Barry A. Borlaug, MD is a cardiologist in Rochester, Minnesota, affiliated with the Mayo Clinic.

Updated HFmrEF Guidelines From HFSA Support Standard HFrEF Treatment

The Heart Failure Society of America (HFSA) has released a new scientific statement encouraging the acceptance of 

heart failure with mildly reduced ejection fraction (HFmrEF)

Prior to the statement’s release, HFmrEF has largely been considered a gray zone in between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), and as a result has been understudied. Initially identified by the European Society of Cardiology (ESC) in 2016 and termed heart failure with mid-range ejection fraction, clinical trials have historically overlooked this patient population, leading to limited available evidence.1,2

“There’s been a little confusion out there, especially in people who are outside of heart failure circles, as to who these patients are, whether they justify their own distinction, what we look for, how we treat them, et cetera,” Barry Borlaug, MD, associate professor of medicine at Mayo Clinic and co-author of the statement, told 

 in an exclusive interview. “That was really the basis for putting together this expert scientific statement.”

Borlaug and colleagues highlight shortcomings with current HF management and diagnosis, noting that although EF is typically used as a benchmark to differentiate between the major categories, it is an intrinsically imperfect measurement. EF is dependent on a variety of factors, including chamber size, which naturally decreases as chamber volume increases, as well as hemodynamic loading conditions.1

Given these limitations in standard disease identification, Borlaug and colleagues created a series of practical considerations for other clinicians, highlighting 5 major points in HFmrEF diagnosis, treatment, and management. These points include the following:

Recognition: Patients with symptoms of HF and EF 41-49% should be identified and followed

Classification: Careful imaging interpretation and consistent EF definitions are needed

Assessment: Evaluation should include structural abnormalities, ischemic burden, and comorbidities

Management: Utilize HFrEF guideline-directed therapies while acknowledging current evidence limitations

Follow-up: Periodic reassessment to account for gradual EF change2

Borlaug and colleagues also created a slide deck containing the top 10 take-home messages from the document, which were drafted as a quick reference guide.

HFmrEF is common - affecting 1 in 4 HF patients - and treatment should mirror GDMT for HFrEF

HFmrEF resembles HFrEF more closely than HFpEF, with high rates of ischemic heart disease, atrial fibrillation, and diabetes

Some studies show ejection fraction as dynamic, emphasizing the need for longitudinal monitoring

Patients with EF 41-49% and symptoms of HF should be followed as having HFmrEF

SGLT2 inhibitors demonstrate benefit across the EF spectrum, including HFmrEF, with a substantial reduction in HF hospitalization or cardiovascular death

GDMT for HFrEF is appropriate for HFmrEF, including beta-blockers, ARNI/ACEi/ARB, and MRAs

Ischemic heart disease is common and prognostically important in HFmrEF - evaluation for ischemia and revascularization consideration may alter EF trajectory outcomes

EF alone is an imperfect measure for myocardial function

Phenotype-specific approaches matter - obesity-related HFmrEF may benefit from GLP-1 RAs

HFmrEF is understudied and under-recognized - dedicated trials are needed to advance the evidence base

Current evidence, according to the team, indicates that HFmrEF is a heterogeneous group, including patients with clinical features indicating HFrEF and others more closely aligned with HFpEF. The most effective treatment options based on existing data are SGLT2 inhibitors, with MRAs, ARBs, beta-blockers, and combined ARB/neprilysin inhibitors showing evidence from subgroup analyses. Borlaug and colleagues determined that treatment with guideline-directed medical therapy for HFrEF is the most reasonable course of action.

“The guidelines haven’t given class 1 indications because there haven’t been specific trials, but I think all of us really feel like these people should be treated just like HFrEF,” Borlaug said. “I think that would be the main takeaway – recognize that it is true, legitimate heart failure, and for the most part, treat these patients as though they have HFrEF, with the pillars that we use in that form of heart failure.”

Editors’ Note: Borlaug reports disclosures with AstraZeneca, Cytokinetics, Merck, Novo Nordisk, Tectronic Therapeutics, BridgeBio Pharmacy, and others.

WILCOX JE, LUND LH, COX ZL, et al. Heart failure with mildly reduced ejection fraction: A Heart Failure Society of America scientific statement. Journal of Cardiac Failure. Published online April 22, 2026. 

Heart Failure Society of America. New HFSA Scientific Statement Provides Practical Guidance for Managing Heart Failure with Mildly Reduced Ejection Fraction. April 22, 2026. Accessed May 15, 2026. 

https://hfsa.org/new-hfsa-scientific-statement-provides-practical-guidance-managing-heart-failure-mildly-reduced

Videos

Barry Borlaug, MD, discusses his recent publication collecting existing evidence on HFmrEF to reflect current data regarding treatment and management.

News

news page, resources on the topics of disease- and specialty-specific medical news and expert insight can be found. Content includes articles, interviews, videos, podcasts, and breaking news on health care research, treatment, and drug development.

Clinical

clinical page is a resource for content on every specialty, disease, and topic available on our medical news site.

Cardiology

Cardiology condition center page is a comprehensive resource for clinical news and insights on cardiovascular and cardiometabolic diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for heart disease and cardiovascular events, as well as associated diabetes, renal failure, and more...

Heart Failure

The HCPLive heart failure page is a resource for medical news and expert insights on HF. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for heart disease, reduced and preserved ejection fraction, and more.

Tim Smith joined the MJH Life Sciences team in 2022 and is currently an associate editor for HCPLive. He is also the executive producer of two podcasts: Skin of Color Savvy and The Medical Sisterhood. Previously, he was the producer of the Lungcast podcast. He graduated from UC Berkeley and worked in multimedia journalism as a staff writer prior to joining MJH. You can contact him at tsmith@mjhlifesciences.com.

Approximately two-thirds of individuals with 

 and prurigo nodules (AD-PN) attained significant reduction in itch within 12 weeks of initiating upadacitinib in real-world clinical settings, recent data suggest.

This analysis was authored in Japan and led by such investigators as Hiroyuki Murota, MD, PhD, from the Nagasaki University Graduate School of Biomedical Sciences’ Department of Dermatology. Murota and colleagues’ research was previously released during the 2026 American Academy of Dermatology (AAD) Annual Meeting in Denver, Colorado.

“The efficacy and safety of [targeted immune modulators], including upadacitinib, have been demonstrated in patients with prurigo nodularis, but those in patients with AD-PN are limited,” Murota and coauthors noted.

AD-PN was described by the investigators as one of the most treatment-resistant types of atopic dermatitis, with patients often facing multiple, widespread nodular skin lesions leading to intense levels of pruritus or itch. Upadacitinib, an oral Janus-kinase (JAK)1 inhibitor, is already approved for moderate-to-severe disease, but its use in the specific AD-PN subtype was not well established in real-world clinical settings prior to this analysis.

The ADMIRE study was designed by Murota et al to address that gap in Japan. ADMIRE was a non-interventional, multi-center, prospective observational analysis involving the enrollment of 120 individuals with moderate-to-severe AD-PN. These patients, located across Japan, were recruited between December 2022 - November 2023. They were followed over 48 weeks.

Murota and coauthors’ main endpoint was at least a 4-point reduction in the Worst Pruritus Numerical Rating Scale (WP-NRS) at the 12-week mark. It was determined to be a meaningful threshold suggesting significant relief from pruritus. In terms of secondary endpoints, the investigative team tracked a broad range of clinical and patient-reported outcomes over the entire 48-week period.

The 119 individuals included in the safety analysis were noted to have an average age of about 33, and 57% were labeled as male. At the point of baseline, those assessed showed a high level of disease burden: an average WP-NRS itch scores of 7.2 out of 10, a 46.3% mean level of body surface area involvement, and a significant level of quality-of-life impairment. Approximately 40% had previously implemented systemic agents, including dupilumab, cyclosporine, and other JAK inhibitors.

Overall, Murota and coauthors’ research achieved its primary endpoint, with 65.7% of those evaluated attaining a ≥4-point improvement in WP-NRS at the 12-week mark. Crucially, meaningful improvements were already visible as early as Week 4 across nearly all measures and continued to deepen through Week 48. The number of visible prurigo nodules dipped dramatically, from an average of 26 at the point of baseline to under 3 by the 48-week mark.

Skin clearance also improved substantially, with over 83% of those evaluated showing near-clear or clear nodule staging by Week 48. Additionally, skin pain scores similarly saw improvement, with the investigators highlighting the roughly 60% showing minimal or no pain at the 48-week mark. Quality of life, measured by the DLQI, also saw improvement, with about 39% of participants reporting no disease impact on daily life by Week 48.

Upadacitinib’s safety profile was consistent with what had been noted in prior phase 3 data. Murota et al noted 60% of those assessed experienced at least a single adverse event (AE), most commonly infections (37%), with nasopharyngitis, acne, and influenza being most frequent. Herpes zoster was seen in 5% of subjects. Notably, a lack of major cardiovascular events, venous thromboembolism, tuberculosis, or malignancy was observed.

ADMIRE provides real-world data suggesting upadacitinib may be an efficacious and well-tolerated oral agent among individuals dealing with the challenging AD-PN phenotype, with rapid and durable improvements in pruritus, skin clearance, and quality of life being highlighted primarily.

Notably, Murota et al found no “new safety signals were identified with the observed safety profile similar to that previously reported in phase 3 clinical trials and post-marketing clinical studies for upadacitinib.”

Editor’s note: These data were summarized with the help of AI tools.

Murota H, Hagino T, Tada Y, et al. A Prospective Study to Evaluate the Effectiveness of Upadacitinib in Moderate-to-Severe Atopic Dermatitis with Prurigo Nodules in the Real World in Japan: ADMIRE. Presented at the 2026 American Academy of Dermatology (AAD) Annual Meeting, March 27–31, 2026, Denver, CO, USA.


Articles

Upadacitinib demonstrated rapid, clinically meaningful pruritus control in moderate-to-severe atopic dermatitis with prurigo nodules in a Japanese prospective real-world cohort. In ADMIRE (n=120; 48-week follow-up), 65.7% achieved a ≥4-point WP-NRS reduction by Week 12, with improvements apparent by Week 4 and deepening through Week 48. Prurigo nodules markedly regressed (mean 26 to <3), skin clearance and pain improved, and DLQI gains were substantial. Safety was consistent with known profiles, dominated by infections.

Patients with atopic dermatitis and prurigo nodules (AD-PN) saw notable itch reduction in 12 weeks after initiating upadacitinib.

Atopic Dermatitis

Atopic Dermatitis condition center page, audiences can find a variety of coverage mediums for medical news and updates, including articles, video interviews, podcasts, and breaking news on dermatitis research, treatment, and drug development.

Dermatology

The HCPLive dermatology page is a resource for medical news and expert insights on skin disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for dermatologic conditions, and more.

ADMIRE: Upadacitinib Efficacious in Atopic Dermatitis with Prurigo Nodules

Marc Ruel, MD, MPH, is a professor and the endowed chair and director of minimally invasive cardiac research in the division of cardiac surgery at the University of Ottawa Heart Institute.

AHA Releases Updated Guidelines for Secondary Prevention Post-CABG

A new statement from the American Heart Association (AHA) has provided updated evidence and suggestions for coronary artery bypass grafting (CABG) and postoperative management in patients with 

The last guideline update published by the AHA on secondary prevention after CABG was in 2015. The document was constructed from 2 2011 AHA and American College of Cardiology Foundation (ACCF) documents, which summarized the use of medical therapy after coronary revascularization. The 2026 update follows over a decade of evidence collection and highlights significant progress in both pre- and postoperative disease management.

“Over the last 11 years, what we’ve seen is not only progress with regards to the type of surgery that we do, but how patients are cared for and the relative safety of the surgery,” Marc Ruel, MD, MPH, a professor and the endowed chair and director of minimally invasive cardiac research in the division of cardiac surgery at the University of Ottawa Heart Institute and co-author of the statement, told 

. “We know now that there are so many interacting factors that can make a patient derive a better outcome – not only with regards to preserving the patency of the grafts but also preventing more cardiometabolic disease or cerebral vascular disease or even coronary artery disease.”

The present document highlights several major areas of focus in postoperative CAD treatment, given that the disease continues to progress after CABG. Among these are lipid management, antithrombotic therapy, and antihypertensive therapy, as well as disease management for patients with diabetes.

 profiles, including high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), or high triglyceride levels. Despite the use of high-intensity statins, many patients fail to attain lipid targets; additionally, LDL-C levels at 1 year following CABG are associated with long-term major adverse cardiovascular events (MACEs).

To address this, the document recommends an LDL-C threshold target of 55 mg/dL, with levels no higher than 70 mg/dL. Additionally, the authors suggest high-intensity or maximally tolerated statin therapy as a first-line therapy, with ezetimibe recommended for second-line and PCSK9 inhibitors or icosapent ethyl as third-line therapies.

Ruel and colleagues note that dual antiplatelet therapy (DAPT) and the addition of oral anticoagulants to antiplatelet therapy frequently increase bleeding risk following CABG. To this end, the document suggests initiating low-dose aspirin within 6 hours of CABG conclusion – this treatment effectively improves graft patency and reduces future cardiovascular events. However, higher doses can potentially increase gastrointestinal bleeding risk. Additionally, the authors suggest DAPT for 1 year following CABG in patients with acute coronary syndrome (ACS), given its association with a lower risk of death and cardiac events. While routine DAPT is not indicated in patients with chronic coronary disease, DAPT with aspirin and clopidogrel or ticagrelor can be considered to prevent graft failure in patients who are not at a high risk of bleeding.

The document implores clinicians to work for extremely strict blood pressure goals, given the activation of several neurohumoral and endogenous vasodilator systems early after CABG – in particular, Ruel and colleagues suggest a target of <130/<80 mmHg. Additionally, the document points out that ACE inhibitors and ARBs are indicated for patients with a clinical indication beyond CABG, including previous MI, diabetes, 

, reduced left ventricular ejection fraction, and 

. Calcium channel blockers are also recommended for the first postoperative year, along with dihydropyridines to help limit radial artery graft spasm.

Following CABG, the guidelines recommend that clinicians prioritize SGLT2 inhibitors for patients with diabetes regardless of baseline HbA1c, primarily for use in reducing MACEs and providing renal protection. Additionally, SGLT2 inhibitors should be utilized in patients with heart failure irrespective of diabetes status or ejection fraction. GLP-1 RAs are also flagged for prioritization in patients with diabetes or a body mass index (BMI) >27 kg/m2 to reduce MACEs.

Ultimately, these guidelines reflect 11 years of evidence collection in both CABG and follow-up therapy, bringing the field substantially further from the 2015 guidelines. However, Ruel and colleagues also acknowledge that further research must be conducted to optimize treatment for all patients both before and after the operation.

“Going forward, I think we can only go up from where we are,” Ruel said. “The 2015 statement helped achieve some strides in various jurisdictions. We’re not there yet, but we are making progress, and hopefully this statement helps.”

Editors’ Note: Ruel reports no relevant disclosures.

Ruel M, Sandner S, Ponnambalam M, et al. Secondary prevention after coronary artery bypass graft surgery: 2026 update: A scientific statement from the American Heart Association. Circulation. Published online May 13, 2026. 

Kulik A, Ruel M, Jneid H, et al. Secondary prevention after coronary artery bypass graft surgery. Circulation. 2015;131(10):927-964. 

Marc Ruel, MD, MPH, discusses the progress made since in the 11 years since the last guidelines, both in treatment and therapy.

Arrhythmia

Dyslipidemia

Venous Thromboembolism

The HCPLive venous thromboembolism page is a resource for medical news and expert insights on VTE. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for thrombotic disease, and more.

Hypertension

The HCPLive hypertension page is a resource for medical news and expert insights on high blood pressure. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for hypertension, and more.

Chelsie Derman is an associate editor for 

who covers allergy and  psychiatry. She joined MJH Life Sciences in September 2023 after graduating from The College of New Jersey with a bachelor’s degree in journalism and professional writing. In her free time, she enjoys creative writing and reading.

Linda Carpenter, MD, professor of psychiatry and human behavior at Brown University, used to arrive at the clinic early to deliver transcranial magnetic stimulation (TMS). If a patient couldn’t make it at the 8 am opening time, she and her colleagues would come at 7:30 am. If a patient could only do 6 pm, Carpenter would stay late for 3 months straight.

“We often made these crazy accommodations for people,” Carpenter told 

Even if Carpenter was willing to accommodate patients with their availability, she had to make sure everyone on the team was on board with adjusted start and end times. Carpenter would not go into the clinic every day, so there had to be someone else willing to treat this patient.

But for patients who live close to a not-so-accommodating office, getting TMS may not be a realistic option. For instance, one patient may want to try TMS but can’t take 6 weeks of morning appointments without risking their job. So, they decline. They relapse.

That scenario may feel familiar to many clinicians. Although TMS has been FDA-cleared since 2008 and is supported by nearly 2 decades of evidence, its traditional delivery schedule (~36 sessions, once daily, 6 – 8 weeks) can still be difficult for patients to sustain.

For patients managing jobs, childcare, and transportation, the time-consuming nature of TMS is often a dealbreaker. TMS may be an effective 

treatment for most patients who complete it, but far too few ever do.

“You have other people who are like, ‘I live an hour and a half away,’ and at the beginning there were a few patients who would still make that ridiculous drive,” Carpenter said. “Luckily, more and more TMS clinics have sprung [up], so people maybe can find them closer to them, but there's still so many people that can't, and it's disappointing.”

In the past 12 months, multiple studies showed that the standard 6-week course can be compressed into just days without compromising outcomes. A retrospective analysis published in March 2026 compared a 5x5 accelerated repetitive TMS, consisting of 5 sessions per day over 5 consecutive days (n = 40), with a conventional, daily 6-week protocol (n = 135).

“[This study] … shows that it's not necessary to have patients come in daily for 6 or 8 weeks,” Andrew Leuchter, MD, a professor and director of the neuromodulation division at UCLA TMS Clinical and Research Services, told 

. “We can actually compress the entire course of TMS treatment down to just 1 week.”

The study showed no significant difference in efficacy between accelerated vs conventional TMS (

 =.07). Mean Patient Health Questionnaire-9 (PHQ-9) scores dropped from 17.68 to 10.98 in the accelerated group and from 17.83 to 8.97 in the conventional group by the end of treatment. 2 The conventional TMS group had greater response and remission rates: 58.5% vs 37.5% and 24% vs 22.5%, respectively.

Leuchter noted a delayed response. Among patients showing minimal early response at day 5, improvement rates jumped from 8% to 36% at 2- to 4-week follow-up (

“It is important to let patients know upfront that while they may feel great after just a couple of days or 5 days of treatment, at the end of five days, they may not yet have felt the benefits,” Leuchter said. “Going into treatment, this is something I tell all our patients: At the end of five days, I'm going to talk with you. We’ll see how you're doing. If you're not feeling [the] benefit, don't be disappointed. I'll talk to you again in 2 weeks, and at that point, the benefits will almost certainly have started to kick in.”

Although accelerated TMS shows promise, the costs stand in the way of patients receiving these treatments. Insurance does not yet reimburse for accelerated protocols. As of now, Medicare covers up to 2 sessions per day, not 5.

A study published in March 2026 found that an accelerated course of deep TMS delivered over 6 days produced comparable clinical outcomes to standard multiweek treatment in patients with major depressive disorder (MDD).

 The accelerated regimen, known as the SWIFT protocol, included 5 daily sessions of intermittent theta burst stimulation (110% rMT, H1 coil) for 6 days, plus 1 additional day per week with 2 sessions over 4 weeks. The standard protocol used high-frequency stimulation (120% rMT, H1 coil) with once-daily sessions for four weeks (20 sessions), followed by 2 sessions per week for an additional 2 weeks (4 sessions).

Response and remission outcomes for accelerated vs standard treatment were 7.8% vs 87.5% and 78.0% vs 87.5%, respectively. 3 The mean time to remission was 21 days (accelerated) vs 28 days (standard). Accelerated deep TMS demonstrated faster symptom reduction by week 2 (median HDRS change, −11.70 vs. −8.590).

Despite differences in devices, designs, and stimulation approaches, both the 5x5 accelerated protocol and the SWIFT deep TMS regimen point to a consistent conclusion: the 6-week treatment course may not be necessary.

The acceleration of in-clinic TMS represents a major advancement. Another is removing the clinic altogether.

On January 12, 2026, the US Food & Drug Administration (FDA) approved the first prescription, physician-directed at-home brain modulation therapy for MDD.

The treatment was indicated for adults who did not achieve satisfactory improvement from ≥ 1 prior antidepressant.

ProlivRx delivers focal, multichannel external Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS), which uses gentle, noninvasive electrical pulses to target neural pathways associated with depression.

The system consists of a headset with 3 pairs of integrated electrodes positioned against the scalp.

“When we talk about TMS, we're talking about a top-down kind of treatment… but with this one… all these nerves come together down deep in the brain stem, and then they have an upward effect regulating all sorts of pathways that are involved in serotonin, dopamine, norepinephrine, and immune regulation,” Carpenter said.

Carpenter and colleagues studied ProlivRx as an adjunctive therapy to antidepressants in the randomized, controlled, multicenter MOOD trial. Participants (aged 22 to 70 years) were randomized 1:1 to the active or sham arm for 8 weeks, followed by an 8-week open-label phase.

Patients receiving ProlivRx had significantly greater remission rates (21.3% vs 6.0%; 

 =.027). During the open-label phase, participants in the ProlivRx arm had a mean reduction of 9.78 points from baseline on the HDRS17 (

 <.0001) and achieved a remission rate of 32%. The treatment had no serious adverse events.

Carpenter said that clinician oversight is central to the model, particularly because psychiatrists need visibility into all concurrent treatments and potential adverse effects. She always has patients use ProlivRx in the clinic for the first time, to make sure they use the device and smartphone application properly, and then she asks about how the treatment felt.

She also explored the uncertain reimbursement landscape following FDA approval, with insurers still evaluating coverage and cost structures. Some patients currently pay several thousand dollars out of pocket.

“I hope people will advocate with their insurance companies and say, ‘Hey, I want coverage for that,’ so they can get it.”

More work is needed before TMS moves up the treatment algorithm, including prospective RCTs confirming 5x5 noninferiority, greater clarity on the optimal number of sessions per day, and defined insurance pathways for accelerated protocols. Carpenter pointed out that insurance does not pay for TMS maintenance. If a patient improves but later relapses, they must wait until their depression becomes severe again to meet insurance coverage criteria.

As TMS protocols gain traction in clinical psychiatry, investigators are continuing to explore the biological mechanisms underlying the therapy’s antidepressant effects. Although repetitive TMS and accelerated intermittent theta burst stimulation (aiTBS) have demonstrated efficacy in MDD, particularly among patients with treatment-resistant disease, the cellular and circuit-level changes associated with these interventions have remained poorly understood.

New preclinical findings provide insight into how accelerated TMS may restore stress-disrupted neural circuitry.

 In a mouse model of chronic stress, investigators reported that aiTBS selectively repaired synaptic structures and restored activity within intratelencephalic neurons in the prefrontal cortex, changes that were associated with sustained improvements in depression-related behaviors.

Although the findings remain preclinical, the study adds a mechanistic context to the growing clinical interest in accelerated neuromodulation strategies. Investigators suggested the work could help inform future efforts to refine stimulation parameters, personalize treatment approaches, and expand circuit-based neuromodulation applications across neuropsychiatric disorders.

“It's remarkable that it's actually having distinct effects on distinct cell types. What would be really cool is if it turns out that we can tune the TMS treatment to target specific circuits and cell types,” said Scott Wilke, MD, PhD, assistant professor of psychiatry and the Penske Family Chair in Neuromodulation at UCLA Health, in an interview with 

The 6-week commitment that made TMS a treatment many patients declined is no longer the only path. The field's obligation now is to make sure clinicians know that and that payers catch up.

“This is not an experimental approach at this point. It's not a last-ditch effort to get people better. This is a legitimate treatment that probably should be considered in the future, something you should do earlier when people are depressed,” Wilke said. “TMS is really the best next step for someone who has not responded to antidepressant medications. This is a field that is rapidly evolving now, and I think there's going to be a lot of exciting changes in the coming years that will make this an even more attractive route for patients.”

Yan J. FDA Approves New Option to Treat Major Depression. 

doi:https://doi.org/10.1176/pn.43.22.0002

Leuchter A. Accelerated 5×5 rTMS Matches Standard Protocols in TRD, With Andrew Leuchter, MD. 

 Published on March 24, 2026. Accessed May 15, 2026. 

https://join.hcplive.com/view/accelerated-5-5-rtms-matches-standard-protocols-trd-andrew-leuchter-md

Derman C. Accelerated Deep TMS Matches Standard Outcomes in TRD in 6 Days. 

. Published on March 18, 2026. Accessed May 15, 2026. 

https://www.hcplive.com/view/accelerated-deep-tms-matches-standard-outcomes-trd-6-days

Derman C. FDA Approves ProlivRx, First At-Home Neuromodulation Device for MDD. HCPLive. Published on January 13, 2026. Accessed May 15, 2026. 

https://www.hcplive.com/view/fda-approves-proliv-rx-first-home-neuromodulation-mdd

Wilke S. Accelerated TMS Moves Toward Circuit-Based Depression Treatment. HCPLive. Published on May 14, 2026. Accessed May 15, 2026. 

https://www.hcplive.com/view/accelerated-tms-circuit-based-depression-treatment

Scientists finally see inside the “black box” of depression treatment. Uclahealth.org. Published May 7, 2026. Accessed May 14, 2026. 

https://www.uclahealth.org/news/release/scientists-finally-see-inside-black-box-depression-treatment

Conventional TMS for major depressive disorder remains underused because 6–8 weeks of daily sessions strain work, caregiving, and travel, driving noninitiation and dropout. Emerging accelerated protocols compress treatment to 5 sessions/day for 5–6 days with broadly comparable symptom reductions, though response may be delayed and reimbursement lags Medicare’s two-sessions/day limit. A newly FDA-approved, prescription at-home neuromodulation system (eCOT-AS; ProlivRx) improved remission versus sham with clinician oversight and minimal safety signals. Mechanistic data suggest accelerated stimulation repairs stress-disrupted prefrontal circuitry, supporting earlier-line use pending RCTs and payer alignment.

Transcranial magnetic stimulation for major depressive disorder is shifting toward accelerated (5x5 and SWIFT protocol) and at-home models (ProlivRx).

Psychiatry

Psychiatry condition center page is a comprehensive resource for clinical news and insights on mental illnesses. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for depression, schizophrenia, bipolar disorder, anxiety, and more.

Major Depressive Disorder

Major Depressive Disorder condition center page, resources on the topics of medical news and expert insight into depression can be found. Content includes articles, interviews, videos, podcasts, and breaking news on MDD research, treatment, and drug development.

TMS for MDD Reimagined: Faster, Fewer Visits, and Now at Home

Abdallah Geara, MD, is an Associate Professor of Clinical Medicine at the University of Pennsylvania.

Corey Cavanaugh, DO, is an academic nephrologist at the Cleveland Clinic. 

is rapidly transitioning into what clinicians described as a “mechanism-first era,” as emerging targeted therapies reshape how nephrologists approach diagnosis, risk stratification, and long-term disease management.

To commemorate IgAN Awareness Day on May 14, 2026, 

 spoke with nephrologists about key evolving concepts in IgAN, including earlier diagnosis, dynamic treatment sequencing, and unresolved questions around biomarkers and remission.

Corey Cavanaugh, DO — Cleveland Clinic nephrologist

Abdallah Geara, MD — Associate Professor of Clinical Medicine, University of Pennsylvania

Edgar Lerma, MD — Clinical Professor of Medicine, University of Illinois Chicago

“We now are in what we call a mechanism-first era,” said Edgar Lerma, MD. “We’re not in a sequencing-consensus era anymore in IgAN.”

Earlier Diagnosis Remains a Major Missed Opportunity

Despite therapeutic advances, clinicians emphasized that earlier recognition of IgAN remains one of the most important unmet needs in practice.

“The early diagnosis is, I think, the most critical,” said Corey Cavanaugh, DO. “That does not necessarily involve a new drug. It doesn’t even involve necessarily a new lab test.”

Instead, clinicians pointed to missed opportunities in routine care, particularly among younger patients presenting with microscopic hematuria, hypertension, or subtle urinary abnormalities.

“We know that 75% of patients with IgA nephropathy, when they’re biopsied, already have established CKD stage 3,” Geara said. “So early diagnosis is something we still need to work on.”

Experts also highlighted the lack of standardized screening approaches, including limited use of urinalysis in routine preventive care.

“If we can get sooner access and just basic things like urinalysis, blood pressure checks, creatinine checks in young people, we can identify a lot of this very early,” Cavanaugh added.

Risk Stratification Becomes More Dynamic and Prognostic

Clinicians described a shift away from static staging toward trajectory-based risk assessment incorporating proteinuria, eGFR slope, histology, and treatment response.

“The old model is that you have IgAN and will monitor kidney function over time,” Lerma said. “The new model is what we call an evidence-driven stratification era.”

He added that treatment response itself is now increasingly prognostic.

“How the patient responds to therapy within 12 months is becoming part of their prognosis,” Lerma said.

Proteinuria remains a central marker in clinical decision-making, despite limitations.

“The most powerful prognostic clinical indicator is proteinuria,” Cavanaugh said. “Unfortunately, it’s not a true biomarker in the sense that it tells us exactly what IgA is doing.”

A key challenge, clinicians added, is disease heterogeneity.

Expanding Treatment Options Complicate Sequencing Decisions

The IgAN treatment landscape now includes RAAS blockade, SGLT2 inhibitors, endothelin receptor antagonists, corticosteroids, targeted-release budesonide, complement inhibitors, and APRIL-directed therapies.

“The cornerstone remains ACE or ARB RAAS inhibition,” Cavanaugh said. “But endothelin receptor antagonists are the new nephron-sparing therapy that is not immunosuppression.”

He noted these agents can reduce proteinuria by approximately 50%, describing this as clinically meaningful for long-term prognosis.

Still, clinicians acknowledged there is no consensus on sequencing.

“The major question is who gets what and when,” Cavanaugh said.

“My core belief right now is nobody knows the right answer,” another clinician added. “The tools we have are inadequate to tell us exactly what to choose and when.”

Most clinicians, experts said, are still using a stepwise escalation approach rather than combination “stacking” of therapies.

Despite rapid innovation, adoption of newer therapies has been slower than expected.

Lerma outlined “five buckets” driving delayed uptake: regulatory burden, skepticism about surrogate endpoints like proteinuria, infrastructure challenges, disease heterogeneity, and physician familiarity.

“Most clinicians view reduction in proteinuria as positive,” Lerma said. “But whether it translates to preventing end-stage kidney disease still has some gray area.”

Additional barriers include prior authorization requirements, REMS programs, and monitoring demands.

“Adoption usually lags evidence by around 3 to 7 years in chronic kidney disease,” Lerma said.

APRIL Inhibition and the Future of Precision Nephrology

APRIL-targeted therapies are among the most closely watched emerging treatments, designed to reduce production of galactose-deficient IgA1 earlier in the disease pathway.

“These agents target upstream B-cell activation and reduce production of galactose-deficient IgA1,” Cavanaugh said.

Lerma added that APRIL inhibition may ultimately become a foundational therapy.

“In this moment, 2026, APRIL inhibition is not an add-on yet in standard practice, but it is a future backbone candidate,” he said.

Questions remain around dual APRIL–BAFF blockade and whether broader immunologic suppression improves outcomes or increases risk.

Despite therapeutic progress, clinicians emphasized that IgAN still lacks validated biomarkers for remission or precise response prediction.

“There’s still no definition of remission that we all agree on,” Cavanaugh said.

He added that improved therapies may ultimately force the field to define these endpoints more clearly.

IgA nephropathy management is shifting to a mechanism-first paradigm as pathway-targeted agents expand beyond supportive care. Earlier recognition through urinalysis, blood pressure, and creatinine screening—particularly in young adults with microscopic hematuria—remains a major gap, with many first biopsied at CKD stage 3. Risk assessment is moving from static staging to trajectory-based prognostication using proteinuria, eGFR slope, histology, and 12‑month treatment response. Sequencing is unsettled amid more options and delayed adoption driven by regulatory, endpoint, infrastructure, and familiarity barriers. APRIL inhibition is a leading future backbone candidate.

On IgAN Awareness Day, clinicians highlight earlier diagnosis, dynamic risk stratification, and emerging targeted therapies reshaping care.

Latest News

Updated HFmrEF Guidelines From HFSA Support Standard HFrEF Treatment

ADMIRE: Upadacitinib Efficacious in Atopic Dermatitis with Prurigo Nodules

AHA Releases Updated Guidelines for Secondary Prevention Post-CABG

TMS for MDD Reimagined: Faster, Fewer Visits, and Now at Home

IgAN Enters “Mechanism-First Era” Reframing Diagnosis, Treatment, and Remission