18F-Florbetaben PET/CT for the Diagnosis and Subtyping of Cardiac Amyloidosis: A Case Series and Review of the Literature.

Objectives: Cardiac amyloidosis (CA) is a type of systemic amyloidosis. Amyloid-targeting positron emission tomography (PET) has shown potential as an imaging method for CA. However, the optimal imaging protocol and role of 18F-florbetaben (FBB) PET in the diagnosis and subtyping of CA have yet to be determined. Methods: Patients with suspected CA who had positive or equivocal results of technetium-99m pyrophosphate (PYP) scintigraphy were enrolled for dynamic and late FBB PET imaging. In addition to visual assessment, a kinetic modeling-based approach including target-to-background ratio (TBR) and myocardial retention fraction (RF) of serial images reconstructed from a 20-min dynamic acquisition, and a late image at 110 min post-injection were performed. We compared FBB PET measures of four typical patients with light chain amyloidosis (AL), wild-type transthyretin amyloidosis (ATTRwt), variant transthyretin amyloidosis (ATTRv), and heart failure, respectively. We also reviewed the literature on the clinical use of amyloid PET in CA. Results: Myocardial tracer retention was only found in the AL patient on the late images. TBR and RF were highest in the AL patient followed by the ATTRwt patient, and lowest in the ATTRv and non-CA patients. Conclusions: FBB PET has potential in the detection and non-invasive subtyping of CA, especially in subjects with equivocal PYP findings or monoclonal gammopathy.

The impact of different reconstruction parameters on quantitative 99mTc-DPD SPECT/CT values in the assessment of cardiac transthyretin amyloidosis.

AIM: To assess in a phantom and in a clinical study the influence of different reconstruction parameters on quantitative SPECT/CT values in the assessment of cardiac transthyretin amyloidosis (ATTR-CA). METHOD: A hybrid SPECT/CT camera with a proprietary software for SPECT/CT-based quantification of myocardial uptake of 99mTc-DPD was used. Images were reconstructed with 6 different protocols, differing in iterations, subset and Gaussian filter. Quantitative values were tested in phantom and clinical studies across different reconstruction protocols. Values were automatically calculated both as kBq/ml and as maximum, mean and peak standardized uptake value (SUV). RESULTS: The standard parameters provided by the manufacturer (reconstruction 1) yielded higher accuracy in quantifying, with measuring 97.1% of the expected activity in the phantom. Reconstructions with higher Gaussian filter caused a systematic underestimation of quantified values of 27.2% (p < 0.01). Results were replicated in the clinical study consisting of 155 patients with suspected ATTR-CA, wherein changing the number of iterations and subsets was not associated with a statistically significant difference in quantitative values compared to reconstruction 1, while a higher Gaussian filter caused inaccurate quantification with up to 24% of difference measured. CONCLUSION: Different reconstruction parameters can impact quantitative values on 99mTc-DPD SPECT/CT. Therefore, parameters should be maintained consistently across different acquisitions and different centres.

Persistent Multiple Colonic Ulcers and Repeated Acute Bloody Diarrhea in an Elderly Patient with Transthyretin Amyloidosis: A Case Report.

The clinical gastrointestinal manifestations of transthyretin amyloidosis (ATTR amyloidosis) are usually non-specific, and colonic bleeding or ulcers are unusual. Here, we report the case of an elderly Japanese man with ATTR amyloidosis who presented with rare gastrointestinal symptoms. An 84-year-old Japanese man was referred to our hospital because of anemia and positive fecal occult blood test results. Endoscopic examination revealed multiple small colonic erosions and/or ulcers; however, the cause remained unknown. The patient repeatedly visited our hospital for one year because of acute bloody diarrhea, anemia, and multiple persistent colonic ulcers. His symptoms improved after symptomatic treatment. The most recent gastric biopsy revealed ATTR amyloidosis, which was retrospectively detected in colon, stomach, and gallbladder specimens obtained six months, six years, and 12 years earlier, respectively. Therefore, ATTR amyloidosis should be considered in the differential diagnosis of colon-related anemia.

Epidemiological Changes in Transthyretin Cardiac Amyloidosis: Evidence from In Vivo Data and Autoptic Series.

Cardiac amyloidosis is an infiltrative disease that causes progressive myocardial impairment secondary to amyloid fibril deposition in the extracellular space of the myocardium. Many amyloid precursors, including transthyretin protein, are known to determine cardiac damage by aggregating and precipitating in cardiac tissue. Transthyretin cardiac amyloidosis may be either caused by rare genetic mutations of the transthyretin gene in the hereditary variant, or may arise as a consequence of age-related mechanisms in the acquired form. Although it has been labeled as a rare disease, in recent years, transthyretin cardiac amyloidosis has stood out as an emerging cause of aortic stenosis, unexplained left ventricular hypertrophy and heart failure with preserved ejection fraction, particularly in the elderly. Indeed, the integration of data deriving from both in vivo imaging techniques (whose advancement in the last years has allowed to achieve an easier and more accessible non-invasive diagnosis) and forensic studies (showing a prevalence of amyloid deposition in cardiac tissue of elderly patients up to 29%) suggests that cardiac amyloidosis is a more common disease than traditionally considered. Thanks to all the improvements in non-invasive diagnostic techniques, along with the development of efficacious therapies offering improvements in survival rates, transthyretin cardiac amyloidosis has been transformed from an incurable and infrequent condition to a relatively more diffuse and treatable disease, which physicians should take into consideration in the differential diagnostic processes in daily clinical practice.

Regional variation in technetium pyrophosphate (PYP) uptake in transthyretin cardiac amyloidosis (ATTR-CA) and concomitant myocardial infarction: A case series.

- Diffuse and patchy myocardial uptake of Tc-99m PYP is well established in cases of ATTR-CA. - Chronic myocardial infarction leads to regional myocardial thinning and lack of vascular supply can present as regional sparing 'cold spot' on Tc-99m PYP imaging. - The absence of Tc-99m PYP uptake in vascular regions should raise the possibility of underlying scar.

Modified ex-PRESS technique versus Ahmed glaucoma valve as primary glaucoma surgery for hereditary transthyretin amyloidosis glaucoma.

BACKGROUND: To compare the efficacy of modified Ex-PRESS technique (ExP) versus Ahmed Glaucoma Valve (AGV) as primary surgery in hereditary transthyretin amyloidosis (ATTRv) secondary glaucoma. METHODS: Retrospective study at the national amyloidosis centre. Success was defined as an IOP ≥ 6 mmHg and ≤ 21 mmHg with no need for further glaucoma surgery or laser trabeculoplasty and without loss of light perception at the time of the last follow-up. Secondary outcomes included surgical complications, need for hypotensive drugs, and endothelial cell loss. Patients submitted to previous glaucoma surgery were excluded. RESULTS: We included 180 eyes of 150 patients, 121 in AGV and 59 in ExP group. No significant baseline differences were found between groups. At the time of last follow-up, both groups exhibited significant intraocular pressure (IOP) reduction (p < .001) and number of glaucoma medications (p < .001). Kaplan-Meyer analysis showed higher cumulative probability of success for AGV group (80.1% vs. 41.1%, p < .001) and higher mean time to failure (54.5 vs. 36.9 months, respectively, p < 0.001) at 60 months follow-up. AGV showed lower hazard (HR 0.21, 95% CI [0.111-0.407], p < .001) for failure. CONCLUSION: AGV and ExP are safe and effective techniques in the treatment of ATTRv secondary glaucoma. However, AGV's efficacy seems to be more durable.

Cardiac amyloidosis: A diagnostic challenge.

Cardiac amyloidosis is indeed a condition characterized by the deposition of amyloid proteins in the myocardium, leading to thickening and stiffening of the heart muscle. These abnormal protein deposits can interfere with the heart's normal functioning and may pose diagnostic challenges due to its varied clinical presentation and resemblance to other heart condition. Here, we present a case of 55-year-old female patient of uncontrolled hypertensions for 15 years. About 15 years ago, she presented with chest pain and was diagnosed with cardiomyopathy (CM) characterized by low left ventricle (LV) function of unknown cause. Despite being on antihypertensive treatment, the patient continued to experience chest heaviness with persistent elevate blood pressure. An echocardiogram revealed increased LV septal wall thickness, valvular thickening, and biatrial dilation. Subsequently, cardiac magnetic resonance imaging (CMR) was performed, which revealed left atrium enlargement and asymmetrical myocardial wall thickening, particularly at the septum. White blood axial image revealed thickened inter atrial septum, while late gadolinium enhancement (LGE) magnetic resonance (LGE MR) images showed patchy LGE at the base relative to the apex of the myocardium, highlighting the base-to-apex gradient, subendocardial pattern enhancement at apical lateral wall, and transmural pattern enhancement of the mid anteroseptal and inferoseptal wall. Additionally, a short axis time to invert T1 scout image of left ventricle displayed an abnormal nulling pattern initially in the myocardium, followed by the blood pool, and finally the spleen. These findings collectively led to the diagnosis of cardiac amyloidosis.

Challenges in the approach to a patient with aortic stenosis and cardiac amyloidosis with ATTR mutation associated with negative scintigraphy - A case report.

Introduction: Cardiac amyloidosis (CA) poses significant diagnostic and therapeutic challenges. In this case report, we detail a patient with CA due to a rare transthyretin (CA-TTR) mutation, manifesting with negative myocardial scintigraphy and requiring genetic testing for diagnosis. The patient also had severe aortic stenosis (AS), necessitating discussion with a heart team to determine the optimal treatment strategy. Case report: A 70-year-old male with a family history of sudden death was previously diagnosed with third-degree atrioventricular block and treated with a pacemaker. He presented with worsening exertional dyspnoea, and examination revealed a third heart sound, a systolic murmur indicative of AS and bilateral muscular atrophy in the thenar region. Transthoracic echocardiography indicated severe AS and moderate left ventricular dysfunction, with images suggesting infiltrative disease. Pyrophosphate scintigraphy revealed no abnormal cardiac tracer uptake. Cardiac magnetic resonance imaging (MRI) revealed extensive, heterogeneous, subendocardial late gadolinium enhancement in both the atria and ventricles, which was consistent with CA. Genetic testing identified the Phe84Leu mutation in the TTR gene. Following heart team discussions, the patient underwent successful transcatheter aortic valve implantation (TAVI) and remained asymptomatic in follow-up, being monitored at an outpatient clinic specializing in CA and using tafamidis. Discussion: CA-TTR can be an autosomal dominant disease with variable penetrance involving abnormal amyloid protein deposition in tissues and can often be diagnosed noninvasively via myocardial scintigraphy. However, some TTR mutations do not affect scintigraphy results, necessitating genetic testing when clinical suspicion is high, potentially avoiding endomyocardial biopsy. Moreover, AS occurs in up to 16 % of TTR amyloidosis patients, with the conditions mutually exacerbating each other. Recent consensus suggests that TAVI reduces mortality in patients with severe AS and amyloidosis. Conclusions: Various diagnostic algorithms emphasize the use of myocardial scintigraphy for suspected CA-TTR. Genetic testing is crucial when scintigraphy results are negative, but clinical suspicion remains high, potentially circumventing invasive procedures. Compared with medical management alone, TAVI has been shown to improve quality of life and survival in patients with concurrent severe AS and CA.

Circulating ECM proteins decorin and alpha-L-iduronidase differentiate ATTRwt-CM from ATTRwt-negative HFpEF/HFmrEF.

AIMS: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is an under-recognized aetiology of heart failure (HF), necessitating early detection for timely treatment. Our study aimed to differentiate patients with ATTRwt-CM from ATTRwt-negative HFpEF/HFmrEF patients by identifying and validating circulating protein biomarkers. In addition, we measured the same biomarkers in patients with cardiomyopathy due to light chain amyloidosis (AL)-CM to gain disease-specific insights. METHODS AND RESULTS: In this observational study, serum concentrations of 363 protein biomarkers were measured in a discovery cohort consisting of 73 ATTRwt-CM, 55 AL-CM, and 59 ATTRwt-negative HFpEF/HFmrEF patients, using multiplex proximity extension assays. Sparse partial least squares analyses showed overlapping ATTRwt-CM and AL-CM biomarker profiles with clear visual differentiation from ATTRwt-negative patients. Pathway analyses with g:Profiler revealed significantly up-regulated proteoglycans (PG) and cell adhesion pathways in both ATTRwt-CM and AL-CM. Penalized regression analysis revealed that the proteoglycan decorin (DCN), lysosomal hydrolase alpha-L-iduronidase (IDUA) and glycosyl hydrolase galactosidase ß-1 (GLB-1) most effectively distinguished ATTRwt-CM from ATTRwt-negative patients (R2 = 0.71). In a prospective validation cohort of 35 ATTRwt-CM patients and 25 ATTRwt-negative patients, DCN and IDUA significantly predicted ATTRwt-CM in the initial analysis (DCN: OR 3.3, IDUA: OR 0.4). While DCN remained significant after correcting for echocardiographic parameters, IDUA did not. DCN showed moderate discriminative ability (AUC, 0.74; 95% CI, 0.61-0.87; sensitivity, 0.91; specificity, 0.52) as did IDUA (AUC, 0.78; 95% CI, 0.65-0.91; sensitivity, 0.91; specificity, 0.61). A model combining clinical factors (AUC 0.92) outperformed DCN but not IDUA, a combination of the biomarkers was not significantly better. Neither DCN nor IDUA correlated with established disease markers. CONCLUSION: ATTRwt-CM has a distinctly different biomarker profile compared with HFpEF/HFmrEF, while ATTRwt-CM patients share a similar biomarker profile with AL-CM patients characterized by up-regulation of proteoglycans and cell-adhesion pathways. The biomarkers DCN and IDUA show the potential to serve as an initial screening tool for ATTTRwt-CM. Further research is needed to determine the clinical usefulness of these and other extracellular matrix components in identifying ATTRwt-CM.

The Mayo ATTR-CM score versus other diagnostic scores and cardiac biomarkers in patients with suspected cardiac amyloidosis.

AIMS: Several scores were developed to help the diagnosis of cardiac amyloidosis (CA). The most recent one, being the Mayo transthyretin amyloidosis cardiomyopathy (ATTR-CM) score, was not externally validated. We compared the diagnostic performance of the ATTR-CM score with previous tools (increased wall thickness [IWT] score, AMYLoidosis Index [AMYLI] score, and cardiac biomarkers) in a cohort of patients evaluated for a suspicion of CA. METHODS AND RESULTS: We analysed 362 consecutive patients referred to a third-level centre for suspected CA. Overall, 132 (36%) had transthyretin CA (ATTR-CA), and 91 (25%) immunoglobulin light chain CA (AL-CA); CA was excluded in 139 (38%). ATTR-CM score had a good diagnostic performance to distinguish ATTR-CA from AL-CA or no CA, with an area under the curve (AUC) of 0.795 (95% confidence interval [CI] 0.747-0.842, p < 0.001), and ATTR-CA from no CA (AUC 0.822, 95% CI 0.774-0.871, p < 0.001). Results were consistent in both patients with preserved (AUC 0.787, 95% CI 0.726-0.848, p < 0.001), and reduced or mildly reduced ejection fraction (AUC 0.790, 95% CI 0.709-0.871, p < 0.001). The ATTR-CM score showed a better discrimination compared to IWT and AMYLI score to distinguish ATTR-CA from AL-CA or no CA (p = 0.002), but not to distinguish ATTR-CA from no CA (p = 0.270). Diagnostic accuracy was significantly higher for the ATTR-CM score as compared to the rule-in cut-off of high-sensitivity troponin T. CONCLUSION: The Mayo ATTR-CM score has a good performance in identifying patients with ATTR-CA, with also better discrimination power when compared to other scores and biomarkers.

DPD Quantification Correlates With Extracellular Volume and Disease Severity in Wild-Type Transthyretin Cardiac Amyloidosis.

Background: The pathophysiological hallmark of wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is the deposition of amyloid within the myocardium. Objectives: This study aimed to investigate associations between quantitative cardiac 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake and myocardial amyloid burden, cardiac function, cardiac biomarkers, and clinical status in ATTRwt-CM. Methods: Forty ATTRwt-CM patients underwent quantitative DPD single photon emission computed tomography/computed tomography to determine the standardized uptake value (SUV) retention index, cardiac magnetic resonance imaging to determine extracellular volume (ECV) and cardiac function (RV-LS), and assessment of cardiac biomarkers (N-terminal prohormone of brain natriuretic peptide [NT-proBNP], troponin T) and clinical status (6-minute walk distance [6MWD], National Amyloidosis Centre [NAC] stage). ATTRwt-CM patients were divided into 2 cohorts based on median SUV retention index (low uptake: <5.19 mg/dL, n = 20; high uptake: ≥5.19 mg/dL, n = 20). Linear regression models were used to assess associations of the SUV retention index with variables of interest and the Mann-Whitney U or chi-squared test to compare variables between groups. Results: ATTRwt-CM patients (n = 40) were elderly (78.0 years) and predominantly male (75.0%). Univariable linear regression analyses revealed associations of the SUV retention index with ECV (r = 0.669, ß = 0.139, P < 0.001), native T1 time (r = 0.432, ß = 0.020, P = 0.005), RV-LS (r = 0.445, ß = 0.204, P = 0.004), NT-proBNP (log10) (r = 0.458, ß = 2.842, P = 0.003), troponin T (r = 0.422, ß = 0.048, P = 0.007), 6MWD (r = 0.385, ß = -0.007, P = 0.017), and NAC stage (r = 0.490, ß = 1.785, P = 0.001). Cohort comparison demonstrated differences in ECV (P = 0.001), native T1 time (P = 0.013), RV-LS (P = 0.003), NT-proBNP (P < 0.001), troponin T (P = 0.046), 6MWD (P = 0.002), and NAC stage (I: P < 0.001, II: P = 0.030, III: P = 0.021). Conclusions: In ATTRwt-CM, quantitative cardiac DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage, providing a valuable tool to quantify and monitor cardiac disease burden.

ELISA-4-amyloid: diagnostic accuracy of an ELISA panel for typing the four main types of systemic amyloidosis in subcutaneous abdominal fat tissue samples.

BACKGROUND: Reliable typing of amyloid is essential. Amyloid extraction from tissue enables immunochemical typing of the precursor protein using an enzyme-linked immunosorbent assay (ELISA). OBJECTIVE: To assess the diagnostic accuracy of a panel of ELISAs for typing the four main types (AA, ATTR, AL-kappa and AL-lambda amyloid). METHODS: From 1996 to 2023 subcutaneous abdominal fat tissue aspirates were obtained from 1339 amyloidosis patients and 868 controls. Amyloid was visually graded 0-4+ in Congo red-stained smears. Amyloid extracted from tissue by Guanidine was typed using a panel comprising four ELISAs. RESULTS: All amyloid protein concentrations in extracts correlated with amyloid grade in smears. Typing sensitivity was low (23.3%) in samples with grade 1+/2+ amyloid. Overall typing sensitivity of the panel was 81.6% for all easily visible amyloid (grade 3+/4+): high for AA (98.8%) and ATTR (96.8%) and fair for AL-kappa (66.7%) and AL-lambda (75.9). Overall typing specificity was 98.0% and the overall positive predictive value was 98.0%. CONCLUSIONS: We describe a highly specific ELISA panel for routine typing of the main amyloid types in fat tissue. Until more sensitive typing techniques will become generally available, typing easily visible amyloid in fat tissue using this ELISA panel is reliable, affordable and straightforward.

[99mTc]Tc-hydroxydiphosphonate uptake in soft tissue is associated with amyloid load in subcutaneous abdominal fat tissue and mortality in wild-type transthyretin amyloidosis patients.

PURPOSE: Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality. METHODS: This prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [99mTc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied. RESULTS: ATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality. CONCLUSION: Soft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality.

Connective tissue amyloidosis in patients referred for orthopedic surgery. CONNECT-AMY study. / Amiloidosis del tejido conectivo en pacientes referidos a cirugía ortopédica. Estudio CONNECT-AMY.

INTRODUCTION AND OBJECTIVE: Clinical manifestations secondary to amyloid deposition in connective tissue may allow early detection of amyloidosis. We sought to identify the prevalence of connective tissue amyloidosis in patients undergoing orthopedic surgery and evaluate for cardiac involvement. MATERIAL AND METHODS: Descriptive cross-sectional study that included patients >50 years referred for orthopedic surgery at our center. A sample of the affected connective tissue was taken during the intervention to evaluate the presence of amyloid material. Those with confirmed amyloidosis were further evaluated with complementary tests for cardiac involvement. RESULTS: Forty-eight patients were included. Mean age was 65.4 years and 41.7% were women. The most frequent surgery was supraspinatus tendon rupture (50%). Transthyretin amyloid deposits were detected in 2 patients (4.2%). The absence of variants in the protein gene established the diagnosis of ATTRwt in both cases. None of them presented cardiac involvement. CONCLUSIONS: In this study, 4.2% of patients referred for orthopedic surgery presented transthyretin amyloidosis in the affected connective tissue.

Incremental prognostic utility of congestion markers in cardiac transthyretin amyloidosis.

BACKGROUND/AIMS: Congestion is prognostically relevant in cardiac transthyretin amyloidosis (ATTR-CA), but whether congestion has an incremental prognostic value beyond the well-established, congestion-sensitive NT-proBNP is unknown. Therefore, we aimed to comparatively evaluate the prognostic utility of several congestion surrogates over NT-proBNP. METHODS: We estimated hazard ratios by Cox proportional hazards regressions with time-varying covariates from a panel data set of the local amyloidosis cohort study AmyKoS. Different models were compared by using chi(χ)2-statistics measuring overall model significance. RESULTS/CONCLUSION: 131 ATTR-CA patients (wild-type 84.0%, hereditary 6.9%, without genetic testing 9.2%; median age 78.7 (quartiles 73.3, 82.1) years; 85.5% male) with 566 observations across a median follow-up of 38.2 (30.6; 48.2) months were analyzed. 83.2% received disease-modifying treatment; 20.6% participated concurrently in placebo-controlled gene silencer trials. Information on congestion improved biomarker-driven risk stratification and identified patients at the highest risk. Echocardiographic congestion markers performed better than clinical findings and daily diuretic use/dosage. Relevant adjusters were daily diuretic dosage, disease-modifying treatment, eGFR, and right atrial volume. NT-proBNP and the tricuspid regurgitation peak velocity (tr-vmax) provided an easy-to-use stratification with overall model performance similar to NAC and Mayo staging systems. Further analyses are necessary for validation and to identify the optimal cut points of the congestion markers.

Liver stiffness as a prognostic parameter and tool for risk stratification in advanced cardiac transthyretin amyloidosis.

BACKGROUND: In light of increasing therapeutic options, risk stratification of advanced cardiac transthyretin amyloidosis (ATTR-CA) is gaining clinical importance to avoid ineffective treatments. Liver stiffness as a marker of hypervolemia and hepatic congestion might predict mortality in advanced ATTR-CA and allow to identify patients at highest risk. METHODS: Proven ATTR-CA patients underwent repeated vibration-controlled transient elastography (VTCE) and standardized serial workup within the local amyloidosis cohort study AmyKoS. Spearman correlation analyses and Cox regressions were performed to evaluate the prognostic value. RESULTS: 41 patients with ATTR-CA were included with median age of 76.6 (55.1-89.1) years, of which 90.2% were male and > 92% wild-type ATTR-CA. In total, 85 VCTE examinations were performed. Median follow-up was 43.7 (2.4-75.6) months; 26.8% of the patients died. At the first clinical evaluation, median left ventricular (LV) absolute global longitudinal strain (GLS) was 11.4 (5.2-19.0) % and median liver stiffness was 6.3 (2.4-22.9) kPa, both significantly correlated with mortality. NT-proBNP possessed statistically significant predictive power in ATTR-CA with more preserved LV function (absolute GLS ≥ 10), whereas stiffness seemed to be more discriminative for ATTR-CA with absolute GLS < 10. The use of alternative congestion surrogates such as liver vein dilation and tricuspid regurgitation peak velocity (tr-vmax) showed congruent results. CONCLUSION: Liver stiffness shows prognostic value regarding all-cause mortality and allows risk stratification in advanced ATTR-CA, particularly in those with markedly impaired longitudinal LV function. These results are transferable to other congestion surrogates.

Response to therapy with tafamidis 61 mg in patients with cardiac transthyretin amyloidosis: real-world experience since approval.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease that causes heart failure due to amyloid fibril deposition. Tafamidis was approved as the first causal treatment in 2020. We here report on real-world data in patients treated with tafamidis for at least 12 months according to the recently defined European Society for Cardiology (ESC) consensus criteria for disease progression. METHODS AND RESULTS: Three hundred and eight wildtype and 31 hereditary ATTR-CM patients were prospectively enrolled after first diagnosis of ATTR-CM and initiation of tafamidis 61 mg once daily treatment. After 12 months, significant deterioration in Karnofsky Index, estimated glomerular filtration rate (eGFR), N-terminal brain natriuretic peptide (NT-proBNP), septum thickness and left ventricular ejection fraction (LVEF) could be observed, significant disease progression was only detected in 25 patients (9%) using ESC consensus criteria. Mean survival time was 37 months with no differences between responders and non-responders. NT-proBNP was the only independent predictor for poor therapy response (p = .008). CONCLUSIONS: The majority of patients showed no significant disease progression according to the ESC consensus criteria after 12 months of therapy with tafamidis. However, at 12 months, treatment response based on the ESC consensus criteria was not associated with improved survival. Moreover, higher levels of NT-proBNP at diagnosis of ATTR-CM appears to predict poorer treatment response, confirming that timely initiation of therapy is advantageous.

Impact of Anemia on Mortality and Morbidity in Transthyretin Amyloid Cardiomyopathy.

Anemia is prevalent in transthyretin amyloid cardiomyopathy (ATTR-CM), but its prognostic significance remains uncertain because of conflicting data mainly in patients not receiving disease-modifying therapy. Additionally, the effect of anemia on morbidity in this population has not been studied. This retrospective study included 270 patients diagnosed with ATTR-CM, receiving disease-modifying treatment (tafamidis), of which 30% (n = 80) were anemic (defined as a hemoglobin level <13 g/100 ml for males and <12 g/100 ml for females according to the World Health Organization). At baseline, patients with anemia were on average older (mean age 79 vs 77 years), more likely to be female (21% vs 12%), and exhibited higher symptom severity based on the New York Heart Association class (42% in class III vs 27%) compared with those without anemia. Additionally, they had a worse Columbia score (mean score 3 vs 5) and Columbia stage (12% in late-stage vs 7.1%) than those without anemia. Kaplan-Meier analysis indicates that anemia was associated with a higher likelihood of mortality, all-cause, and cardiovascular (CV) hospitalizations (p <0.05). However, in the Cox regression analysis, after adjusting for baseline age, ATTR genotype, and Columbia score, anemia was only associated with a higher risk of all-cause hospitalizations (hazard ratio 1.9 (1.3 to 2.7), p <0.001) and CV-related hospitalizations (hazard ratio 1.9 (1.2 to 2.9), p = 0.006). In conclusion, this study indicates that anemic patients with ATTR-CM have higher risks of CV and all-cause hospitalizations compared with nonanemic ATTR-CM patients. Further research is needed to understand how treating anemia may improve outcomes in this high-risk patient population.