Search Results (161)

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

Cardiomyopathies are traditionally classified by structural and genetic phenotypes, but emerging evidence highlights chronic myocardial inflammation as a pivotal driver of disease progression across different etiologies. This review synthesizes the current literature on the cellular and molecular inflammatory mechanisms underlying hypertrophic cardiomyopathy, Anderson–Fabry disease, cardiac amyloidosis, arrhythmogenic cardiomyopathy, and dilated cardiomyopathy. Across these distinct conditions, endogenous triggers such as metabolic substrates, misfolded amyloid fibrils, mechanical stress, or viral genomes act as damage-associated molecular patterns. These stimuli activate innate and adaptive immune cascades, notably the Toll-like receptors, the NF-κB pathway, and the NLRP3 inflammasome. This immune activation establishes a pro-inflammatory microenvironment that promotes fibroblast reprogramming, myocardial edema, and progressive fibrotic or fibro-fatty remodeling. Inflammation is an active, core pathophysiological mechanism rather than a passive secondary bystander in cardiomyopathies. Recognizing these shared immune pathways provides a framework for improved risk stratification and highlights the potential for targeted immunomodulatory therapies to alter disease trajectories. 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

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

Cardiac positron emission tomography (PET) has undergone substantial development in recent years, moving beyond conventional perfusion imaging toward a multiparametric and increasingly quantitative assessment of cardiovascular disease. This article provides a critical narrative overview of the recent cardiac PET literature, with particular emphasis on studies published over the last five years, and discusses both established tracers and emerging radiopharmaceuticals in contemporary cardiology. Among established applications, 18F-FDG remains relevant for myocardial viability assessment and selected inflammatory indications, although its prognostic and therapeutic implications are less uniform than earlier narratives suggested. For myocardial perfusion imaging, 13N-ammonia and 82Rb PET provide robust assessment of myocardial blood flow and myocardial flow reserve, but their clinical interpretation remains strongly influenced by acquisition protocols, software reproducibility, and methodological standardization. The review also addresses newer tracers, including 68Ga-FAPI for fibroblast activation, 18F-flurpiridaz for high-performance perfusion imaging, 18F-FDOPA for cardiac sympathetic dysfunction, and amyloid-binding PET radiopharmaceuticals for cardiac amyloidosis. Overall, recent evidence supports cardiac PET as a powerful platform for physiologic and molecular imaging, but not as a uniform or methodologically neutral technology. Its current value lies in selective, question-driven clinical use, whereas broader implementation will depend on tracer-specific validation, harmonized quantitative workflows, and clear demonstration of incremental benefit over existing imaging strategies. Full article

Disease-specific alpha-synuclein (αsyn) strains have been linked to different synucleinopathies. Current αsyn biomarkers are limited to binary detection of pathogenic αsyn in peripheral tissue biopsies or fluids, limiting differential diagnosis. Hence, there is an urgent need for methods that allow strain-specific detection and characterization of αsyn strain architecture. Notably, luminescent conjugated oligothiophenes (LCOs) have been successfully used to detect distinct protein strain conformers in prion diseases and Alzheimer’s disease, highlighting their utility in differentiating disease-specific amyloid structures. Species-dependent differences in αsyn structure are increasingly recognized as one of the critical aspects that shape how fibrils form, propagate and interact with molecular LCO probes. Here, we evaluate the potential of the LCO h-FTAA to differentiate species-specific αsyn strains and conduct a translational investigation using peripheral cardiac tissue of a gut-first synucleinopathy rodent model. Our in vitro data demonstrate strain-specific probe–fibril interactions, reflecting a differential strain architecture and cellular micro-environment. While h-FTAA binds with comparable efficiency to mouse (mo-) and human (hu-) pre-formed fibrils (PFFs), h-FTAA exhibits markedly lower quantum yield when bound to moPFFs versus huPFFs. Spectral imaging revealed h-FTAA-moPFF binding produces blue-shifted maxima (505–550 nm), contrasting with the red-shifted maxima (545–580 nm) of huPFFs. Fluorescence lifetime imaging microscopy confirmed h-FTAA’s intrinsic sensitivity to species-dependent variations through distinct temporal fluorescence signatures (moPFFs: ~0.60–1.5 ns vs. huPFFs: ~0.65–1.0 ns). Our translational investigation showed h-FTAA binding to peripheral cardiac pathology exhibits comparable red-shifted emission, but distinct fluorescence lifetimes of h-FTAA-bound aggregates in moPFF-injected (~1.0–1.4 ns) versus huPFF-injected (~0.69–0.8 ns) rats. Interestingly, we observed distinct blue-shifted emission profiles in a few selected regions of the heart of moPFF-injected rodents, further characterized by extra-long fluorescence decay shifts (~1.5–1.9 ns), reflecting differences in both aggregate conformation and maturity in moPFF-induced compared with huPFF-induced rats. Taken together, our findings underscore the potential of LCO ligands, like h-FTAA, to enable more precise disease staging and diagnosis through peripheral biopsies, complementing existing αsyn biomarker methods. 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

Cardiac amyloidosis (CA) remains underrecognized due to overlapping features with other cardiovascular conditions, including hypertrophic cardiomyopathy and hypertensive heart disease. Certain ‘red flag’ features across the clinical and imaging spectrum help identify CA. However, these features are often absent, subtle, or inconsistently recognized, particularly in early disease, and are atypical phenotypes. This leads to frequent delays in diagnosis and presentation at advanced stages. Artificial intelligence (AI) offers a promising approach to detect subtle disease signatures by integrating multimodal and longitudinal data beyond human pattern recognition. AI-enhanced electrocardiography has emerged as a scalable screening tool, demonstrating high diagnostic performance and enabling earlier detection. In parallel, echocardiographic AI has evolved toward video-based analysis, improving standardization and reducing inter-reader variability. Similarly, AI applications in cardiac magnetic resonance and nuclear scintigraphy allow for automated quantification and more reproducible assessment of amyloid burden. Beyond diagnosis, emerging models support disease phenotyping, risk stratification, and treatment monitoring. This review synthesizes current applications of AI across multimodal testing in the evaluation and diagnosis of CA. Full article

Cellular protein quality control comprises the ubiquitin proteasome system, autophagy, and molecular chaperones, which maintain proteostasis in healthy tissues. The failure of these cellular and molecular pathways, which normally safeguard the proteome, can cause and even exacerbate amyloidoses, the abnormal accumulation of proteins into amyloid fibrils that drive neurodegeneration. Amyloidoses can also damage peripheral organs; examples include light chain amyloidosis, cardiac amyloidosis, and renal amyloidosis. Restoring proteostasis and preventing protein aggregation is therefore an active area of research, with several promising strategies under investigation. Among these approaches, small-molecule modulators that restore proteostasis are attractive candidates because they may simultaneously rescue multiple quality control mechanisms and remodel aggregates to improve their accessibility to endogenous degradation pathways. Here, we propose that amyloid pathology disrupts multiple proteostasis pathways simultaneously, creating a feedforward cascade in which the breakdown of interconnected proteostasis networks drives progressive protein aggregation, which in turn propels proteostasis collapse. Pharmacological interventions targeting protein aggregation offer opportunity to rescue interconnected proteostasis networks, which could, in turn, cooperatively manage or eliminate pathogenic amyloid burden. 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

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

Background: Amyloidosis involving the heart is one of the types of the disease recognized in humans and has been previously described in dogs. To date, no data regarding the presence of amyloid in cardiac tissues of a large group of feline patients have been published. Our research aimed to analyze the presence and localization of amyloid in the atrial and ventricular cardiac tissue in retrospectively enrolled cats diagnosed with various types of primary cardiomyopathies, hyperthyroidism-induced cardiomyopathy, myocarditis, and generalized disorders. Methods: This study was conducted on atrial specimens obtained from 119 animals and on ventricular specimens obtained from 69 animals from that group. The atrial and ventricular specimens obtained from the enrolled animals were stained with Congo Red and evaluated in a light microscope and polarized light for the presence of amyloid deposits. Results: Five cases from the enrolled group turned out positive for amyloid deposits: three cats diagnosed with feline hyperthyroidism, one cat diagnosed with kidney glomerulonephritis, and one cat diagnosed with restrictive cardiomyopathy. In all positive cats, the amyloid deposits were present within the small intramural coronary arteries of the left ventricular free wall and interventricular septum and/or left and right atrium. No myocardial amyloid deposits were identified in the study group. Conclusions: In conclusion, cardiac coronary arterial amyloidosis, although infrequent, can be observed in cats. Full article