Search Results (205)

Background/Objectives: Early diagnosis of cardiac amyloidosis is crucial to improve patient outcomes. Although ^99mTc-MDP is less sensitive than other bone-avid tracers for detecting ATTR-CA, it is widely used for routine bone imaging in this region. Incidental cardiac uptake on ^99mTc-MDP bone scintigraphy may therefore offer a practical opportunity for identifying suspected ATTR-CA in resource-limited settings. To evaluate incidental cardiac uptake, warranting further evaluation for ATTR-CA on routine ^99mTc-MDP bone scans as an incidental flag method for patients who require further evaluation and to propose a referral pathway in resource-limited settings. Methods: A retrospective review of 229 patients was performed. The assessment of myocardial uptake was performed using the Perugini visual score and H/CL ratio analysis. Patients’ medical records were reviewed, and available cardiac imaging reports were evaluated for further assessment of cardiac involvement. Results: Nine patients demonstrated a Perugini score = 2; of these, five underwent echocardiography, demonstrating abnormalities that may indicate amyloid involvement. No patient had confirmatory ATTR-CA testing, AL-CA exclusion testing, (CMR), biopsy, or amyloid typing. In patients without prior cardiac disease, echocardiographic abnormalities may potentially represent subclinical disease, such as cardiac amyloidosis, though this requires further confirmation. In patients with HTN or diabetes, the echocardiographic changes may be attributed to the underlying conditions. Echocardiographic characteristics suggestive, but not specific, for cardiac amyloidosis were observed in patients selected based on positive ^99mTc-MDP uptake. Conclusions: Incidental cardiac uptake with a Perugini score ≥ 2 can highlight patients for ATTR-CA investigation. These results provide preliminary evidence that incidental ^99mTc-MDP cardiac uptake can flag patients who require further evaluation for ATTR-CA and support the implementation of a referral pathway from local evaluation to a specialized center. Full article

Background: Amyloidosis is an infiltrative cardiomyopathy caused by amyloid deposition into the myocardium. In recent years, recognition of this treatable cause of heart failure has increased. There are striking sex differences in the diagnosis, clinical course and outcome of the disease. Notably, women have a worse prognosis than men with similar amounts of cardiac involvement. Methods: This review provides an overview of the current state of knowledge regarding the epidemiology, clinical features, diagnosis and treatment of amyloid heart disease. The differences observed between men and women are discussed, and recent advances in the field are highlighted. Results: Compared to men, women are generally older at diagnosis, appear to have less severe cardiac disease at the time of impairment and are more frequently diagnosed late. The less apparent disease manifestations in women may be responsible for the delay in diagnosis. Moreover, women may be underdiagnosed when sex-neutral diagnostic criteria are used. Conclusions: Addressing diagnostic disparities may require the use of sex-specific diagnostic thresholds, as well as a more expansive use of multimodality imaging. Future clinical trials should aim to enroll a greater number of female participants to inform optimal therapeutic approaches and to define the sex-specific disease phenotype for this increasingly treatable disease. Full article

Background: Advances in diagnostic criteria for transthyretin cardiac amyloidosis (ATTR-CM) and expanded insurance coverage for bone scintigraphy have facilitated earlier detection of ATTR-CM. However, whether these changes have translated into improved clinical outcomes among patients receiving disease-modifying therapy remains uncertain, especially in non-high-volume centers. Methods: Consecutive patients with ATTR-CM who started disease-modifying therapy at our institute between May 2019 and March 2025 were retrospectively analyzed. Baseline characteristics and clinical outcomes were compared between the early period (2019–2021) and the late period (2021–2025). Results: A total of 31 patients (median age 77 years, 77% male) were included. Duration of heart failure was significantly shorter and the dose of loop diuretics at baseline was significantly lower in the late period (p < 0.05 for both). The prevalence of National Amyloid Center (NAC) stage I at baseline tended to be higher in the late period (75.0% versus 53.5%, p = 0.273). The cumulative incidence of worsening heart failure hospitalization and all-cause death was significantly lower in the late period (6.3% versus 44.2%, p = 0.024) during a median follow-up of 5 years. NAC stage I at baseline was independently associated with the lower primary outcome with an adjusted hazard ratio of 0.10 (95% confidence interval 0.01–0.90, p = 0.040). Conclusions: Patients with ATTR-CM in the late group experienced more favorable clinical outcomes after disease-modifying therapy, probably due to earlier diagnosis and therapeutic intervention, although further studies are warranted to verify the hypothesis. Full article

Transthyretin amyloidosis (ATTR) is a multisystemic disorder associated with extracellular accumulation of misfolded transthyretin (TTR) protein forming insoluble amyloid deposits. Depending on the TTR genotype, ATTR is classified as hereditary ATTR (ATTRv) with pathogenic gene variants and wild-type ATTR (ATTRwt) with a normal TTR genotype. Two cardinal clinical manifestations of ATTR are amyloid cardiomyopathy and peripheral neuropathy, but multisystemic deposition of amyloid may also manifest with ocular and leptomeningeal amyloidosis, various orthopedic complications (carpal tunnel syndrome, spinal stenosis), nephropathy, and gastrointestinal and pulmonary amyloidosis. The natural history of untreated ATTR is characterized by progressive worsening and 25% of patients may die within 24 months from the onset. The first treatment for ATTR was liver transplantation which slows the disease progression, but its use was limited by the scarcity of available liver allografts and complex post-transplant morbidities associated with immunosuppression and various metabolic disturbances. Recent introduction of TTR stabilizers and gene silencing has significantly changed the outcomes and reduced ATTR-related morbidities and mortality, and early diagnosis remains important for improved outcomes. In our narrative expert review, we are discussing epidemiological and clinical features of ATTR, its pathophysiology and available treatments as rapidly progressive fatal disease is being transformed into a treatable chronic disease. Full article

Background: The care of patients with transthyretin amyloid cardiomyopathy (ATTR-CM) is often fragmented and routine datasets rarely capture real-world clinical trajectories and reasons for diagnosis. We introduce a novel approach, called forensic data acquisition and pathway analysis, to examine the real-world experiences of patients with ATTR-CM in our district general hospital. Methods: We retrospectively evaluated inpatient and outpatient healthcare records for our hospital between 2019 to 2025 as a part of a quality improvement project. Results: We identified 26 cases of confirmed or likely wild-type ATTR-CM and four hereditary cases from two families carrying the S77Y variant and estimate the prevalence of transthyretin cardiac amyloidosis to be 1 per 10,000 patients. Many red flags were present in patients, including carpal tunnel syndrome (63.3%) and lumbar spinal stenosis (26.7%), as well as echocardiographic features of left ventricular hypertrophy (86.7%), left atrial dilatation (76.7%), right ventricular hypertrophy (43.3%), and a dense or speckled myocardial appearance (43.3%). Among patients with wild-type disease, the most frequent trigger for further investigation was the presence of suspicious features on transthoracic echocardiography, accounting for 13 cases. Incidental abnormalities detected on cardiac MRI contributed to another six diagnoses. In two patients, non-invasive imaging did not provide sufficient diagnostic certainty, and myocardial biopsy was required to confirm ATTR-CM. Conclusions: Forensic data acquisition and pathway analysis provides a powerful approach for revealing real-world clinical activity in ATTR-CM, exposing diagnostic patterns and missed opportunities that remain hidden in routine datasets. Full article

Transthyretin (TTR) amyloidosis is a systemic, progressive, and fatal disease. TTR is integral in vitamin A (retinol) transport via its binding to retinol binding protein 4 (RBP4). Current and emerging therapies for TTR amyloid cardiomyopathy (ATTR-CM), including RNAi therapies and potentially CRISPR-based therapies, reduce hepatic transthyretin production and hence decrease serum RBP4, which decreases circulating vitamin A levels. However, despite these reductions in circulating vitamin A, hepatic reserves and alternative delivery mechanisms may prevent clinical manifestations of vitamin A deficiency. Vitamin A functions as a key regulator of immunity, antioxidant function, cell growth and differentiation and vision. This paper aims to serve as a comprehensive review of vitamin A and its metabolites, their transport, and their function in human health and disease. Additionally, we seek to synthesize the relevant outcomes and safety data of TTR silencing therapies and how they relate to circulating vitamin A levels and vitamin A-related clinical outcomes in a manner that is relevant to the cardiac amyloidosis specialist. Full article

Wearable sensors enable continuous recording of electrocardiographic, photoplethysmographic, and inertial signals and have accelerated the development of digital biomarkers in cardiovascular medicine. Transthyretin amyloidosis (ATTR) is a progressive multisystem disease characterized by arrhythmia, conduction disturbances, hemodynamic impairment, autonomic dysfunction, and gait abnormalities, making it theoretically suitable for multimodal wearable monitoring. This review summarizes current knowledge on wearable applications in amyloidosis with ATTR serving as an illustrative case, evaluates the plausibility of extrapolating signal-based biomarkers from related cardiovascular and neurological cohorts, and outlines methodological and implementation challenges. ATTR-specific data remain limited to small observational studies, mainly on long-term rhythm monitoring and supervised functional assessment. More comprehensive findings support the extraction of metrics such as atrial fibrillation burden, activity patterns, gait variability, and heart rate variability. However, ATTR-related structural remodeling and high arrhythmia burden may distort conventional digital biomarkers, necessitating disease-specific preprocessing and prospective validation. Wearable monitoring in ATTR is technically feasible and biologically plausible but remains investigational. Before routine integration into care pathways can be recommended, standardized, phenotype-stratified studies are needed that link wearable-derived characteristics to assessed clinical outcomes. Full article

Background: The clinical significance of circulating serum transthyretin (sTTR) levels in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains incompletely defined, particularly in patients treated with tafamidis in real-world clinical practice. We aimed to evaluate the relationship between sTTR levels, disease severity, longitudinal changes during tafamidis therapy, and clinical outcomes. Methods: We conducted a retrospective, exploratory study based on prospectively collected data, including consecutive patients with ATTR-CM initiating tafamidis therapy at a tertiary referral center. sTTR levels were measured at baseline and after six months. Associations between sTTR, markers of disease severity, functional status, and outcomes were assessed. Cox regression, receiver operating characteristic (ROC) analysis, and Kaplan–Meier survival analysis were performed. Results: A total of 107 patients (mean age 79.6 ± 8.5 years, 84 males) were enrolled and followed for 24 ± 6 months. Tafamidis therapy was associated with a significant increase in sTTR levels at six months (from 24.7 ± 8.8 to 36.9 ± 6.4 mg/dL; p = 0.006). Baseline sTTR levels were inversely correlated with NT-proBNP (ρ = –0.349; p = 0.037) and were significantly lower in non-survivors compared with survivors (14.2 ± 3.1 vs. 23.5 ± 5.2 mg/dL; p < 0.001). Each 1 mg/dL increase in baseline sTTR was associated with a 13% reduction in all-cause mortality risk (HR 0.87, 95% CI 0.83–0.91; p < 0.001). A baseline sTTR cut-off of 20 mg/dL was associated with an increased risk of mortality (AUC 0.85), and patients with sTTR < 20 mg/dL showed significantly reduced survival. Higher on-treatment sTTR levels at six months were associated with better functional capacity (r = 0.52; p = 0.009) and, when >26 mg/dL, with lower observed mortality during follow-up. Conclusions: In a real-world cohort of patients with ATTR-CM treated with tafamidis, serum transthyretin levels were associated with disease severity, functional status, and survival. Baseline and early on-treatment sTTR measurements may represent useful biomarkers for risk stratification and treatment monitoring. Full article

Cardiac amyloidosis is a rare and progressive condition characterized by the extracellular deposition of amyloid fibrils in multiple organs. Wild-type transthyretin amyloidosis (ATTR-wt) is the most common type affecting subjects above 60 years old. Recent and growing evidence suggests a potential link between GM and cardiac amyloidosis. In this scenario, the aim of the present study is to characterize the gut microbiota (GM), related metabolites and inflammatory biomarkers in ATTR-wt patients. In the ATTR patients we identified Prevotella_9 as the core OTUs (Operational Taxonomic Unit) of this group, alongside Prevotella 7, Prevotellaceae_UCG-003 and Prevotellaceae_NK3B31. In addition, there were increased levels of long fatty acids, including tetradecanoic, hexadecanoic and octadecanoic acids, in the ATTR group. The data obtained suggest that ATTR patients have an altered gut microbiota that could be used as a potential biomarker in metabolic and cardiovascular diseases, as well as a potential predictor of adverse prognosis in ATTR patients. In addition, the intestinal dysbiosis in ATTR patients could be associated with low-grade endotoxemia promoting a pro-inflammatory state due to the translocation of bacterial components, such as LPS (lipopolysaccharide), into blood circulation. Full article

Among cardiac storage diseases, amyloidosis has emerged as a common cause of heart failure (HF), particularly in older people: it is diagnosed in up to 13–19% of patients with heart failure and preserved ejection fraction. Current treatments for transthyretin amyloidosis (ATTR) focus on stopping the misfolding of the TTR protein or reducing TTR production and treating the symptoms with cardiac medication, while systemic chemotherapy is the focus for light-chain amyloidosis (AL). New fibril clearance agents and gene therapies are currently in development. In addition to clinical and laboratory observations, multimodal imaging is essential for the monitoring of the effects of treatment on the progression of heart disease, but it is not yet included in established staging systems. This narrative review collects current multimodal imaging parameters that have been evaluated in clinical trials to assess the progression of cardiac amyloidosis and used in phase III intervention studies. These evolving findings are compared with current consensus recommendations to identify gaps in knowledge for specific imaging modalities, particularly cardiac MRI. Ultimately, the goal should be to standardize imaging of disease progression in cardiac amyloidosis so that the therapeutic effects of new pharmacological treatment options can be compared with the current standard of care. Full article

Background: The number of patients with transthyretin amyloid cardiomyopathy (ATTR-CM) has been increasing recently, and the early diagnosis and treatment of it are important. ^99mTc pyrophosphate scintigraphy (^99mTc-PYP) plays a key role in the early diagnosis of ATTR-CM. In patients who underwent ^99mTc-PYP, the early diagnosis of ATTR-CM by echocardiography was evaluated, focusing on left ventricular myocardial form and left ventricular wall thickness. Methods: The present study was conducted on 144 patients who underwent ^99mTc-PYP between February 2020 and March 2024. A comparison was made between the ^99mTc-PYP positive (P) and negative (N) groups, and significant factors were subjected to multivariate analysis. Results: 17 of 144 patients were positive (14.9%), and 15 patients were diagnosed with ATTR-CM by myocardial or skin (fat) biopsy. Other positive patients were also clinically considered to have ATTR-CM based on findings such as poor cardiac function and cerebral hemorrhage. ^99mTc-PYP positive had a significantly larger CTR (60.3% in the P group vs. 53.9% in the N group, p = 0.007) and a larger left atrial diameter (42.8 mm in the P group vs. 40.0 mm in the N group, p = 0.047). On the other hand, the mean LV wall thickness was significantly thicker (15.7 mm in the P group vs. 12.8 mm in the N group, p < 0.001); however the LV end-diastolic diameter was smaller (41.9 mm in the P group vs. 48.4 mm in the P group, p < 0.001). The LV mass was similar in both groups, thus the relative left ventricular wall thickness (RWT), which indicates relative wall thickening, was significantly higher in the P group (0.85 in the P group vs. 0.52 mm in the N group, p < 0.001). The receiver operating characteristic curve of RWT for assessing ^99mTc-PYP positivity had a cut-off value of 0.717 (area under the curve 0.862, 95%CI 0.763–0.961). Conclusions: The evaluation of wall thickness and RWT on echocardiography is important for diagnosing ATTR-CM. Full article

Background: Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure with preserved ejection fraction, resulting from myocardial deposition of misfolded amyloid fibrils derived predominantly from transthyretin (ATTR wild-type [ATTRwt] or variant [ATTRv]) or immunoglobulin light chains (AL). Despite advances in noninvasive imaging and disease-modifying therapies, delayed diagnosis remains common, and clinically actionable molecular biomarkers for early detection, phenotypic discrimination, and therapeutic monitoring are limited. MicroRNAs (miRNAs), small noncoding regulators of post-transcriptional gene expression, have emerged as key modulators of cardiovascular remodeling and systemic amyloid biology. Methods: We performed a comprehensive review of experimental, translational, and clinical studies to evaluate the role of miRNAs in transthyretin and light-chain cardiac amyloidosis, incorporating data from myocardial tissue analyses, circulating miRNA profiling, and mechanistic studies in cellular and animal models. Results: Dysregulated miRNA networks contribute to amyloid-induced cardiac injury by modulating mitochondrial energetics, oxidative stress, inflammation, fibrosis, proteostasis, and neurocardiac signaling. Specific miRNAs, including members of the miR-21, miR-29, and miR-30 families, as well as miR-150-5p and miR-339, have been associated with amyloid burden, adverse myocardial remodeling, plasma cell biology, and disease severity. Distinct circulating and tissue miRNA signatures differentiate transthyretin from light-chain cardiac amyloidosis and correlate with functional status, heart failure biomarkers, and clinical outcomes. Conclusions: MiRNAs represent promising diagnostic and prognostic biomarkers in cardiac amyloidosis and offer mechanistic insights into disease pathogenesis. Integration of miRNA profiling with multimodality imaging and emerging RNA-based therapeutics may enable earlier diagnosis and support precision management of amyloid-related heart failure. Full article

Transthyretin amyloidosis (ATTR) is a progressive disease characterized by systemic deposition of transthyretin-derived amyloid. Although the recent advent of disease-modifying therapies has expanded treatment options, substantial unmet needs remain, such as understanding disease heterogeneity, predicting treatment response, and prognostic stratification. In this review, we highlight the current and emerging roles of omics technologies in both clinical and research settings of ATTR, including genomics and its integration with other modalities. Currently, omics technologies are applied in clinical settings for accurate disease typing. Clinical samples are utilized to identify risk factors beyond specific transthyretin variants via genomics and epigenomics and to discover promising biomarkers via proteomics. Accumulating findings from omics analyses using cell and animal models are also facilitating the elucidation of the complex pathology of ATTR. Nevertheless, the application of omics analysis in ATTR research is still developing. Moving forward, it is expected to play a central role in accumulating datasets, leveraging cutting-edge technologies, utilizing integrated multi-omics, and bridging basic and clinical research. These advancements are expected to further accelerate the implementation of next-generation therapeutic strategies and precision medicine. Full article

Transthyretin amyloidosis (ATTR) is a progressive multisystem disorder characterized by extracellular deposition of misfolded transthyretin fibrils, leading to neurological, cardiac, gastrointestinal, urogenital, sexual, and ophthalmological involvement. While disease-modifying therapies have significantly improved survival and slowed disease progression, a substantial proportion of patients continue to experience a high symptomatic burden that markedly impairs quality of life. Symptomatic manifestations often occur early, may precede the diagnosis, and frequently persist despite etiological treatment. This review provides a comprehensive overview of the symptomatic management of ATTR, with particular emphasis on autonomic dysfunction and its systemic consequences. We discuss current therapeutic strategies for orthostatic hypotension, gastrointestinal dysmotility, nutritional impairment, sexual dysfunction, lower urinary tract dysfunction, and ophthalmological involvement, highlighting both pharmacological and non-pharmacological approaches. Special attention is given to treatment limitations related to cardiac involvement, autonomic failure, and drug tolerability. Despite the clinical relevance of symptom control in ATTR, evidence-based recommendations remain scarce, and no dedicated guidelines currently exist. Most therapeutic approaches are derived from observational studies, expert opinion, and clinical experience. Improved awareness of symptomatic manifestations, early intervention, and a multidisciplinary, individualized approach are essential to optimize patient outcomes. Future research should focus on prospective studies and the development of structured symptomatic treatment algorithms to complement disease-modifying therapies and enhance patient-centered care in ATTR. Full article

Background: Early diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) remains challenging. Although ECG and morphological abnormalities at diagnosis are well-described, their temporal evolution has not been systematically evaluated. This study characterized the prevalence and longitudinal progression of electrical and structural cardiac abnormalities preceding ATTR-CM diagnosis. Methods: We retrospectively analyzed patients with confirmed ATTR-CM evaluated at a specialist amyloidosis center between 2006 and 2023. Diagnosis was established by grade 2–3 myocardial uptake on 99mTc-DPD scintigraphy. Standard 12-lead ECGs and transthoracic echocardiograms were reviewed at diagnosis and at baseline, 3–5 years earlier. Results: Sixty-three patients (79% men; mean age 77 ± 8 years) were studied, including 33 (52%) with hereditary ATTR (ATTRv) and 30 (48%) with wild-type ATTR (ATTRwt). Overall, 95% had a NAC score ≤ 2, consistent with less advanced disease at diagnosis. During the prediagnostic phase, 79% of patients exhibited pathological ECGs. Non-specific ST–T abnormalities (40%), prolonged QTc (38%), left-axis deviation (35%), first-degree AV block (33%) and anterior infarction pattern (33%) were each observed in at least one-third of patients. From baseline to diagnosis, significant prolongation was observed in the PR interval (+26 ms), QRS duration (+11 ms), and QTc interval (+22 ms) (p < 0.001 for all), and a leftward shift observed in the electrical axis (−12.03°, p = 0.011). Low voltage was uncommon at both time points. Although interventricular septal thickness increased significantly (+3.42 mm; p < 0.001), left ventricular ejection fraction and dimensions were relatively stable. Conclusions: In this proof-of-concept study, electrical remodeling precedes functional changes and outperforms low voltages to raise clinical suspicion of ATTR-CM. Full article