Cardiac Amyloidosis

This study aims to better quantify the improvements in heart failure symptoms and exercise tolerance before and after the heart rate elevation in a cohort of 10 cardiac amyloidosis patients with preexisting pacemakers.

Numerous clinical trials have demonstrated that transthyretin (TTR)-directed medical therapies can reduce the rate of functional decline in patients with transthyretin cardiac amyloidosis (ATTR-CM). However, patients treated with these therapies often experience a progressive reduction in exercise capacity despite treatment. Further, no randomized controlled trials (RCTs) have assessed the effects of exercise intervention in patients with ATTR-CM receiving TTR-directed therapy.

Cardiac amyloidosis (CA) is an infiltrative disease characterized by deposits of amyloid proteins of genetic or acquired origin (often in elderly patients), leading to heart failure and arrhythmias. More than 98% of currently diagnosed cases of cardiac amyloidosis result from fibrils composed of monoclonal immunoglobulin light chains (AL) or transthyretin (ATTR), in its hereditary (ATTRv) or acquired (ATTRwt) form. Its prevalence is rising sharply due to an aging population and improved diagnostic techniques. Atrial fibrillation is responsible, in particular, for heart failure, arrhythmias, conduction disorders, and ischemic strokes, and is associated with significant morbidity and mortality. These patients have a much higher-than-normal risk of stroke because they are in a procoagulant state in the left atrium, even in the absence of atrial fibrillation. Intracardiac thrombi (ICTs) are present in 28% of patients with AC requiring cardioversion, compared with 2.5% of patients without AC, 50% of whom are on anticoagulants. It has also been shown that the CHA2DS2-VASc score is not effective in predicting thromboembolic risk, and that direct oral anticoagulants (DOACs) are as effective as vitamin K antagonists (VKAs) in preventing embolisms. The prevalence and factors associated with the development of intracardiac thrombi in patients with cardiac amyloidosis are unknown, as the available retrospective studies focused only on selected high-risk patients. Furthermore, tafamidis is now available to stabilize the course of cardiac amyloidosis and improve prognosis, but its effect on thromboembolic risk remains unknown.

\[18F\]FT8, a derivative of 1-(4-pyridyl)-4-piperazinyl arene (\[18F\]TPZA), exhibits high affinity for AL amyloid in myocardial tissue sections and shows no significant binding to transthyretin amyloid. By comparing its diagnostic performance against established clinical methods, including echocardiography, contrast-enhanced MRI, and relevant laboratory tests, this study aims to establish \[18F\]FT8 as the basis for a robust PET protocol for the direct visualization and differential diagnosis of AL amyloidosis . The study preimarily evaluates the safety and diagnostic efficacy of \[18F\]FT8 PET imaging in human subjects.

To evaluate the potential usefulness of 18F-92/AV45/TPZA/FT8, 11C-PIB positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various Pan-Amyloid-related disease patients.

This is a mono-center observational ambispective study in which patients with cardiac amyloidosis evaluated at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Rome, Italy) will be enrolled. The primary aim is to investigate echocardiographic findings, particularly using advanced echocardiographic techniques, such as two- and three-dimensional speckle-tracking analysis, that may be helpful in the differential diagnosis between cardiac amyloidosis and other cardiomyopathies with hypertrophic phenotype. Secondary aims are: 1) to evaluate the reversibility of myocardial damage, assessed by echocardiography, in response to a newly available specific treatment for patients with transthyretin-related cardiac amyloidosis (tafamidis) and its correlation with the clinical response 2) to investigate potential novel echocardiographic predictors of adverse cardiovascular outcomes.

The goal of this study is to learn whether PET-CT imaging using evuzamitide can help diagnose transthyretin cardiac amyloidosis (ATTR-CA) in patients whose standard nuclear imaging results are unclear but who have elevated TAD1 levels in their blood. The main question it aims to answer is: Can evuzamitide PET-CT imaging detect signs of cardiac amyloidosis in patients with non-diagnostic nuclear scintigraphy but elevated TAD1 levels? Participants who meet eligibility criteria will receive a single PET-CT scan with evuzamitide and will be followed for approximately 28 days to monitor safety and collect additional clinical information.

Recently, treatment with tafamidis in patients with cardiac ATTR lead to a significant reduction in mortality. The Perugini score is commonly used on planar bone scans to differentiate cardiac ATTR from other amyloidosis or normal patients but fails to evaluate amyloid burden and patient prognosis. Although semi-quantitative methods have been suggested to evaluate the amyloid burden, there a need for quantitative methods for longitudinal assessment of the disease.

Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive infiltrative cardiomyopathy caused by the deposition of misfolded transthyretin protein within the myocardium. Current disease staging and follow-up strategies mainly rely on cardiac biomarkers and renal function; however, the systemic nature of ATTR suggests that additional organ involvement may provide valuable prognostic information. The purpose of this prospective observational study is to investigate liver dysfunction and coagulation abnormalities in patients with wild-type or hereditary ATTR-CA and to evaluate their potential role as novel markers of disease severity and progression. Patients with ATTR-CA will be compared with an age-matched control population with non-amyloid hypertrophic cardiomyopathy. Clinical, laboratory, echocardiographic, hepatic ultrasound, liver stiffness, and coagulation parameters will be assessed at baseline and during follow-up. The study will also evaluate changes in these parameters after 6 and 12 months of treatment with tafamidis. The results may improve the understanding of cardio-hepatic interactions in ATTR-CA and identify new tools for disease staging and longitudinal monitoring.

Patients operated for carpal tunnel syndrome (CTS) at Ålesund Hospital (200 patients) will have a biopsy to diagnose ATTR amyloidosis. Patients with positive biopsy will be examined to decide wether they have cardiac amyloidosis. All patients with positive biopsy will be followed closely for 10 years wit echocardiography an clinically.

Determining the etiology of cardiomyopathy is of high clinical importance for optimal treatment strategy and prediction of prognosis. There is increased risk for cardiovascular disease and higher propensity for cardiovascular related mortality among Black and non-Hispanic White patients. Recently, advanced cardiac imaging has become a vital tool in diagnosis and risk stratification of cardiovascular disease. Very limited data is available on the prevalence and characteristics of different cardiovascular diseases in Hispanic and African American minority groups, therefore, studying different racial and ethnic minority groups in the Bronx population is an exceptionally valuable source to determine the prevalence of cardiomyopathies among minority groups along with study survival in this population. This study aims to determine the etiology of cardiovascular disease in a diverse patient population by utilizing various cardiovascular imaging modalities, with a focus on cardiac magnetic resonance (CMR) imaging and to develop risk stratification models by applying advanced cardiovascular imaging markers.

This study is an open-label study to evaluate and characterize test-retest reliability of \[18F\]florbetaben PET in subjects with AL-CA and ATTR-CA compared to non-CA subjects. Quantification of the \[18F\]florbetaben parameters related to the deposition of amyloid in the heart (such as Myocardial Tracer Retention (MTR) or Retention Index (RI)), and the variability in these parameters after repeated imaging will be evaluated. Measurement of blood metabolites and comparison of invasive with non-invasive quantification of \[18F\]florbetaben uptake in the heart will be performed.

This multicenter prospective study aims to evaluate the diagnostic performance of right ventricular sensing amplitude measured during cardiac implantable electronic device (CIED) implantation (pacemaker or defibrillator) to identify cardiac amyloidosis in patients with left ventricular hypertrophy and conduction abnormalities. Patients aged 65 years or older referred for CIED implantation will be included. During the procedure, electrophysiological parameters will be recorded. Additional assessments will be performed, including cardiac scintigraphy, biological analyses, and subcutaneous adipose tissue biopsy. The results of these investigations will be used to confirm or rule out cardiac amyloidosis. Diagnostic performance will be assessed using the area under the receiver operating characteristic curve (AUROC).

Despite rapidly advancing developments in targeted therapeutics and genetic sequencing, persistent limits in the accuracy and throughput of clinical phenotyping has led to a widening gap between the potential and the actual benefits realized by precision medicine. Recent advances in machine learning and image processing techniques have shown that machine learning models can identify features unrecognized by human experts and more precisely/accurately assess common measurements made in clinical practice. The investigators have developed an algorithm, termed EchoNet-LVH, to identify cardiac hypertrophy and identify patients who would benefit from additional screening for cardiac amyloidosis and will prospectively evaluate its accuracy in identifying patients whom would benefit from additional screening for cardiac amyloidosis.

The primary goal of this pilot study is to determine whether \[64Cu\]FBP8, a novel fibrin-binding positron emission tomography (PET) probe, can identify intracardiac thrombi when paired with simultaneous hybrid cardiac PET/MRI in twenty (20) individuals with transthyretin or light chain cardiac amyloidosis and atrial fibrillation (AF) or atrial flutter (AF). The primary hypothesis of this study is that \[64Cu\]FBP8 PET/MRI can identify intracardiac thrombi in \>90% of subjects with confirmed intracardiac thrombi based on transesophageal echocardiogram (TEE). In secondary analyses, the investigators will seek to determine associations between intracardiac thrombi and left atrial function and left ventricular amyloid burden.

Exercise training in patients with heart failure and preserved ejection fraction (HFpEF) has been associated with an improvement in cardiorespiratory fitness and quality of life.

Cardiac amyloidosis is a condition where the heart muscle, amongst other tissues, is infiltrated by the abnormal build-up of proteins called amyloid. This stiffens and thickens the heart muscle over time which makes it less efficient and puts further stress and strain on the other chambers of the heart, leading to heart failure. The commonest form, that affects predominantly the elderly, is called 'wild-type' ATTR amyloid (TTR is the protein that accumulates). In this condition a patient has a 60% chance of admission to hospital each year after diagnosis. There is no current treatment for ATTR amyloid other than using water tablets to reduce excess fluid and prevent more serious fluid build up in lungs and other tissues. Increasing body weight is the most reliable clinical sign of this fluid build up. Tele-monitoring is the practice of monitoring patients from a distance and has been shown to reduce heart failure admissions and death in patients with heart failure from any cause. Due to reduced access to primary and secondary care during COVID-19 the investigators instigated tele-monitoring of heart failure in ATTR amyloid patients. This appeared to be an effective intervention in the pilot study. The investigators propose to monitor the weight of patients with cardiac amyloidosis at home and intervene where a build up of fluid is observed by telephone discussion with a doctor. The investigators propose to evidence this in a prospective clinical trial. The investigators will evaluate the effect fairly by comparing tele-monitoring with usual care.

Cardiac amyloidosis is characterized by deposition of misfolded protein in the myocardium causing mainly heart failure symptoms with preserved left ventricular ejection fraction. There are also specific clinical (bilateral carpal tunnel syndrome, polyneuropathy, skin bruising, ruptured biceps tendon…), biomarkers (disproportionally elevated NT-proBNP to the degree of heart failure, persistent elevated troponin, proteinuria..), electrocardiographic (reduced voltage of QRS, atrial fibrillation..) and echocardiographic features (concentric left ventricular hypertrophy, dilated atria, reduced global longitudinal strain with typical pattern of apical sparing, diastolic dysfunction…). Early diagnosis of the disease is crucial to identify patients that may benefit from appropriate treatment. Suspected cardiac amyloidosis on echocardiography or on cardiac magnetic resonance needs to prompt the request of serum free-light chain quantification and serum and urine immunofixation as well as single photon emission computed tomography (SPECT) using bone radiotracers. Echocardiography is the imaging technique of first choice to evaluate patients with dyspnea complaints and suspected heart failure as well as other pathologies. Echocardiography is a technique of first choice to evaluate patients with cardiovascular risk factors such as arterial hypertension and diabetes and many of those patients may have echocardiographic features that can be observed in early phases of cardiac amyloidosis. Currently, identification of patients with cardiac amyloidosis with available echocardiographic tools remains challenging. However, novel artificial intelligence (AI)-based algorithms applied to echocardiographic images for analysis may help the cardiologists in the identification of early phase of cardiac amyloidosis. Early diagnosis of cardiac amyloidosis is key to implement effective therapies that have demonstrated to improve survival. Several studies have demonstrated the accuracy of AI-based algorithms applied to echocardiography for the diagnosis of cardiac amyloidosis. The hypothesis of the present prospective study is to evaluate the accuracy of the AI-based algorithm to identify patients with echocardiographic findings suggestive of cardiac ATTR amyloidosis using as ground truth the subsequent analysis with imaging techniques that permit its diagnosis such as 99mTc-pyrophosphate (PYP) SPECT and cardiac magnetic resonance as well as hematologic tests. If needed, histological confirmation on cardiac or extracardiac tissue could be performed, as recommended by recent consensus document from the Heart Failure Association of the European Society of Cardiology. In addition, this study will help to answer the true prevalence of ATTR cardiac amyloidosis among patients referred to transthoracic echocardiography that present red flags for ATTR cardiac amyloidosis. The AI-based algorithm is the software Us2.ai which has been used in other populations for this purpose, as previously published.

Primary objective: To identify older adults with transthyretin cardiac amyloidosis (ATTR-CA) early in the course of the illness, at a time when disease modifying therapies are most effective. The specific aims of this epidemiologic investigation include: 1. To identify subjects with previous lumbar spinal stenosis (LSS) Surgery who have evidence of transthyretin (TTR) amyloid deposits in spinal specimens and could be at risk for ATTR cardiac amyloidosis. 2. To evaluate for ATTR-CA among those with localized TTR in the spinal tissue. The study will also explore the following: 1. The prevalence of amyloid in lumbar spinal stenosis specimens by Congo Red staining. 2. The prevalence of TTR deposits among subjects with amyloid as determined by mass spectrometry. 3. Evaluation of a novel artificial intelligence technique for that can identify amyloid histologically with standard H\&E staining. 4. Difference in ATTR-CA prevalence between subjects with TTR and indeterminate amyloid deposits in subject's spine by myocardial uptake of technetium pyrophosphate scan (Tc99-PYP).

Transthyretin cardiac amyloidosis (ATTR-CA) is traditionally diagnosed using planar bone scintigraphy with a Perugini visual score ≥ 2. Fast cardiac CZT-SPECT will be evaluated for its ability to reproduce this classification and provide reproducible quantitative myocardial uptake metrics.

This study aims to determine the positive predictive value of incidental cardiac uptake on bone scintigraphy for diagnosing transthyretin cardiac amyloidosis, in patients who underwent scintigraphy for reasons other than suspected amyloidosis. The study is an observational, descriptive, multicenter, national study using retrospective data from routine care. Patients with incidental cardiac uptake will be recalled for further diagnostic assessment.

Cardiac amyloidosis is a condition where abnormal protein deposits build up in the heart, making it stiff and causing it to work less effectively. One common type is caused by a normal blood protein called transthyretin (TTR), which can become unstable and form these deposits. When this happens, it is called ATTR-CM, a form of heart disease caused by TTR protein buildup. This can lead to symptoms like tiredness, shortness of breath, or swelling. Bilateral carpal tunnel syndrome (CTS) is recognized as an early clinical sign of systemic amyloidosis, especially in the context of TTR amyloidosis, where amyloid deposits accumulate in the median nerve. Early identification of cardiac amyloidosis, particularly in patients with bilateral CTS, may allow for earlier intervention with disease-modifying therapies, such as tafamidis, which has been shown to improve survival and reduce hospitalizations in patients with cardiac amyloidosis. The purpose of this study is to identify patients to evaluate them for previously undiagnosed cardiac amyloidosis. The collected information will help estimate the prevalence of cardiac amyloidosis among participants with prior bilateral CTS using a PYP nuclear scan (technetium-99m pyrophosphate scan). A PYP scan is a special heart imaging test that helps doctors see if certain abnormal proteins are building up in the heart. It's mainly used to help diagnose cardiac amyloidosis.

This study investigates the clinical efficacy of a non-invasive screening protocol using AI-ECG and CT-ECV analysis for cardiac amyloidosis. The study targets on atrial fibrillation(AF) patients with "red-flag" indicators. Participants are randomized 1:1 into either an early screening or usual care group. * Early screening group : AI- ECG and/or CT-ECV analysis + AF treatment * Usual care group : AF treatment Both groups followed for 2 years to compare CA detection rates and clinical outcomes.

The purpose of this study is to deploy and evaluate informational AI-Echo algorithms that assist echo clinicians in interpreting core echocardiographic parameters (e.g., LV/RV size and function, valvular disease severity) and stratifying disease progression risk. The primary outcome is clinician usability, interpretive consistency, and workflow integration. Second, we will conduct a pragmatic, stepped-wedge clinical trial with multiple arms evaluating diagnostic AI-Echo algorithms designed to identify specific cardiovascular diseases- such as genetic cardiomyopathy, ischemic heart disease, and cardiac amyloidosis-and assess whether AI deployment increases diagnostic testing and shortens time to diagnosis. Trials will be conducted using EHR-based notification systems with cluster-level randomization.

Tne aim purpose of this observational, multicentre and propective study is to determine the prevalence of cardiac amyloidosis in geriatric patients aged 80 years and older hospitalized within the last 12 months for heart failure with left ventricular hypertrophy (septum ≥ 12 mm) on echocardiography