James Januzzi, MD

Released on July 23, 2026, the most recent update to the American College of Cardiology (ACC) Expert Consensus Decision Pathway (EDCP) aims to redefine, recategorize, and reestablish treatment criteria for 

heart failure with preserved ejection fraction (HFpEF)

ACC Expert Consensus Decision Pathway Updates HFpEF Definition, Diagnosis & Treatment

Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026

, James Januzzi, MD, chief scientific officer and C. Michael Gibson Chair in Medicine at the Baim Institute for Clinical Research and Adolph Hutter Professor of Medicine at Harvard Medical School and co-author of the new guidelines, discusses their implications for HFpEF care moving forward.

“In the document, we acknowledge that heart failure with preserved ejection fraction is unique compared to other forms of heart failure, such as reduced ejection fraction,” Januzzi told 

. “We argued that clinicians need to take a very careful look at each patient on an individual level before deciding on specific therapeutic interventions.”

The original EDCP was published in 2023 – the present update shifts the definition of HFpEF from an individual cardiac condition to a multisystem syndrome driven by inflammatory pathways, visceral adiposity, and metabolic dysfunction. Additionally, the document highlights the distinct patient phenotypes prevalent in HFpEF and the individualized care required for these groups.

Among the key components of the new guideline is the critical importance of accurate diagnoses. Januzzi and colleagues provide a structured approach to evaluating patients, composed of 3 main steps: identifying patients with possible HFpEF based on characteristic signs and symptoms, assessing for HFpEF noncardiac and cardiac mimics, and implementing an HFpEF management plan incorporating comorbidities and nonpharmacologic management in addition to optimal medical therapy.

Additionally, the document provides an extensive list of potential cardiac and noncardiac mimics, recommending a diagnostic evaluation for each potential confounder to eliminate the possibility of HFpEF. These mimics can range from kidney disease, obesity, and pulmonary disease on the noncardiac side to aortic stenosis, ischemic heart disease, and cardiac amyloidosis.

Following diagnosis, the document offers a variety of guidelines regarding treatment and medication. Part of the impetus for the update was additional research conducted in the years following the 2023 release – this includes positive trial data supporting the use of SGLT2 inhibitors, nonsteroidal mineralocorticoid receptor agonists, and incretin-based therapies like GLP-1 receptor agonists. The new guidelines recommend dosing and titration strategies for a wide range of medications in each of these classes.

However, Januzzi places a significant amount of importance on the diagnostic process itself. Given the long list of potential causes of HFpEF, he stresses that underdiagnosis is a prevalent threat as components of HFpEF are addressed individually rather than seeing the bigger picture.

“I would argue that underdiagnosis is probably more of a concern than overdiagnosis, given the fact that a person who has dyspnea, atrial fibrillation, and obesity, even before we start off with diagnostic testing, most likely has heart failure with preserved ejection fraction,” Januzzi said. “Clinicians therefore really need to have a high index of suspicion for the presence of heart failure because treatment in that situation can improve quality of life and functional capacity and can potentially reduce mortality and hospitalization risk.”

Editors’ Note: Januzzi reports disclosures with Abbott Laboratories, AbbVie, Inc., Eli Lilly, AstraZeneca Pharmaceuticals, Jana Care, Siemens, and others.

Kittleson MM, Panjrath GS, Bates K, et al. Management of heart failure with preserved ejection fraction: 2026 ACC expert consensus decision pathway. JACC. 2026;88(15):1817-1846. 

American College of Cardiology. Updated ACC Expert Consensus Decision Pathway Addresses Management of HFpEF. 

. July 23, 2026. Accessed October 14, 2026. 

https://www.acc.org/latest-in-cardiology/journal-scans/2026/07/22/17/25/updated-acc-ecdp-addresses-management-of-hfpef

Videos

James Januzzi, MD, discusses the recently released guideline update and how it should change clinicians’ priorities in addressing and preempting HFpEF.

A combination of measurements of transthyretin stabilization (sTTR) with a later myocardial stress marker like NT-proBNP creates a biomarker ratio that may predict clinical outcomes in patients with 

transthyretin amyloid cardiomyopathy (ATTR-CM)

Ratio of sTTR and NT-proBNP Change May Predict Treatment Results in ATTR-CM

These data, from an analysis of the ATTRibute-CM trial, were presented at the 

 in Phoenix, Arizona, by James Januzzi, MD, chief scientific officer and C. Michael Gibson Chair in Medicine at the Baim Institute for Clinical Research and Adolph Hutter Professor of Medicine at Harvard Medical School.

“Acoramidis is an oral therapy used to stabilize transthyretin, and it’s known that treatment with acoramidis leads to an early increase in transthyretin, and it’s known that treatment leads to an early increase in transthyretin concentrations that are actually favorable,” Januzzi told 

 in an exclusive interview. “We hypothesized that the increase in transthyretin might predict changes in NT-proBNP later after treatment.”

ATTRibute-CM was a phase 3, randomized, double-blind, placebo-controlled study comparing acoramidis to placebo in ATTR-CM. Patients were eligible for inclusion if they had either wild-type or variant ATTR-CM and a history of 

, among other criteria. Patients with acute myocardial infarction, hemodynamic instability, or primary light chain amyloidosis, among other criteria, were excluded.

A total of 632 patients were enrolled in the study and randomly assigned in a 2:1 ratio to either acoramidis hydrochloride at 800 mg twice daily or matching placebo. Over 30 months, investigators evaluated a 4-step hierarchical analysis of death from any cause, cardiovascular-related hospitalization, change in NT-proBNP from baseline, and change in 6-minute walk distance from baseline.

This primary analysis ultimately favored acoramidis, with a corresponding win ratio of 1.8 (95% CI, 1.4 to 2.2) and 63.7% of pairwise comparisons favoring acoramidis. All-cause mortality and cardiovascular hospitalization contributed >50% of the wins and losses to the win ratio, while NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses.

For the present post-hoc evaluation, Januzzi and colleagues used observed biomarker data from the intention-to-treat population to conduct time-to-event analyses. Samples were collected from this population at baseline, day (D)28, and every 3 months (M) from then on; sTTR and NT-proBNP were measured centrally. The team constructed an integrated biomarker ratio of log2-transformed D28 sTTR/log2-transformed M12 NT-proBNP from these data.

Of the 632 intention-to-treat patients, 587 had baseline and M30 biomarker values. The mean age among these patients was 77 +/- standard deviation (SD) 7 years. 90% of patients had wild-type ATTR-CM, 72% were New York Heart Association functional class 2, and 59% were National Amyloidosis Centre stage 1. Median sTTR and NT-proBNP were 23 mg/dL and 2324 ng/L, respectively.

Early changes in sTTR preceded later changes in NT-proBNP, with the former increasing rapidly by D28 and remaining elevated with acoramidis compared to little change with placebo. NT-proBNP increased to a lesser extent with acoramidis versus placebo. These changes correlated weakly when measured at the same time point, but correlations between D28 sTTR change and later NT-proBNP change were stronger.

This ratio was also strongly associated with all-cause mortality and cardiovascular hospitalization risks in M12 landmark analyses. Januzzi and colleagues found that each 0.1-unit increase in the ratio was associated with a 63% lower adjusted risk of these endpoints (HR, 0.37; 95% CI, 0.24 to 0.58; 

 <.001). The team observed a continuous biomarker-risk gradient, and mediation analyses revealed that the effect of acoramidis treatment on all-cause mortality and cardiovascular hospitalization was associated with an HR of 0.66.

Ultimately, Januzzi and colleagues concluded that, while these data may reflect an effective and accurate predictor of cardiovascular risk in ATTR-CM, several potential study limitations may hamper the ratio’s accuracy in real-world practice. To this end, they determined that further research is necessary to fully validate the biological pathway linking these targets with long-term clinical benefit with acoramidis.

“I think the most important thing that we can say is that biomarker testing really can be extremely informative, not just about the presence and severity of ATTR-CM, but also with respect to its response to treatment,” Januzzi said. “We need more data about the role of biomarkers to help people manage transthyretin cardiomyopathy, but I would argue that the future is very bright in this regard.”

Myhre P, Murtagh G, Gaggin H, et al. Implications of Serum Transthyretin to NT-proBNP Ratio in Transthyretin Amyloid Cardiomyopathy: Insights From ATTRibute-CM. 

https://doi.org/10.1016/j.jchf.2026.103493

Gillmore JD, Judge DP, Cappelli F, et al. Efficacy and safety of ACORAMIDIS in transthyretin amyloid cardiomyopathy. New England Journal of Medicine. 2024;390(2):132-142. 

Eidos Therapeutics. Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy (ATTRibute-CM). ClinicalTrials.gov Identifier: NCT03860935. Updated June 27, 2026. Accessed October 14, 2026. 

https://clinicaltrials.gov/study/NCT03860935

James Januzzi, MD, discusses his post-hoc analysis of the ATTRibute-CM study, revealing a potential predictive ratio between these 2 measurements.

Moving the Needle in Medicine: Mentorship, Medicine, and the Making of an Innovator, With Jim Januzzi, MD

The shift from purely clinical heart failure diagnosis to biomarker-guided management unfolded over decades of incremental evidence, institutional skepticism, and a handful of pivotal decisions by a small number of physician-scientists willing to champion tools before their adoption became mainstream.

 host Alexander Hajduczok, MD, a cardiologist and heart failure specialist at Oklahoma Heart Institute, interviews Jim Januzzi, MD, the Adolph Hutter Professor of Medicine at Harvard Medical School, chief scientific officer and Gibson chair at the Baim Institute for Clinical Research, and a cardiologist at Massachusetts General Hospital, to explore the formative experiences, clinical innovations, and leadership principles that shaped his career and, more broadly, the evolution of modern cardiology.

Januzzi described nearly declining the opportunity to conduct the first US-based clinical studies with NT-proBNP in 2002, having positioned himself primarily as a troponin and acute coronary syndrome researcher. The foundational diagnostic and prognostic work he ultimately led at MGH established the NT-proBNP cutoffs now used internationally, and the test has since evolved from an emergency department dyspnea evaluation tool into a biomarker used across all phases of heart failure management. He noted sacubitril/valsartan as a particularly meaningful convergence of therapeutic and biomarker science, consistently producing substantial reductions in NT-proBNP regardless of baseline value, a finding he has incorporated as a practical signal of adequate neurohormonal blockade.

On the broader arc of guideline-directed medical therapy (GDMT), Januzzi reflected on witnessing the introduction of beta-blockers for heart failure as a fellow, a shift once considered counterintuitive, and tracing the subsequent addition of each pillar as a reminder that even well-established treatment paradigms remain open to displacement by rigorous evidence. He described his involvement in the endpoint committee for the EMPA-REG OUTCOME trial as the entry point for his work with SGLT2 inhibitors in heart failure, another opportunity initially approached with ambivalence. Despite four-pillar GDMT, he noted residual event rates underscore the continued need for novel therapeutics, and he expressed enthusiasm for gene-editing approaches and RNA-silencing therapies now entering cardiovascular development pipelines.

Across the conversation, Januzzi returned to the role of mentorship and deliberate career planning, including maintaining clinical trial involvement from early protocol design rather than joining established programs at the phase three stage, advocating for sponsorship alongside mentorship, and structuring academic evolution in intentional five-year increments. The discussion positions biomarker-guided heart failure care not as a completed project but as a framework still being refined as the disease's diagnostic boundaries and therapeutic options continue to expand.

Podcasts

Hear Jim Januzzi, MD, discuss how he overcame academic shortcomings to become one of the preeminent voices in cardiology biomarkers.

Making Heart Failure Prevention Accessible

A joint statement by the American Society for Preventive Cardiology (ASPC) and the Heart Failure Society of America (HFSA), published on August 13, 2025, shifts the focus of 

 from recovery to prevention for the first time. “The Continuum of Prevention and Heart Failure in Cardiovascular Medicine” provides clinicians with a framework of strategies to apply across all stages of heart failure, irrespective of ejection fraction.

Instead of viewing the condition as an inevitable outcome, this statement recontextualizes heart failure as a preventable condition. It encourages clinicians to identify and manage risk factors earlier through methods such as glucose management, genetic risk screening, lifestyle interventions, weight loss, and blood pressure control.

In the seventh and final episode of a 7-part 

, moderator James Januzzi, MD, is joined by Martha Gulati, MD, MS, and Anu Lala, MD, to discuss the urgent need to bridge the gap between prevention and heart failure care.

Januzzi highlights ongoing inequities in cardiovascular care, noting that heart failure and related risk factors disproportionately affect marginalized populations with limited access to quality healthcare. He stresses that addressing these disparities will require significant health system and policy changes, especially as demographic shifts in the U.S. are projected to increase the burden of disease in these communities.

Lala adds 5 key takeaways for primary care: heart failure is preventable; prevention applies across the lifespan; screening should start early using tools like natriuretic peptides and UACR; patient care must take a whole-person, whole-team approach; and clinicians should proactively prescribe effective therapies such as SGLT2 inhibitors, ARNIs, and aggressive blood pressure control.

, is the Hutter Family Professor of Medicine at Harvard and the Director of Heart Failure and Biomarker Trials at the Balm Institute for Clinical Research. Januzzi serves as the moderator for this conversation.

, is the associate director of the Barbra Streisand Women Heart Center and the director of CVD Prevention at the Smidt Heart Institute at Cedars Sinai Medical Center. She was also the president of the ASPC from 2022-2024.

, is an associate professor of medicine at the Zena & Michael A Wiener Cardiovascular Institute, and a member of the Department of Population Health Science and Statistics at Icahn School of Mount Sinai and Mount Sinai Hospital.

Editors’ Note: Januzzi reports disclosures with Abbott Laboratories, AbbVie, Inc., Eli Lilly, AstraZeneca Pharmaceuticals, Jana Care, Siemens, and others. Gulati reports disclosures with the American Society of Preventive Cardiology, Eli Lilly, Merck & Co., Boehringer Ingelheim Pharmaceuticals, Medtronic, Zoll, and others. Lala reports disclosures with Abiomed, AstraZeneca, Merck & Co., Novo Nordisk, Sequana, Bayer, and others.

Heart Failure Society of America. Heart Failure Society of America and American Society for Preventive Cardiology Joint Statement Calls for a Shift in Heart Failure Prevention and Care. 

 August 13, 2025. Accessed September 9, 2025. 

https://www.prnewswire.com/news-releases/heart-failure-society-of-america-and-american-society-for-preventive-cardiology-joint-statement-calls-for-a-shift-in-heart-failure-prevention-and-care-302529062.html

Lala A, Beavers C, Blumer V, et al. The continuum of prevention and heart failure in Cardiovascular Medicine: A joint scientific statement from the Heart Failure Society of America and the American Society for Preventive Cardiology. American Journal of Preventive Cardiology. Published online August 13, 2025:101069. 

In the final segment of this 7-part HCPLive Special Report, experts discuss the recently released ASPC/HFSA heart failure prevention statement.

James Januzzi, MD

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