Deep Learning-Enabled Quantification of 99mTc-Pyrophosphate SPECT/CT for Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR CA) is increasingly recognized as a cause of heart failure in older patients, with 99mTc-pyrophosphate imaging frequently used to establish the diagnosis. Visual interpretation of SPECT images is the gold standard for interpretation but is inherently subjective. Manual quantitation of SPECT myocardial 99mTc-pyrophosphate activity is time-consuming and not performed clinically. We evaluated a deep learning approach for fully automated volumetric quantitation of 99mTc-pyrophosphate using segmentation of coregistered anatomic structures from CT attenuation maps. Methods: Patients who underwent SPECT/CT 99mTc-pyrophosphate imaging for suspected ATTR CA were included. Diagnosis of ATTR CA was determined using standard criteria. Cardiac chambers and myocardium were segmented from CT attenuation maps using a foundational deep learning model and then applied to attenuation-corrected SPECT images to quantify radiotracer activity. We evaluated the diagnostic accuracy of target-to-background ratio (TBR), cardiac pyrophosphate activity (CPA), and volume of involvement (VOI) using the area under the receiver operating characteristic curve (AUC). We then evaluated associations with the composite outcome of cardiovascular death or heart failure hospitalization. Results: In total, 299 patients were included (median age, 76 y), with ATTR CA diagnosed in 83 (27.8%) patients. CPA (AUC, 0.989; 95% CI, 0.974-1.00) and VOI (AUC, 0.988; 95% CI, 0.973-1.00) had the highest prediction performance for ATTR CA. The next highest AUC was for TBR (AUC, 0.979; 95% CI, 0.964-0.995). The AUC for CPA was significantly higher than that for heart-to-contralateral ratio (AUC, 0.975; 95% CI, 0.952-0.998; P = 0.046). Twenty-three patients with ATTR CA experienced cardiovascular death or heart failure hospitalization. All methods for establishing TBR, CPA, and VOI were associated with an increased risk of events after adjustment for age, with hazard ratios ranging from 1.41 to 1.84 per SD increase. Conclusion: Deep learning segmentation of coregistered CT attenuation maps is not affected by the pattern of radiotracer uptake and allows for fully automatic quantification of hot-spot SPECT imaging such as 99mTc-pyrophosphate. This approach can be used to accurately identify patients with ATTR CA and may play a role in risk prediction.

Resolution of Cardiac Infiltration Following Autologous Stem Cell Transplantation for AL Amyloidosis.

A 43-year-old man presented with severe heart failure secondary to high-risk light chain cardiac amyloidosis. He underwent chemotherapy and autologous stem cell transplantation with complete hematologic response. Serial cardiac magnetic resonance imaging post-transplant demonstrated gradual normalization of biventricular function and myocardial T1, a surrogate measure of disease burden.

Sex-based Differences in the Phenotypic Expression and Prognosis of Idiopathic Non-ischemic Cardiomyopathy: A Cardiovascular Magnetic Resonance Study.

AIMS: We sought to characterize sex-related differences in CMR-based cardiovascular phenotypes and prognosis in patients with idiopathic non-ischemic cardiomyopathy (NICM). METHODS AND RESULTS: Patients with NICM enrolled in the Cardiovascular Imaging Registry of Calgary (CIROC) between 2015 and 2021 were identified. Z-score values for chamber volumes and function were calculated as standard deviation from mean values of 157 sex-matched healthy volunteers, ensuring reported differences were independent of known sex-dependencies. Patients were followed for the composite outcome of all-cause mortality, heart failure admission, or ventricular arrhythmia.A total of 747 patients were studied, 531 (71%) males. By Z-score values, females showed significantly higher left ventricular (LV) ejection fraction (EF; median difference 1 SD) and right ventricular (RV) EF (difference 0.6 SD) with greater LV mass (difference 2.1 SD; p-value<0.01 for all) versus males despite similar chamber volumes. Females had a significantly lower prevalence of mid-wall striae (MWS) fibrosis (23% versus 36%; p-value<0.001). Over a median follow-up of 4.7 years, 173 patients (23%) developed the composite outcome, with equal distribution in males and females. LV EF and MWS were significant independent predictors of the outcome (respective HR [95% CI] 0.97 [0.95-0.99] and 1.6 [1.2-2.3]; p-value=0.003 and 0.005). There was no association of sex with the outcome. CONCLUSIONS: In a large contemporary cohort, NICM was uniquely expressed in females versus males. Despite similar chamber dilation, females demonstrated greater concentric remodelling, lower reductions in bi-ventricular function, and a lower burden of replacement fibrosis. Overall, their prognosis remained similar to male patients with NICM.

Effect of Tafamidis on Cardiac Function in Patients With Transthyretin Amyloid Cardiomyopathy: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial.

Importance: Tafamidis has been shown to improve survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with placebo. However, its effect on cardiac function has not been fully characterized. Objective: To examine the effect of tafamidis on cardiac function in patients with ATTR-CM. Design, Setting, and Participants: This was an exploratory, post hoc analysis of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), a multicenter, international, double-blind, placebo-controlled phase 3 randomized clinical trial conducted from December 2013 to February 2018. The ATTR-ACT included 48 sites in 13 counties and enrolled patients aged 18 to 90 years with ATTR-CM. Data were analyzed from July 2018 to September 2023. Intervention: Patients were randomized to tafamidis meglumine, 80 mg or 20 mg, or placebo for 30 months. Main Outcomes and Measures: Patients were categorized based on left ventricular (LV) ejection fraction at enrollment as having heart failure with preserved ejection fraction (≥50%), mildly reduced ejection fraction (41% to 49%), or reduced ejection fraction (≤40%). Changes from baseline to month 30 in LV ejection fraction, LV stroke volume, LV global longitudinal strain, and the ratio of early mitral inflow velocity to septal and lateral early diastolic mitral annular velocity (E/e') were compared in patients receiving tafamidis, 80 mg, vs placebo. Results: A total of 441 patients were randomized in ATTR-ACT, and 436 patients had available echocardiographic data. Of 436 included patients, 393 (90.1%) were male, and the mean (SD) age was 74 (7) years. A total of 220 (50.5%), 119 (27.3%), and 97 (22.2%) had heart failure with preserved, mildly reduced, and reduced LV ejection fraction, respectively. Over 30 months, there was less pronounced worsening in 4 of the echocardiographic measures in patients receiving tafamidis, 80 mg (n = 176), vs placebo (n = 177) (least squares mean difference: LV stroke volume, 7.02 mL; 95% CI, 2.55-11.49; P = .002; LV global longitudinal strain, -1.02%; 95% CI, -1.73 to -0.31; P = .005; septal E/e', -3.11; 95% CI, -5.50 to -0.72; P = .01; lateral E/e', -2.35; 95% CI, -4.01 to -0.69; P = .006). Conclusions and Relevance: Compared with placebo, tafamidis, 80 mg, attenuated the decline of LV systolic and diastolic function over 30 months in patients with ATTR-CM. Approximately half of patients had mildly reduced or reduced LV ejection fraction at enrollment, suggesting that ATTR-CM should be considered as a possible diagnosis in patients with heart failure regardless of underlying LV ejection fraction. Trial Registration: ClinicalTrials.gov Identifier: NCT01994889.

The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

Right Ventricular Systolic Pressure Trajectory as a Predictor of Hospitalization and Mortality in Patients With Chronic Heart Failure.

Background: Pulmonary hypertension is common among patients with heart failure (HF). Right ventricular systolic pressure (RVSP) is frequently used to assess its presence and severity. Although RVSP has been associated with adverse outcomes, the importance of serial measurements has not been studied. We evaluated associations between serial RVSP measurements and cardiovascular events in patients with HF. Methods: Patients with HF and 2 echocardiograms performed ≥ 6 months apart were included. RVSP was categorized, using the second echocardiogram, as follows: normal (< 40 mm Hg); severely elevated (≥ 60 mm Hg); moderately elevated (50-59 mm Hg); or mildly elevated (40-49 mm Hg). Patients also were classified according to change in RVSP categories between echocardiograms. The primary outcome was time to HF hospitalization (HFH) or all-cause mortality (ACM) after the second echocardiogram. Results: In total, 4319 patients were included (median age: 78 years; 52.1% female). During a median follow-up period of 19.4 months, HFH/ACM occurred in 2714 patients (62.8%). In multivariable analysis, baseline RSVP that was mildly elevated (1069 patients, hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.12-1.54), moderately elevated (797 patients, HR 1.54, 95% CI 1.30-1.82), or severely elevated (837 patients, HR 1.92, 95% CI 1.60-2.31) was independently associated with HFH/ACM. Additionally, improving RVSP was associated with increased HFH/ACM in both categorical (HR 1.16, 95% CI 1.01-1.33) and continuous analyses. Conclusions: RVSP measurements identify patients at increased risk who may require more-aggressive monitoring and medical therapy. Our study raises the hypothesis that, in addition to the absolute value of RVSP, improving RVSP category may identify higher-risk patients, but further study is needed to elucidate the underlying reasons.

Contexte: L'hypertension pulmonaire est fréquente chez les patients atteints d'insuffisance cardiaque. La pression systolique ventriculaire droite (PSVD) est souvent utilisée pour évaluer la présence et la gravité de l'hypertension pulmonaire. Bien que la PSVD ait été associée à des complications, l'importance de mesures répétitives n'a pas été étudiée. Nous avons évalué les liens entre des mesures répétitives de la PSVD et des événements cardiovasculaires chez des patients atteints d'insuffisance cardiaque. Méthodologie: Ont été inclus des patients atteints d'insuffisance cardiaque pour lesquels on disposait de deux échocardiogrammes réalisés dans un intervalle ≥ 6 mois. La PSVD a été catégorisée comme suit, au moyen du deuxième échocardiogramme : normale (< 40 mmHg); gravement élevée (≥ 60 mmHg); modérément élevée (50 à 59 mmHg) ou légèrement élevée (40 à 49 mmHg). Les patients ont également été classés dans des catégories en fonction de la variation de la PSVD d'un échocardiogramme à l'autre. Le paramètre d'évaluation principal était le temps écoulé avant une hospitalisation pour insuffisance cardiaque ou un décès, toutes causes confondues, après le second échocardiogramme. Résultats: Au total, 4 319 patients ont été inclus (âge médian de 78 ans; 52,1 % de sexe féminin). Pendant une période de suivi médian de 19,4 mois, une hospitalisation pour insuffisance cardiaque ou un décès, toutes causes confondues, se sont produits chez 2 714 patients (62,8 %). Une analyse multivariée a déterminé qu'une PSVD initiale légèrement élevée (1 069 patients, rapport de risques instantanés [RRI] de 1,31, intervalle de confiance [IC] à 95 % de 1,12 à 1,54), modérément élevée (797 patients, RRI de 1,54, IC à 95 % de 1,30 à 1,82) ou gravement élevée (837 patients, RRI de 1,92, IC à 95 % de 1,60 à 2,31) était indépendamment associée à une hospitalisation pour insuffisance cardiaque ou à un décès, toutes causes confondues. En outre, l'amélioration de la PSVD était associée à une hausse des hospitalisations pour insuffisance cardiaque ou des décès, toutes causes confondues, dans les analyses des catégories (RRI de 1,16, IC à 95 % de 1,01 à 1,33) et continues. Conclusions: Les mesures de la PSVD ont permis de repérer les patients présentant un risque accru qui pourraient nécessiter une surveillance et un traitement médical plus intenses. Notre étude incite à poser l'hypothèse voulant qu'en plus de la valeur absolue de la PSVD, l'amélioration des catégories de PSVD puisse permettre de repérer les patients présentant un risque accru, mais des études plus approfondies sont nécessaires pour élucider les raisons sous-jacentes.

Characteristics of Carpal Tunnel Syndrome in Wild-Type Transthyretin Amyloidosis.

BACKGROUND: Carpal tunnel syndrome (CTS) is one of the most common extra-cardiac manifestations of wild-type transthyretin amyloidosis (wtATTR); however, the characteristics of CTS in this population remain poorly understood. METHODS: This retrospective cohort study reports findings from a single-centre experience of comprehensive neurological screening at the time of wtATTR diagnosis by nerve conduction studies (NCS) and neurologist assessment. RESULTS: Seventy-nine patients underwent neurological screening, 73 (92%) males, mean age 79.2 ± 7.5 years. Seventy-four (94%) had electrodiagnostic findings of median neuropathy at the wrist (MNW), 37 (50%) of which had a prior diagnosis of CTS and 37 (50%) had a new diagnosis of MNW. Over half of wtATTR patients (42, 53%) had bilateral MNW on screening. Most with pre-existing CTS had bilateral disease (28, 76%) and underwent bilateral carpal tunnel release (CTR) (23, 62%) prior to screening. Twenty-one (19%) wrists had mild MNW, 43 (38%) moderate and 49 (43%) severe. Twenty-one (28%) wtATTR patients with MNW were asymptomatic, 10 of which (48%) had moderate disease. Nineteen (36%) wtATTR patients with symptomatic MNW had recurrent disease despite previous CTR. As a result of screening, 36 (68%) patients with symptomatic MNW were referred for CTR. CONCLUSIONS: MNW is exceptionally common at the time of wtATTR diagnosis, affecting 94% of our patients. Most had severe, bilateral MNW on NCS. Some were asymptomatic, despite having moderate disease. The rate of recurrence following CTR was observed to be higher in wtATTR patients than the general population.

Patients with non-ischemic cardiomyopathy and mid-wall striae have similar arrhythmic outcomes as ischemic cardiomyopathy.

PURPOSE: While implantable cardioverter-defibrillator (ICD) therapy provides clear benefit in patients with ischemic cardiomyopathy (ICM), this is less clear in patients with non-ischemic cardiomyopathy (NICM). Mid-wall striae (MWS) fibrosis is an established cardiovascular magnetic resonance (CMR) risk marker observed in patients with NICM. We evaluated whether patients with NICM and MWS have similar risk of arrhythmia-related cardiovascular events as patients with ICM. METHODS: We studied a cohort of patients undergoing CMR. The presence of MWS was adjudicated by experienced physicians. The primary outcome was a composite of implantable cardioverter-defibrillator (ICD) implant, hospitalization for ventricular tachycardia, resuscitated cardiac arrest, or sudden cardiac death. Propensity-matched analysis was performed to compare outcomes for patients NICM with MWS and ICM. RESULTS: A total of 1,732 patients were studied, 972 NICM (706 without MWS, 266 with MWS) and 760 ICM. NICM patients with MWS were more likely to experience the primary outcome versus those without MWS (unadjusted subdistribution hazard ratio (subHR) 2.26, 95% confidence interval [CI] 1.51-3.41) with no difference versus ICM patients (unadjusted subHR 1.32, 95% CI 0.93-1.86). Similar results were seen in a propensity-matched population (adjusted subHR 1.11, 95% CI 0.63-1.98, p = 0.711). CONCLUSION: Patients with NICM and MWS demonstrate significantly higher arrhythmic risk compared to NICM without MWS. After adjustment, the arrhythmia risk of patients with NICM and MWS was similar to patients with ICM. Accordingly, physicians could consider the presence of MWS when making clinical decisions regarding arrhythmia risk management in patients with NICM.

Anderson-Fabry disease cardiomyopathy: an update on epidemiology, diagnostic approach, management and monitoring strategies.

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by deficient activity of the enzyme alpha-galactosidase. While AFD is recognized as a progressive multi-system disorder, infiltrative cardiomyopathy causing a number of cardiovascular manifestations is recognized as an important complication of this disease. AFD affects both men and women, although the clinical presentation typically varies by sex, with men presenting at a younger age with more neurologic and renal phenotype and women developing a later onset variant with more cardiovascular manifestations. AFD is an important cause of increased myocardial wall thickness, and advances in imaging, in particular cardiac magnetic resonance imaging and T1 mapping techniques, have improved the ability to identify this disease non-invasively. Diagnosis is confirmed by the presence of low alpha-galactosidase activity and identification of a mutation in the GLA gene. Enzyme replacement therapy remains the mainstay of disease modifying therapy, with two formulations currently approved. In addition, newer treatments such as oral chaperone therapy are now available for select patients, with a number of other investigational therapies in development. The availability of these therapies has significantly improved outcomes for AFD patients. Improved survival and the availability of multiple agents has presented new clinical dilemmas regarding disease monitoring and surveillance using clinical, imaging and laboratory biomarkers, in addition to improved approaches to managing cardiovascular risk factors and AFD complications. This review will provide an update on clinical recognition and diagnostic approaches including differentiation from other causes of increased ventricular wall thickness, in addition to modern strategies for management and follow-up.

Diagnostic accuracy of bone scintigraphy imaging for transthyretin cardiac amyloidosis: systematic review and meta-analysis.

BACKGROUND: Bone scintigraphy imaging is frequently used to investigate patients with suspected transthyretin cardiac amyloidosis (ATTR-CM). However, the reported accuracy for interpretation approaches has changed over time. We performed a systematic review and meta-analysis to determine the diagnostic accuracy of visual planar grading, heart-to-contralateral (HCL) ratio, and quantitative analysis of SPECT imaging and evaluate reasons for shifts in reported accuracy. METHODS: We performed a systematic review to identify studies of the diagnostic accuracy of bone scintigraphy for ATTR-CM from 1990 until February 2023 using PUBMED and EMBASE. Studies were reviewed separately by two authors for inclusion and for risk of bias assessment. Summary receiver operating characteristic curves and operating points were determined with hierarchical modeling. RESULTS: Out of a total of 428 identified studies, 119 were reviewed in detail and 23 were included in the final analysis. The studies included a total of 3954 patients, with ATTR-CM diagnosed in 1337 (39.6%) patients and prevalence ranging from 21 to 73%. Visual planar grading and quantitative analysis had higher diagnostic accuracy (.99) than HCL ratio (.96). Quantitative analysis of SPECT imaging had the highest specificity (97%) followed by planar visual grade (96%) and HCL ratio (93%). ATTR-CM prevalence accounted for some of the observed between study heterogeneity. CONCLUSIONS: Bone scintigraphy imaging is highly accurate for identifying patients with ATTR-CM, with between study heterogeneity in part explained by differences in disease prevalence. We identified small differences in specificity, which may have important clinical implications when applied to low-risk screening populations.

Prevalence, incidence and clinical outcomes of epicardial coronary artery disease among transthyretin amyloidosis cardiomyopathy patients.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients are often older and may be at risk for obstructive epicardial coronary artery disease (oeCAD). While ATTR-CM may cause small vessel coronary disease, the prevalence and clinical significance of oeCAD is not well described. METHODS AND RESULTS: The prevalence and incidence of oeCAD and its association with all-cause mortality and hospitalization among 133 ATTR-CM patients with ≥ 1-year follow-up was evaluated. The mean age was 78 ± 9 years, 119 (89%) were male, 116 (87%) had wild-type and 17 (13%) had hereditary subtypes. Seventy-two (54%) patients underwent oeCAD investigations, with 30 (42%) receiving a positive diagnosis. Among patients with a positive oeCAD diagnosis, 23 (77%) were diagnosed prior to ATTR-CM diagnosis, 6 (20%) at the time of ATTR-CM diagnosis, and 1 (3%) after ATTR-CM diagnosis. Baseline characteristics between patients with and without oeCAD were similar. Among patients with oeCAD, only 2 (7%) required additional investigations, intervention or hospitalization after ATTR-CM diagnosis. After a median follow-up of 27 months there were 37 (28%) deaths in the study population, including 5 patients with oeCAD (17%). Fifty-six (42%) patients in the study population required hospitalization, including 10 patients with oeCAD (33%). There was no significant difference in the rates of death or hospitalization among ATTR-CM patients with and without oeCAD, and oeCAD was not significantly associated with either outcome by univariable regression analysis. CONCLUSIONS: While oeCAD is prevalent in ATTR-CM patients, this diagnosis is frequently known at time of ATTR-CM diagnosis and characteristics are similar to patients without oeCAD.

Cost-effectiveness of immediate initiation of dapagliflozin in patients with a history of heart failure.

AIMS: To compare the cost-effectiveness of immediate and 12-month delayed initiation of dapagliflozin treatment in patients with a history of hospitalization for heart failure (HHF) from the UK, Canadian, German, and Spanish healthcare perspectives. METHODS AND RESULTS: A cost-utility analysis was conducted using a decision-analytic Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire scores, type 2 diabetes mellitus status and incidence of heart failure (HF) events. Patient-level data for patients with prior HHF from the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial were used to inform the model inputs on clinical events and utility values. Healthcare costs were sourced from the relevant national reference databases and the published literature. Compared to standard therapy, immediate initiation of dapagliflozin decreased HHF (187 events), urgent HF visits (32 events) and cardiovascular mortality (18 events). Standard therapy was associated with lifetime costs of £13 224 and 4.02 quality-adjusted life years (QALYs). Twelve-month delayed initiation of dapagliflozin was associated with total discounted lifetime costs and QALYs of £16 660 and 4.61, respectively, compared to £16 912 and 4.66, respectively, for immediate initiation. Compared to standard therapy, immediate and 12-month delayed initiation of dapagliflozin yielded an incremental cost-effectiveness ratio (ICER) of £5779 and £5821, respectively. Compared to 12-month delayed initiation, immediate initiation of dapagliflozin had an ICER of £5263. Results were similar from the Canadian, German, and Spanish healthcare perspectives. CONCLUSION: Both immediate and 12-month delayed initiation of dapagliflozin are cost-effective. However, immediate initiation provides greater clinical benefits, with almost 10% additional QALYs gain, compared to 12-month delayed initiation of dapagliflozin and should be considered standard of care.

Monoclonal Gammopathy of Undetermined Significance in Patients With Transthyretin Amyloidosis (ATTR): Analysis Using the iStopMM Criteria.

INTRODUCTION: To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin amyloid (ATTR). We used the iStopMM study revised reference ranges for serum free light-chain (sFLC) corrected for eGFR to identify ATTR patients with light-chain MGUS (LC-MGUS). Characteristics and frequencies of the ATTR cohort with underlying MGUS was compared to a cohort of MGUS patients without ATTR. PATIENTS AND METHODS: A retrospective analysis of ATTR and MGUS patients evaluated at our center between January 2014 to December 2021. A total of 149, predominantly male (87.5%) ATTR patients with a median age of 82 were included. This cohort was compared to 228 MGUS patients. RESULTS: Of the 149 ATTR patients, 27 (18.1%) had coexisting MGUS. Among ATTR patients with MGUS, 12/27 (44%) had LC-MGUS based on sFLC abnormalities assessed using the iStopMM reference ranges. Of the MGUS only cohort, 44/228 (19.3%) met criteria for LC-MGUS. Utilizing the iStopMM reference ranges, 6 ATTR patients did not meet criteria for abnormal sFLCs, uncovering a 20% false-positive rate. CONCLUSION: We noted higher rates of MGUS, particularly LC-MGUS, among ATTR patients when compared to our MGUS only cohort. The high prevalence remained after utilizing the iStopMM sFLC corrected for eGFR reference ranges. Additionally, 6 ATTR patients with renal-dysfunction would have met MGUS criteria if not evaluated using the iStopMM revised measures. These findings emphasize careful interpretation of sFLC abnormalities and encourage providers to keep ATTR on the differential when work-up uncovers sFLC aberrations.