Transthyretin-related Cardiac Amyloidosis Research Articles

Reproducibility of the quantitative assessment of myocardial 99mTc-labeled diphosphonate uptake in patients with suspected transthyretin-related cardiac amyloidosis: A test-retest study

Reproducibility of the quantitative assessment of myocardial 99mTc-labeled diphosphonate uptake in patients with suspected transthyretin-related cardiac amyloidosis: A test-retest study

Role of Imaging in Cardiomyopathies.

Imaging has a central role in the diagnosis, classification, and clinical management of cardiomyopathies. While echocardiography is the first-line technique, given its wide availability and safety, advanced imaging, including cardiovascular magnetic resonance (CMR), nuclear medicine and CT, is increasingly needed to refine the diagnosis or guide therapeutic decision-making. In selected cases, such as in transthyretin-related cardiac amyloidosis or in arrhythmogenic cardiomyopathy, the demonstration of histological features of the disease can be avoided when typical findings are observed at bone-tracer scintigraphy or CMR, respectively. Findings from imaging techniques should always be integrated with data from the clinical, electrocardiographic, biomarker, genetic and functional evaluation to pursue an individualised approach to patients with cardiomyopathy.

Risk stratification in transthyretin-related cardiac amyloidosis.

Transthyretin related cardiac amyloidosis (TTR-CA) is an infiltrative cardiomyopathy that cause heart failure with preserved ejection fraction, mainly in aging people. Due to the introduction of a non invasive diagnostic algorithm, this disease, previously considered to be rare, is increasingly recognized. The natural history of TTR-CA includes two different stages: a presymptomatic and a symptomatic stage. Due to the availability of new disease-modifying therapies, the need to reach a diagnosis in the first stage has become impelling. While in variant TTR-CA an early identification of the disease may be obtained with a genetic screening in proband's relatives, in the wild-type form it represents a challenging issue. Once the diagnosis has been made, in order to identifying patients with a higher risk of cardiovascular events and death it is necessary to focus on risk stratification. Two prognostic scores have been proposed both based on biomarkers and laboratory findings. However, a multiparametric approach combining information from electrocardiogram, echocardiogram, cardiopulmonary exercise test and cardiac magnetic resonance may be warranted for a more comprehensive risk prediction. In this review, we aim at evaluating a step by step risk stratification, providing a clinical diagnostic and prognostic approach for the management of patients with TTR-CA.

Anxious/Depressive Symptoms Alter the Subjective Perception of Heart Failure Severity in Transthyretin Cardiac Amyloidosis

The subjective perception of cardiac symptom severity is considered a main treatment target in the management of transthyretin-related cardiac amyloidosis (CA), as opposed to objective prognostic markers such as N-terminal pro b-type natriuretic peptide (NT-proBNP), which objectively reflects the severity of heart disease. Nevertheless, anxious and depressive symptoms in patients with CA might affect subjects perceptions of disease, creating a potential gap between objective and subjective parameters. We assess the impact of such bias in consecutive patients with CA. A total of 60 patients aged 62 to 88years with CA were recruited. The level of anxiety and depression was measured by the Hospital Anxiety and Depression Scale and the subjective perception of symptoms severity by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Finally, NT-proBNP plasma levels at rest and glomerular filtration rate were measured. Nearly 1/2 of the patients (48%) reported clinically relevant levels of psychologic symptoms. Higher levels of anxious and depressive symptoms were significantly linked to lower KCCQ scores. Furthermore, the relation between NT-proBNP and KCCQ was significant only when anxious and depressive symptoms were low (β=-0.86, p=0.002; β=-0.86, p=0.002, respectively) and medium (β=-0.49, p=0.004; β=-0.45, p=0.004, respectively) but was otherwise lost. Depression and anxiety in patients with transthyretin-related CA required assessment and management. In conclusion, patients with depression/anxiety have a clear disconnect between their personal assessment and objective measures of cardiac symptoms, with a major influence on the patients' wellbeing and on their subjective response to treatments in clinical trials.

Ten questions about transthyretin amyloidosis

Systemic amyloidosis is a hereditary or acquired disease characterized by deposition of amyloid insoluble fibrils into body organs and tissues, causing structural abnormalities and organ dysfunction, i.e. heart failure. This disease is classified according to the precursor protein involved; immunoglobulin light chains, transthyretin and apolipoprotein A1 underlie the cardiac involvement. Amyloid cardiomyopathy is characterized by symmetric biventricular hypertrophy, preserved systolic function, and pronounced diastolic dysfunction. Although transthyretin-related cardiac amyloidosis has always been considered a rare disease, in the last few years it has been found to be one of the most common causes of hypertrophic cardiomyopathy, thanks to better diagnostic algorithms and considerable improvements in cardiac imaging. Achieving an early diagnosis is a challenge for the modern cardiologist since new disease-modifying therapies have been developed in recent years. This article aims to answer to the main questions about transthyretin-related cardiac amyloidosis: when to suspect it, how to diagnose it and how to treat it.

Tc-99m HMDP bone scintigraphy for cardiac amyloidosis diagnosis: A false positive case

A 68-year-old man with heart failure (left ventricular ejection fraction = 30%) and normal coronary angiography underwent bone scintigraphy for suspected transthyretin-related cardiac amyloidosis (CA).1 He received 532 MBq (14.3 mCi) Tc-99m hydroxy-methyl-diphosphonate (HMDP) and data were acquired 2 hours after injection. On anterior and posterior whole-body scans (Figure 1 A and B), diffuse cardiac, hepatic, and soft-tissue uptake of the radiotracer was seen, in association with low skeletal uptake. It was established that the patient had recently been hospitalized for heart failure exacerbation and had received an intravenous iron injection, which is a recommended treatment for heart failure.2 In consultation with our hospital’s cardiology team, it was decided to repeat the bone scan at a time when the patient had received no recent iron infusion. Two months after the first bone scan, the patient received 556 MBq (15 mCi) of 99m-Tc HMDP, and no cardiac, hepatic, or soft-tissue uptake was detected (Figure 1C and D).

Determining patterns of vascular function and structure in wild-type transthyretin cardiac amyloidosis. A comparative study

BackgroundThe impact of wild-type transthyretin-related cardiac amyloidosis (ATTRwt) on functional and structural peripheral vascular measures is unknown. In the present study, we explored patterns of vascular dysfunction in patients with ATTRwt in comparison to diseases with similar cardiac phenotype. MethodsTreatment-naïve patients with ATTRwt (n = 32) were compared to: 1. Age-and sex-matched reference population without amyloidosis (n = 32), 2. Age-and sex-matched patients with systemic AL amyloidosis (n = 32), and 3. patients with cardiac AL amyloidosis (AL-HF, n = 23) or elderly patients with heart failure with preserved ejection fraction (HFpEF) (n = 16). All subjects underwent peripheral vascular assessment using carotid artery ultrasonography, brachial artery flow-mediated dilation (FMD), measurement of arterial stiffness and aortic hemodynamics including heart rate-adjusted time of return of reflected waves (Tr/HR). ResultsAfter adjustment for traditional cardiovascular risk factors and coronary artery disease (core model), peripheral and aortic blood pressures (BP) were lower in patients with ATTRwt (p < 0.05) whereas other vascular markers were preserved compared to the reference non-amyloidosis group. ATTRwt was independently associated with lower BP and longer Tr/HR compared to AL. Compared to AL-HF, FMD was lower in ATTRwt (p = 0.033). ATTRwt patients had lower BP and higher Tr/HR than HFpEF (p < 0.05). By ROC analysis, Tr/HR discriminated ATTRwt vs. AL-HF (sensitivity 93%, specificity 75%) and HFpEF (sensitivity 100%, specificity 94%) and lower FMD increased the likelihood for ATTRwt at low Tr/HR values. ConclusionATTRwt patients present a distinct peripheral vascular fingerprint which is different from AL-HF or HFpEF, consisting of lower peripheral and aortic BP, prolonged Tr/HR and FMD at reference-population range.

An Autopsy Case of Transthyretin-Related Cardiac Amyloidosis (TTR-CA), Which Fell into Low-Output Syndrome after Cardiac Surgery

An Autopsy Case of Transthyretin-Related Cardiac Amyloidosis (TTR-CA), Which Fell into Low-Output Syndrome after Cardiac Surgery

Prevalence and diagnostic value of extra-left ventricle echocardiographic findings in transthyretin-related cardiac amyloidosis

Background Cardiac amyloidosis (CA) is cardiomyopathy with a hypertrophic phenotype characterised by diffuse deposition of anomalous fibrillar proteins in the extracellular matrix. Objectives To evaluate the prevalence and diagnostic value of extra left ventricle echocardiographic findings in patients with left ventricular (LV) hypertrophic phenotype and amyloid deposition. Methods A group of 146 patients with LV thickness ≥15 mm were enrolled: 70 patients who received a definite diagnosis of sarcomeric hypertrophic cardiomyopathy (HCM group) and 76 patients with transthyretin cardiac amyloidosis (CA group). Echocardiographic analysis of crista terminalis (CriT), atrio-ventricular plane (AVP), mitro-aortic lamina (MAL), anterior ascending aortic wall, interatrial septum (IAS), Eustachian valve (EusV) and coumadin ridge (CouR) was performed in all patients, and these structures were compared among the two groups. Results CA group showed significantly higher dimensions of CriT, IAS, CouR, AVP, MAL and IAS compared to the HCM group. The logistic analysis showed that LV EF, LV septal thickness, CriT presence, CriT area, MAL and IAS were all predictors of CA in univariate analyses. The stepwise multivariate analysis showed independent predictors of CA: CriT area, MAL and LVEF. According to areas under the receiver operating characteristic curves the best cut-off values to determine CA were identified (IAS > 9 mm, MAL > 7 mm, CriT > 9 mm2). Among these 3 independent predictors, IAS > 9 mm had the best specificity (96%) and positive predictive value (93%) in identifying CA. Conclusions evidence of extra left ventricle sites of amyloid deposition is a frequent finding in CA. In the context of hypertrophic phenocopies, an increased thickness of IAS, and/or CT and/or MAL should suggest a diagnosis of transthyretin CA.

Quantitation of myocardial 99mTc-HMDP uptake with new SPECT/CT cadmium zinc telluride (CZT) camera in patients with transthyretin-related cardiac amyloidosis: Ready for clinical use?

BackgroundThe aim of this study was to investigate the feasibility of assessing absolute myocardial 99mTc-HMDP uptake in patients with suspected cardiac ATTR using SUV with a whole-body CZT SPECT-CT camera (DNM670CZT). MethodsFifteen patients with suspected cardiac ATTR (Perugini ≥ 2) underwent a conventional 99mTc-HMDP planar imaging and a thoracic SPECT/CT using a DNM 670CZT. A control group consisted of 15 patients with negative scintigraphy (Perugini < 2). SUVmax (mg·L−1) and percentage of injected dose (%ID) were calculated in a cardiac volume of interest (VOI) encompassing the left ventricle. VOIs were also placed in the lung, the right pectoris major, and the sternum. A heart-to-lung SUVmax ratio (HLR) was calculated. ResultsAll ATTR patients demonstrated an increased cardiac HMDP SUVmax (12.2 ± 3.7 mg·L−1) vs controls (3.5 ± 1.2, P < .0001). Percentage of ID, pectoral uptake and HLR were significantly higher in the ATTR group (1.1 ± 0.3 vs 0.15 ± 0.8, P < .0001; 1.5 ± 0.3 vs 0.9 ± 0.3, P < .0001; 9.7 ± 3 vs 4.3 ± 2.2, P < .0001). Bone uptake was not statistically different between the two groups. ConclusionThis study demonstrated the feasibility of quantitative 99mTc-HMDP SUVmax measurement using a whole-body SPECT/CT CZT camera in patients with suspected cardiac ATTR.

Mid-basal left ventricular longitudinal dysfunction as a prognostic marker in mutated transthyretin-related cardiac amyloidosis

Aim: Mutated transthyretin (TTRv) cardiac amyloidosis (CA) represents an uncommon form of CA. Our study aimed to assess the best echocardiographic prognostic parameter in the early stage of TTRv amyloidosis with cardiomyopathy. Methods: In total, 99 patients with TTRv in New York Heart Association class I or II and with no clinical history of previous cardiac disease were studied. Assessment with 99mTc-DPD whole-body scan showed CA in 46 patients. At the first medical contact, an echocardiographic examination was performed. In addition to conventional left ventricular (LV), echocardiographic measurements [ejection fraction (EF), dimensions and diastolic function, global longitudinal strain (GLS), longitudinal strain of the 4 apical segments, longitudinal strain of the 12 mid-basal segments (MBLS)] and their ratio [relative regional strain ratio (RRSR)] were obtained. Patient outcome was evaluated during a follow-up with an average duration of six years. Cardiac death and appropriate implantable cardiac defibrillator (ICD) shock were considered major events. Results: A higher value of LV thickness, E/E’, and RRSR and lower LV volumes, EF, GLS, MBLS were observed in patients with CA than the ones with only TTRv. During follow-up (median of 7.7 years), 25 major events (23 cardiac death and 2 appropriate ICD shocks) occurred. The logistic univariate analyses showed that LV EF, LV septal thickness, E/E’, GLS, and MBLS were all predictors of cardiovascular death. In multivariate analysis, MBLS was the only independent predictor of major events. A cut off of -14 of MBLS was selected as the best value to discriminate a worse prognosis on Kaplan-Meyer analysis. Conclusion: Longitudinal dysfunction is observed in the early stages of ATTRv amyloidosis with cardiomyopathy. Medio-basal LV longitudinal dysfunction is a strong independent echocardiographic predictor of cardiac death.

373 Utility of the early phase of DPD scintigraphy in the diagnosis of correlated TT-R cardiac amyloidosis

Abstract Aims The importance of cardiac scan with phosphonate-based radiotracers in the diagnosis of cardiac amyloidosis is now well established. Standard imaging is performed 3 h after tracer injection with a planar view on the cardiac region. This study sought to evaluate the predictive role of early-phase myocardial uptake (10 min after injection) of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) compared compared with standard late acquisition, in patients with suspected hereditary transthyretin-related cardiac amyloidosis (TTR-CA). Methods and results Fifty five patients with suspected of TTR-CA with typical aspects of the relative apical sparing at two-dimensional speckle-tracking echocardiography, reported as a specific pattern for cardiac amyloidosis, were enrolled after having signed informed written consent. They have been subjected to a 99mTc-DPD cardiac scintigraphy with planar acquisition at 10 min and 3 h after tracer injection (13 Mbq/Kg). Patients with cardiac uptake on the planar images concluded the examination with a SPECT-CT (cardiac protocol) to assess the affected myocardial segments. On planar images the heart-to-mediastinum-ratio was measured. Subsequently, the diagnosis of amyloidosis has to be confirmed with morphologic examinations such as biopsy and genetic tests. Of the enrolled patients with clinical and echocardiographic aspect of TTR-CA, 22 were positive for cardiac amyloidosis. All of them showed tracer uptake in both early and late images. In patients with positive results, the early-phase showed a Heart-to-mediastinum-ratio &amp;gt;1.2. SPECT/CT showed involvement of almost two myocardial segments: in all patients the ventricular septum showed significant tracer uptake. Conclusions Our small group of patients showed that 99mTc-DPD myocardial uptake intensity on early-phase scintigraphy can be used to anticipate the results of late images in diagnosis of TTR cardiac amyloidosis.

Peripheral vascular involvement in transthyretin cardiac amyloidosis. A comparative analysis with AL amyloidosis

Abstract Background The pattern of peripheral vascular involvement in the wild type transthyretin-related cardiac amyloidosis (ATTRwt) and its diagnostic utility in differentiating this infiltrating cardiomyopathy from light chain (AL) cardiac amyloidosis (AL-CA) and heart failure with preserved ejection fraction (HFpEF) of different origin have not been explored. Aims To characterize the pattern of peripheral vascular involvement in ATTRwt and evaluate its value in differentiating ATTRwt from AL-CA and HFpEF. Methods Newly diagnosed patients with ATTRwt (n=42) were consecutively recruited from our amyloidosis center. These patients were matched 1:1 for age and sex to patients with AL-CA (n=32) and subjects without amyloidosis (n=32) and also matched 2:1 to HFpEF patients (n=16). All subjects underwent a series of non-invasive vascular examinations for the assessment of: 1. subclinical carotid atherosclerosis with B-mode ultrasonography, 2. Arterial stiffness with measurement of carotid-femoral pulse wave velocity, 3. Reactive vasodilation with flow-mediated dilation (FMD) and 4. Aortic blood pressures and arterial wave reflections with augmentation index (AI) and return time of reflected wave (Tr). Results ATTRwt patients had lower peripheral (pBP) and aortic blood pressure (aBP) markers compared to non-AL controls (p&amp;lt;0.05 for all). ATTRwt grouping was an independent determinant of these markers, after adjustment for cardiovascular risk factors (CVRF), including history of hypertension, hyperlipidemia and diabetes, glomerular filtration rate, body mass index and smoking status (core model). ATTRwt had lower aDBP and increased Tr compared to AL subjects. In a comparison between ATTRwt and AL patients with cardiac involvement, AI and Tr were higher and FMD lower in ATTRwt patients. ATTRwt was an independent determinant of these markers, after adjustment for the core model (p&amp;lt;0.05 for all). Compared to HFpEF, patients with ATTRwt had lower peripheral and central BP and higher Tr (p&amp;lt;0.05 for all). By ROC analysis, Tr provided high diagnostic value for ATTRwt vs. AL-CA (Area Under the Curve, AUC=0.809, CI: 0.65–0.96) and for ATTRwt vs combined AL-CA and HFpEF (AUC=0.880, CI: 0.79–0.97). Finally, AI was closely correlated with posterior (Spearman's Rho=−0.30) and intraventricular wall thickness (Rho=−0.329) and left ventricular global longitudinal strain (Rho=−0.4) and lower cDBP with higher Gilmore and New York Heart Association stage (p&amp;lt;0.05). Conclusion ATTRwt patients present differential characteristics of peripheral vascular function and aortic hemodynamics as compared to AL, HFpEF and healthy controls. The clinical value of these characteristics merit further investigation since differential diagnosis among amyloidosis types is clinically challenging, while it may have prognostic implications. Funding Acknowledgement Type of funding sources: None.

Yield of bone scintigraphy screening for transthyretin-related cardiac amyloidosis in different conditions: Methodological issues and clinical implications.

BackgroundTransthyretin‐related cardiac amyloidosis (TTR‐CA) is thought to be particularly common in specific at‐risk conditions, including aortic stenosis (AS), heart failure with preserved ejection fraction (HFpEF), carpal tunnel syndrome (CTS) and left ventricular hypertrophy or hypertrophic cardiomyopathy (LVH/HCM).MethodsWe performed a systematic revision of the literature, including only prospective studies performing TTR‐CA screening with bone scintigraphy in the above‐mentioned conditions. Assessment of other forms of CA was also evaluated. For selected items, pooled estimates of proportions or means were obtained using a meta‐analytic approach.ResultsNine studies (3 AS, 2 HFpEF, 2 CTS and 2 LVH/HCM) accounting for 1375 screened patients were included. One hundred fifty‐six (11.3%) TTR‐CA patients were identified (11.4% in AS, 14.8% in HFpEF, 2.6% in CTS and 12.9% in LVH/HCM). Exclusion of other forms of CA and use of genetic testing was overall puzzled. Age at TTR‐CA recognition was significantly older than that of the overall screened population in AS (86 vs. 83 years, p = .04), LVH/HCM (75 vs. 63, p < .01) and CTS (82 vs. 71), but not in HFpEF (83 vs. 79, p = .35). In terms of comorbidities, hypertension, diabetes and atrial fibrillation were highly prevalent in TTR‐CA‐diagnosed patients, as well as in those with an implanted pacemaker.ConclusionsScreening with bone scintigraphy found an 11–15% TTR‐CA prevalence in patients with AS, HFpEF and LVH/HCM. AS and HFpEF patients were typically older than 80 years at TTR‐CA diagnosis and frequently accompanied by comorbidities. Several studies showed limitations in the application of recommended TTR‐CA diagnostic algorithm, which should be addressed in future prospective studies.

Nonamyloidotic light chain deposition cardiomyopathy.

A 56-year-old woman with a newly diagnosed monoclonal plasma cell dyscrasia and kappa light-chain cast nephropathy was referred for exclusion of cardiac involvement prior to autologous stem-cell transplantation. Patient history revealed mild exertional dyspnoea with elevated natriuretic peptides (NT-proBNP 2010 ng/mL) and mildly elevated high-sensitivity cardiac troponin T (26 ng/L). Her electrocardiogram was not specific for cardiac amyloidosis and without conduction abnormalities. In spite of normal chamber dimensions, normal systolic function and absence of restrictive cardiomyopathy in transthoracic echocardiography (Supplementary data online) and cardiovascular magnetic resonance (CMR) scan (Panel A), CMR revealed a highly elevated myocardial extracellular volume (ECV) of ≥45% (Panel B) and presence of mild bilateral pleural as well as pericardial effusion (Panel A). There was no evidence of myocardial oedema, focal fibrosis, or myocardial infarction. 99mTc-DPD scintigraphy excluded transthyretin-related (ATTR) cardiac amyloidosis (Perugini Score = 0). Cardiac biopsy did...

Early Impairment of Right Ventricular Morphology and Function in Transthyretin-Related Cardiac Amyloidosis.

Background:Our study aimed to evaluate right ventricular (RV) morphology and strain (S) in the early stage of familial transthyretin (TTR) cardiac amyloidosis (CA).Methods and Results:Thirty-seven patients with transthyretin mutation underwent 99mTc-3,3-diphosphono-1,2 propanodicarboxylic acid (99mTc-DPD) scans and/or cardiac magnetic resonance (CMR) to identify TTR CA. Each patient underwent echocardiography to quantify RV dimensions, tricuspid annular plane systolic excursion (TAPSE), systolic pulmonary artery pressure (sPAP), longitudinal (L) strain of the RV free wall, left ventricular (LV) septal thickness (ST), ejection fraction, E/E', LV global (G) L, radial (R), and circumferential (C) S. 99mTc-DPD and CMR revealed the accumulation in 22 of 37 patients (CA group) and no accumulation in 15 patients (no-CA group). Left ventricular (LV) septal thickness (ST) was higher (P < 0.0001) while LV ejection fraction and E/E' were lower (P < 0.05) in the CA group than the no-CA group. LV-global longitudinal strain (LS) was lower (P < 0.0001) in the CA-group than the no CA-group, whereas LV-global circumferential strain and LV-global radial strain were similar. The CA group showed higher values of RV dimensions (P < 0.05) and sPAP (0.02) and a lower (P = 0.002) TAPSE. Globally, RV-LS was lower (P = 0.005) in the CA group than the no-CA group. Basal and mid segments of the RV free wall showed a lower LS in the CA group than the no-CA group (P < 0.01), while apical S was similar between groups.Conclusions:RV deformation, particularly in basal and mid segments, is early impaired in CA.

Disease-Modifying Pharmacological Therapies for Transthyretin Cardiac Amyloidosis

Transthyretin-related cardiac amyloidosis is a disease that is poorly understood and challenging to manage; however, pharmacotherapeutic developments in recent years has raised awareness and promoted earlier diagnosis. Transthyretin protein is a thyroid hormone-binding protein which transports thyroxine from the bloodstream to the brain, and cardiac involvement is either acquired or hereditary. This protein can misfold and lead to abnormal fibril formation, causing the extracellular deposition of ATTR into the heart. Further fibril deposition leads to irreversible organ dysfunction. Disease-modifying pharmacological therapies can be divided into three categories: ATTR stabilizers (diflunisal, tafamidis, and AG10), ATTR silencers (patisiran and inotersen), and ATTR disruptors (doxycycline and ursodeoxycholic acid and polyphenol (-)-epigallocatechin gallate). This manuscript reviews these emerging pharmacological treatments available and under study for ATTR cardiac amyloidosis.

Identification and typing of cardiac amyloidosis by noninvasive imaging: Two cases for two patterns

Cardiac amyloidosis is a restrictive infiltrative cardiomyopathy burdened by high mortality. The two more common forms are immunoglobulin light-chain amyloidosis and transthyretin-related amyloidosis with different prognoses and treatments. However, distinguishing between them is challenging. Appropriate utilization of the different available imaging techniques in the evaluation of patients with known or suspected cardiac amyloidosis is mandatory. We report two cases with cardiac amyloidosis of different etiology and with distinct imaging patterns. In the first case, the negative 99mTc-diphosphonate imaging was useful to support the diagnosis of cardiac amyloid light-chain; the second case emphasized the utility of whole-body scintigraphy in recognizing transthyretin-related cardiac amyloidosis and the potential role of cadmium-zinc-telluride SPECT imaging for the evaluation of segmental distribution of cardiac disease. Both cases support the growing interest in looking for noninvasive methods to type cardiac amyloidosis in the place of invasive myocardial biopsy highlighting both possibilities and limitations of available imaging techniques in diagnosis and treatment monitoring.

Biomarkers and Prediction of Prognosis in Transthyretin-Related Cardiac Amyloidosis: Direct Comparison of Two Staging Systems

BackgroundThe severity of heart disease varies widely among patients with transthyretin-related cardiac amyloidosis (ATTR-CA) at presentation, and availability of tools able to predict prognosis is essential for clinical and research purposes. Currently, two biomarker-based staging systems are available. The aim of this study was to compare their predictive performance. MethodsA total of 175 patients diagnosed with ATTR-CA (133 wild-type and 42 hereditary) were stratified into different stages based on 2 systems: the first system included N-terminal pro–B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR), and the second one included NT-proBNP and troponin I (TnI). Survival estimates and age-adjusted survival for all-cause mortality were analysed over a median follow-up of 27 months (interquartile range 16-43 months). ResultsPredictive performance was more accurate when NT-proBNP and eGFR were used, resulting in effective survival stratification: 64.4 months for stage 1, 44.6 months for stage 2, and 20.5 months for stage 3 (P < 0.01 for stages 1 vs 2; P < 0.0001 for stages 1 vs 3; P < 0.0001 stages 2 vs 3). The combination of NT-proBNP and TnI was unable to effectively differentiate survival: 64.5 months for stage 1, 50.9 months for stage 2, and 27.3 months for stage 3 (P = 0.223 for stages 1 vs 2; P < 0.0001 for stages 1 vs 3; P < 0.0001 for stages 2 vs 3). The same results were seen after age adjustment. ConclusionsA staging system using NT-proBNP and eGFR had better prognostic accuracy for ATTR-CA patients compared with one using NTproBNP and TnI.

Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis

ObjectivesThe aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation. BackgroundDiagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations. MethodsA total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)–diphosphonate (DPD) or 99mTc–hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini’s method. ResultsAmong 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings. ConclusionsThe sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations.