Mathew S. Maurer

FEB 2007MaurerJournal of the American College of Cardiology

Hypertensive HFNEF is linked to larger LV diastolic dimensions and higher stroke volume than controls.

Characterizes ventricular phenotypes in hypertensive HFpEF; extends observational data but leaves open therapeutic implications.

Amyloidosis-suggestive echo reporting is linked to ~9.6-fold higher odds of downstream diagnostic testing.

Report phrasing may influence diagnostic pursuit in suspected amyloidosis; hypothesis-generating for strategies to reduce underdiagnosis pending prospective validation.

The logistic regression model using 3 miRNAs (miR-454-3p, miR-98-5p, and miR-5581-3p) had an area under the receiver-operating characteristic curve of 0.95 (95% CI: 0.93-0.97) with a sensitivity of 0.95 and a specificity of 0.90 in the test set.

A panel of three circulating plasma microRNAs (miR-454-3p, miR-98-5p, and miR-5581-3p) accurately distinguishes hypertrophic cardiomyopathy from hypertensive LVH, ATTR-CM, and aortic stenosis with high sensitivity and specificity.

Multiple musculoskeletal procedures over time and the risk of amyloidosis: a Danish nationwide cohort study

Letter to the editorSystemic amyloidosis is characterized by extracellular deposition of misfolded proteins in multiple organs and connective tissues. In cardiac amyloidosis (CA), myocardial deposi...

Deprescribing CV medications in multimorbid older adults reduces medication burden and adverse drug reactions.

Deprescribing may ease burden in multimorbid older adults; leaves open confirmation in randomized trials.

Machine Learning of Echocardiographic Left Ventricular Myocardial Radiomics for Identification of Transthyretin Amyloid Cardiomyopathy

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an important cause of heart failure (HF) with increased left ventricular (LV) wall thickness that can be challenging to distinguish from other LV hypertrophic processes. Echocardiographic myocardial radiomic texture analysis may identify imperceptible amyloid-induced structural changes. OBJECTIVES: The study aims to develop and validate an echocardiography-based machine learning model using myocardial radiomics to identify ATTR-CM. METHODS: In this retrospective and prospective multicenter study, 854 echocardiographic scans were analyzed. Conventional and novel radiomic features were extracted from parasternal short-axis views at basal, mid, and apical LV levels, with incorporated age and sex from echocardiogram metadata. A machine learning pipeline was developed using a balanced training set (150 ATTR-CM, 150 nonamyloid HF). Performance was evaluated on an independent internal validation set (50 ATTR-CM, 399 nonamyloid HF) and an external validation set (10 ATTR-CM, 10 immunoglobulin light-chain-amyloid, 10 hypertrophic cardiomyopathy, 75 nonamyloid HF). RESULTS: In internal validation, the model achieved 86% sensitivity (95% CI: 73.8%-93%), 92% specificity (95% CI: 88.9%-94.3%), 57.3% positive predictive value (95% CI: 46.1%-67.9%), 98.1% negative predictive value (NPV) (95% CI: 96.2%-99.1%), and receiver operating characteristic-area under the curve 0.938 (95% CI: 0.891-0.985). Performance was consistent in the external validation (100% sensitivity, 78.9% specificity, 33.3% positive predictive value, 100% NPV, and receiver operating characteristic-area under the curve of 0.917). The model correctly classified 77.3% of nonamyloid HF, 70% of AL-amyloid cases, and 100% of hypertrophic cardiomyopathy cases as non-ATTR in subgroup analysis. CONCLUSIONS: We developed an echocardiographic radiomics-based tool to identify ATTR-CM with excellent discrimination and very high NPV in a cohort that approximates clinical experience. These preliminary findings require validation in larger, more diverse cohorts.

SEP 21MaurerCirculation

Response by Maurer and Fontana to Letter Regarding Article, “Coramitug, a Humanized Monoclonal Antibody for the Treatment of Transthyretin Amyloid Cardiomyopathy: A Phase 2, Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial”

AUG 30García‐PavíaNature Medicine

Eplontersen with and without background transthyretin stabilizers in transthyretin amyloid cardiomyopathy: secondary analysis of a phase 3, randomized controlled trial

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) therapies include both TTR gene silencers and TTR stabilizers. The role of TTR gene silencers added to background TTR stabilizer therapy is unknown, and the effects of silencer treatment in the absence of stabilizer use are unclear. In the CARDIO-TTRansform study, 1,432 patients ( n = 135 (9.4%) women and n = 1,297 (90.6%) men) with ATTR-CM were randomized (1:1) and treated with the antisense oligonucleotide eplontersen (45 mg every 4 weeks) that targets TTR or with placebo for up to 140 weeks. At baseline, 57% of the patients were taking TTR stabilizers. In the overall study, treatment with eplontersen did not reduce the primary composite endpoint. Here, in a prespecified analysis, we show that the primary endpoint (a composite of cardiovascular mortality and recurrent cardiovascular events) was modified by baseline stabilizer use ( P interaction = 0.017). Benefits were observed in those patients not on stabilizers at baseline (rate ratio (RR) = 0.71, 95% confidence interval (CI) 0.54 to 0.93, P = 0.012), whereas no benefits were observed in those on stabilizers at baseline (RR = 1.14, 95% CI 0.85 to 1.53, P = 0.39). The safety profile of eplontersen was favorable, irrespective of baseline stabilizer use. Treatment with eplontersen versus placebo demonstrated a clinically meaningful benefit among patients not receiving background stabilizers but provided no additional clinical benefit in those on background stabilizer therapy. These findings of a strong treatment effect modification may offer insight for therapeutic decision-making in clinical practice. ClinicalTrials.gov registration: NCT04136171 .

Emerging therapies and translational tools for drug development in systemic amyloidosis: insights from the International Society of Amyloidosis Scientific Workshop

BACKGROUND: Amyloidosis is caused by deposition of misfolded proteins as amyloid fibrils in multiple organs. Over the past decade, disease-modifying therapies have markedly improved outcomes in both amyloid light-chain (AL) amyloidosis and amyloid transthyretin (ATTR) amyloidosis. Progress in AL amyloidosis has been driven by advances in plasma cell-directed therapies that suppress production of the precursor light chains. In ATTR amyloidosis, therapies target distinct phases of the amyloid cascade. The efficacy of multiple therapies that block production or misfolding of transthyretin has led to regulatory approvals. By contrast, limited efficacy has been observed to date with amyloid-targeting antibodies designed to clear existing amyloid deposits. METHODS: This perspective article presents insights from experts representing the International Society of Amyloidosis reviewing current and emerging treatments for AL and ATTR amyloidosis, discussed at the 2025 Scientific Workshop. RESULTS: Recent advances in research tools (animal and induced pluripotent stem cell (iPSC)-based models) are discussed as valuable approaches for disease modeling and preclinical evaluation of novel therapies. Lastly, the growing role of artificial intelligence in accelerating drug discovery in systemic amyloidosis is examined. CONCLUSIONS: Alongside recent successes and ongoing progress, there are key unmet needs and limitations that must be overcome to further improve patient outcomes.

Phenotypic Considerations for Tafamidis Use in a Real-World Cohort of Older Patients with Transthyretin Amyloid Cardiomyopathy

Tafamidis in ATTR-CA molecular subtype A is linked to ~76% lower mortality vs no treatment.

Comprehensive plasma proteomics profiling can identify molecular subtypes of transthyretin cardiac amyloidosis that have distinct survival risks and heterogeneous treatment responses to tafamidis.

AUG 30WangCirculation

Effect of Anselamimab on Cardiac Structure and Function in Patients With Light Chain Amyloidosis: Insights From the CARES Clinical Trials