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Aims: Despite their potential, sodium–glucose cotransporter 2 inhibitors (SGLT2i) have not been well‐studied in transthyretin amyloid cardiomyopathy (ATTR‐CM) as randomized trials have excluded patients with this morbid disease. We performed a retrospective study assessing the short‐term efficacy and safety of SGLT2i in ATTR‐CM. Methods and results: We screened consecutive patients seen at a tertiary care centre and identified 87 ATTR‐CM patients treated with SGLT2i and 95 untreated control patients. Endpoints included changes in weight, loop diuretic dose, and cardiac/renal biomarkers. The median age of the overall population was 79 (interquartile range [IQR] 11) years. Nearly 90% of patients were male, and 93% were on a transthyretin stabilizer. Control patients demonstrated generally less severe disease at baseline compared to SGLT2i‐treated patients, with lower median Columbia risk score (p < 0.001). Median follow‐up time was 5.6 (IQR 5.2) and 8.4 (IQR 2.1) months in the SGLT2i and control cohorts, respectively. Compared with controls, SGLT2i treatment was associated with significantly greater reductions from baseline in weight, loop diuretic dose, and uric acid during follow‐up (p < 0.001). While no significant between‐group differences were observed on cardiac biomarkers, estimated glomerular filtration rate was significantly reduced versus controls 1 month after SGLT2i initiation (p = 0.002), but no significant differences were observed at later timepoints. Results were similar in a propensity score‐matched analysis (n = 42 per cohort). A total of 10 (11.5%) patients discontinued SGLT2i, most commonly due to genitourinary symptoms. Conclusion: Sodium–glucose cotransporter 2 inhibitors were well tolerated by most patients with ATTR‐CM and appeared to improve volume status and combat diuretic resistance. Randomized studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

The name Amyloid is derived from the word "Oid", which means semi-starch, which is a protein that transforms into the shape or amyloid state when a distortion or a change occurs in its secondary structure as it becomes insoluble, shaped, and assembled as beta folded sheets. The structure of the amyloid protein can be seen by the electronic microscope as a group of non-branched fibers, with unspecified lengths and cross-sections between (7.5--10) nanometers. Also, the distinguished structure (the folded beta sheets) is clearly seen, and this structure is responsible for the unique pigmentation that is shown by the amyloid proteins with the Congo red stain. [ABSTRACT FROM AUTHOR]

Background: Transthyretin (ATTR) amyloidosis is often diagnosed in an advanced stage, when irreversible cardiac damage has occurred. Lumbar spinal stenosis (LSS) may precede cardiac ATTR amyloidosis by many years, offering the opportunity to detect ATTR already at the time of LSS surgery. We prospectively assessed the prevalence of ATTR in the ligamentum flavum by tissue biopsy in patients aged >50 years undergoing surgery for LSS. Methods: Ligamentum flavum thickness was assessed pre-operatively on axial T2 magnetic resonance imaging (MRI) slices. Tissue samples from ligamentum flavum were screened centrally by Congo red staining and immunohistochemistry (IHC). Results: Amyloid in the ligamentum flavum was detected in 74/94 patients (78.7%). IHC revealed ATTR in 61 (64.9%), whereas amyloid subtyping was inconclusive in 13 (13.8%). Mean thickness of ligamentum flavum was significantly higher at all levels in patients with amyloid (p < .05). Patients with amyloid deposits were older (73.1 ± 9.2 vs. 64.6 ± 10.1 years, p = .01). No differences in sex, comorbidities, previous surgery for carpal tunnel syndrome or LSS were observed. Conclusions: Amyloid, mostly of the ATTR subtype, was found in four out of five patients with LSS and is associated with age and ligamentum flavum thickness. Histopathological work-up of ligamentum flavum might inform future decision making. [ABSTRACT FROM AUTHOR]

ObjectivesThis study has been conducted to investigate the non-invasive diagnostic journey of patients with a transthyretin amyloid cardiomyopathy (aTTR-CM) in Turkey, identify the challenges and uncertainties encountered on the path to diagnosis from the perspectives of expert physicians, and develop recommendations that can be applied in such cases.MethodsThis study employed a three-round modified Delphi method and included 10 cardiologists and five nuclear medicine specialists. Two hematologists also shared their expert opinions on the survey results related to hematological tests during a final face-to-face discussion. A consensus was reached when 80% or more of the panel members marked the “agree/strongly agree” or “disagree/strongly disagree” option.ResultsThe panelists unanimously agreed that the aTTR-CM diagnosis could be established through scintigraphy (using either 99mTc-PYP, 99mTc-DPD, or 99mTc-HMPD) in a patient with suspected cardiac amyloidosis (CA) without a further investigation if AL amyloidosis is ruled out (by sFLC, SPIE and UPIE). In addition, scintigraphy imaging performed by SPECT or SPECT-CT should reveal a myocardial uptake of Grade ≥2 with a heart-to-contralateral (H/CL) ratio of ≥1.5. The cardiology panelists recommended using cardiovascular magnetic resonance (CMR) and a detailed echocardiographic scoring as a last resort before considering an endomyocardial biopsy in patients with suspected CA whose scintigraphy results were discordant/inconclusive or negative but still carried a high clinical suspicion of aTTR-CM.ConclusionThe diagnostic approach for aTTR-CM should be customized based on the availability of diagnostic tools/methods in each expert clinic to achieve a timely and definitive diagnosis.

Anuja Roy,1 Andrew Peterson,2 Nick Marchant,1 Jose Alvir,3 Rahul Bhambri,4 Jason Lynn,4 Darrin Benjumea,5 Sapna Prasad,6 Alex O’Brien,6 Yong Chen,7 Jason Kemner,8 Bhash Parasuraman8 1Global HEOR, Patient & Health Impact, Rare Diseases BU, Pfizer Inc, New York, NY, USA; 2Department of Pharmacy Practice/Pharmacy Administration, University of the Sciences, Philadelphia, PA, USA; 3Statistical Research and Data Science Center Global Product Development, Pfizer Inc, New York, NY, USA; 4Medical Affairs, Pfizer Inc, New York, NY, USA; 5Evidence Strategy, Genesis Research, Hoboken, NJ, USA; 6Clarify Insights Services, Clarify Health Solutions, New York, NY, USA; 7Rare Disease, Pfizer Inc, Collegeville, PA, USA; 8Patient & Health Impact, Pfizer Inc, Collegeville, PA, USACorrespondence: Anuja Roy, Global HEOR, Patient & Health Impact, Rare Diseases BU, Pfizer Inc, New York, NY, USA, Email Anuja.Roy@pfizer.comIntroduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a serious, underrecognized condition, which leads to heart failure and early mortality if left untreated. Until recently, heart transplantation was the only treatment for ATTR-CM. Regulatory approval of tafamidis transformed treatment for patients. In the phase 3 Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT), which established the safety and efficacy of tafamidis, medication adherence was high with 97.2% of patients taking ≥ 80% of scheduled doses. Evidence of real-world adherence to cardiology drugs demonstrates low adherence and suboptimal outcomes; however, real-world adherence to tafamidis has not been investigated. The main objective of this study was to describe adherence patterns of patients filling tafamidis in the Symphony Health database.Methods: This retrospective analysis of the Symphony Health Solutions claims database used secondary adherence measures, including modified medication possession ratio (MPRm), days between fills adherence rate, and compliance rate, to assess adherence patterns of 2020 patients filling tafamidis free acid 61-mg capsules or tafamidis meglumine 4x20-mg capsules from June 1, 2019 to August 31, 2020.Results: Patients receiving a tafamidis formulation had characteristics consistent with the expected patient population; 71.6% were aged 75– 84 years, 83.2% were male, and the highest proportion resided in the Northeast region (30.5%) of the United States. Adherence for tafamidis was high, as 75% to 100% of the patients across subgroups met or exceeded the commonly defined adherence threshold of 80%. Median number of refills ordered and received was six refills per patient. Most patients received refills with no gap (n=1633) or a gap < 30 days (n=1267/1317 patients). Adherence was high across follow-up time, sex, and age subgroups. Adherence varied by geographic region, with the Northeast being significantly higher than the Midwest (mean MPRm 94.41% vs 88.21%, p=0.0007).Conclusion: These results provide evidence that real-world adherence to tafamidis in patients with ATTR-CM is high.Keywords: claims analysis, amyloidosis, cardiomyopathy, transthyretin amyloid, adherence

Despite the rapid expansion of noninvasive (nonbiopsy) diagnosis, contemporary patients with cardiac amyloidosis too often present with advanced features of disease, such as diminished quality of life, elevated natriuretic peptides, and advanced heart failure. Therapeutics for transthyretin cardiomyopathy (ATTR-CM) are most effective when administered before significant symptoms of cardiac dysfunction manifest, making early identification of affected individuals of paramount importance. Community engagement and ensuring that a broad range of clinicians have working knowledge of how to screen for ATTR-CM in everyday practice will be an important step in moving disease identification further upstream. However, reliance on the appropriate and timely diagnosis by individual clinicians may continue to underperform. This review highlights how targeted screening of special populations may facilitate earlier diagnosis. Systems of care that operationalize screening of high-risk subpopulations and prospective validation of novel approaches to ATTR-CM identification are needed. [ABSTRACT FROM AUTHOR]

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure. Given the expansion of noninvasive diagnosis with 99mTc-pyrophosphate (99mTc-PYP) scanning, and clinical use of the transthyretin stabilizer, tafamidis, we sought to examine the interplay of planar imaging heart-to-contralateral lung (H/CL) ratio, cardiac biomarkers, and survival probability in a contemporary cohort of patients referred for noninvasive evaluation of ATTR-CM.Methods: This single-center retrospective cohort study included 351 consecutive patients who underwent a standardized imaging protocol with 99mTc-PYP scanning for the evaluation of ATTR-CM from January 1, 2018, to January 1, 2020. After the exclusion of light chain amyloidosis, patients were characterized as scan consistent with ATTR (+ATTR-CM) or scan not consistent with ATTR (-ATTR-CM) using current guidelines. Linear regression was used to examine the relationship between biomarkers and H/CL and univariate Cox proportional hazards models were used to assess the probability of transplant-free survival.Results: We included 318 patients in the analysis (n = 86 patients +ATTR-CM; n = 232 patients -ATTR-CM). The median follow-up time was 20.1 months. During the study period, 67% of +ATTR-CM patients received tafamidis (median treatment duration, 17 months). The median H/CL ratio was 1.58 (interquartile range, 1.40-1.75). An H/CL ratio of more than 1.6 or less than 1.6 did not seem to have an impact on survival probability in +ATTR-CM patients (P = .30; hazard ratio, 0.65; 95% confidence interval, 0.31-1.41). Cardiac biomarkers were poorly correlated with H/CL (troponin T, R2 = 0.024; N-terminal pro-B-type natriuretic peptide, R2 =0.023). The Gillmore staging system predicted survival probability in +ATTR-CM as well as in the entire cohort referred for scanning. There was a trend toward longer survival among those who were -ATTR-CM compared with +ATTR-CM (P = .051; hazard ratio, 0.64; 95% confidence interval, 0.40-1.00).Conclusions: At a large referral center, the intensity of 99mTc-PYP uptake (H/CL ratio) has neither correlation with cardiac biomarker concentrations nor prognostic usefulness in an analysis of intermediate term outcomes in the early therapeutics era. The H/CL ratio has diagnostic value, but offers little prognostic value in patients with ATTR-CM. Established staging schema were predictive of survival in this contemporary cohort, re-emphasizing the importance of cardiac biomarkers and renal function in assessing disease severity and prognosis. [ABSTRACT FROM AUTHOR]

Amyloidosis refers to a group of conditions where abnormal protein—or amyloid—deposits in tissues or organs, often leading to organ malfunction. Amyloidosis affects nearly any organ system, but especially the heart, kidneys, liver, peripheral nervous system, and gastrointestinal tract. Neuromuscular deficits comprise some of its ubiquitous manifestations. Amyloidosis can be quite challenging to diagnose given its clinical heterogeneity and multi-system nature. Early diagnosis with accurate genetic and serologic subtyping is key for effective management and prevention of organ decline. In this review, we highlight the value of a multidisciplinary comprehensive amyloidosis clinic. While such a model exists at numerous clinical and research centers across the globe, the lack of more widespread adoption of such a model remains a major hindrance to the timely diagnosis of amyloidosis. Such a multidisciplinary care model allows for the timely and effective diagnosis of amyloidosis, be it acquired amyloid light amyloidosis (AL), hereditary transthyretin amyloidosis (hATTR), or wild type amyloidosis (TTR-wt), especially in the current era of personalized genomic medicine. A multidisciplinary clinic optimizes the delivery of singular or combinatorial drug therapies, depending on amyloid type, fibril deposition location, and disease progression. Such an arrangement also helps advance research in the field. We present our experience at The Ohio State University, as one example out of many, to highlight the centrality of a multi-disciplinary clinic in amyloidosis care.

Abstract Transthyretin amyloid cardiomyopathy (ATTR-CM) continues to be an easily overlooked, life-threatening, yet treatable cause of heart failure. Furthermore, its elusive diagnosis leads to late or misdiagnosis. As therapeutic advancements such as tafamidis usher in a promising new era in the management of ATTR-CM, the need for disease awareness and efficient diagnostic evaluation is crucial. With newer inexpensive imaging modalities and techniques, such as longitudinal strain imaging, T1 mapping on cardiac magnetic resonance imaging, and cardiac scintigraphy, the diagnosis of ATTR-CM no longer requires invasive evaluation with tissue biopsy. Here, the authors review current diagnostic tools to help clinicians diagnose ATTR-CM.

Cardiac amyloidosis arises when there is a deposition of abnormal proteins, called amyloids, in the myocardium. It can manifest as overt heart failure, conduction abnormalities, atrial and ventricular arrhythmia, cardiomyopathy, and aortic stenosis. Two main types of proteins identified in cardiac amyloidosis are light-chain amyloid and transthyretin amyloid. Cardiac amyloidosis, although common, is an underdiagnosed cause of heart failure in many cases. A high index of suspicion is needed to make a diagnosis, given that symptoms are not specific. Early diagnosis and treatment of cardiac amyloidosis are associated with reduced morbidity and improved survival. We present a case of a 73-year-old African American male with decompensated heart failure with reduced ejection fraction intolerant to guideline-directed medical therapy who was later found to have cardiac amyloidosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Cape Fear Valley Health Institutional Review Board issued approval 0115-24. Your case report and abstract have been reviewed and acknowledged by the research director of legal services. You may submit your abstract for publication or presentation. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ene et al.)

Cardiac amyloidosis is an infiltrative disease characterized by the extracellular deposition of misfolded protein in the myocardium, leading to increased stiffness and an eventual restrictive cardiomyopathy. The slow onset of symptoms and overlap with other cardiomyopathies make prompt diagnosis a challenge. Clinicians should be alerted and include amyloidosis in their differential diagnosis, particularly in patients with heart failure with preserved ejection fraction, unexplained left ventricle hypertrophy, particularly in those shown intolerance to previous antihypertensive medication, and early orthopedic manifestations of the disease such as carpal tunnel syndrome and spinal stenosis. The workup requires the exclusion of monoclonal gammopathies and technetium-99m pyrophosphate nuclear scintigraphy ( 99m Tc-PYP) studies with single-photon emission computerized tomography (SPECT) imaging. Several therapies are now available and can prolong life with significantly improved quality of life, particularly when the diagnosis of amyloidosis is made early. We present the case of a 77-year-old with a delayed diagnosis by five years to highlight the need for heightened clinical suspicion and an appropriate diagnostic algorithm for cardiac amyloidosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Stehlik et al.)

Transthyretin amyloid cardiomyopathy (ATTR-CM) continues to be an easily overlooked, life-threatening, yet treatable cause of heart failure. Furthermore, its elusive diagnosis leads to late or misdiagnosis. As therapeutic advancements such as tafamidis usher in a promising new era in the management of ATTR-CM, the need for disease awareness and efficient diagnostic evaluation is crucial. With newer inexpensive imaging modalities and techniques, such as longitudinal strain imaging, T1 mapping on cardiac magnetic resonance imaging, and cardiac scintigraphy, the diagnosis of ATTR-CM no longer requires invasive evaluation with tissue biopsy. Here, the authors review current diagnostic tools to help clinicians diagnose ATTR-CM. [ABSTRACT FROM AUTHOR]

Objectives: This study has been conducted to investigate the non-invasive diagnostic journey of patients with a transthyretin amyloid cardiomyopathy (aTTR-CM) in Turkey, identify the challenges and uncertainties encountered on the path to diagnosis from the perspectives of expert physicians, and develop recommendations that can be applied in such cases., Methods: This study employed a three-round modified Delphi method and included 10 cardiologists and five nuclear medicine specialists. Two hematologists also shared their expert opinions on the survey results related to hematological tests during a final face-to-face discussion. A consensus was reached when 80% or more of the panel members marked the "agree/strongly agree" or "disagree/strongly disagree" option., Results: The panelists unanimously agreed that the aTTR-CM diagnosis could be established through scintigraphy (using either 99mTc-PYP, 99mTc-DPD, or 99mTc-HMPD) in a patient with suspected cardiac amyloidosis (CA) without a further investigation if AL amyloidosis is ruled out (by sFLC, SPIE and UPIE). In addition, scintigraphy imaging performed by SPECT or SPECT-CT should reveal a myocardial uptake of Grade ≥2 with a heart-to-contralateral (H/CL) ratio of ≥1.5. The cardiology panelists recommended using cardiovascular magnetic resonance (CMR) and a detailed echocardiographic scoring as a last resort before considering an endomyocardial biopsy in patients with suspected CA whose scintigraphy results were discordant/inconclusive or negative but still carried a high clinical suspicion of aTTR-CM., Conclusion: The diagnostic approach for aTTR-CM should be customized based on the availability of diagnostic tools/methods in each expert clinic to achieve a timely and definitive diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Çavuşoğlu, Başarıcı, Tüfekçioğlu, Özpelit, Özdemir, Sivrikoz, Altay, Değertekin, Dinçer, İkitimur, Kahveci, Bozkurt, Erkılıç, Kaya, Beksaç, Salihoğlu and Tokgözoğlu.)

Transthyretin-related (ATTR) cardiac amyloidosis is currently lacking a disease-modifying therapy. Despite demonstration of effectiveness in halting amyloid deposition, no study focused on epigallocatechin-3-gallate (EGCG) impact on patient survival. We sought to explore prognostic impact of EGCG in a cohort of lone cardiac ATTR patients. From the Florence Tuscan Regional Amyloid Centre database, we retrospectively selected ATTR patients treated with EGCG (675mg daily dose) for a minimum of 9 months, between March 2013 and December 2016. As a control group, we selected ATTR patients who received guideline-directed medical therapy alone. End point of the study was time to all cause death or cardiac transplantation. Sixty-five patients (30 treatment groups vs. 35 control groups) had a median follow-up of 691 days. There were no differences in baseline characteristics between groups. Five deaths occurred in EGCG group versus eight in control group; one patient underwent effective cardiac transplantation in EGCG group. There was no difference in survival estimates between EGCG and control group (60 ± 15% vs. 61 ± 12%, p = 0.276). EGCG was well tolerated, without major safety concerns. In a real-world cohort of ATTR patients with lone cardiac involvement, EGCG was a safe therapeutic option, but was not associated with survival improvement. [ABSTRACT FROM AUTHOR]

Amyloidosis is an infiltrative disease characterized by deposition of amyloid fibrils within the extracellular tissue of one or multiple organs. Involvement of the heart, cardiac amyloidosis, is recognized as a common cause of restrictive cardiomyopathy and heart failure. The two major types of cardiac amyloidosis are cardiac amyloid light-chain (AL) and transthyretin-related cardiac amyloidosis (ATTR, mutant and wild types) (Nat Rev Cardiol 2010;7:398-408). While early recognition of cardiac amyloidosis is of major clinical importance, so is the ability to differentiate between subtypes. Indeed, both prognosis and therapeutic options vary drastically depending on the subtype. While endomyocardial biopsy with immunostaining is considered the gold standard, advances in imaging provide an attractive non-invasive alternative. Currently, electrocardiography, echocardiography, and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy. Yet, none of these modalities can effectively differentiate the cardiac amyloid subtypes. Recent data with Tc-phosphate derivatives, previously used as bone seeking radioactive tracers, have shown promising results; these radiotracers selectively bind ATTR, but not AL subtype, and can differentiate subtypes with high diagnostic accuracy. This review will initially present the non-radionuclide imaging techniques and then focus on the radionuclide imaging techniques, particularly Tc-DPD and Tc-PYP, mechanism of action, performance and interpretation of the study, diagnostic accuracy, prognostic value, future clinical perspective, and outlook. [ABSTRACT FROM AUTHOR]

Amyloidosis refers to a group of conditions where abnormal protein-or amyloid-deposits in tissues or organs, often leading to organ malfunction. Amyloidosis affects nearly any organ system, but especially the heart, kidneys, liver, peripheral nervous system, and gastrointestinal tract. Neuromuscular deficits comprise some of its ubiquitous manifestations. Amyloidosis can be quite challenging to diagnose given its clinical heterogeneity and multi-system nature. Early diagnosis with accurate genetic and serologic subtyping is key for effective management and prevention of organ decline. In this review, we highlight the value of a multidisciplinary comprehensive amyloidosis clinic. While such a model exists at numerous clinical and research centers across the globe, the lack of more widespread adoption of such a model remains a major hindrance to the timely diagnosis of amyloidosis. Such a multidisciplinary care model allows for the timely and effective diagnosis of amyloidosis, be it acquired amyloid light amyloidosis (AL), hereditary transthyretin amyloidosis (hATTR), or wild type amyloidosis (TTR-wt), especially in the current era of personalized genomic medicine. A multidisciplinary clinic optimizes the delivery of singular or combinatorial drug therapies, depending on amyloid type, fibril deposition location, and disease progression. Such an arrangement also helps advance research in the field. We present our experience at The Ohio State University, as one example out of many, to highlight the centrality of a multi-disciplinary clinic in amyloidosis care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bumma, Kahwash, Parikh, Isfort, Freimer, Vallakati, Redder, Campbell, Sharma, Efebera and Stino.)

We report the fourth case of transthyretin amyloidosis (ATTR) Ser23Asn in a 41-year-old Ecuadorian male. He has a pedigree that spans seven generations and involves 24 family members who suffered early cardiac death. Salient presenting symptoms were fatigue, shortness of breath, and peripheral neuropathy. The diagnosis of cardiac amyloid was confirmed by immunohistochemical staining of an endomyocardial biopsy, genotyping and by technetium pyrophosphate (99mTc-PYP) scintigraphy, which remains to be established as a reliable tool to visualize myocardial amyloid involvement in patients with the Ser23Asn transthyretin (TTR) variant. The patient underwent successful combined heart and liver transplant. We add to the current ATTR literature that in patients with the rare Ser23Asn mutation, peripheral nerve in addition to cardiac involvement can occur and 99mTc-PYP scintigraphy can be used as an imaging modality to visualize myocardial amyloid. [ABSTRACT FROM AUTHOR]

Background: We present a patient with late-onset progressive polyneuropathy and a Congo-red positive staining of sural nerve biopsy, where routine immunohistochemical analysis failed to determine the type of amyloid deposited. Since precise determination of the amyloid type has crucial therapeutic implications, we employed our new biochemical micro-techniques, together with molecular biology methods, to characterize the amyloid protein deposited. Methods: We used a micro-method for extraction of amyloid proteins, amyloid typing by Western blotting, DNA sequencing, and restriction enzyme site analysis. Results: Our new micro-technique for biochemical analysis of fat aspirate demonstrated transthyretin (TTR) amyloid (ATTR) deposition in the patient's tissue. Sequence analysis of the TTR-encoding DNA identified a single mutation, causing a valine to alanine substitution (V32A). Conclusions: Although there are approximately 100 known TTR variants associated with peripheral neuropathy, in Israel only one patient with familial amyloid polyneuropathy (FAP), a patient of Ashkenazi origin with ATTR due to an F33I mutation, has been reported so far. Our study identified a second case of ATTR in the Israeli population, this time in a patient of Iranian-Jewish extraction. The study also emphasizes the importance of our new biochemical micro-techniques in elucidating the type of amyloid protein. Clin Chem Lab Med 2007;45:625–8. [ABSTRACT FROM AUTHOR]

Background: Advanced interatrial block (aIAB), which is associated with incident atrial fibrillation and stroke, occurs in the setting of blocked interatrial conduction. Atrial amyloid deposition could be a possible substrate for reduced interatrial conduction, but the prevalence of aIAB in patients with transthyretin cardiac amyloidosis (ATTR-CA) is unknown. We aimed to describe the prevalence of aIAB and its relationship to left atrial function in patients with ATTR-CA in comparison to patients with HF and left ventricular hypertrophy but no CA., Methods: The presence of aIAB was investigated among 75 patients (49 patients with ATTR-CA and 26 with HF but no CA). A comprehensive echocardiographic investigation was performed in all patients, including left atrial strain and strain rate measurements., Results: Among patients with ATTR-CA, 27% had aIAB and in patients with HF but no CA, this figure was 21%, ( p = 0.78). The presence of aIAB was associated with a low strain rate during atrial contraction (<0.91 s -1 ) (OR: 5.2 (1.4-19.9)), even after adjusting for age and LAVi (OR: 4.5 (1.0-19.19))., Conclusions: Advanced interatrial block is common among patients with ATTR-CA, as well as in patients with heart failure and left ventricular hypertrophy but no CA. aIAB is associated with reduced left atrial contractile function.

We report a 57-year-old man with pathognomonic bilateral vitreo-lenticular amyloid opacities (pseudopodia lentis) in whom a novel transthyretin (TTR) mutation was identified. The patient presented due to bilateral floaters. The vitreous cavities of both eyes showed course, fibrilar opacities attached to the posterior lens surface with pseudopodia. There was a history of bilateral carpal tunnel syndrome. Nerve conduction studies showed upper and lower limb axonal polyneuropathy. Magnetic resonance imaging of the brain and spinal cord, renal and cardiac function were normal. Vitreous and conjunctival biopsies confirmed the diagnosis of TTR-related amyloidosis. Genetic analysis of exon 2 of the TTR gene revealed that the patient was heterozygous for a single nucleotide substitution c.160 A>G, resulting in replacement of arginine with glycine at position 34 of the mature protein (Arg34Gly). Five years later the patient developed increasing sensory and motor neuropathy of both lower limbs, and neovascular glaucoma in one eye. We hypothesize that the reason for his neovascular glaucoma was retinal ischaemia secondary to amyloid retinal vasculopathy. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to determine the incidence and prevalence of atrial fibrillation (AF) in transthyretin cardiac amyloidosis (ATTR-CA); to study the factors associated with the development of AF in this population; to study the prognostic implications of AF and maintenance of normal sinus rhythm (NSR) in patients with ATTR-CA; and to determine the impact of ATTR-CA stage on AF prevalence, outcomes, and efficacy of rhythm control strategies., Background: AF is common in patients with ATTR-CA. The aim of this study was to determine the predictors, prevalence, and outcomes of AF in patients with ATTR-CA in addition to the efficacy of rhythm control strategies., Methods: This was a retrospective cohort study of 382 patients with ATTR-CA diagnosed at our institution between January 2004 and January 2018. Means testing, and univariable and multivariable models were used., Results: AF occurred in 265 (69%) patients. Factors associated with the development of AF included older age, advanced ATTR-CA stage, and higher left atrial volume index. Antiarrhythmic therapy (AAT) was used in 35% of patients with AF; cardioversion was performed in 45%, and 5% underwent AF ablation. Rhythm control strategies were substantially more effective when performed earlier in the disease course. During a mean follow-up of 35 months, no difference in mortality between patients with AF and those without AF was observed (65% vs. 49%; p = 0.76). On Cox proportional hazards analyses, maintenance of normal sinus rhythm and tafamidis use were associated with improved survival, whereas advanced ATTR-CA stage and higher New York Heart Association functional class were associated with increased mortality., Conclusions: With advancing ATTR-CA stage, AF became more prevalent, occurring in 69% of our entire study cohort. Rhythm control strategies including AAT, direct-current cardioversion, and AF ablation were substantially more effective when performed earlier during the disease course., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiac amyloidosis (CA) is an infiltrative disease characterized by the extracellular deposition of fibrils, amyloid, in the heart. The vast majority of patients with CA has one of two types between transthyretin amyloid (ATTR) and immunoglobulin light chain associated amyloid (AL), that have different prognosis and therapeutic options. CA is often underdiagnosed. The histological analysis of endomyocardial tissue is the gold standard for the diagnosis, although it has its limitations due to its invasive nature. Nuclear medicine now plays a key role in the early and accurate diagnosis of this disease, and in the ability to distinguish between the two forms. Recent several studies support the potential advantage of bone-seeking radionuclides as a screening technique for the most common types of amyloidosis, in particular ATTR form. This review presents noninvasive modalities to diagnose CA and focuses on the radionuclide imaging techniques (bone-seeking agents scintigraphy, cardiac sympathetic innervation and positron emission tomography studies) available to visualize myocardial amyloid involvement. Furthermore, we report the case of an 83-year old male with a history of prostate cancer, carcinoma of the cecum and kidney cancer, submitted to bone scan to detect bone metastasis, that revealed a myocardial uptake of 99mTC-HMPD suggestive of ATTR CA. An accurate and early diagnosis of CA able to distinguish beyween AL and ATTR CA combined to the improving therapies could improve the survival of patients with this disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening, progressive, infiltrative disease caused by the deposition of transthyretin amyloid fibrils in the heart, and can often be overlooked as a common cause of heart failure. Delayed diagnosis due to lack of disease awareness and misdiagnosis results in a poorer prognosis. Early accurate diagnosis is therefore key to improving patient outcomes, particularly in the context of both the recent approval of tafamidis in some countries (including the United States) for the treatment of ATTR-CM, and of other promising therapies under development. With the availability of scintigraphy as an inexpensive, noninvasive diagnostic tool, the rationale to screen for ATTR-CM in high-risk populations of patients is increasingly warranted. Here the authors propose a framework of clinical scenarios in which screening for ATTR-CM is recommended, as well as diagnostic "red flags" that can assist in its diagnosis among the wider population of patients with heart failure., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)