 I want to give us all an opportunity to give some advice or practice pearls to all of our viewers including other hematologists, maybe focusing a bit on red blood cell health or other areas that you think are important including decreasing long term organ damage. I’ll start with you Elna. What advice or practice pearls do you have for our audience?

 I think it is the shifting paradigm that yes sickle cell is an anemia and it causes pain, but the thing that reduces survival and still has maintained the early mortality in sickle cell disease patients compared to the general population is not necessarily the pain or the pain episodes. It is the progressive organ dysfunction and so we should slowly move away from the deception of sickle cell being a mild disease. We should consider it like diabetes or hypertension and that the organ damage is also a silent killer. If we shift that paradigm the way we approach them and how we approach our practice even towards them, we will shift an emphasis in embracing and offering disease-modifying agents to almost all of our patients and having the discussion of the impact of end organ dysfunction and damage in overall longevity and mortality.

 Thank you so much, Elna. Nirmish, you’re next.

 I would just extend the conversation in the sense that educate and be real, continue to educate. I love the descriptions that came up in our conversation today. As I told Matt, I’m going to use some of those. I’m very graphic about drawing pictures and being in the room and getting them to really understand and see what’s happening inside of them because that gives them a little bit of control of knowing what’s happening to themselves. Otherwise, it’s a chronic disease that they have no control of. What control can you give them? It’s educating them about the disease and being able to tell others about what’s happening to them. I think the pearl for me is to educate them and that includes education about these new therapies, and the new drugs that are available now. I even actually started to talk to them about the new drugs that potentially could come.

When we talk about gene therapy, I still kind of give a teaser about it. We’re not there yet. It’s all about being real with them. We don’t have the data. I’m trying to get them to understand that’s why research studies are occurring; this is what we hope that patients can be involved enough with. The patients, I can’t say this enough, they’re really smart. They’re really savvy about connecting to others and they want the information. They just take it up and soak up this information and I think it’s good for the community. Those are some of the pearls. And I mentioned it before, talk about these new medicines when they don’t need it. Talk about everything but pain until you have to talk about pain. Elna brought this up, that there might be the pediatrician inside of us trying to think about the whole world and not the adult side, but I think that our adult colleagues, and I know Biree you do this as well, I think we’re understanding that the quality of life is a big deal. Thus, I think those are some things to consider as we have our colleagues continue to see patients with these new drugs.

 I’ll leave you with 2 more images or analogies that I use because I think that there’s nothing sexy about having a chronic disease and a lot of it is just persistence of the patients, families, and providers in meeting the treatment goals and treatment plan. As I tell families when they’re going for their annual ophthalmology visit or their annual TCD [Trans Cranial Doppler], there’s nothing sexy about this. It’s like changing the oil in your car. It’s a pain. It’s annoying. It costs a little money. But if you don’t do it, what happens to the car? All the kids know the answer to that. It breaks down. Thus, that’s why [there is] this constant persistent pressure to keep on the plan is really very important.

The other one that I find useful to try and sometimes improve adherence to the treatment plan is the idea that organs are like a rock on the beach and the waves every day hit the beach, and they hit that rock and every day you don’t see anything. It’s just like the damage which is done every day with sickling even though you have no symptoms. There’s some clinical inexorable accrual of organ damage is what my mentor used to call it. There’s a little bit of damage every day that’s imperceptible. When you come back to that beach at the end of high school and you see the rock there, it’s still getting pounded by the wave and then you go away to college and then you have kids and you come back and all of a sudden there’s no rock on the beach. It’s just sand. It’s that daily pounding of that rock by a wave that you don’t notice the rock changes, but it’s becoming sand slowly and that’s what we’re trying to prevent with the daily damage of sickle cell disease on your organs.

Hydroxyurea and other disease-modifying agents are trying to prevent that from the daily point of view so that, as Nirmish pointed out or Elna pointed out, we’re trying to improve the overall health and organs of our patients who we present to our adult colleagues so that they can ultimately hopefully have a prolonged life and that sickle will no longer be an either immediately life-threatening or life-limiting disease, but hopefully have normal lifespan and quality of life. That’s really the goal. It’s hard. It’s hard to do that as a child, as a teen, and as an adult with so many other pressures on us but to encourage them to continue to follow the treatment plan with what we have while also being cognizant of what’s coming and what might be until something better comes along, as I say. Let’s follow this plan now. My promise is to keep them informed of what’s potentially available, both experimental and approved, and then they can choose collaboratively with us to potentially take on some of those new therapies.

Thank you, Matt. I really love the imagery in those analogies. I think we’ll all start to use them. I just wanted to add that I think when I speak to colleagues, clinicians of any specialty, patients, the community, family members who help to support their loves ones living with sickle cell disease; I really tell them that the tide is changing in sickle cell disease and it’s changing pretty quickly. Not only do we have more therapies available now, but our understanding of new potential targets is also growing exponentially and we’re seeing that playing out in the clinical trials that are available and that will be emerging in the near future. I think that sickle cell disease as we know it is changing. It is changing. Our patients may not feel that way today, but I do talk to my pediatric colleagues including some of you on the webinar today and I’m always heart-warmed when I hear the hydroxyurea story, for example. My colleagues say that ever since we’ve been giving it to babies starting at 9 months of age, we have such a healthier kindergarten class when we see those 5-year-old’s go off. That just warms my heart.

I think as an adult practitioner I’ve not yet begun fully to that extent to see the effects of novel agents or disease-modifying therapies or even transplant for that matter because we don’t do enough of it in the adult world. But I think that that tide is really changing. Just like hemophilia, for example, where we’ve come a long way, the expectation in hemophilia management is no leads. When we think about HIV care and we were making people toxic, sick with therapy as we knew it a few decades ago, and now people can be on 1 pill once a day. I think that there’s the potential in the very near future, hopefully in all of our lifetimes, to see that amazing impact on those affected by sickle cell disease. I’d say the future is definitely bright. I want to thank Elna, Nirmish, and Matt. And I want to thank you all for watching this 

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A panel of experts in hematology discuss the future directions for sickle cell disease and share practice pearls for disease management. 

Practice Pearls for the Management of SCD

Biree Andemariam, MD

Future Directions in the Management Atopic Dermatitis in Adult Patients

Video content above in prompted by the following:

Please provide your final thoughts on the future of atopic dermatitis treatments.

Panelists discuss how the future of atopic dermatitis treatments is evolving with novel biologics, Janus kinase inhibitors, and precision medicine targeting immune pathways. Advances in gene therapy, microbiome modulation, and personalized treatments offer promising long-term management options.

Brad P. Glick, DO, MPH

Brian Schroer, MD, is an allergist-immunologist at the Cleveland Clinic Children's Hospital.

In this video, part 1 of a 5-part series, panelists discuss on recent advancements in pediatric food allergy and anaphylaxis management.

RX Review: Advances in Pediatric Food Allergy and Anaphylaxis Management

, Brian Schroer, MD, moderates a discussion with Colleen Kraft, MD, and Russell Traister, MD, on recent advancements in pediatric food allergy and anaphylaxis management.

Traister highlights omalizumab’s (Xolair) approval for food allergy, noting its potential for patients with multiple allergens. He also discusses the introduction of intranasal epinephrine, which offers an alternative to injectable auto-injectors. Recent data from the omalizumab trials suggest long-term tolerance benefits even after stopping treatment.

Kraft emphasizes the shift in primary care toward early introduction of allergenic foods at four to six months of age to prevent allergies. She also notes the growing role of oral immunotherapy (OIT) and non-injectable epinephrine in improving patient adherence.

Schroer underscores the movement toward personalized management, with allergists now assessing individual food tolerance thresholds. These innovations mark a shift from the traditional avoidance-only approach to a more tailored strategy that includes immune modulation and improved emergency treatment options.

 is an allergist immunologist at the Cleveland Clinic Children's Hospital. Board-certified in internal medicine, pediatrics, and allergy and immunology, Schroer serves as the moderator for this panel discussion.

 is a clinical professor of Pediatrics at the Keck School of Medicine of USC and an attending physician at the Children’s Hospital Los Angeles. In addition to these roles, Kraft is also the former president of the American Academy of Pediatrics.

 is a pediatric allergy and immunology specialist at Allegheny Health Network’s Pediatric Institute. Board-certified in allergy, immunology, and internal medicine, Traister serves as the third panelist for our discussion.

Relevant disclosures for Schroer include Genzyme, AstraZeneca, Amgen, GSK, and Sobi. Relevant disclosures for Kraft include Sanofi and Sobi. Relevant disclosures for Traister  include Abbvie.

Brian Schroer, MD

Experts conclude this series highlighting what is on the horizon of retinal disease care. 

Perspectives on the Future of Retinal Disease Management

In this final segment, the participants share their excitement for the future of retina care this year and beyond. Across the panel, experts express enthusiasm for the constant evolution of therapies, techniques, and technologies in the field of retina. They touch on the ongoing trials and current research, acknowledging the challenges and complexities of developing new drugs but remains optimistic about potential breakthroughs. Experts circle back to gene therapy, emphasizing the potential for game-changing developments once challenges like inflammation are addressed. The physicians across the panel are excited at the prospect of higher durability agents to continue improving patient quality of life.

This summary was AI-generated and edited for clarity.

David Brown, MD

Jim, I want to close by discussing how patients are discharged, which is usually outside your purview. I don’t anticipate you discharge many of these patients, but I want to talk about the admission fully. If a patient who is admitted with HE [hepatic encephalopathy] is nearing discharge, some things that are important to keep in mind are how we can strategize for them to get appropriate, follow-up, treatment, and hopefully not end up back in the emergency department [ED] within a month or so. At my institution [Weill Cornell Medical College], we try and educate the patient about the disease. It’s not necessarily straightforward for them to understand why their brain is affected by cirrhosis and how that has a lot to do with bacteria in their intestines. The medications lactulose and rifaximin help prevent that, but we try to discuss the basics of the pathophysiology of hepatic encephalopathy, how ammonia plays a role in having adequate bowel movements, and how taking this antibiotic can help prevent them from ending up back in the hospital.

We prescribe them the medications they need. Rifaximin often requires prior authorization, so we want to make those prescriptions clear in terms, saying that the indication is overt hepatic encephalopathy and they were hospitalized with it. If they’re intolerant of lactulose or if they failed lactulose, it’s important to include the right ICD-10 [International Classification of Diseases, Tenth Revision] code. We try to start that process early so that they don’t run into a lapse in medications. That brings up a question for you. Do you see patients whose major reason for coming in is that they didn’t have access to medication?

 That’s a challenge for a lot of patients, particularly those living on their own. Perhaps they don’t have a strong support network. Maybe they did have a strong support network, but recurrent HE sometimes exhausts family members and leaves patients on their own. It’s a challenge if they can’t get support, don’t know how to get it, or won’t get it. The No. 1 thing we can do is provide good follow-up for these patients.

I imagine you have a great case manager network at your facility. We have it at our facility too, although I don’t discharge most of these patients. On the backside, when hospitalists discharge them, we have case managers calling these patients to make sure they’re getting their medication and to see how they’re doing. Those 2 open-ended questions—are you getting your medications? How are things going?—are helpful to minimize progression for relapse.

In the emergency department, the most important thing we can do to help with this continuity of understanding of HE and ongoing treatment is to diagnose HE. Rather than admitting the patient with a diagnosis of a generic altered mental status, which doesn’t help much, try to refine it: yes, they did have a GI [gastrointestinal] bleed plus or minus SBP [spontaneous bacterial peritonitis], but also mention hepatic encephalopathy explicitly because that will help them then get the medication as an inpatient but also as an outpatient.

Such important points. I completely agree with the case-management aspect. We can prevent a significant subset of admissions by someone just calling them and picking up on early encephalopathy that can be managed at home. For example, sometimes patients need to take a little extra lactulose. That could avoid an emergency department visit or an admission that can be costly in a number of ways: outcome, days in the hospital, dollars spent. Sometimes they need a sooner follow-up appointment than what’s been scheduled for them. If someone is checking in the first few days and they recognize that, that can potentially be a way of keeping them out of the hospital. Thank you for bringing that up and the importance of attaching that diagnosis to their hospitalization, even though they might have several diagnoses. These patients are medically complex, but in terms of access to medications, having that HE diagnosis—both in the hospitalization and potentially on the prescription—is important.

We learned this decades ago with congestive heart failure as it proliferated: when we have close follow-up with case management, we can minimize any recurrence of ED visits or hospitalizations and access to medications. That’s key. No. 1 you have to make the diagnosis, and No. 2, you have to take your medication to treat it.

Exactly. If we can do that reliably or achieve that on behalf of our patients, we’ll be taking much better care of them and preventing a lot of admissions, or at least the preventable ones.

 Thank you for this rich and informative discussion. Before we conclude, I’d like to get final thoughts from you. Dr Williams, is there anything you want to add?

It’s been a pleasure having this conversation with you and our colleagues. Thank you for the opportunity. My final thought is that in the emergency department, when you have complex patients with altered mental status, you have to at least consider hepatic encephalopathy, as not just the sole diagnosis but often a joint diagnosis. You have to treat both aggressively and start early just as you would any other patient in the emergency department. Remember, it’s not a unifying diagnosis of a singular diagnosis of sepsis. We typically have to treat sepsis and HE aggressively. Even if it’s subtle, if it’s not over. With HE, which is easy to diagnose, you want to start treatment early and don’t want to depend on your serum ammonia level. It’s a clinical diagnosis.

 I like that as a closing thought: don’t depend on your serum ammonia level. Thank you. To our viewing audience, we hope you found this 

 to be useful and informative. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming 

Drs Arun Jesudian and James William discuss approaches for proper discharge planning and transition of care and how this can reduce readmission for patients with hepatic encephalopathy.

Discharge Planning and Transition of Care in HE

James Williams, MS, DO, FACEP

For what it’s worth, I interview a lot of doctors. I’ve done a lot of panels. What struck me about you folks—the folks who deal with diabetics every day, or people with diabetes—I’m informed that diabetics is not the best term.

Not good—so, people with diabetes, people dealing with this disease. What I noticed is that you listen. Every 1 of you talks about listening to people. Doctors are bad at that, as a group, but not you. Did you select this because you like listening, or did you learn to listen because that’s what you do? I don’t know. It was just an observation. Call it a hunch. Look, we have come to the end of this discussion, but I don’t want to leave without giving each of you an opportunity to say something that you feel we may have omitted or something that you want to leave our audience with. Why don’t we go around, and each of you can take about 30 seconds and give us some final thoughts. Why don’t we start with you, Elaine?

 I’m just thinking back on the patients that I saw today. One of the biggest challenges of diabetes, and dealing with highs or lows, is that you could do everything perfectly Monday to Monday. With other things like saving money, or training for a marathon, you have something to build on. Maybe on the eighth day you can take a day off. That’s not the case with diabetes. You’ve got to start all over again that eighth day and do it all over again, and it may be the worst day of the eight. It’s such a marathon to run, and you don’t have an end line, or point, to look forward to. As a provider, you have to place yourself in that reality. You have to see through the patient’s eyes every day, and if you don’t do that, then you won’t understand their struggles and you miss the boat. That’s what I strive to do every day for them.

Wow, that was well said. Thank you. We really need to understand that, as Elaine has said, diabetes never gives the patient a break; it’s 24-7. Hypoglycemia is incredibly scary and really does limit so much of what the patient can and can’t do if we aren’t careful with educating our patients, assisting with quality of life, and making sure patients have a good understanding of their medications. We need to provide good education on prevention and treatment, and the use of continuous glucose monitoring [CGM] to try and help patients prevent hypoglycemia. We all need to take it seriously and make sure that we ask the right questions every time we touch the patient, so that hopefully we can have a better outcome for them.

I’m going to say something completely different, but I agree with what Elaine and Davida said. I want a system in which the pharmacist tells the patient and me every 2 years when their glucagon is going to expire, so I know to write a new prescription. Because what makes me crazy is when I’ve forgotten and the patient has forgotten to ask, and then they have a bad low and they don’t have their glucagon. Why can’t the pharmacists do this? I get bugged all the time about everything. Why can’t the pharmacist just say, “Patient X needs a prescription for glucagon”? That’s no skin off my back. They should probably just do it without a prescription. Why does this even have to require a prescription? That’s another issue. We need a system so patients and providers are reminded to do the refills. I don’t know why it doesn’t exist, so we need to create that solution.

Could that be built into the EMR [electronic medical record]?

When you click the prescription, it should pop up in 2 years.

 It should just say, “This is due.” Why not?

Jay Shubrook, DO, FACOFP, FAAFP, BC-ADM: 

Hypoglycemia is certainly something that’s very important to our patients, and most providers underestimate the frequency of it. Please ask your patient and the family at every visit about hypoglycemia. There’s no better time than today because we have plenty of tools to identify hypoglycemia, such as CGM, or continuous glucose sensors. We have ways that we can help patients have less hypoglycemia—particularly patients with type 2 diabetes—with novel therapies, and we have very effective treatments that can abort a hypoglycemic episode. Making sure you use the right treatment at the right time really is going to empower your patients not to be paralyzed by hypoglycemia but to be an informed and active crusader to prevent it and treat it earlier.

I want to thank all of you for being with us. This has been eye-opening for me because I don’t treat diabetes on a daily basis. I always thought, “It’s about sugar, for sure; usually it’s about hyperglycemia.” This hypoglycemic problem is real, significant, and tricky. These new therapies that I’ve learned about from you are strikingly interesting. Thank you all for being here.

I want to thank all of you at home for watching this 

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Thought leaders in diabetes provide closing remarks about the importance of continuous awareness of glycemic control in patients as well as the need for effective communication between patients and providers. 

Final Thoughts: Awareness and Communication in Diabetes 

Jay Shubrook, DO, FACOFP, FAAFP, BC-ADM, Touro University California College of Osteopathic Medicine 

Orly Vardeny, PharmD, MS is a professor of medicine at the University of Minnesota. 

Orly Vardeny, PharmD: Finerenone for Heart Failure with EF >40% in FINEARTS-HF

22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC)

, Orly Vardeny, PharmD, a professor of medicine at the University of Minnesota, discussed findings from the FINEARTS-HF trial, focusing on the efficacy and safety of finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), in patients with 

heart failure (HF) with mildly reduced or preserved ejection fraction

The trial enrolled patients with symptomatic HF, elevated natriuretic peptide levels, and structural heart disease. Finerenone reduced the risk of cardiovascular death and total worsening HF events compared to placebo. Vardeny indicated the drug’s pharmacologic properties, including kidney-protective effects and a lower propensity for hyperkalemia compared to steroidal MRAs, marking it as a promising treatment option. Despite a twofold increase in hyperkalemia (potassium levels ≥5.5 mmol/L) incidence (14% vs. 7% with placebo), Vardeny noted severe hyperkalemia events were rare, and finerenone also mitigated the risk of hypokalemia, a known driver of arrhythmic events.

Dr. Vardeny emphasized that FINEARTS-HF provided evidence supporting the use of finerenone in patients with HF and preserved EF, addressing a critical unmet need alongside treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors. The trial also demonstrated improvements in patient-reported functional status, measured by the Kansas City Cardiomyopathy Questionnaire. However, Vardeny highlighted the challenge of translating trial findings into clinical practice, citing the historically slow adoption of novel therapies in the HF community. She added that future research, including real-world evidence, could further validate these findings and enhance widespread implementation to improve outcomes for this patient population.

Relevant disclosures for Vardeny include Cardior, Bayer, Moderna, and Cardurion.

Vardeny O. FINEARTS-HF - Finerenone in Heart Failure with EF > 40%. Presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC). Los Angeles, California. December 12-14, 2024.

Orly Vardeny, PharmD, MS explores the efficacy of nonsteroidal MRAs in heart failure with mildly reduced or preserved ejection fraction in the FINE-ARTS trial.

Orly Vardeny, PharmD, MS: Finerenone for Heart Failure with EF >40% in FINEARTS-HF

Orly Vardeny, PharmD, MS

The panel offers their final recommendations for physicians managing patients with asthma.

Advice for Clinicians Managing Asthma

Robert Sporter, MD

 Before we conclude, I’d like to get some final thoughts from each of you, if you have any. Let’s start with you, Dr Nordberg.

 From my perspective, treatment-resistant depression and other complex mental health challenges are systems challenges as much as they are clinical challenges. We haven’t moved the needle in treatment effectiveness in about 50 years, and in no small respect that may be because we haven’t changed our systems that provide care. I’m a big fan of looking at developing systems where we’re doing a lot more precision referral work, and to Martin’s earlier point, identifying different providers, clinics, and centers of strength, and referring to strengths. The only way to do that is to collect the data.

There are challenges around collecting the data. It creates vulnerability and a lot of visibility where there hasn’t been historically. One of the things that we’re working on at Reliant Medical Group is trying to be more precise about how and who we refer. A lot of that involves understanding the patient that we’re being presented with, and also understanding how that person matches up with what we believe is the most likely treatment to be effective for them based on data.

I’m pretty confident that if we can do that work in naturalistic settings, we’ll get past the archaic requirement of failing 2 bonafide medication interventions and get more rapidly to something that’s going to allow a care delivery organization to say, “This is a patient with treatment-resistant depression,” and a payer to say “No problem,” and then allows that care delivery organization to connect that patient with a reimbursed intervention that has a likely shot of helping them. That’s a lot of work to be done, but it starts with measurement and having the confidence to integrate that measurement into your clinical routine.

 Well said. To your original point, we haven’t moved the needle much in these past 50 years. You’re calling for improved systems, better measurement, and moving toward precision care. Hopefully that will be supported by the validation of some biomarkers that can lead to more precise and predictive treatments. Would you also agree that part of this as well is that we haven’t had very many new tools in the past 50 years, and potentially having some effective new tools in the toolbox may also help move that needle?

 It may. We also know that there’s a lot of variability between different providers and that there are different kinds of treatments that appeal more to different kinds of patients. The biomarker research is sexy and exciting because of that possibility of carving nature at its joints and being precise. It’s also a long way off. RDoC [Research Domain Criteria] didn’t deliver the promise of precision opportunities for understanding and deep learning about what drives mental health on a physiological level.

We still have a lot of opportunities with the systems and treatments that are already out there. This system still has a lot of room for optimization. It starts with having the courage to collect more data and letting those data start to tell us what kind of a patient this is and the best place for the patient to go based on what we’ve already learned about similar patients. That’s where my focus is, less so on developing novel interventions. It’s important to figure out where the patients that we’ve been discussing fit in that overall model, but we’re not going to be able to figure that out if we’re not collecting the right data.

 For those of us who deal with the fun stuff, the insurance and billing portion of things, like I’ve been saying this whole time, it’s important to make sure that you understand your payers and their guidelines and policies. You have to play that middleman role between the insurance carriers, providers, and patients. We need to make sure that we’re educating our providers so that they know if there are any changes to these policies so that they can find the right fit for patients.

It’s also important to educate the patients in regard to what qualifies them as having treatment-resistant depression and what’s available out there. Be an advocate for the patient with the payer and keep them involved in the process so that they’re not at home wondering, “What’s going on with my prior authorization? When is my treatment going to start?” Let them know everything along the way and be there for them.

 The theme that I’d leave with is the idea of “better together.” If you think about it, there are 3 participants in the goal here. Front and foremost is the patient because they want to get better. They’re suffering. There’s the provider who’s trying their best to figure out the appropriate care. There’s also the payer who wants to make sure that the patient gets access to the benefit that they deserve and that they’re able to go on and live a healthier and happier life. You have to see that triad.

There’s a likelihood that you can blame the insurer or blame someone else, but at the end of the day, it’s about figuring out how to work better together, that triad, because we have a common interest in improving the life of that patient. That’s the part that I like to focus on. What are we doing this for? Who matters the most? The other stuff can be worked out.

 Thank you. Last but not least, Dr Ares-Romero.

 I love that. I love how you ended with that. Because as somebody who treats treatment-resistant depression regularly, I’m very passionate about having my patients improve their lives. Their quality of life is what’s important, and that they get passion and fulfillment from their lives. It’s beautiful to hear that, that we can work together. That’s key, getting the payer together with a provider. It’s not about you or me. It’s about the patient and how can we come together to work together. I love that.

Despite the hurdles and challenges and everything we’ve talked about, it’s an exciting time in psychiatry. This is a time when we have new modalities, new things, all the data collection, all the systems, and the artificial intelligence that we have now that we haven’t explored. There are so many wonderful things coming that I’m excited. I’m excited for our patients. I’m excited for everything that we’re doing.

 Thank you all again. To our viewing audience, we hope you found this 

® panel discussion to be useful and informative.

An expert panel shares insight on the future treatment landscape for treatment-resistant depression. 

Optimizing the Management of TRD

Samuel Nordberg, PhD

The Pathophysiology of ATTR-CM, Differentiating Between wtATTR-CM and hATTR-CM

Summary for Physicians: Pathophysiology of ATTR-CM and the Importance of Differentiating Between wtATTR-CM and hATTR-CM

 (ATTR-CM) is a form of systemic amyloidosis where misfolded transthyretin (TTR) proteins accumulate as amyloid deposits in various organs, primarily in the heart. TTR is a protein responsible for transporting thyroid hormones and retinol-binding proteins, and it is produced mainly in the liver. When TTR undergoes misfolding due to mutations (in hereditary forms) or aging (in wild-type forms), it forms amyloid fibrils that deposit in tissues, leading to organ dysfunction, particularly in the heart.

, the amyloid fibrils accumulate in the myocardium, causing 

. Over time, this amyloid deposition can lead to stiffening of the heart muscle, impairing its ability to contract and relax, which results in reduced cardiac output and symptoms such as shortness of breath, fatigue, and arrhythmias.

Differentiating Between Wild-Type ATTR-CM (wtATTR-CM) and Hereditary ATTR-CM (hATTR-CM)

This form of ATTR-CM occurs due to the accumulation of normal (wild-type) TTR proteins that misfold and form amyloid deposits as people age. It primarily affects older individuals, especially men, and is commonly associated with heart failure with preserved ejection fraction. wtATTR-CM is often seen in patients older than 60 years and may be more prevalent than previously recognized, but it tends to progress more slowly and is often diagnosed later in the disease course.

hATTR-CM results from mutations in the TTR gene, which causes the production of abnormal TTR proteins that are prone to misfolding and amyloid deposition. The mutations may cause a more aggressive form of the disease that can present earlier in life, often in patients aged 30 to 50 years. hATTR-CM is inherited in an autosomal dominant manner, so there may be a family history of the disease. Certain mutations, such as the V30M mutation, are associated with more severe clinical outcomes, including earlier cardiac involvement, neuropathy, and multiorgan dysfunction.

Importance of Differentiating Between wtATTR-CM and hATTR-CM

: Treatment for wtATTR-CM focuses on symptom management, particularly heart failure treatment, as there are fewer disease-modifying therapies currently available for this form. However, emerging treatments, such as tafamidis, are starting to show promise in slowing disease progression.

: For hATTR-CM, specific disease-modifying treatments are available, such as 

 strategies. These therapies target the misfolded TTR protein directly and can prevent further amyloid deposition, improve cardiac function, and potentially halt disease progression. Early diagnosis and genetic testing are crucial for the timely initiation of these treatments.

 mutation is important not only for treatment but also for 

. Family members may be at risk, and early screening can help identify asymptomatic carriers who may benefit from early treatment.

 tends to have a slower progression, and the patient’s prognosis may be better compared to 

, which can progress rapidly and result in multiorgan damage. Understanding whether the patient has wtATTR-CM or hATTR-CM helps predict disease course and guide clinical decision-making.

 is critical for ensuring the correct diagnosis, appropriate treatment selection, and better management of patient outcomes. Although both forms share similar pathophysiology with TTR amyloid deposits in the heart, the underlying causes, progression, and treatment strategies differ significantly. Early diagnosis of hATTR-CM is particularly important for initiating disease-modifying therapies and providing genetic counseling to at-risk family members.

Panelists discuss how differentiating between wild-type transthyretin amyloid cardiomyopathy (wATTR-CM) and hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is essential for accurate diagnosis, tailored treatment strategies, and better management of patient outcomes, given their distinct pathophysiologies, disease progression, and treatment options.

Authors