Sharmila Dorbala, MD, MPH, is the director of nuclear cardiology at Brigham and Women’s Hospital and the director of amyloidosis research at Mass General Brigham Heart & Vascular Institute.

Sharmila Dorbala, MD, MPH

I-124 evuzamitide positron emission tomography (PET)/computed tomography (CT) is both highly sensitive and specific in diagnosing 

 while maintaining an acceptable safety profile.

REVEAL: I-124 Evuzamitide PET/CT Specific, Sensitive for Cardiac Amyloidosis Diagnosis

European Society of Cardiology (ESC) Congress 2026

 in Munich, Germany, by Sharmila Dorbala, MD, MPH, director of nuclear cardiology at Brigham and Women’s Hospital and director of amyloidosis research at Mass General Brigham Heart & Vascular Institute, these data represent the culmination of the phase 3 REVEAL trial.

“I think this is a huge leap from the previous scenario, where we had multiple complex tests interpreted by different folks,” Dorbala told 

 in an exclusive interview. “With this particular approach, it doesn’t matter where the patient goes, but if cardiac amyloid is in the differential and you perform a PET scan, you may be able to detect amyloid deposits in multiple organ systems. Therefore, this approach can potentially reduce the time to diagnosis significantly.”

REVEAL was an open-label multicenter evaluation of I-124 evuzamitide as a PET imaging agent. Dorbala and colleagues enrolled patients ≥18 years of age who were suspected of having cardiac amyloidosis and were or would undergo a diagnostic evaluation of any kind. Patients were excluded if they had an established diagnosis of cardiac amyloidosis or systemic amyloidosis with known organ involvement, among other criteria.

The trial was divided into a primary and safety analysis and an image-evaluable analysis. The primary endpoints of the study were the specificity and sensitivity of PET/CT imaging with I-124 evuzamitide ≤60 days following administration based on visual scan interpretations. Secondary endpoints included specificity and sensitivity for the diagnosis of ATTR amyloidosis and AL amyloidosis, as well as the incidence of treatment-emergent adverse events ≤30 days after administration.

A total of 195 patients were enrolled at 18 sites across the US, of whom 170 were ultimately included in the safety and intent-to-image cohorts following administration and PET/CT imaging. Of these patients, 76 (44.7%) had cardiac amyloidosis – 54 with ATTR, 21 with light chain, and 1 with indeterminate type – and 93 *54.7%) did not, based on the truth standard consensus.

Dorbala and colleagues found that overall majority-decision sensitivity was 94% (95% CI, 85-98%), while specificity was 86% (95% CI, 77-92%). Positive predictive value was 85% (95% CI, 75-92%), and negative predictive value was 94% (95% CI, 87-98%). All 4 values were consistent across the individual readers. Additionally, the secondary endpoints in ATTR and AL amyloidosis also met the predefined success criteria – among the 54 patients with confirmed ATTR amyloidosis, 52 had positive imaging by majority decision, and of the 21 with AL amyloidosis, 20 had positive imaging.

Among the 170 patients receiving I-124 evuzamitide, 55 (32.4%) exhibited ≥1 treatment-emergent adverse event by day 30. Of these patients, 11 (6.5%) had a serious event, and only 1 – fatigue – was considered relevant to the treatment. Additionally, no deaths occurred during the study period, and none of the serious adverse events were related to I-124 evuzamitide.

Ultimately, Dorbala and colleagues concluded that this imaging strategy is extremely effective in identifying these patients, with an excellent safety profile and substantial specificity and sensitivity. Dorbala also expressed excitement for the future of amyloidosis treatment following this trial, as she believes it demonstrates a significant step forward in diagnosis that will allow for more focus on treatment.

“In order to do all of this, we will need to perform randomized clinical trials of treatment in these patients to see what the optimal time is to initiate therapy in some of these patients who don’t have symptoms or who don’t have changes on echo or MRI,” Dorbala said. “It’s a very exciting time for the field to be able to, as a first step, detect these early deposits, but the future is going to be more exciting, since we’ll need more trials to study whether we can prevent cardiac amyloid heart failure by early therapy.”

Editors’ Note: Dorbala reports disclosures with Attralus, AstraZeneca, BridgeBio, GE Healthcare, Medtrace, Pfizer, and others.

Dorbala S. A Phase 3 Clinical Trial of I124-evuzamitide to Diagnose Cardiac Amyloidosis. Presented at the European Society of Cardiology (ESC) Congress 2026, Munich, Germany. August 28-31, 2026.

Dorbala S. REVEAL – Research With I-124 EVuzamitide to Elucidate Cardiac AmyLoidosis (REVEAL). ClinicalTrials.gov Identifier: NCT06788535. Updated April 30, 2026. Accessed September 8, 2026. 

https://clinicaltrials.gov/study/NCT06788535

Dorbala S, Maurer MS, Cuddy SA, et al. I-124 evuzamitide positron emission tomography/computed tomography for diagnosing cardiac amyloidosis. 

Videos

Sharmila Dorbala, MD, MPH, discusses how this treatment and imaging strategy may lead to a diagnostic overhaul for patients with amyloidosis.

A Look Into the Future of ATTR-CM Clinical Trials

Summary for Physicians: Designing Future Trials in ATTR-CM

 (transthyretin amyloid cardiomyopathy) should focus not only on evaluating the efficacy of 

, including amyloid depleters, but also on enhancing our understanding of the mechanisms driving 

 to current treatments. Key considerations for trial design include:

 Trials should incorporate biomarkers (eg, NT-proBNP, troponin, TTR, amyloid-related markers) to assess how therapies impact both amyloid burden and cardiac dysfunction. This will help define the relationship between amyloid deposition and heart failure progression.

 mutations) and advanced techniques such as 

 could help identify specific molecular mechanisms underlying disease progression, particularly in wild-type ATTR-CM and in nonresponders.

 with advanced imaging techniques could provide insights into amyloid infiltration, inflammation, and fibrosis, allowing for a deeper understanding of the pathological changes in the heart.

 Trials should stratify patients into distinct groups (eg, wild-type vs hereditary ATTR, responders vs nonresponders) to assess differential responses to therapies. This approach can identify factors that contribute to lack of response in certain patients and guide more personalized treatment strategies.

 Include long-term follow-up data to capture how treatments impact disease progression over time, particularly for patients with wild-type disease, who may have a slower progression.

 In addition to traditional clinical outcomes such as mortality or hospitalization, surrogate end points (eg, improvement in biomarkers, cardiac imaging findings, or exercise capacity) should be included to more quickly evaluate therapeutic effects.

 should be incorporated to assess the broader impact of therapy on daily functioning and patient well-being.

Trials should explicitly include patients who have shown little to no benefit from current therapies (eg, tafamidis, diflunisal) to better understand the reasons behind therapy resistance. This can help identify potential new therapeutic targets or biomarkers associated with nonresponsiveness.

 Investigating combination therapies, including amyloid depleters and other novel agents targeting different pathways involved in cardiac dysfunction (eg, inflammation, fibrosis), may provide insights into better treatment strategies for nonresponders.

 collection and collaboration across centers to enhance the diversity of the patient population and improve generalizability. Multicenter collaborations, including registries and biobanks, could facilitate a deeper understanding of disease variability and therapeutic outcomes.

In conclusion, future clinical trials for ATTR-CM should integrate 

 to better understand and address the underlying causes of cardiac dysfunction, leading to more effective, personalized treatment strategies.

Panelists discuss how future clinical trials in transthyretin amyloid cardiomyopathy (ATTR-CM) should focus on incorporating mechanistic research, patient stratification, and diverse end points, while also including nonresponders to current therapies to better understand cardiac dysfunction and develop more personalized treatment strategies.

Prognostic Indicators of Disease Progression in ATTR-CM

Summary for Physicians: Prognostic Indicators and Detection of Progression in ATTR-CM

 (transthyretin amyloid cardiomyopathy), identifying and monitoring progression is crucial for optimal patient management. Several 

 and methods for detecting progression include:

 Increasing shortness of breath, fatigue, and edema suggest cardiac deterioration.

 New-onset atrial fibrillation, sustained ventricular arrhythmias, or worsening arrhythmias signal disease progression.

 A reduction in exercise tolerance or worsening ability to perform daily activities.

 Progression can be indicated by worsening left ventricular ejection fraction, increased wall thickness, or diastolic dysfunction.

 Increased gadolinium retention (suggesting amyloid deposition) or worsening myocardial edema may indicate progression.

 In patients with bone tracer uptake, an increase in uptake may reflect more extensive amyloid deposition.

 An increase in NT-proBNP levels indicates worsening heart failure and may suggest progression.

 Continuous or rising levels of cardiac troponin reflect myocardial injury and may signal disease progression.

 Changes in these biomarkers may indicate disease progression or response to treatment.

 A decline in the distance walked may reflect worsening functional status.

 Tools assessing functional capacity and patient-reported symptoms, such as the Kansas City Cardiomyopathy Questionnaire, can provide insight into disease progression.

 Lack of response or disease stabilization despite treatment may signal progression.

 Worsening symptoms of other organ involvement (eg, neuropathy, carpal tunnel syndrome) may also be indicative of disease progression.

 in ATTR-CM is defined by a combination of clinical, imaging, biomarker, and functional assessments. Monitoring these factors regularly helps physicians detect progression early, enabling timely interventions to manage the disease effectively.

Panelists discuss how monitoring clinical indicators, cardiac imaging, biomarkers, and functional assessments—such as NT-proBNP, troponin, and the 6-minute walk test—helps detect progression in transthyretin amyloid cardiomyopathy (ATTR-CM), allowing for early intervention and optimal disease management.

Using Biomarkers to Monitor ATTR-CM

Summary for Physicians: Long-Term Monitoring in ATTR-CM and Biomarkers Used

 (transthyretin amyloid cardiomyopathy) involves regular clinical assessments, imaging studies, and biomarker evaluations to track disease progression and manage complications. Key aspects of monitoring include:

Regular assessment of cardiac symptoms such as heart failure, arrhythmias, and functional status

Monitoring for signs of organ involvement beyond the heart, as ATTR-CM can affect other organs, such as the liver and nervous system

 to assess left ventricular function and wall thickness

 to evaluate myocardial involvement and amyloid deposits

 to detect amyloid deposition in the heart

N-terminal pro B-type natriuretic peptide (NT-proBNP):

 A marker for heart failure, often elevated in ATTR-CM

 Can indicate myocardial injury or stress, which may be elevated in patients with ATTR-CM

 Helpful in distinguishing ATTR-CM from other forms of amyloidosis, such as light chain amyloidosis

 Can be elevated in systemic inflammation associated with amyloidosis

TTR genetic testing and serum TTR concentration

 may help to confirm the diagnosis and assess familial risk.

, including exercise tolerance and quality of life (using tools such as the 6-minute walk test and patient-reported outcome measures).

Monitoring these biomarkers, alongside clinical and imaging evaluations, helps physicians track the progression of ATTR-CM, adjust therapies, and intervene early in cases of disease progression or complications. Regular follow-up is essential for optimizing management and improving patient outcomes.

Panelists discuss how long-term monitoring in transthyretin amyloid cardiomyopathy (ATTR-CM) involves regular clinical assessments, imaging studies, and biomarker evaluations—such as NT-proBNP, troponin, and TTR testing—to track disease progression, manage complications, and optimize patient outcomes.

Sharmila Dorbala, MD, MPH

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