Episode Transcript:

Dr. Maddux: Cardiovascular disease is the leading cause of death in individuals with chronic kidney disease and is highly prevalent in individuals on maintenance dialysis. Fresenius Medical Care teams throughout Latin America are implementing a range of interventions to improve cardio protective strategies for patients with chronic kidney disease. These initiatives vary from country to country, though all are focused on developing personalized and precise treatment options. Cardiologist Maria Mercedes Resk, Fresenius Medical Care's Medical Director for the Caribbean and Central America, joins us today to discuss how this region is taking a more personalized approach to kidney replacement therapy, and reducing the high incidence and burden of cardiovascular disease and death among individuals with kidney disease. Welcome, Maria. Thanks for joining me.

Dr. Maria Resk: Thank you, very much for this opportunity.

Dr. Maddux: We know that our patients with end-stage kidney disease have really almost malignant cardiovascular risk and disease, describe a little bit how you see the evolution of the pathophysiology across the continuum of kidney disease.

Dr. Maria Resk: So, as you know, arrhythmias are caused by a change in the electrical signal of the heart. This may be an abnormal signal or a problem with how the signal moves through the heart.  This may happen because there are more than one or two initiatives that can be placed. First of all, is the heart’s pacemaker (Sinoatrial (SA) node) is not working as it should, damage to the heart as a coronary artery disease or heart muscle damage. We can also have a signal that with the contract start in the area outside the sinoatrial node. And there are a lot of factors outside the body that can affect the rhythm to the heart. And as you may know, cardiac arrhythmias are highly sensitive to volume and electrolyte shifts like in our patients in chronic kidney disease patients going through dialysis. So, the primary cause of death in these patients is cardiovascular, as you said, and from our registry that we have from French REIN registry and the US registry, the annual mortality rate in these patients undergoing dialysis is more than 50%, with 25%, being cardiovascular death. So, in addition, other conditions leading to cardiac arrhythmias, such as ischemic, hypertrophic, dilated cardiomyopathy, are all extremely prevalent in this population. But a cause that makes me happen is that the common arrhythmias in dialysis patients or kidney chronic disease patients is not as we know, the ventricular arrhythmias but the bradyarrhythmia’s. I have seen what Dr. Bernard has explained, and it's very important to understand that these patients are half an autonomous dysfunction, that with an increased sympathetic activity in chronic kidney disease and dialysis patients makes an imbalance in nervous tones. So, are these arrhythmias so difficult to manage? In particular, bradyarrhythmia’s and we know that sleep disorders in dialysis patients should be taken and consider as a cardiovascular risk factor. Are we taking care of them? If I'm not sure of that.

Dr. Maddux: I agree with you. And I think when we studied the long intradialytic interval, we also landed on this parasympathetic-sympathetic imbalance that occurs with regard to the conduction system stimulus in the heart. And I do think these rhythm disturbances are substantial. What are your thoughts about monitoring the cardiac rhythms in patients with end-stage kidney or advanced kidney disease? Do you think that's important?

Dr. Maria Resk: I have to say that having chronic kidney disease means that you are more likely to get a heart disease. So, this is the fight between nephrologist and cardiologist. CKD can cause heart disease; heart disease can cause CKD. So, which is first? In fact, heart disease is the most common cause of death among people on dialysis. So, we are not talking about who is first.  No, the best way to prevent is, prevent or treat the problems that can cause this, such as diabetes, high blood pressure, and anemia. And we know that it is very difficult for us to, not for us, but for patients to maintain this controls. High blood pressure, diabetes, anemia are very difficult to maintain. So, which is the best options? Maybe we can add some tests, some cardiologists test, heart disease, to know if we have any of this risk in our patients. For example, ECG or Holter monitor, or even though our echocardiogram? Maybe the answer to this question, how do we monitor cardiac consents in in kidney patients, who would be great to have a score, a risk score to prevent, or know, which of these patients are more likely in risk to having sudden death. When they begin dialysis program, maybe we can have these criterias, however, waiting for this course to be available, and maybe this could be discussed at least, the last of the of the conversation. Maybe we can suggest, in cardiology point of view, having an ECG baseline, or in the entering CKD programs customizing and individualizing the patients. Having a follow up in annual controls such as in patients with atrial fibrillation, or other arrhythms with potential complications, and maybe prevent with a correct diagnosis. Now, maybe criterias to monitor cardiac rhythms in this dialysis or even pre-dialysis. We need to personalize more the treatment to our patients. Thinking about patient’s profile. No, but certainly depending on the patient risk and their profile, there is several approaches to start providing this best treatment options to specific patients.

Dr. Maddux: You've hit on several topics that I think are fundamentally important here. And one is the recognition that repeated cardiac assessment as people progress through the stages of CKD is critically important because the early or mid-stage CKD patient has a different cardiac disease than the late-stage patient. We know that statins become less useful, the longer the vintages from somebody having end-stage kidney disease and rhythm disturbances become more prominent as part of that. So, I think your idea about wanting to do more active aggressive and proactive assessment of cardiac status and where an individual patient is, is really quite important.  I've seen a number of these, and I've read quite a bit about these various patches that are interconnected to healthcare systems. Many doctors have said: well, we're going to see a lot of rhythms we have no idea how to interpret or respond to. My response originally was: well, there are a few rhythms I know we would know what to do with that are quite dangerous Bradyarrhythmia and things. What's your perspective on these patch devices that might effectively give us sort of ongoing rhythm monitoring of these patients? What do you think about that?

Dr. Maria Resk: I think that classifying patients in high risk would maybe justify an inter-dialysis monitoring. The question would be, do we have any type of risk score of sudden death during dialysis? Who is going to interpretate, analyze, and evaluate this? This electrical thing? It is important that we can have a stratified patients in dialysis with an ECG from the baseline maybe? Or with the greatest changes from arrhythmias to sudden death. For example, those ones that have atrial fibrillations relations with high ventricular response, or patients with prolonged QT. As we monitor and manage these patients, prevention of  bradyarrhythmia or ventricular fibrillation; we as cardiologists, you know that we are going through guidelines and the American Heart Association made a guideline that is published in circulation 2018. They have two recommendations that I would like to share with you. 1B recommendation is in patients with a suspected bradycardia or conditions disorders: At least one 12 lead ECG is recommended to document rhythm, rate, and conduction, and to screen for structural heart disease or systemic illness. Other recommendations from this guideline, 1B recommendation also, is in the evaluation of patients with documented or suspected bradycardia or conduction disorders; Cardiac rhythm monitoring is useful to establish correlation between heart rate or conduction abnormalities with symptoms. With a specific type of cardiac monitor chosen based on the frequency and nature of symptoms as well, as patient’s preference. In the same guideline the American Heart Association has a table like, you know, types of monitor, device description, and patient selection and When they talk about this external patch recorders, they said that it is very useful considering as an alternative to external loop recorder. However, unlike Holter monitor and other external monitors, this offer is only 1 lead recorder. So, we have to ask ourselves who is going to interpretate and read these monitors? And is enough 1 lead? Or can we do better? I'm not sure of that.

Dr. Maddux: I think that the question about one or multi lead monitoring to look beyond simply the core rhythm is actually quite an interesting question. I do think the strategies that you're proposing that we look aggressively at,  are their predictive models that would select patients at higher risk is something I know you're interested in. Tell me a little bit about the strategy you would like to consider our Global Medical Office spend some time trying to employ?

Dr. Maria Resk: We were just thinking, how can we improve? Or maybe how can we stratify our patients? What happens if we could centralize in a very central storage, our ECG with an interpretation, very blind interpretation, and maybe having some features to this stratification risk, and manage stations. There is ECG analyze program from the University of Glasgow. It’s simply an idea from Dr. McFarland. He has an ECG analyzer program that has been in continuous development for over 20 years, It has been adapted to meet the needs of different users and keep us a breast of changes in the terminology. Also, they apply its applicate to neonates and also to adults, but they have taken into account variations in waves amplitudes, and the many variates features of this could help us in identifying these patients. Maybe Fresenius has a very interesting in introducing technology. Maybe we can centralize the reading of an ECG and having more perspective on having this score that we were talking about before the patient even starts dialysis. Or when they start, and maybe having some score, you know, those scores where you have major findings, minor findings to with one, those patients that you have to take care a little bit more, and maybe they should have a monthly or quarterly evaluation with a cardiologist. This could be part of the of the things that we were thinking in Latin America.

Dr. Maddux: I think you're on the right track that we need to be fundamentally paying more attention to what proactively we can do for cardioprotection, beyond prescription of dialysis, but actually directly in interacting with the heart and collaborating with our cardiology partners better.

Dr. Maria Resk: The second would be possible to sit down in a same table and maybe having other disciplines meet and compare our isolate knowledge for a protocol of care. Cardiologists, nephrologist, endocrinologist, and other disciplines in order to, be all together in a more multidisciplinary task. Just looking forward for our patients and for the business would be also good because if we delay these kind of outcomes, and we have more time to have our patients, our business will be happy too. So, it'd be a win-win.

Dr. Maddux: I think the opportunity to have those multidisciplinary sessions that allow us to define what are the key elements that we want to land on with regard to either stratification of patients, interventions that might need to be required on that stratified population, or in fact, other device level or connected health level approaches where we want to actually watch people quite differently? I think there are absolutely opportunities for us to employ those kinds of sessions and mature the cardioprotection discussions that we've had as an organization. I'm curious just a little bit about how you have looked at whether we, in our nephrology world, spend enough time thinking about the pharmacologic interventions that are either opportunities to protect the heart or actually are things we should be more aware of to protect the heart. And on one side, the aggressive things that may change electrolytes like, drugs that will increase potassium or other such things. And on the other hand, this very low utilization of SGLT2 to inhibitors as a cardio protective, kind of care for the CKD patient. Your thoughts on either of these arms of polypharmacy?

Dr. Maria Resk: Here, in Latin America, Fresenius Medical Care has programs for advanced CKD period to dialysis in association in stage 3B to 5 CKD. These programs are in place in Argentina. It’s named CERCA (Cuidado de la Enfermedad Renal Cronica Avanzada) and also in Colombia, we have the  FMEPrever. These strategies implemented to improve cardiovascular health, including medication management, as you were saying prioritization is of angiotensin-converting enzyme inhibitors,  angiotensin II receptor antagonists, and also the sodium glucose cotransporter 2 inhibitors SGLT2 inhibitors. So, this is strategy have demonstrated a positive impact on reduction of cardiovascular complications, early mortality, disease progression, and improvement in quality of life for patients. So, I think, yes.

Dr. Maddux: When we're talking about the prescription for dialysis, I'd be interested in your thoughts about whether you think the slightly higher impact on morbidity and mortality we see on Mondays and Tuesdays after the long intradialytic interval occurs. Whether that's something you think we should be actively approaching, adjusting the cadence of therapy in such things. As a cardiologist, what's your viewpoint on that?

Dr. Maria Resk: As a cardiologist, when I used to work in my medical practice in my previous life. We used to say Mondays are the worst day for cardiologists. Because patients Saturday and Sundays are, having parties, and they do not take their medications, and eat whatever they want. So, Mondays were the most working days for us from the normal consult and going through the stents or whatever the other parts of cardiologist were part of. So, I think that we are talking about cardioprotecting our patients or cardioprotection for our patients and at Fresenius we have, this marvelous therapy from a talking about not only high volume HDF, but also these programs such as we have in Brazil, that is five, six times a weekly HV HDF, and also using our BCM, then the body composition monitor that we have at Fresenius. For example, in Chile, they have this repeating the measure with four weeks intervals, for at least in the first three months of their kidney replacement therapy. So, talking about cardioprotection, weekends are yes, very hard. But what if we go a little bit more advanced? Talking about how can we improve this? How can we protect them?

Dr. Maddux: I agree with you. I think trying to look at those proactive cardioprotective techniques that can be used are the things that we really need to do. So, before we finish, I'd like to just let you go back and refresh that recommendation that you made about what are the things you think we should be doing to create a higher level and a more mature cardioprotective focus for the company?

Dr. Maria Resk: In Latin America, we are talking about multidisciplinary teams as a specific cardiovascular related care strategy, including thorough cardiac screening,  risk assessment, evaluations for patients in lifestyles factors. Considering these treatment options, such as home-based therapy also, and ongoing management in dialytic complication. As you know, in one of our countries, Ecuador, has implemented as a mandatory every patient has an interview with a cardiologist and follow up if they need it. So, they're detecting and controlling not only fluid overload, hypertension, cardiac arrhythmias, and all vascular calcification, can likewise significantly improve this cardiovascular health. It is appropriate to mention that we suggest that we be great to have a comprehensive training program or some kind of a local table where we can talk with cardiologist, nephrologist, endocrinologist, and other disciplines. Meeting and inspiring their excellent knowledge in the true protocol of care. This is our first, suggestion. And the last but not least, having a central storage of ECG with an interpretation, maybe using technology, and maybe even develop a risk score for patients. That could be very useful. Because you don't have to be an expert reading an ECG or a monitor, you will have this centralized. So, I think those are our main suggestions and maybe we can work together in that.

Dr. Maddux: Thank you, Maria. So, I've been here today on dialogues talking with cardiologist, Maria Mercedes Resk and talking about what can we do to mature our cardio protective focus for the management of our patients with mid-stage to advanced and end-stage kidney disease. And I thank you so much, Maria, for talking with me today and giving me your insights into some of the things that I think are most important for our patients. Thanks for being here.

Dr. Maria Resk: Thank you to all. Thank you, Frank.