The Corvia Intra-atrial shunt device (IASD) lowers left atrial pressure by creating a small left atrial to right atrial shunt. Preliminary clinical studies have shown promise for these types of devices to improve HFpEF patient outcomes.
An illustration showing the implantation of the CVRx neo baroreflex activation therapy for heart failure.
In the past few years there have been a number of device therapies developed to treat heart failure (HF). This is partly in response to the Centers for Medicare and Medicaid Services (CMS) targeting HF to reduce the staggering costs of treating patients in an HF crisis, rather than less expensive outpatient treatments. Heart failure costs the United States about $30.7 billion each year, according the Centers for Disease Control. HF is also one of the single largest costs for CMS, which is why the agency has targeted HF readmissions with payment penalties to force hospitals to better manage these patients.
About 5.7 million adults in the United States have heart failure, and one in nine deaths in 2009 included heart failure as a contributing cause. About half of the people who develop heart failure die within five years of diagnosis. This makes HF a possible large growth area to increase patient volumes with device therapies for cardiology departments in the coming years.
“We have entered a fabulous era of interventional heart failure technologies after spending the last three decades exploring drug therapies for heart failure, and now we have finally realized device therapies can also be useful in improving the way our patients feel and helping keep them out of the hospital, and perhaps even prolonging their lives,” said William Abraham, M.D., FACC, director of the division of cardiovascular medicine and a professor of internal medicine, physiology and cell biology at The Ohio State University Wexner Medical Center. He spoke on HF technologies at the 2016 Transcatheter Cardiovascular Therapeutics (TCT) meeting.
Abraham said TCT 2016 was really exciting because of the large number of new interventional therapies presented for heart failure.
“CMS is clearly interested in reducing the risk or the rate of heart failure readmissions, and I think most importantly, they are interested in patient-centered outcomes, such as making patients feel better and improving their quality of life,” he added. “The interventional heart failure therapies really promise to make patients feel better — a major goal for CMS — and to also keep them well and out of the hospital. Of course, there will be a cost associated with this explosion of implantable devices for heart failure, but if we can show it is clearly to the betterment of patients and also cost-effective, then we will really have a formula for success.”
Pulmonary Pressure Monitoring to Prevent Hospitalizations
Abraham served as principal investigator of the CHAMPION Trial for the CardioMEMS device. The CardioMEMS HF system is a wireless pulmonary artery pressure monitoring system and was one of the biggest advances in HF technology in the past decade. Cleared by the U.S. Food and Drug Administration (FDA) in May 2014, it detects fluid retention due to worsening congestive HF symptoms and can alert clinicians prior to the patient needing hospitalization.
“It allows us to manage heart failure in a very proactive way, rather than in a reactive way,” Abraham said. “If pressures become elevated, we can adjust drug therapies to lower them and we can keep them there. This really creates a situation in which the patient is at the lowest risk for rehospitalization.”
“Since the original study, where we demonstrated a marked reduction in the risk of recurrent heart failure rehospitalizations, we have now looked at the data from the CHAMPION Trial in a variety of ways, including HFpEF (HF with preserved ejection fraction) and HFrEF (HF with reduced ejection fraction), and patients with numerous co-morbidities, such as chronic kidney disease, the effects on 30-day readmissions and on and on. No matter how you cut it, the trial comes out markedly positive, so we know pulmonary pressure-guided heart failure management substantially improves outcomes.”
“The reduction in readmissions has been truly remarkable; on average annually, regardless of patient ejection fraction, it has been a 33 percent reduction,” Abraham explained. “Remarkably, if you look at the HFpEF patients, the diastolic heart failure population for whom we have no proven therapies or approaches, there is a 50 percent reduction in the rate of heart failure rehospitalization.”
Intra-atrial Shunt Devices
One of the most exciting new device concepts is the use of a transcatheter delivered intra-atrial shunt device (IASD) to lower left atrial pressure by creating a small left atrial to right atrial shunt. Abraham said these devices are in the early stages of development, with small studies to show proof of concept and demonstrate safety.
“If you look at the totality of data around the intra-atrial shunt therapies, they are consistently positive, so hopes are really high that this approach to treating heart failure will be a winner.”
HFpEF has a complex pathophysiology and has been challenging to treat. This includes elevated left atrial pressure, especially during exercise. This leads to pulmonary venous hypertension, resulting in pulmonary ingestion and dyspnea. IASDs are designed to reduce these pressures.
Corvia Medical’s IASD System recently completed a 64-patient pilot study. One-year results from the REDUCE LAP-HF trial were presented at the American Heart Association (AHA) 2016 meeting last November. There were meaningful improvements in New York Heart Association (NYHA) heart failure class, quality of life score and in the six-minute walk distance, said David M. Kaye, M.D., Ph.D., senior cardiologist in the Heart Failure-Transplant Unit at the Alfred Hospital, and senior principal research fellow at the Baker IDI Heart and Diabetes Institute, Melbourne, Australia. He presented the data on behalf of the study researchers. He said these benefits were maintained through one-year of follow up. Implantation of the shunt appeared to be safe and had an acceptable major adverse cardiac and cerebrovascular event (MACCE) rate through one year of follow-up. The device maintained potency through one year.
Pacemakers for Heart Failure
Clinical data has suggested there may be an imbalance between the sympathetic and parasympathetic nervous systems (increased sympathetic stimulation and decreased parasympathetic tone) that adversely affects congestive heart failure symptoms and prognosis. These systems play a role in other disease states outside of cardiology, and neurostimulation has been used to effectively treat the conditions. Several therapeutic strategies have recently been investigated to alter autonomic imbalance as a novel therapy for congestive heart failure.
These therapies include vagal nerve stimulation (VNS), spinal cord stimulation (SCS), baroreflex activation therapy (BAT) and renal denervation therapy.
“The clinical trials have been somewhat disappointing,” explained Farrell Mendelsohn, M.D., director interventional hypertension therapies program, cardiology, PC, Birmingham, Ala. He presented on these technologies at TCT 2016.
Vagal nerve stimulation (VNS) was first approved 20 years ago to treat epilepsy. It uses a cuff electrode placed surgically around the left or right cervical vagus nerve and it is connected to a pacemaker-like implantable impulse generator. Pre-clinical VNS for HF displayed great promise with improved LV function, decreased inflammatory markers and increased survival, Mendelsohn said. Three pilot trials with less than 100 patients each (CARDIOFIT, NECTAR-HF and ANTHEM-HF) showed some promise with improved LV function and HF status. However, the largest trial to date, INNOVATE-HF, failed to show any significant difference in all-cause mortality or hospitalizations than the standard of care in 730 patients, Mendelsohn said.
SCS is a similar approach, which has been used for about 40 years for chronic pain management. However, while preclinical studies showed promise, four clinical trials to date (SCS HEART, DEFEAT-HF, Methodist SCS and TAME-HF) were neutral in meeting their primary endpoints, Mendelsohn said.
BAT uses an electrode surgically placed on the carotid bulb to stimulate the baroreceptor there. Mendelsohn explained the afferent nerve stimulation is supposed to lead to decreased sympathetic outflow and increased parasympathetic tone. Pre-clinical and early clinical studies (RHEOS DHF and Barostim neo HF) showed promise, reducing sympathetic tone and improving LV function and patient symptoms. The large BeAT-HF randomized trial of 800 patients is currently enrolling and expects results by 2021.
Catheter-based radio-frequency ablation denervation of the renal arteries is another area of research. The idea is to ablate the afferent and efferent nerves running to and from the kidneys along the renal artery. This results in less sodium and fluid retention, renin release and renal artery vasoconstriction, leading to decreased sympathetic outflow. The REACH Pilot study of seven patients showed improvements in all patients. Two further studies are currently pending, REACH and RDT-PEF, which will include about 30 patients.
Other interventional HF technologies discussed at TCT 2016 included several types of structural heart partitioning devices that reduce the left ventricular (LV) volume following an intra-apical myocardial infarction. Reducing LV volume makes it easier for the heart to pump blood and can exclude the areas in infarct, where there is inefficient contraction.
Changing Hospital Protocol and Leveraging IT
While device therapies have generated the most interest regarding new technology to combat heart failure, many hospitals have been able to leverage electronic medical records and other types of health information technology (IT) to reduce readmissions. Additionally, changes in how hospitals address these patients in policy and protocols also can have an impact on readmissions.
“It really is a marriage between IT and protocol — you have to have the two together so you have the information you need to act upon,” Abraham said. “This includes information you receive from home monitoring systems, which needs to be directly actionable. That is where implantable hemodynamic monitoring systems and some of the newer noninvasive wearable technologies that can offer an absolute measurement of lung fluid content are valuable. But, then you have to know what to do with the data, and that is one of the big key questions we are answering, in how to use all of the new information we are getting from sensor technologies that is becoming available to us.”
Gathering data on patients is not difficult, but monitoring it, sorting through it and knowing what to do with it is an issue. This is where health IT software systems will play a bigger role in the coming years, not just for heart failure, but for all conditions in cardiology. Being able to data mine patient records, especially in an automated way, is rapidly becoming more important, Abraham said.
“Data mining is the key term,” he said. “Clearly we run the risk of providing too much information to the clinicians. Clinicians are busy and they cannot possibly sift through all the information that is currently available now, or may be available in the future, so we have to be able to mine that data and come up with smart systems that present only the important data to clinicians, and maybe in the long run to patients, so that information can be acted upon in a way that will reduce the risk of heart failure rehospitalization.”
Since adding staff to sift through massive amounts of data to identify clinically relevant, actionable information is not possible in today’s healthcare economic climate, smart machines will begin to play a much larger role in the coming years. Artificial intelligence (also called machine learning or deep learning) is already being developed and commercialized for this type of data mining and monitoring application. Advanced analytics software, including predictive analytics, recently began entering the healthcare IT market and may also offer a way to tackle the issue of sorting through vast amounts of patient data and alert clinicians when it finds an issue prior to a patient seeking medical care.
Population health software began entering the healthcare market a few years ago and is projected, along with analytics software, to be the next major wave of hospital IT implementations. These systems leverage data from hospital information systems, ADT, lab reporting systems, cardiology information systems, radiology information systems and many other electronic data sources to identify patients that may be high risk for readmission. Population health software is ideal to help identify heart failure patients and determine if they are high risk for readmissions based on their medication compliance. This might be based on whether the patient has a car, the location of their nearest pharmacy, the socioeconomic details of the neighborhood where the patient's address is, whether they have health insurance, if they have a live-in care giver and many other data parameters that might be outside the traditional realm of health IT data management. However, identification of patients that are likely to be non-compliant with medication or follow-up with their physicians can be targeted with the limited resources of hospitals to make sure they do not need to return to the emergency room.
There will likely be an explosion of new clinical decision support (CDS) software in 2017 and 2018 as new CMS rules go into effect next year requiring CDS documentation for full reimbursements. CDS related to adhering to heart failure guidelines may be another tool for hospitals to reduce readmission rates. However, hospital-developed discharge and required patient follow-up protocols also can have a major impact on preventing readmissions.
1. Centers for Disease Control, Division for Heart Disease and Stroke. “Heart Failure Fact Sheet.” www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_heart_failure.htm. Accessed Feb. 10, 2017.
2. 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 Mar 26;387(10025):1298-304. doi: 10.1016/S0140-6736(16)00704-2.