Robert Underwood, MD (Host): Welcome to Advancing Worsening Heart Failure Treatment, exploring cutting-edge therapies and addressing disparities. I'm Dr. Bob Underwood. And I'm joined once again today by my esteemed colleague who is the Director of Women's Cardiovascular Health Research and Associate Director of Preventive Cardiology at the Johns Hopkins University School of Medicine, Co-Director of the Impact Center at Johns Hopkins University and Co-Editor-in-Chief of the American Journal of Preventive Cardiology, Dr. Erin Michos. Welcome and thanks for coming back.

Erin D. Michos, MD: Thank you.

Host: Yep. For full relevant financial disclosure information, please see iridiumce.com/hf. This educational activity is supported by an independent educational grant from Merck, Sharp, and Dohm, and we would like to thank them for their support of this initiative.

The learning objective for this program is discuss health disparities in the diagnosis and treatment of heart failure and strategies to reduce these disparities. Dr. Michos, welcome back. Welcome to Part 4, the last in this series on worsening heart failure.

Erin D. Michos, MD: Yeah. Well, thank you for having me back on your program.

Host: Absolutely. So, the first question is really kind of a two-part question. So, what influence does race and ethnicity have on the risk of developing heart failure? And are there associations between race and ethnicity on the diagnosis and treatment of heart failure? So, the first is developing heart failure and the second question is diagnosis and treatment.

Erin D. Michos, MD: Yeah. So unfortunately, there's healthcare disparities, and for both of those parts of the question. So, for the first part, yes, there is differences in both the rate, the diagnosis, and treatments of heart failure among patients of minority racial and ethnic background. Black individuals, followed by Hispanic individuals, are more likely to develop heart failure than white adults. And this can be influenced by having a higher prevalence of baseline comorbidities, such as obesity, hypertension, and diabetes that are big drivers for heart failure risk. There can be disparities by socioeconomic status, other social determinants of health. And the social determinants of health that affect cardiovascular health are things such as having limited access to healthy food source; having less safe places to exercise for reduction in physical activity; you know, employment, because a lot of insurance is tied, unfortunately, into employment, and so there can be limited access to healthcare, individuals who have more adverse social determinants can be under chronic stress, and chronic stress can both have indirect and direct effects on the cardiovascular risk. So, indirect effects when you're under chronic stress, you may have poor coping habits such as, increased smoking, increased alcohol use, not seeking preventative care, not getting regular physical activity. But there also can be direct biological effects when you're under chronic stress. There can be a subclinical inflammation. There's that activation of that sympathetic nervous system, increase in stress hormones like cortisol that can have, you know, an adverse cardiovascular profile.

And then, there can be a lot of distrust, and perhaps rightfully so, of healthcare clinicians because many patients of minority racial and ethnic background have encountered some systemic biases in the healthcare system, and that might affect their willingness or ability to effectively seek care for their heart failure condition. It seems that people of African descent appear to have a higher risk of heart failure. It's a little unclear because we think of race predominantly being a social construct with really probably not much genetic differences between individuals. So, maybe some of this is related to these social determinants of health, but there may be physiologic differences that affect production of nitric oxide and natriuretic peptides. But if you just look at hospitalizations, they vary by race. Unfortunately, Black adults are 200% more likely to be hospitalized for heart failure than white individuals. I mean, that's really striking.

Host: It is.

Erin D. Michos, MD: Even heart failure mortality is higher among Black men and women compared to white men and women respectively. And in the second part, where you asked about disparities in treatment and, unfortunately, structural racism and implicit bias may affect treatment because we see that Black patients compared to white patients are less likely to be treated for hypertension and hyperlipidemia, or if treated, they're not treated as intensively. They're less likely to be followed by a cardiologist when they're hospitalized for heart failure. They're less likely to receive a heart transplant. They're more likely to have worse outcomes if they do get a transplant. And they often end up having higher hospitalization costs. And so, we need to figure out how we can bridge and overcome and mitigate these disparities to improve outcomes for all adults with heart failure.

Host: Yeah, absolutely. And I think you mentioned a lot of things that are really coming more and more to fruition and becoming part of the normal conversation around diagnosis and treatment. I think that's incredibly important that it has become part of the discussion and there's action going in that direction now.

So, we've already discussed a little bit on the differences in heart failure between male and female patients. So, are there differences in the symptoms that female patients tend to have compared to males?

Erin D. Michos, MD: Yeah. So, heart failure can be a little different between the sexes. Females are more likely to have heart failure with preserved ejection fraction, where men might be more likely to have heart failure with reduced ejection fraction. Women can be more symptomatic in terms of having more edema, more shortness of breath and perhaps a higher prevalence of some baseline comorbidities like hypertension and diabetes in the setting of their heart failure. Men, on the other hand might have a higher prevalence of having obstructive coronary artery disease than females.

Host: Got it. So, now onto the kind of the second part of the question we asked before, what about the diagnosis and treatment for heart failure in female patients? Are there differences there as well?

Erin D. Michos, MD: Yeah. I think females are less likely to undergo diagnostic testing than males and so their disease, their diagnosis, is much later in the disease progression. I think sometimes this is because women are more likely to have heart failure of preserved ejection fraction. And often when they are complaining of shortness of breath and symptoms, they may be told that they're just deconditioned or it's related to their weight, and it may not get the same level of attention. But maybe they had the same weight and activity level, you know, a year ago, but they can do so much less now. And so, it's really important to be considering heart failure for these symptoms and not just write it off that they're just deconditioned and overweight. So, they're less likely to be diagnosed.

And then when you think about advanced heart failure treatment, female patients are less likely to receive a heart transplant. There's various issues related to body size and also that women have more autoimmunity related to pregnancy, so sometimes finding a match can be a little bit more challenging. Females are less likely to get ICDs and they're less likely to get mechanical circulatory devices like LVADs because, again, females are generally smaller body size than men, although that's not always the case, but they're less likely to get these advanced heart failure procedures.

But on the other hand, I did want to point out some things positive things and why it's so important that we make the diagnosis and treat women appropriately. You know, if you look in HFpEF, actually some of the therapies that we have may actually work better in women. I think we talk about this a little in our segment three. But in the Paragon heart failure trial of patients with HFpEF, ARNIs, that's the valsartan/sacubitril combination, that seems to reduce heart failure hospitalizations in women more so than men. So, women benefit more from ARNIs than men in the setting of HFpEF. And then in the TOPCAT trial, which was also HFpEF patients. Now, this was an exploratory post hoc analysis, so we always consider this with caution, but female patients treated with spironolactone actually had reduced all-cause mortality substantially compared to females in the placebo group, where male patients treated with spironolactone didn't have that mortality benefit in the setting of HFpEF. So, it may be that ARNIs, and MRAs actually work better in female patients in the setting of HFpEF.

Host: Yep. And so, diagnosis is really important in the disparity there. So, let's talk about how to reduce some of these disparities amongst our patients. So, what are some techniques that can help reduce the risk of heart failure and improve diagnosis and treatment of heart failure in Black individuals and in females?

Erin D. Michos, MD: Yes. First of all, to take symptoms seriously, and if somebody's really complaining of dyspnea, shortness of breath, to make sure that heart failure is on your radar and not necessarily attribute it to other causes, because I think we talked about our first episode, how we may have imaging and biomarker techniques to help support the diagnosis of heart failure. So although heart failure is a clinical diagnosis, if there is perhaps suspicion, you could get imaging like an echocardiogram to see if there is evidence of diastolic dysfunction or increased feeling pressures. You could get a BNP level. So, I think we really need to just have increased recognition of heart failure.

You know, a lot in this program we've been talking about guidelines and clinical trials. And clinical trials, randomized clinical trials, serve as the evidence base for which we make our treatment recommendations. It's so important that we learn so much from clinical trials. And that's why it's really important that trials are representative of the patients we take care of in clinical practice. And we really need to include the proportion of individuals of underrepresented racial and ethnic background such as Black adults as well as females in clinical trials so that we know if these therapies, if we understand whether they're both efficacious and safe in these patient groups similar to their counterparts. So, that's really important.

Host: Yeah, absolutely. And one of the clinical trials that you made mention of in an earlier episode actually had an over preponderance of males and a great lack of females in the study.

Erin D. Michos, MD: Yes. So, we need to do better with improving diversity in clinical trials. And then, cardiovascular disease and heart failure is really on the spectrum. And I think in the first episode, we talked about the stages of heart failure, where stage A was just risk factors, and stage B was sort of pre-heart failure, where there may be evidence of structural heart disease, but there's not yet been clinical signs. And then, stage C is clinical heart failure. And D, you know, is sort of advanced heart failure. So, we really want to prevent progression down the spectrum. And that means early interventions, starting with, lifestyle from utero and childhood.

So, early in childhood, young adults, we want to promote healthier lifestyles to prevent the development of those risk factors like obesity and hypertension that can lead to heart so that includes things of early access to healthy foods and eliminating food deserts, increasing safe places to exercise and get physical activity, making sure that all adults have access to healthcare in an equitable fashion. And that means that sometimes in low-income areas and rural areas that we have enough clinics available to see these individuals to really help promote prevention across the life course. Healthcare is very expensive in the United States. And so, trying to reduce the financial burden so that our patients can take the medications to keep them well and expanding access. And there's things to utilize all hands on deck. And so, things like community centers and, churches and involving maybe some groups that are even not healthcare groups, but groups that can be advocate for their populations, especially in underserved areas. You know, we even saw studies like the Barbershop Study where we had barbers trained on how to measure blood pressure in Black men and be able to, give them feedback based on AHA guidelines. And so, I think the more we can think about how to utilize these other community and faith-based centers in a way that can help our patients is really good. And of course, we want to also use these venues to improve health literacy. And I think that will help hopefully reduce the distrust that some may have of the healthcare system because they're engaging with organizations they trust, like their barbers, like their faith-based organizations, their churches. And for those that have rural areas particularly that have limited access, there can be novel ways we deliver healthcare such as telemedicine to kind of reach those that may not have easy access to coming in for a clinic visit.

Host: Yeah, absolutely a different social approach if you live in a city versus in a very rural area, for example, where I am geographically. You need to approach it in innovative ways. So, all right, let's move on to doing a patient case. So, I'll give a scenario. So, let's say Belinda is a 60-year-old Hispanic woman of Mexican descent. And she's been diagnosed with worsening heart failure and has a preserved ejection fraction. Now, Belinda also has hypertension and a BMI of 30. So, how would you approach that?

Erin D. Michos, MD: Okay. Well, we see a lot of patients like Blinda that can be challenging. And ideally, it would have been great to have met her earlier in her life and really promoted that healthy lifestyle, the dietary modifications. You know, an exercise program to help prevent some of these comorbidities that led to her worsening heart failure. So, we'd certainly still encourage healthy lifestyle, salt restriction, dietary modifications. We need to control the risk factor she has, so she has hypertension, so she needs good blood pressure control. If she has any atherosclerotic cardiovascular disease risk, we would want to modify that as well, such as with statin therapy for prevention, but she already has worsening heart failure.

So, you know, it sounds like she needs diuretics to reduce her congestion, to reduce her edema and reduce her breathlessness. She would be a great candidate for an SGLT2 inhibitor. And we got great data now from the EMPEROR-Preserved and the DELIVER trials, which specifically enrolled patients with HFpEF, that SGLT2 inhibitors reduce heart failure hospitalizations and cardiovascular death. And so now, they have a class 2 indication for HFpEF. They already have a class 1 indication for HFrEF, but they've now been shown a benefit in HFpEF too, which is exciting enough therapy that helps in HFpEF.

Now, I would still consider using a spironolactone and an ARB or an ARNI in this patient. She has hypertension, so I think an ARB and ARNI would be good. The 2022 Heart Failure Guidelines gave ARB and ARNI and MRAs a 2b indication in HFpEF. And I mentioned this earlier when we talked about sex differences in heart failure, that female patients who have heart failure with preserved ejection fraction seem to benefit perhaps even more than men do from ARNIs, an aldosterone antagonist. So, I would put her on spironolactone, and either an ARB or an ARNI. And then finally, I would address her for chronic weight management. We need to address obesity like we would any other risk factor, because this is really impacting her heart failure.

And earlier last year, we saw the results of the STEP-HFpEF trial of patients who had HFpEF, an EF above 45%, and obesity, a BMI above 30. And those randomized to semaglutide 2.4 milligrams per week compared to placebo. This is a GLP-1 receptor agonist. These patients with semaglutide treatment had significant improvement in their clinical symptoms by that Kansas City cardiomyopathy clinical score. And they also had a reduction in body weight, they had a reduction in their BNP, they had improvement in their six-minute walk time. So, that was all really exciting. And this was a small trial, so it wasn't really powered for events, but we actually did see less heart failure hospitalizations with the semaglutide group versus placebo. So, I would really consider a GLP-1 in this patient, assuming that we've really tried giving lifestyle a good try for at least six months for her weight reduction. And of note, women tend to lose more weight with GLP-1 receptor agonist therapy than the men do. So, I would actually consider that in her too, as well.

Host: Wonderful. Wonderful discussion. Really, really appreciate it. So, we've reached the end of this episode, which is the last episode of a four-part series. So Dr. Michos, thank you so much for this informative discussion.

Erin D. Michos, MD: Thank you again for having me be part of this.

Host: We'd also like thank Dr. Bott, who was with us with a previous couple of episodes as well. We'd also like to thank Merck for their support of this program. So, be sure to claim your CME by filling out the evaluation and the post-test. And also, make sure you're following Iridium on X, Facebook, and LinkedIn to see more free CME programs. Thanks for being part of our show today.