Innovative Heart Failure Therapies and Clinical Trials

Podcast Transcript

Announcer:

Welcome to Cardiac Consult, brought to you by the Sydell and Arnold Miller Family, Heart, Vascular and Thoracic Institute at Cleveland Clinic. This podcast will explore the latest innovations, medical and surgical treatments, diagnostic testing, research, technology and practice improvements.

Amanda Vest, MBBS:

We’re very pleased to have the opportunity to talk to you about some of the things that are new about heart function and heart recovery. My name's Amanda Vest. I'm the Section Head of Heart Failure and Transplant Cardiology here and a transplant cardiologist.

Edward Soltesz, MD:

Hi, I am Ed Soltesz. I'm one of the cardiac surgeons here, and I'm the Surgical Director of the Kaufman Center for Heart Failure and Recovery on the surgical side. Today we'd like to share with you some of the advances in heart failure therapies that we are offering patients here at the Cleveland Clinic. With over 6 million patients in the United States suffering from heart failure, this is certainly something that is on our minds, so we'd like to share some of what we have to offer for our patients today. Amanda?

Amanda Vest, MBBS:

One of the first questions that patients often ask is what might cause these heart conditions that we're talking about. There are things that can be contributors towards the condition we call heart failure. That really means that the body isn't quite being met in its needs by the blood flow going around. This can either be because the heart is weak and not able to push enough blood around, or it can be because the heart is stiff. In that first situation, we call that heart failure with reduced ejection fraction, where the pumping function is weak. In the second situation, you'll hear that referred to as heart failure with preserved ejection fraction, where the heart is stiff. In that scenario, we mostly see heart failure with preserved ejection fraction in people as they age, with major risk factors being high blood pressure, excess weight, physical inactivity, and things like smoking, atrial fibrillation and chronic kidney disease.

For those with weak hearts, there can be a lot of different causes. Some people have a genetic cause, meaning it's an inherited issue through their family. Others may have had a heart attack that leads to an error of weakness in the heart. For some people, there may be another medical condition, maybe a thyroid abnormality or something like that, which sometimes can be reversible. In some cases, it's an arrhythmia of the heart that's really driving the weakness. It’s super important to be working with a heart specialist and figure out when a low pumping function is found, what might be the cause and could there be anything reversible.

Edward Soltesz, MD:

Amanda, we've heard a lot about some recent advances in medical therapy for heart failure. A lot of patients who have both types of heart failure can be managed reasonably well for quite a while with medical therapy. Can you tell us a little bit about that?

Amanda Vest, MBBS:

That's right. For some years, patients with stiff hearts really had very limited options. Really, we only had the water medicines, diuretics to get the fluid off. But now we do have one type of pill called SGLT-II inhibitors, that's dapagliflozin, empagliflozin, which improve the body's metabolism, which help to reduce symptoms, keep people out of hospital and living longer. There’s some really interesting work coming through in the past year for those individuals who have some extra weight in the setting of having a stiff heart. There are medications that can be injected once a week that help with metabolism and can really improve breathing and help keep people out of the hospital.

Then, for our patients with a weak pumping function, we talk about the four pillars of medical therapy. There are four classes of medications that have been shown over a few decades now, in multiple clinical trials, to help that weak and enlarged heart to start to shape up and, in many cases, even get back towards normal or even normal pumping strength to help keep people out of the hospital and help them live longer.

These medicines, such as a group called the beta blockers that protect the heart from adrenaline, the angiotensin receptor antagonists, that group, and the mineralocorticoid antagonists and those SGLT-II inhibitors as well are the four groups that can be very helpful to help people feel better. If you're in this situation, certainly speak to your doctor and make sure all the appropriate medicines are prescribed. Now, going beyond that, for particularly people with weak pumping function, there may be other procedures, other devices for those with symptoms that are not completely improving with the medicines. Can you tell us a little bit about some of those?

Edward Soltesz, MD:

Sure, Amanda. Some patients, as Amanda had mentioned, have poor heart function because of coronary artery disease or valvular heart disease. Oftentimes, we are able to offer them conventional cardiac surgery, that is either valve repair or replacement or coronary bypass surgery, which will help improve not only their symptoms, but also their survival, and sometimes even return their heart function to more normal levels. That's what we start with for some patients. But there are of course, other patients who maybe have normal coronary arteries and they really have a cardiomyopathy of an unknown origin who've been treated medically for quite some time successfully, who then begin to require what we call more advanced therapies. Advanced therapies are particularly things like left ventricular assist device therapy or heart transplantation.

In the past when we talked about these two, putting pumps in patients and replacing their hearts, this was really something reserved for a very small group of patients. But now, we've really come to a revolution in this technology. We have a lot more hearts available for patients for transplantation, and we also have an amazing pump now, the HeartMate III left ventricular assist device pump, which is offering patients improved survival and significantly improved quality of life compared to previous generations of pumps. There is not something like it that used to exist years ago. This is very new technology, and many, many people are taking advantage of this. Amanda, can you talk a little bit about who you would feel is a good candidate for one of these advanced therapies?

Amanda Vest, MBBS:

Absolutely. With every patient with a weak pumping function, we're firstly thinking about the medications that you've heard, lifestyle measures that may include what we can do with exercise and with dietary approaches. For those who are still having heart failure hospitalizations or still having a lot of symptoms and limitation in their life, then we may be going through perhaps some of those intermediate measures, sometimes also either invasive or non-invasive devices to monitor the patient at home and to be able to tweak those medicines more precisely to get them feeling better. But for patients who are still having a lot of shortness of breath, maybe having a lot of issues with fluid retention on the body, those individuals who have had more than one hospitalization in a year, and especially patients who have been very sick and in our intensive care units, perhaps where the kidneys or the liver are not getting enough blood flow, those are really high risk situations.

So in those scenarios, the care team is talking to patients about how unfortunately with the best of efforts, those medicines and other less invasive devices may not be doing enough, may not be giving the patient the quality of life that they're looking for and indeed may not be enough to keep them alive for a long enough period of time. Those are the scenarios where we're starting to talk to patients about whether either heart transplantation or the left ventricular assist device heart pump might be the next step to achieve those goals of feeling better, staying out of hospital and living longer. Here at Cleveland Clinic, we're so fortunate to have a wonderful multidisciplinary team who helps patients and families all the way through that spectrum of lifestyle, medication, device and transplantation options. Would you like to speak a little to that team?

Edward Soltesz, MD:

Sure, Amanda. Amanda spoke just recently about a care team, and that truly is what it is, a multidisciplinary care team composed of cardiologists, cardiac surgeons, social workers, nurse practitioners and physician assistants, a whole group of caregivers who are focused on making the best experience and the best outcome for each individual patient. I think what really sets us apart here at the Cleveland Clinic is the tremendous depth of experience that we have and the true multidisciplinary nature of our practice. We truly do individualize each patient's care, looking at not only medication management, but device management, lifestyle management, nutritional management. We bring all that together, and we really are able to offer the patient a focused approach that truly is precision medicine in the 21st century. I think that's really what sets us apart at the Cleveland Clinic.

We have a number of trials here at the Cleveland Clinic and heart failure therapies both on the medical side as well as on the surgical side. On the surgical side, we are one of the largest sites right now in the IMPACT trial. This is sponsored by Abiomed, and it is investigating whether or not Impella-assisted heart surgery, doing conventional heart surgery but with the assistance of the Impella temporary left ventricular assist pump, will benefit patients. We are one of a number of sites across the country that are enrolling patients in this trial, and we really expect this to be groundbreaking for patients who have low heart function and are undergoing high-risk heart surgery. We are also investigating one of the new heart pumps, the BrioVAD left ventricular assist device. This is in trial right now throughout the United States, and we are a participating center. Again, we’re looking forward to enrolling patients in that trial as well. Amanda, can you fill us in on some of the medical trials?

Amanda Vest, MBBS:

Absolutely. We have a range of trials across the medications and devices for patients with heart failure with reduced or preserved ejection fraction. For example, we have a trial of protein supplementation in patients with low ejection fractions to look at muscle mass. We also have the COMET-HF trial coming soon, which is omecamtiv mecarbil on top of standard heart failure with reduced ejection fraction medical therapy to look for improvements of outcomes with enhanced myocardial contractility.

We have a number of device trials. For example, inpatients with mid-range ejection fraction, there's the cardiac contractility modulation trial called AIM HIGHer. That's a device that stimulates contractility in the heart for that intermediate group that is not currently covered by FDA approval. For patients with heart failure with preserved ejection fraction, we still have some of those interatrial shunt trials with the concept being that unloading the left atrium by allowing blood to flow over to the right atrium may help to keep down those exercise-induced high pulmonary artery pressures, which we think contribute towards shortness of breath in the heart failure with preserved ejection fraction syndrome.

So, a range of exciting trials there across HFrEF, HFpER. I'll also just call out the depth of trials that we have for our patients with Transthyretin cardiac amyloidosis because this is such a hot area, and for patients with a range of severity of disease, there are a number of trials of additional therapies open at this time, including the DEPLETA study, which is a monoclonal antibody that seeks to determine whether it's possible to actually remove some of those Transthyretin deposits from the heart even after the disease is fairly well established. It’s an exciting set of trials currently available for patients to consider.

Edward Soltesz, MD:

Amanda, if a provider or a patient were interested in participating in the trial or to see if their patient is a candidate, who should they reach out to?

Amanda Vest, MBBS:

Certainly patients could make an appointment to speak to a heart failure cardiologist with a regular appointment. That's always certainly an option. But it's also possible to go either onto the Cleveland Clinic Clinical Trials website and browse through specific trials or to use clinicaltrials.gov, which allows you to filter for areas of the country that you're located in. Those two locations will always give you a number for a member of the study team who would be able to provide some more information about what the eligibility might be and what the requirement in terms of number of visits to Cleveland could be for that specific study.

Edward Soltesz, MD:

You've heard a lot about some of the new trials and devices that we are testing. We are more than happy to offer a second opinion and a consultation to see if your patient would be a candidate. Amanda, what's the right time to refer a patient for advanced therapies or to an advanced heart failure provider?

Amanda Vest, MBBS:

It's a great question. The international societies do have some guidance on this. Referring physicians may be familiar with the I NEED HELP mnemonic, which summarizes some of the high-risk features that a patient with heart failure may have, including recurrent hospitalizations, ICD shots, higher diuretic doses, need for an inotrope and so forth. However, although we're delighted to see patients who meet those criteria, the message is really, feel free to refer early because we very much appreciate the opportunity to meet a patient early on, to begin to talk with them about the opportunities for future treatments should they need it, and to meet a patient before they get too sick. Because unfortunately, sometimes patients do come to us already with end organ dysfunction and too sick for some of these therapies to be able to really get the benefit out of them.

Having said that, for people in the Northeast Ohio region who may transfer inpatients to us, we have a well-defined process for those patients who are very sick and in cardiogenic shock. When calling in through the transfer center to place a patient request for transfer to Cleveland Clinic, there is the option to convene a shock team. Can you tell us what a shock call is?

Edward Soltesz, MD:

Yes, Amanda, seven years ago, as you know, we developed the cardiogenic shock team, and this is really a team of teams approach to dealing with cardiogenic shock. The shock team convenes at a moment's notice, providers in cardiac surgery, cardiology, heart failure cardiology, anesthesia, ICU, nursing and our structural cardiologists, with the goal of defining what is the best strategy for patients in cardiogenic shock. We work together with our Cleveland Clinic transport team, who has access to a fixed wing as well as helicopter transport from various other facilities throughout Northeast Ohio and, in fact, neighboring states. We routinely bring patients here who are in cardiogenic shock for advanced therapy. We use all different sorts of devices from VA-ECMO to the Impella series of pumps to stabilize patients, and that gives us an opportunity to understand what they need next.

Are they candidates for transplant? Are they candidates for LVAD? Do they just need a tuning up of medical regimen? Maybe they've never been diagnosed with heart failure before, and this is a new diagnosis. But either way, this gives us time to stabilize a patient and put all of our collective heads together to understand the best care path for the patient. We've been very proud of the outcomes of our cardiogenic shock team. It truly is a team of teams approach, and we work very closely together with all the colleagues in providing the best care for the patient. If you are interested in transferring a patient utilizing the shock team, please reach out at the Cleveland Clinic Transfer Center and ask them to activate a shock team call.

Amanda Vest, MBBS:

Well, to speak with one of our specialists or to submit a referral, please call 855.751.2469. That's 855.751.2469. Thank you for listening to Cardiac Consult.

Announcer:

Thank you for listening to Cardiac Consult. We hope you enjoyed the podcast. For more information or to refer a patient to Cleveland Clinic, please call 855.751.2469. That's 855.751.2469. We welcome your comments and feedback. Please contact us at heart@ccf.org. Like what you heard? Subscribe wherever you get your podcasts or listen at clevelandclinic.org/CardiacConsultPodcast.