Cardiac amyloid

BACKGROUND: Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the disease form and the type of deposited amyloid. Coexistence of clinical conditions such as old age, monoclonal gammopathy, chronic inflammation, or peripheral neuropathy in a patient with cardiomyopathy creates a differential diagnosis between the major types of CA: amyloidosis light chains (AL), amyloidosis transthyretin (ATTR) and amyloidosis A (AA)...

INTRODUCTION: While pyrophosphate uptake imaging with Technetium-99 m pyrophosphate (Tc-99 m PYP) is frequently used for cardiac ATTR amyloid imaging, its role in determining the timing of acute myocardial infarction (AMI) is near forgotten. We present a case that demonstrates the clinical benefit of pyrophosphate uptake imaging in differentiating recent from remote infarction as a reminder of the continued utility of pyrophosphate uptake imaging for this indication. CASE AND OUTCOMES: A 68-year-old male was referred for surgical replacement of his bicuspid aortic valve with severe aortic regurgitation...

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...

Cardiac amyloidosis is increasingly recognized as a treatable form of heart failure. Highly effective specific therapies have recently become available for the 2 most frequent forms of cardiac amyloidosis: immunoglobulin light chain amyloidosis and transthyretin (ATTR) amyloidosis. Nevertheless, initiation of specific therapies requires recognition of cardiac amyloidosis and appropriate characterization of the amyloid type. Although noninvasive diagnosis is possible for ATTR cardiac amyloidosis, histological demonstration and typing of amyloid deposits is still required for a substantial number of patients with ATTR and in all patients with light chain amyloidosis and other rarer forms of cardiac amyloidosis...

Although most patients with cardiac amyloidosis are diagnosed with either light chain (AL) or transthyretin (ATTR) disease, coexisting amyloid subtypes can occur. We present three cases of coexisting AL and ATTR cardiac amyloidosis and demonstrate the importance of clinical history and endomyocardial biopsy in diagnosis of this rare entity.

BACKGROUND: Cardiac amyloidosis is a fatal disease of severe heart failure caused by the accumulation of amyloid in the myocardium. This disease is often advanced by the time cardiac symptoms appear; therefore, early detection and treatment are critical for a good prognosis. Recently, it has been suggested that cardiac amyloidosis is implicated in several orthopedic diseases, including carpal tunnel syndrome (CTS), which is often reported to precede cardiac dysfunction. Shoulder disease has also been suggested to be associated with cardiac amyloidosis; however, there have been no reports investigating the rate of amyloid deposition in shoulder specimens and the simultaneous prevalence of cardiac amyloidosis...

Although amyloid material in the heart is not infrequently encountered at autopsy it may on occasion be difficult to determine the significance in terms of possible contributions to the terminal mechanisms of death. A review was undertaken of the literature and of autopsy cases at Forensic Science SA over a 20-year-period (2003-2022) for all cases where significant amyloid material had been encountered on microscopy of the heart. Sixteen cases were found consisting of 11 cases where cardiac amyloid was involved in the lethal episode, and five where it was considered an incidental feature...

IMPORTANCE: Cardiopulmonary exercise testing (CPET) has an established role in the assessment of patients with heart failure. However, data are lacking in patients with transthyretin (ATTR) amyloidosis. OBJECTIVE: To use CPET to characterize the spectrum of functional phenotypes in patients with ATTR amyloidosis and assess their association with the cardiac amyloid burden as well as the association between CPET parameters and prognosis. DESIGN, SETTING AND PARTICIPANTS: This single-center study evaluated patients diagnosed with ATTR amyloidosis from May 2019 to September 2022 who underwent CPET at the National Amyloidosis Centre...

BACKGROUND: Hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has a long latency phase before clinical onset, creating a need to identify subclinical disease. We hypothesized circulating transthyretin (TTR) and retinol binding protein 4 (RBP4) levels would be associated with TTR carrier status and correlated with possible evidence of subclinical ATTRv-CA. METHODS: TTR and RBP4 were measured in blood samples from V122I TTR carriers and age-, sex- and race-matched non-carrier controls (1:2 matching) among Dallas Heart Study participants (phases 1 (DHS-1) and 2 (DHS-2))...

IMPORTANCE: Systemic amyloidosis from transthyretin (ATTR) protein is the most common type of amyloidosis that causes cardiomyopathy. OBSERVATIONS: Transthyretin (TTR) protein transports thyroxine (thyroid hormone) and retinol (vitamin A) and is synthesized predominantly by the liver. When the TTR protein misfolds, it can form amyloid fibrils that deposit in the heart causing heart failure, heart conduction block, or arrhythmia such as atrial fibrillation. The biological processes by which amyloid fibrils form are incompletely understood but are associated with aging and, in some patients, affected by inherited variants in the TTR genetic sequence...

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR cardiac amyloidosis) is caused by variant (ATTRv) or wild type (ATTRwt) transthyretin. While gait abnormalities have been studied in younger patients with ATTRv amyloidosis, research on gait in older adults with ATTR cardiac amyloidosis is lacking. Given ATTR cardiac amyloidosis' association with neuropathy and orthopedic manifestations, we explore the gait in this population. METHODS: Twenty-eight older male ATTR cardiac amyloidosis patients and 11 healthy older male controls walked overground with and without a dual cognitive task...

Amyloidosis is a local or systemic disease caused by the deposition of misfolded proteins outside the cell, with rapid progression, and dire prognosis. Common types of cardiac amyloidosis are monoclonal immunoglobulin light chain amyloidosis (AL-CA) and transthyretin cardiac amyloidosis (ATTR-CA). Nuclear medicine examinations can be accurate, rapid, and non-invasive to help diagnose diseases and can effectively predict the prognosis of patients with CA. Technetium (99 Tcm )-labeled bisphosphonate imaging has been included in the consensus of experts and has become the first-line imaging method for the diagnosis of ATTR-CA...

The brain vascular system receives one-fifth of the total oxygen from the cardiac output, and this transport system is highly dependent on blood-brain barrier (BBB) integrity. The cerebral blood flow is controlled by neurovascular coupling through neurovascular units (NVUs). The NVU includes different types of cells, such as mural cells, astrocytes, pericytes, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs). The cellular composition of NVU varies throughout the vascular tree. Amyloid β (Aβ) is abundantly present in the central nervous system, but the pathological accumulation of misfolded Aβ protein causes vascular damage, resulting in neurovascular dysfunction...

INTRODUCTION: Myocardial injury in elderly Omicron variant patients is a leading cause of severe disease and death. This study focuses on elucidating the clinical characteristics and potential risk factors associated with myocardial injury in elderly patients infected with the Omicron variant. METHODS: Myocardial injury was defined based on elevated cardiac troponin concentrations exceeding the 99th percentile upper reference limit. Among 772 elderly Omicron-infected patients, categorized into myocardial injury ( n  = 263) and non-myocardial injury ( n  = 509) groups...

This study aimed to assess the frequency and association between transthyretin-derived (ATTR) amyloidosis and sarcoidosis in a large autopsy cohort including many cases of sudden cardiac death (SCD). We identified 73 sporadic ATTR amyloidosis cases and 11 sarcoidosis cases, among which we found two cases with concomitant ATTR amyloidosis and sarcoidosis (2.4% of all cases; 2.7% within the sporadic ATTR group). The first case involved a 92-year-old man who experienced SCD. In this patient's heart, we observed ATTR deposition and noncaseating epithelioid granulomas consistent with sarcoidosis...

Cardiomyocytes activate the unfolded protein response (UPR) transcription factor ATF6 during pressure overload-induced hypertrophic growth. The UPR is thought to increase ER protein folding capacity and maintain proteostasis. ATF6 deficiency during pressure overload leads to heart failure, suggesting that ATF6 protects against myocardial dysfunction by preventing protein misfolding. However, conclusive evidence that ATF6 prevents toxic protein misfolding during cardiac hypertrophy is still pending. Here, we found that activation of the UPR, including ATF6, is a common response to pathological cardiac hypertrophy in mice...

Background and Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a rare disease caused by pathogenic variants in the transthyretin ( TTR ) gene. More than 140 different disease-causing variants in TTR have been reported. Only a few individuals with a rare TTR variant, c.302C>T, p.(Ala101Val) (historically known as p.(Ala81Val)), primarily associated with cardiac ATTRv, have been described. Therefore, our aim was to analyze the clinical characteristics of individuals with the identified c.302C>T TTR variant at our center...

BACKGROUND: Cardiac arrhythmias are a common health problem. Both common and rare genetic risk factors exist for cardiac arrhythmias. Cardiac amyloidosis is a rare disease that may manifest various arrhythmias. Few large-scale whole exome sequencing studies elucidating the contribution of rare variations to arrhythmias have been published. OBJECTIVE: To access gene collapsing analysis of rare variations for different types of cardiac arrhythmias in UK Biobank. Identified genes were analyzed in silico for probability to form amyloid fibrils...

BACKGROUND: The echocardiographic determination of cardiac causes of stroke focuses on the presence of left ventricular thrombus, valvular vegetations, and patent foramen ovale. Transoesophageal echocardiogram (TEE) is indicated when the transthoracic echocardiogram (TTE) is inconclusive or when there is clinical suspicion of cardiac causes that may have been missed by TTE. The presence of severe diastolic dysfunction on TTE in the absence of any other cardiac abnormality or cardiac history is not usually considered a clue to the cause of stroke...

BACKGROUND: Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a growing interest in prognostication of patients with cardiac amyloidosis using cardiac magnetic resonance imaging (CMR). In this systematic review and meta-analysis, we aimed to examine the prognostic significance of myocardial native T1 and T2, and extracellular volume (ECV). METHODS: Observational cohort studies or single arms of clinical trials were eligible...