Cardiac amyloidosis, increasingly recognized for its significant impact on global heart health and patient survival, demands a thorough review to understand its complexity and the urgency of improved management strategies. As a cause of cardiomyopathy and heart failure, particularly in patients with aortic stenosis and atrial fibrillation, this condition also relates to higher incidences of dementia in the affected populations. The objective of this review was to integrate and discuss the latest advancements in diagnostics and therapeutics for cardiac amyloidosis, emphasizing the implications for patient prognosis. We evaluated the latest literature from major medical databases such as PubMed and Scopus, focusing on research from 2020 to 2024, to gather comprehensive insights into the current landscape of this condition. Insights from our review highlight the complex pathophysiology of cardiac amyloidosis and the diagnostic challenges it presents. We detail the effectiveness of emerging treatments, notably gene silencing therapies like patisiran and vutrisiran, which offer transformative potential by targeting the production of amyloidogenic proteins. Additionally, the stabilization therapy acoramidis shows promise in modifying disease progression and improving clinical outcomes. This review underscores the critical need for updated clinical guidelines and further research to expand access to groundbreaking therapies and enhance disease management. Advocating for continued research and policy support, we emphasize the importance of advancing diagnostic precision and treatment effectiveness, which are vital for improving patient outcomes and addressing this debilitating disease globally.

BACKGROUND: The usefulness of monitoring treatment effect of tafamidis using magnetic resonance imaging (MRI) extracellular volume fraction (ECV) has been reported.
OBJECTIVE: we conducted a meta-analysis to evaluate the usefulness of this method.
METHODS: Data from 246 ATTR-CMs from six studies were extracted and included in the analysis. An inverse variance meta-analysis using a random effects model was performed to evaluate the change in MRI-ECV before and after tafamidis treatment. The analysis was also performed by classifying the patients into ATTR-CM types (wild-type or hereditary).
RESULTS: ECV change before and after tafamidis treatment was 0.33% (95% CI: -1.83-2.49, I2 = 0%, p = 0.76 for heterogeneity) in the treatment group and 4.23% (95% CI: 0.44-8.02, I2 = 0%, p = 0.18 for heterogeneity) in the non-treatment group. The change in ECV before and after treatment was not significant in the treated group (p = 0.76), but there was a significant increase in the non-treated group (p = 0.03). There was no difference in the change in ECV between wild-type (95% CI: -2.65-3.40) and hereditary-type (95% CI: -9.28-4.28) (p = 0.45).
CONCLUSIONS: The results of this meta-analysis suggest that MRI-ECV measurement is a useful imaging method for noninvasively evaluating the efficacy of tafamidis treatment for ATTR-CM.

Cardiac amyloidosis is the most frequent infiltrative disease caused by the deposition of misfolded proteins in the cardiac tissue, leading to heart failure, brady- and tachyarrhythmia and death. Conduction disorders, atrial fibrillation (AF) and ventricular arrhythmia (VA) significantly impact patient outcomes and demand recognition. However, several issues remain unresolved regarding early diagnosis and optimal management. Extreme bradycardia is the most common cause of arrhythmic death, while fast and sustained VAs can be found even in the early phases of the disease. Risk stratification and the prevention of sudden cardiac death are therefore to be considered in these patients, although the time for defibrillator implantation is still a subject of debate. Moreover, atrial impairment due to amyloid fibrils is associated with an increased risk of AF resistant to antiarrhythmic therapy, as well as recurrent thromboembolic events despite adequate anticoagulation. In the last few years, the aging of the population and progressive improvements in imaging methods have led to increases in the diagnosis of cardiac amyloidosis. Novel therapies have been developed to improve patients\' functional status, quality of life and mortality, without data regarding their effect on arrhythmia prevention. In this review, we consider the latest evidence regarding the arrhythmic risk stratification of cardiac amyloidosis, as well as the available therapeutic strategies.

OBJECTIVE: The efficacy of beta-blockers in cardiac amyloidosis (CA) is unclear, and concerns persist that neurohormonal blockade could worsen symptoms of heart failure. We aimed to assess whether beta-blocker therapy is associated with improved survival in patients with CA.
RESULTS: We conducted a systematic review and meta-analysis to examine the impact of beta-blocker therapy on mortality in patients with CA. A search of MEDLINE and EMBASE was performed in August 2023. Data were extracted from observational studies and synthesized with pooling and random effects meta-analysis. Thirteen studies including 4215 patients with CA were incorporated in this review (3688 transthyretin amyloid cardiomyopathy (ATTR-CM), 502 light chain amyloid cardiomyopathy (AL-CM), 25 not specified; age 74.8 ± 5.5 years, 76% male). Over half of the cohort (52%) received beta-blockers and the rate of beta-blocker withdrawal was 28%. All-cause mortality was 33% (range: 13-51%) after a median follow-up ranging from 13 to 36 months. There was an inverse association between the pooled risk of mortality and the use of beta-blocker therapy at any time point (RR 0.48, 95% CI 0.29-0.80, I2 = 83%, P = 0.005, seven studies). There was no association between mortality and beta-blocker use (RR 0.65, 95% CI 0.29-1.47, I2 = 88%, P = 0.30) in the three studies that only included patients with ATTR-CM. The three studies that included patients with both ATTR-CM and AL demonstrated an association of beta-blocker use with reduced mortality (OR 0.43, 95% CI 0.29-0.63, I2 = 4%, P < 0.001). The only study that solely included 53 patients with AL-CM, demonstrated improved survival among the 53% who were able to tolerate beta-blocker therapy (RR 0.26, 95% CI 0.08-0.79, P = 0.02). The absence of information on staging of CA is an important limitation of this study.
CONCLUSIONS: Treatment with beta-blockers may be associated with a survival benefit in patients with CA, but these findings are subject to selection and survivor biases. Definitive prospective randomized trials of conventional heart failure therapies are needed in CA.

Technetium-99m pyrophosphate (Tc-99m PYP) cardiac imaging is a simple, widely available, noninvasive method to identify patients with transthyretin-type cardiac amyloidosis (ATTR), and it has remarkably high diagnostic accuracy with very high sensitivity and specificity. Visual scores of 0, 1, 2, and 3 indicate non-myocardial uptake, uptake less than rib, equal to rib, and greater than rib uptake, respectively. Semiquantitative assessment using the heart-to-contralateral lung ratio of more than 1.5 at 1 hour accurately distinguishes ATTR from the cardiac amyloid light chain subtype. However, there are several incidental non-cardiac findings that can be seen in planar images, rotating single-photon emission computed tomography (SPECT) images, maximum intensity projection images, or computed tomography images acquired for attenuation correction. These findings may lead to the early detection of a noncardiac condition that may require additional treatment. The intent of this review is to demonstrate several incidental noncardiac abnormalities that have an impact on patient management and follow-up.

Cardiac amyloidosis, characterized by amyloid fibril deposition in the myocardium, leads to restrictive cardiomyopathy and heart failure. This review explores recent advancements in imaging techniques for diagnosing and managing cardiac amyloidosis, highlighting their clinical applications, strengths, and limitations. Echocardiography remains a primary, non-invasive imaging modality but lacks specificity. Cardiac MRI (CMR), with Late Gadolinium Enhancement (LGE) and T1 mapping, offers superior tissue characterization, though at higher costs and limited availability. Scintigraphy with Tc-99m-PYP reliably diagnoses transthyretin (TTR) amyloidosis but is less effective for light chain (AL) amyloidosis, necessitating complementary diagnostics. Amyloid-specific PET tracers, such as florbetapir and flutemetamol, provide precise imaging and quantitative assessment for both TTR and AL amyloidosis. Challenges include differentiating between TTR and AL amyloidosis, early disease detection, and standardizing imaging protocols. Future research should focus on developing novel tracers, integrating multimodality imaging, and leveraging AI to enhance diagnostic accuracy and personalized treatment. Advancements in imaging have improved cardiac amyloidosis management. A multimodal approach, incorporating echocardiography, CMR, scintigraphy, and PET tracers, offers comprehensive assessment. Continued innovation in tracers and AI applications promises further enhancements in diagnosis, early detection, and patient outcomes.

Amyloidosis is a systemic disease initiated by deposition of misfolded proteins in the extracellular space, due to which multiple organs may be affected concomitantly. Cardiac amyloidosis, however, remains a major cause of morbidity and mortality in this population due to infiltrative /restrictive cardiomyopathy. This review attempts to focus on contemporary medical and surgical therapies for the different types of cardiac amyloidosis. Amyloidosis affecting the heart are predominantly of the transthyretin type (acquired in the older or genetic in the younger patients), and the monoclonal immunoglobulin light chain (AL) type which is solely acquired. A rare form of secondary amyloidosis AA type can also affect the heart due to excessive production and accumulation of the acute-phase protein called Serum Amyloid A\" (SAA) in the setting of chronic inflammation, cancers or autoinflammatory disease. More commonly AA amyloidosis is seen in the liver and kidney. Other rare types are Apo A1 and Isolated Atrial Amyloidosis (AANF). Medical therapies have made important strides in the clinical management of the two common types of cardiac amyloidosis. Surgical therapies such as mechanical circulatory support and cardiac transplantation should be considered in appropriate patients. Future research using AI driven algorithms for early diagnosis and treatment as well as development of newer genetic engineering technologies will drive improvements in diagnosis, treatment and patient outcomes.

Cardiac amyloidosis (CA) is an underdiagnosed form of infiltrative cardiomyopathy caused by abnormal amyloid fibrils deposited extracellularly in the myocardium and cardiac structures. There can be high variability in its clinical manifestations, and diagnosing CA requires expertise and often thorough evaluation; as such, the diagnosis of CA can be challenging and is often delayed. The application of artificial intelligence (AI) to different diagnostic modalities is rapidly expanding and transforming cardiovascular medicine. Advanced AI methods such as deep-learning convolutional neural networks (CNNs) may enhance the diagnostic process for CA by identifying patients at higher risk and potentially expediting the diagnosis of CA. In this review, we summarize the current state of AI applications to different diagnostic modalities used for the evaluation of CA, including their diagnostic and prognostic potential, and current challenges and limitations.

Cardiac amyloidosis (CA) is a condition characterized by the accumulation of amyloid fibrils in the heart muscle, resulting in an infiltrative cardiomyopathy. The presence of amyloid protein can impact different parts of the heart, including the valves. Limited data is available on the prevalence and prognostic significance of valvular heart disease (VHD) in CA. However, advancements in imaging technology have allowed for accurate noninvasive diagnosis of CA, eliminating the need for confirmatory endomyocardial biopsy and improving our understanding of this dual pathology. The development of targeted drug therapies for CA and transcatheter valve replacement or repair for VHD has significantly improved the prognosis for patients with both conditions. This review will discuss the findings of this original research and provide an overview of current researches on VHD in CA, as well as the progress in diagnosing and treating CA with VHD.

Cardiac amyloidosis (CA) is related to the aggregation of insoluble fibrous deposits of misfolded proteins within the myocardium. Transthyretin amyloidosis (ATTR) and immunoglobulin light-chain amyloidosis are the main forms of CA. Atrial fibrillation (AF) is a common arrhythmia in CA patients, especially in those with ATTR amyloidosis. Increased atrial preload and afterload, atrial enlargement, enhanced atrial wall stress, and autonomic dysfunction are the main mechanisms of AF in CA patients. CA is associated with the formation of endocardial thrombi and systemic embolism. The promoters of thrombogenesis include endomyocardial damage, blood stasis, and hypercoagulability. The prevalence of thrombi in patients with AF remains elevated despite long-term anticoagulation. Consequently, transesophageal ultrasound examinations before cardioversion should be performed to exclude endocardiac thrombi despite anticoagulation. Furthermore, the CHA2DS2-VASc score should not be used to assess the thromboembolic risk in CA patients with AF. Rate control is challenging in patients with CA, while rhythm control is the preferred treatment option, especially in the early stages of the disease process. Although catheter ablation is an effective treatment option, more data are needed to explore the role of the procedure in CA patients.