think the ability to eventually move ventricular assistance into the hands of interventional cardiologists is in the future.”

Beyond Hypertension: Renal Denervation for HF

Although it has been primarily studied for the treatment of recalcitrant hypertension, renal denervation has begun to gain traction as a potential treatment for HF as well.

“The concept of renal denervation really began around HF,” Abraham said. “We saw that it might have great potential in HF, since the kidney and neural/hormonal activation play such a key role in HF disease progression, morbidity and mortality.”

Renal denervation is a minimally invasive catheter procedure that currently uses radiofrequency ablation to decrease the sympathetic outflow to the kidneys.

“Essentially, renal denervation offers great promise in treating refractory hypertension — and may also have promise in treating HF — by reduction in systemic sympathetic nervous system activation,” Mehra said. “Conversely, vagal nerve stimulation can increase the parasympathetic component of the autonomic nervous system.”

Decreasing the activation of the sympathetic nervous and renin angiotensin systems can not only reduce BP, Abraham said, but also be valuable in interrupting the cycle of cardiorenal syndrome.

“As we moved into the first-in-man studies of renal denervation, mostly for safety, we decided to go into hypertension first, and it turned out that renal denervation had a huge impact on high BP,” he said. “So, to date, most of these studies have been in high BP, and the results have been exciting. But now we’ve come full circle, and are studying renal denervation in HF, where the concept began; it appears to be quite promising.”

The Symplicity HTN-3 clinical trial, which is investigating Medtronic’s Symplicity renal denervation system in resistant hypertension, is currently under way. A Symplicity HF feasibility study, which is now enrolling patients in Europe and Australia, will investigate the Symplicity system in 40 patients with HF.

“Right now, the randomized studies [of renal denervation] are focused on hypertension control,” O’Neill said. “They’re going to be looking at it for congestive HF, but that’s down the road.”

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Implantable Hemodynamic Monitors

Monitoring intracardiac or pulmonary artery pressures remotely on a daily basis is a proactive approach to treating HF as early as possible. Abraham said wireless implantable sensors allow cardiologists to measure patients’ pressures each day, without requiring the patients to leave their homes.

“There are two companies, St. Jude Medical and CardioMEMS, that have implantable hemodynamic monitor systems under investigation,” he said. “And in one large trial of 550 patients, called the CHAMPION trial, the CardioMEMS system was shown to produce a very large reduction in the risk of HF hospitalization.”

Abraham, who co-chaired the CHAMPION trial, said the risk of HF hospitalization in that study decreased by about 28% at 6 months with the CardioMEMS system, and 37% over an average follow-up of 15 months. The sensor for CardioMEMS is a miniature device that is implanted into the patient’s pulmonary artery using a simple, catheter-based technique, according to the company’s website. Likewise, St. Jude Medical’s HeartPod system can be percutaneously implanted inside the left atrium.

Stem Cell Delivery for Myocardial Repair

As innovations in stem cell therapy continue to progress, this burgeoning field of medicine is also being utilized to repair the structural damage seen in HF, Mehra said.

“In the realm of repair and restoration, we have not only these new devices, but also the whole field of stem cell therapy,” he said. “By delivering targeted stem cells to the heart, we can potentially repair and reconstruct tissue in patients with HF.”

Mehra said interventional techniques are being developed for targeted delivery of these stem cells to the damaged heart.

“Techniques have been developed to deliver the stem cells by developing three-dimensional LV endocardial maps or electromechanical maps to navigate an injection catheter and characterize underlying tissue for targeting injections. Similarly, stem cells can be infused indirectly through infusion into the coronary blood vessels,” he said. “Another way is to deliver the cells intrapericardially.”

O’Neill said stem cell injection has delivered promising results in a study conducted at the University of Miami.

Joshua M. Hare, MD, and Alan W. Heldman, MD, are doing a great deal of work in this field, and they are finding that in patients with ischemic cardiomyopathy, injection of stem cells into the jeopardized or non-functioning myocardium yields improvement in regional wall motion and improvement in ejection fraction,” he said. “They presented that data at the 2012 American Heart Association Scientific Sessions, and I think this is going to be a very important and promising approach.”

Right Ventricular Rescue

Mandeep R. Mehra

Mandeep R. Mehra

Mehra discussed a first-in-human study of a transcatheter Potts shunt for use in patients with severe pulmonary arterial hypertension and progressive medically refractory right HF. The study was published by Mehra and colleagues in the April issue of the Journal of Heart and Lung Transplantation.

According to the study, the surgical placement of a Potts shunt carries an unacceptable mortality risk for the adult population with pulmonary arterial hypertension.

“This is a highly innovative, minimally invasive technique, in which we place a stent between the two great vessels,” he said. “The creation of a transcatheter Potts shunt is a new approach to right ventricular rescue.”

Transcatheter Valve Reconstruction

Interventional approaches are also being used for valve reconstruction in patients with valvular heart disease related HF.

“Typically, the interventions are for aortic stenosis and HF, using transcatheter aortic valve replacement,” Mehra said. “The second type of intervention is mitral valve repair, using interventional techniques for functional mitral valve regurgitation that happens in the setting of HF.”

O’Neill said the MitraClip (Abbott Vascular), which was recently endorsed by the FDA Circulatory System Devices Panel Advisory Committee in March, has been shown to provide symptomatic relief in patients with functional mitral regurgitation and HF.

“In patients that have diastolic HF, the mitral annulus dilates and then the mitral valves don’t coapt,” he said. “Based on the data from the original trials, patients with functional mitral regurgitation do very well with the MitraClip. The ventricle remodels and the size of the diastolic chamber shrinks, and patients have very important symptomatic benefits. That’s another ‘here-and-now’ type of therapy that is going to be offered.”

A New Breed of Interventionalist

As the ongoing need for viable HF treatments continues to drive more sophisticated — and less invasive — devices and procedures, an interesting new subspecialty is beginning to emerge.

“There’s probably going to be a sub-discipline of interventional HF doctors who are going to specialize in trying to find interventional treatments for these patients,” O’Neill said.

Mehra said given the need for less invasive approaches to this disabling condition, this disciplinary overlap makes sense.

“We had basically hit a ceiling in which pharmacological support for HF showed limited benefit or was even demonstrating reversal of benefit,” he said. “So these new approaches are basically filling a critical gap in these sick patients by developing minimally invasive techniques where surgical risks can be reasonably avoided or reduced and hemodynamic benefits restored for these patients.”

O’Neill, who has been involved in the COAPT trial testing the MitraClip, said the management of mitral valve regurgitation in HF exemplifies this collaborative approach.

“For this trial, a HF specialist, a heart surgeon and an interventional cardiologist all have to be involved to see the patient and make sure they are receiving optimal medical therapy,” he said. “I think this paradigm is going to be used a lot for managing these patients with HF.”

He emphasized that these new approaches are also likely to necessitate effective working relationships between specialists.

“There’s going to have to be a really good relationship, a tripartite relationship, between the heart surgeon, interventional cardiologists and electrophysiologists, because you need all three of those people involved,” O’Neill said. “The patients may need bypass surgery, they may need valve repair or replacement, they may need defibrillators or biventricular pacers. So, ideally, having multidisciplinary clinicians and a multidisciplinary approach to these patients would be the best.” – by Jennifer Byrne

References:
Adamson PB. J Card Fail. 2011;17:3-10.
Bezerra H. Abstract #3147. Presented at: European Society of Cardiology Congress 2012; Aug. 25-29; Munich.
Costa MA. Am Heart J. 2013;165:531-536.
Curtis AB. N Engl J Med. 2013;368:1585-1593.
Esch JJ. J Heart Lung Transplant. 2013;32:381-387.
Hare JM. JAMA. 2013; 309:1458-1459.
Kandzari DE. Clin Cardiol. 2012;35:528-535.
O’Neill WW. Circulation. 2012;126:1717-1727.
William T. Abraham, MD, can be reached at Ohio State University, 473 W. 12th Ave., Room 110P, Columbus, OH 43210; email: william.abraham@osumc.edu.
Marco Costa, MD, can be reached at the University Hospitals Case Medical Center, 11100 Euclid Ave., Cleveland, OH 44106; email: marco.costa@uhhospitals.org.
Mandeep R. Mehra, MD, can be reached at Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115; email: mmehra@partners.org.
William W. O’Neill, MD, can be reached at Henry Ford Hospital, 2799 W Grand Blvd., Detroit, MI 48202; email: woneill1@hfhs.org.

Disclosure: Abraham is a consultant for Abbott Vascular, Biotronik, Cornerstone Therapeutics, Medtronic, St. Jude Medical and is on the advisory board of Abbott Vascular, Biotronik, CardioKinetix, CardioMEMS, CVRx, Medtronic, Novartis, Respicardia, St. Jude Medical and Sunshine Heart V-Wave; Costa has consulting agreements with and is a proctor for procedures for CardioKinetix; Mehra has consulting agreements with Abbott Vascular, the American Board of Internal Medicine, Boston Scientific, Janssen, Medtronic, St. Jude’s Medical and ThoraTec; O’Neill is a consultant for Medtronic.