Functional Status and Quality of Life in Light-Chain Amyloidosis: Advanced Imaging, Longitudinal Changes, and Outcomes.

Background: In light-chain (AL) amyloidosis, whether functional status and heart failure-related quality of life (HF-QOL) correlate with cardiomyopathy severity, improve with therapy, and are associated with major adverse cardiac events (MACE) beyond validated scores is not well-known.

Objectives: The authors aimed to: 1) correlate functional status and HF-QOL with cardiomyopathy severity; 2) analyze their longitudinal changes; and 3) assess their independent associations with MACE.

Methods: This study included 106 participants with AL amyloidosis, with 81% having AL cardiomyopathy.

Quantitative Tc-pyrophosphate myocardial uptake: Changes on transthyretin stabilization therapy.

Background: Quantitative technetium-99m-pyrophosphate cardiac single-photon emission computed tomography (Tc-PYP SPECT/CT) is an emerging method for estimating myocardial burden of transthyretin cardiac amyloidosis (ATTR-CA), but its efficacy in monitoring longitudinal changes remains uncertain. We aimed to investigate longitudinal changes in cardiac ATTR amyloid burden following transthyretin stabilization therapy using visual and quantitative Tc-PYP SPECT/CT and to relate these with changes in cardiac biomarkers and function.

Methods: This prospective longitudinal cohort study investigated changes in Tc-PYP SPECT/CT in 23 participants with ATTR-CA on transthyretin stabilization therapy (median: 2.

Myocardial Characteristics, Cardiac Structure, and Cardiac Function in Systemic Light-Chain Amyloidosis.

Background: In systemic light-chain (AL) amyloidosis, cardiac involvement portends poor outcomes.

Objectives: The authors' objectives were to detect early myocardial alterations, to analyze longitudinal changes with therapy, and to predict major adverse cardiac events (MACE) in participants with AL amyloidosis using cardiac magnetic resonance imaging (MRI).

Methods: Recently diagnosed participants were prospectively enrolled.

Prognostic Value of Left Ventricular F-Florbetapir Uptake in Systemic Light-Chain Amyloidosis.

Background: Positron emission tomography/computed tomography (PET/CT) with F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden in systemic light-chain (AL) amyloidosis. However, its prognostic value is not known.

Objectives: The authors' aim was to evaluate the prognostic value of LV amyloid burden quantified by F-florbetapir PET/CT, and to identify mechanistic pathways mediating its association with outcomes.

Mechanisms of left ventricular systolic dysfunction in light chain amyloidosis: a multiparametric cardiac MRI study.

Background: Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood.

Purpose: This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis.

Methods: Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.

Quantification of right ventricular amyloid burden with 18F-florbetapir positron emission tomography/computed tomography and its association with right ventricular dysfunction and outcomes in light-chain amyloidosis.

Aims: In systemic light-chain (AL) amyloidosis, quantification of right ventricular (RV) amyloid burden has been limited and the pathogenesis of RV dysfunction is poorly understood. Using 18F-florbetapir positron emission tomography/computed tomography (PET/CT), we aimed to quantify RV amyloid; correlate RV amyloid with RV structure and function; determine the independent contributions of RV, left ventricular (LV), and lung amyloid to RV function; and associate RV amyloid with major adverse cardiac events (MACE: death, heart failure hospitalization, cardiac transplantation).

Methods And Results: We prospectively enrolled 106 participants with AL amyloidosis (median age 62 years, 55% males) who underwent 18F-florbetapir PET/CT, magnetic resonance imaging, and echocardiography.

Myocardial Characterization for Early Diagnosis, Treatment Response Monitoring, and Risk Assessment in Systemic Light-Chain Amyloidosis.

Aims: In systemic light-chain (AL) amyloidosis, cardiac involvement portends poor prognosis. Using myocardial characteristics on magnetic resonance imaging (MRI), this study aimed to detect early myocardial alterations, to analyze temporal changes with plasma cell therapy, and to predict risk of major adverse cardiac events (MACE) in AL amyloidosis.

Methods And Results: Participants with recently diagnosed AL amyloidosis were prospectively enrolled.

Prognostic Value of Left Ventricular F-Florbetapir Uptake in Systemic Light-Chain Amyloidosis.

Background: Myocardial immunoglobulin light-chain (AL) amyloid deposits trigger heart failure, cardiomyocyte stretch and myocardial injury, leading to adverse cardiac outcomes. Positron emission tomography/computed tomography (PET/CT) with F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden, but its prognostic value is not known. Therefore, we aimed to evaluate the prognostic value of LV amyloid burden quantified by F-florbetapir PET/CT and to identify mechanistic pathways mediating its association with outcomes.

Cardiac Amyloid Quantification Using I-Evuzamitide (I-P5+14) Versus F-Florbetapir: A Pilot PET/CT Study.

Background: Cardiac amyloid quantification could advance early diagnosis of amyloid cardiomyopathy (CMP) and treatment monitoring. However, current imaging tools are based on indirect measurements. I-evuzamitide is a novel pan-amyloid radiotracer binding to amyloid deposits from multiple amyloidogenic proteins.

Age Dependency of Cardiovascular Outcomes With the Amyloidogenic pV142I Transthyretin Variant Among Black Individuals in the US.

Importance: Hereditary transthyretin cardiac amyloidosis is an increasingly recognized cause of heart failure (HF) with distinct treatment. The amyloidogenic pV142I (V122I) variant is present in 3% to 4% of Black individuals in the US and increases the risk for atrial fibrillation (AF), HF, and mortality. Since hereditary transthyretin cardiac amyloidosis demonstrates age-dependent anatomic penetrance, evaluation later in life may identify survivors at particularly high risk.

Tc Bone-Avid Tracer Cardiac Scintigraphy: Role in Noninvasive Diagnosis of Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is an overlooked cause of heart failure, with substantial morbidity and mortality. The emergence of several novel therapies has fueled the interest in early and accurate diagnosis of ATTR-CA so that potentially life-saving pharmacologic therapy can be administered in a timely manner. The most promising imaging modality and biomarker is SPECT imaging with technetium 99m (Tc)-radiolabeled bone-seeking tracers, which have high specificity in the diagnosis of ATTR-CA, potentially obviating biopsy.

Optimal Echocardiographic Parameters to Improve the Diagnostic Yield of Tc-99m-Bone Avid Tracer Cardiac Scintigraphy for Transthyretin Cardiac Amyloidosis.

Background: Echocardiographic deformation-based ratios and novel multi-parametric scores have been suggested to discriminate transthyretin cardiac amyloidosis (ATTR-CM) from other causes of increased left ventricular wall thickness among patients referred for ATTR-CM evaluation. Their relative predictive accuracy has not been well studied. We sought to (1) identify echocardiographic parameters predictive of ATTR-CM and (2) compare the diagnostic accuracy of these parameters in patients with suspected ATTR-CM referred for technetium-99m-pyrophosphate scintigraphy.

Effect of tafamidis on global longitudinal strain and myocardial work in transthyretin cardiac amyloidosis.

Aims: In patients with transthyretin amyloid cardiomyopathy (ATTR-CM), the effect of tafamidis on myocardial function using serial speckle tracking echocardiography has not been reported. The purpose of this study was to describe the natural history of myocardial function in untreated ATTR-CM and determine the effect of tafamidis on myocardial functional parameters over 12 months of treatment.

Methods And Results: A total of 45 subjects with ATTR-CM were retrospectively studied: 23 treated with tafamidis and 22 untreated.

Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study.

Background: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis.

Methods: Both were uncontrolled open-label studies.

Myocardial Composition in Light-Chain Cardiac Amyloidosis More Than 1 Year After Successful Therapy.

Objectives: The goals of this study were to characterize myocardial composition during the active and remission phases of light-chain (AL) cardiac amyloidosis.

Background: Cardiac dysfunction in AL amyloidosis is characterized by dual insults to the myocardium from infiltration and toxicity from light chains during the active phase and by infiltration alone in the remission phase.

Methods: Prospectively enrolled subjects with cardiac AL amyloidosis (21 remission AL amyloidosis; age: 63.

Effect of Tafamidis on Serum Transthyretin Levels in Non-Trial Patients With Transthyretin Amyloid Cardiomyopathy.

Background: Transthyretin amyloid (ATTR) cardiomyopathy is slowed by tafamidis, which stabilizes the TTR molecule and reduces the formation of amyloidogenic oligomers. Stabilizers in clinical doses raise serum TTR, which may be a surrogate for the degree of stabilization.

Objectives: This study aims to determine, in a non-trial, unselected population of patients with ATTR cardiomyopathy, the effect of tafamidis on serum levels of TTR, and to compare these with published data of changes in TTR.

Rhabdomyolysis in the Setting of Concomitant Use of Tafamidis, Atorvastatin, and Amiodarone.

An 85-year-old women with transthyretin cardiac amyloidosis presented with generalized weakness, elevated liver function test levels, and creatinine kinase consistent with rhabdomyolysis 1 week after starting tafamidis. She was already taking atorvastatin and amiodarone, raising the possibility of a drug-drug interaction inhibiting the breakdown and excretion of atorvastatin, causing drug-induced rhabdomyolysis. ().